bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Hypoxia-Inducible Factor HIF-1A as Transcriptional Regulator of the A2B Adenosine Receptor during Acute Lung Injury
Authors: Eckle Tobias , Kewley Emily M. , Brodsky Kelley S. , Tak Eunyoung , Bonney Stephanie , Gobel Merit , Anderson Devon , Glover Louise E. , Riegel Ann K. , Colgan Sean P. , Eltzschig Holger K.
Published: January 2014

Although acute lung injury (ALI) contributes significantly to critical illness, resolution often occurs spontaneously through endogenous pathways. We recently found that mechanical ventilation increases levels of pulmonary adenosine, a signaling molecule known to attenuate lung inflammation. In this study, we hypothesized a contribution of transcriptionally controlled pathways to pulmonary adenosine receptor (ADOR) signaling during ALI. We gained initial insight from microarray analysis of pulmonary epithelia exposed to conditions of cyclic mechanical stretch, a mimic for ventilation-induced lung disease. Surprisingly, these studies revealed a selective induction of the ADORA2B. Using real-time RT-PCR and Western blotting, we confirmed an up to 9-fold induction of the ADORA2B following cyclic mechanical stretch (A549, Calu-3, or human primary alveolar epithelial cells). Studies using ADORA2B promoter constructs identified a prominent region within the ADORA2B promoter conveying stretch responsiveness. This region of the promoter contained a binding site for the transcription factor hypoxia-inducible factor (HIF)-1. Additional studies using site-directed mutagenesis or transcription factor binding assays demonstrated a functional role for HIF-1 in stretch-induced increases of ADORA2B expression. Moreover, studies of ventilator-induced lung injury revealed induction of the ADORA2B during ALI in vivo that was abolished following HIF inhibition or genetic deletion of Hif1a. Together, these studies implicate HIF in the transcriptional control of pulmonary adenosine signaling during ALI.
Mannan-Binding Protein, a C-Type Serum Lectin, Recognizes Primary Colorectal Carcinomas through Tumor-Associated Lewis Glycans
Authors: Nonaka Motohiro , Imaeda Hirotsugu , Matsumoto Shogo , Yong Ma Bruce , Kawasaki Nobuko , Mekata Eiji , Andoh Akira , Saito Yasuharu , Tani Tohru , Fujiyama Yoshihide , Kawasaki Toshisuke
Published: January 2014

Mannan (mannose)-binding protein (MBP) is a C-type serum lectin that plays a key role in innate immunity. MBP forms large multimers (200–600 kDa) and exhibits broad specificity for mannose, N-acetylglucosamine, and fucose. MBP exhibits high affinity for unique oligosaccharides that have been isolated from human colorectal carcinoma (SW1116) cells and characterized as highly fucosylated high m.w. type 1 Lewis glycans. In this study, we first demonstrated that MBP recognizes human primary colorectal carcinoma tissues through tumor-associated MBP ligands. We performed fluorescence-based histochemistry of MBP in human colorectal carcinoma tissues and showed that MBP clearly stained cancer mucosae in a Ca2+-dependent manner. Coincubation with plant (Aleuria aurantia) lectin, but not Con A, blocked MBP staining, indicating that fucose, rather than mannose, is involved in this interaction. The expression of MBP ligands was detected in 127 of 330 patients (38.5%), whereas, most significantly, there was no expression in 69 nonmalignant tissues. The MBP-staining pattern in cancer mucosae significantly overlapped with that of Lewis b [Fucα1-2Galβ1-3(Fucα1-4)GlcNAc] staining, but the Lewis b staining in normal tissues was not associated with MBP staining. In addition, the MBP staining correlated inversely with the expression of CA19-9 Ag, and MBP stained 11 of 25 (44%) CA19-9 (sialyl Lewis a [NeuAc(α2-3)Galβ1-3(Fucα1-4)GlcNAc])− colorectal carcinoma tissues. We found a favorable prognosis in patients with MBP ligand+ tumors. These results suggest that selective recognition of cancer cells by endogenous MBP seems to be associated with an antitumor effect and that tissue staining with MBP in combination with CA19-9 may serve as a novel indicator of colorectal carcinoma tissues.
Activation of the Epidermal Growth Factor Receptor in Macrophages Regulates Cytokine Production and Experimental Colitis
Authors: Lu Ning , Wang Lihong , Cao Hailong , Liu Liping , Van Kaer Luc , Washington Mary K. , Rosen Michael J. , Dubé Philip E. , Wilson Keith T. , Ren Xiubao , Hao Xishan , Polk D. Brent , Yan Fang
Published: January 2014

Macrophages regulate innate immunity to maintain intestinal homeostasis and play pathological roles in intestinal inflammation. Activation of the epidermal growth factor receptor (EGFR) promotes cellular proliferation, differentiation, survival, and wound closure in several cell types. However, the impact of EGFR in macrophages remains unclear. This study was to investigate whether EGFR activation in macrophages regulates cytokine production and intestinal inflammation. We found that EGFR was activated in colonic macrophages in mice with dextran sulfate sodium (DSS)–induced colitis and in patients with ulcerative colitis. DSS-induced acute colitis was ameliorated, and recovery from colitis was promoted in Egfrfl/flLysM-Cre mice with myeloid cell–specific deletion of EGFR, compared with LysM-Cre mice. DSS treatment increased IL-10 and TNF levels during the acute phase of colitis, and increased IL-10 but reduced TNF levels during the recovery phase in Egfrfl/flLysM-Cre mice. An anti–IL-10 neutralizing Ab abolished these effects of macrophage-specific EGFR deletion on DSS-induced colitis in Egfrfl/flLysM-Cre mice. LPS stimulated EGFR activation and inhibition of EGFR kinase activity enhanced LPS-stimulated NF-κB activation in RAW 264.7 macrophages. Furthermore, induction of IL-10 production by EGFR kinase-blocked RAW 264.7 cells, in response to LPS plus IFN-γ, correlated with decreased TNF production. Thus, although selective deletion of EGFR in macrophages leads to increases in both pro- and anti-inflammatory cytokines in response to inflammatory stimuli, the increase in the IL-10 level plays a role in suppressing proinflammatory cytokine production, resulting in protection of mice from intestinal inflammation. These results reveal an integrated response of macrophages regulated by EGFR in intestinal inflammatory disorders.
Engulfment of Apoptotic Cells by Macrophages: A Role of MicroRNA-21 in the Resolution of Wound Inflammation
Authors: Das Amitava , Ganesh Kasturi , Khanna Savita , Sen Chandan K. , Roy Sashwati
Published: January 2014

At an injury site, efficient clearance of apoptotic cells by wound macrophages or efferocytosis is a prerequisite for the timely resolution of inflammation. Emerging evidence indicates that microRNA-21 (miR-21) may regulate the inflammatory response. In this work, we sought to elucidate the significance of miR-21 in the regulation of efferocytosis-mediated suppression of innate immune response, a key process implicated in resolving inflammation following injury. An increased expression of inducible miR-21 was noted in postefferocytotic peripheral blood monocyte-derived macrophages. Such induction of miR-21 was associated with silencing of its target genes PTEN and PDCD4. Successful efferocytosis of apoptotic cells by monocyte-derived macrophages resulted in the suppression of LPS-induced NF-κB activation and TNF-α expression. Interestingly, bolstering of miR-21 levels alone, using miR mimic, resulted in significant suppression of LPS-induced TNF-α expression and NF-κB activation. We report that efferocytosis-induced miR-21, by silencing PTEN and GSK3β, tempers the LPS-induced inflammatory response. Macrophage efferocytosis is known to trigger the release of anti-inflammatory cytokine IL-10. This study demonstrates that following successful efferocytosis, miR-21 induction in macrophages silences PDCD4, favoring c-Jun–AP-1 activity, which in turn results in elevated production of anti-inflammatory IL-10. In summary, this work provides direct evidence implicating miRNA in the process of turning on an anti-inflammatory phenotype in the postefferocytotic macrophage. Elevated macrophage miR-21 promotes efferocytosis and silences target genes PTEN and PDCD4, which in turn accounts for a net anti-inflammatory phenotype. Findings of this study highlight the significance of miRs in the resolution of wound inflammation.
The SOCS3-Independent Expression of IDO2 Supports the Homeostatic Generation of T Regulatory Cells by Human Dendritic Cells
Authors: Trabanelli Sara , Očadlíková Darina , Ciciarello Marilena , Salvestrini Valentina , Lecciso Mariangela , Jandus Camilla , Metz Richard , Evangelisti Cecilia , Laury-Kleintop Lisa , Romero Pedro , Prendergast George C. , Curti Antonio , Lemoli Roberto M.
Published: January 2014

Dendritic cells (DCs) are professional APCs that have a role in the initiation of adaptive immune responses and tolerance. Among the tolerogenic mechanisms, the expression of the enzyme IDO1 represents an effective tool to generate T regulatory cells. In humans, different DC subsets express IDO1, but less is known about the IDO1-related enzyme IDO2. In this study, we found a different pattern of expression and regulation between IDO1 and IDO2 in human circulating DCs. At the protein level, IDO1 is expressed only in circulating myeloid DCs (mDCs) and is modulated by PGE2, whereas IDO2 is expressed in both mDCs and plasmacytoid DCs and is not modulated by PGE2. In healthy subjects, IDO1 expression requires the presence of PGE2 and needs continuous transcription and translation, whereas IDO2 expression is constitutive, independent from suppressor of cytokine signaling 3 activity. Conversely, in patients suffering from inflammatory arthritis, circulating DCs express both IDO1 and IDO2. At the functional level, both mDCs and plasmacytoid DCs generate T regulatory cells through an IDO1/IDO2-dependent mechanism. We conclude that, in humans, whereas IDO1 provides an additional mechanism of tolerance induced by proinflammatory mediators, IDO2 is stably expressed in steady-state conditions and may contribute to the homeostatic tolerogenic capacity of DCs.
An Alternative Splicing Isoform of MITA Antagonizes MITA-Mediated Induction of Type I IFNs
Authors: Chen Honghe , Pei Rongjuan , Zhu Wandi , Zeng Rui , Wang Yun , Wang Yanyi , Lu Mengji , Chen Xinwen
Published: January 2014

Mediator of IFN regulatory transcription factor 3 activation (MITA) is an important adaptor protein to mediate the induction of type I IFNs. In this study, we identified an alternatively spliced isoform of MITA lacking exon 7, termed MITA-related protein (MRP). MRP shares the N-terminal portion aa 1–253 with MITA but possesses a unique 30-aa sequence at the carboxyl terminal part, therefore lacking the conserved domains including TANK-binding kinase 1 (TBK1) and cyclic diguanylate binding domain. MRP is expressed in multiple tissues and distinct cell lines. Overexpression of MRP inhibited MITA-mediated activation of IFN-β promoter by sendai virus infection and cyclic diguanylate treatment but enhanced that in HSV-1 infection. Interestingly, MRP expression was reduced after Sendai virus infection but was upregulated after HSV-1 infection. Overexpression of MRP inhibited MITA-mediated induction of IFN-β via TBK1-IFN regulatory transcription factor 3 by disrupting the MITA-TBK1 interaction. However, NF-κB pathway was still activated by MRP, as MRP retained the ability to interact with inducible inhibitor of NF-κB (iκB) kinase. Thus, MRP acts as a dominant negative regulator of MITA-mediated induction of IFN production.
A Novel Mitochondrial MAVS/Caspase-8 Platform Links RNA Virus–Induced Innate Antiviral Signaling to Bax/Bak-Independent Apoptosis
Authors: El Maadidi Souhayla , Faletti Laura , Berg Birgit , Wenzl Christin , Wieland Katrin , Chen Zhijian J. , Maurer Ulrich , Borner Christoph
Published: January 2014

Semliki Forest virus (SFV) requires RNA replication and Bax/Bak for efficient apoptosis induction. However, cells lacking Bax/Bak continue to die in a caspase-dependent manner. In this study, we show in both mouse and human cells that this Bax/Bak-independent pathway involves dsRNA-induced innate immune signaling via mitochondrial antiviral signaling (MAVS) and caspase-8. Bax/Bak-deficient or Bcl-2– or Bcl-xL–overexpressing cells lacking MAVS or caspase-8 expression are resistant to SFV-induced apoptosis. The signaling pathway triggered by SFV does neither involve death receptors nor the classical MAVS effectors TNFR-associated factor-2, IRF-3/7, or IFN-β but the physical interaction of MAVS with caspase-8 on mitochondria in a FADD-independent manner. Consistently, caspase-8 and -3 activation are reduced in MAVS-deficient cells. Thus, after RNA virus infection MAVS does not only elicit a type I antiviral response but also recruits caspase-8 to mitochondria to mediate caspase-3 activation and apoptosis in a Bax/Bak-independent manner.
MicroRNA-155 and MicroRNA-21 Promote the Expansion of Functional Myeloid-Derived Suppressor Cells
Authors: Li Limin , Zhang Jing , Diao Wenli , Wang Dong , Wei Yao , Zhang Chen-Yu , Zen Ke
Published: January 2014

Myeloid-derived suppressor cells (MDSC) are one of the main cell populations that negatively regulate immune responses. However, the mechanism underlying the expansion of MDSC remains unclear. Using miRNA microarray and TaqMan probe–based quantitative RT-PCR assay, we identified microRNA (miR)-155 and miR-21 as the two most upregulated miRNAs during the induction of MDSC from the bone marrow cells by GM-CSF and IL-6. High levels of miR-155 and miR-21 also were detected in bone marrow and spleen MDSC isolated from tumor-bearing mice. Our results also showed that TGF-β promoted the induction of MDSC through upregulating miR-155 and miR-21 expression. Overexpression of miR-155 and miR-21 enhanced whereas depletion of miR-155 and miR-21 reduced the frequencies of cytokine-induced MDSC. Subpopulation analysis indicated that miR-21 and miR-155 induced the expansion of both monocytic and granulocytic MDSC. Furthermore, miR-155 and miR-21 showed a synergistic effect on MDSC induction via targeting SHIP-1 and phosphatase and tensin homolog, respectively, leading to STAT3 activation. Finally, dexamethasone treatment strongly enhanced MDSC expansion through upregulating miR-155 and miR-21 expression, and the effect of dexamethasone on MDSC induction was abolished by depleting cellular miR-155 and miR-21. These results demonstrate a novel miR-155/miR-21–based regulatory mechanism that modulates functional MDSC induction.
The (1→6)-β-Glucan Moiety Represents a Cross-Reactive Epitope of Infection-Induced Malignancy Surveillance
Authors: Dong Hongliang , Dai Hui , Hu Xiaomin , Xiong Si-Dong , Gao Xiao-Ming
Published: January 2014

Exposure to pathogen-associated molecular patterns (PAMPs) by vaccination or infection is known to have beneficial effects on neoplastic diseases, although the underlying molecular mechanisms are so far unclear. In this article, we report that Abs against (1→6)-β-d-glucan, a typical microbial PAMP and a major target for high titer circulating natural Abs in healthy human subjects, cross-recognize a novel tumor-associated carbohydrate Ag on cancer cells. The (1→6)-β-glucan cross-reactive moiety is immunologically dominant in tumor cells, as C57BL/6 mice harboring EL-4 solid tumors produced anti-(1→6)-β-glucan Abs and the titer of which significantly correlated with enhanced survival and smaller tumor burden. Moreover, the (1→6)-β-glucan–specific Abs exhibited potent tumoricidal activities in vitro. C57BL/6 mice immunized with Candida albicans produced protective immunity against inoculated EL-4 tumors, which was attributed to the formation of (1→6)-β-glucan–specific Abs. Importantly, (1→6)-β-glucan–specific Abs significantly prolonged the survival and reduced the tumor size in mice inoculated with EL-4 tumors. Our results demonstrate that the (1→6)-β-glucan cross-reactive moiety represents a focal point between infection immunity and cancer surveillance, and natural Abs against this epitope may contribute to the first-line antitumor surveillance in humans. Our data also provide important explanation for the long-observed relationship between feverish infection and concurrent remission from cancer.
Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Faslpr Mice
Authors: Fujita Yoshimasa , Fujii Takao , Mimori Tsuneyo , Sato Tomomi , Nakamura Takuji , Iwao Haruka , Nakajima Akio , Miki Miyuki , Sakai Tomoyuki , Kawanami Takafumi , Tanaka Masao , Masaki Yasufumi , Fukushima Toshihiro , Okazaki Toshiro , Umehara Hisanori
Published: January 2014

Leptin is secreted by adipocytes, the placenta, and the stomach. It not only controls appetite through leptin receptors in the hypothalamus, it also regulates immunity. In the current study, we produced leptin-deficient MRL/Mp-Faslpr mice to investigate the potential role of leptin in autoimmunity. C57BL/6J-ob/ob mice were backcrossed with MRL/Mp-Faslpr mice, which develop human systemic lupus erythematosus (SLE)-like lesions. The effects of leptin deficiency on various SLE-like manifestations were investigated in MRL/Mp-Faslpr mice. The regulatory T cell population in the spleen was analyzed by flow cytometry, and the effects of leptin on regulatory T cells and Th17 cells were evaluated in vitro. Compared with leptin-producing MRL/Mp-Faslpr mice, leptin-deficient MRL/Mp-Faslpr mice showed less marked splenomegaly and a particularly low population of CD3+CD4−CD8−B220+ T cells (lpr cells). Their serum concentrations of Abs to dsDNA were lower, and renal histological changes at age 20 wk were ameliorated. Regulatory T cells were increased in the spleens of leptin-deficient MRL/Mp-Faslpr mice. Leptin suppressed regulatory T cells and enhanced Th17 cells in vitro. In conclusion, blockade of leptin signaling may be of therapeutic benefit in patients with SLE and other autoimmune diseases.
Attenuation of Respiratory Syncytial Virus–Induced and RIG-I–Dependent Type I IFN Responses in Human Neonates and Very Young Children
Authors: Marr Nico , Wang Ting-I , Kam Sarah H. Y. , Hu Yuan Shen , Sharma Ashish A. , Lam Angie , Markowski Joy , Solimano Alfonso , Lavoie Pascal M. , Turvey Stuart E.
Published: January 2014

Newborn infants, including those born at term without congenital disorders, are at high risk of severe disease from respiratory syncytial virus (RSV) infection. Indeed, our current local surveillance data demonstrate that approximately half of children hospitalized with RSV were ≤3 mo old, and 74% were born at term. Informed by this clinical epidemiology, we investigated antiviral innate immune responses in early life, with the goal of identifying immunological factors underlying the susceptibility of infants and young children to severe viral lower respiratory tract infections. We compared RSV-induced innate cytokine production in blood mononuclear cells from neonates, young children aged 12–59 mo, and healthy adults. RSV-induced IFN-α production was primarily mediated by plasmacytoid dendritic cells (pDCs), and was significantly lower in term infants and young children < 5 y of age than in adults (p < 0.01). RSV-induced IFN-α production in human pDCs proceeded independently of endosomal TLRs, and human pDCs from healthy adult donors produced IFN-α in a retinoic acid–inducible gene I protein (RIG-I)–dependent manner. Of interest, young age and premature birth were independently associated with attenuated RIG-I–dependent IFN-α responses (p < 0.01). In contrast to IFN-α production, proinflammatory IL-6 responses to RSV were mediated by monocytes, appeared less dependent on RIG-I, and were significantly impaired only among preterm infants, not in term infants and young children. Our results suggest that human pDCs are less functional in early life, which may contribute to the increased susceptibility of infants and young children to severe RSV disease.
C-Type Lectin Receptors Differentially Induce Th17 Cells and Vaccine Immunity to the Endemic Mycosis of North America
Authors: Wang Huafeng , LeBert Vanessa , Hung Chiung Yu , Galles Kevin , Saijo Shinobu , Lin Xin , Cole Garry T. , Klein Bruce S. , Wüthrich Marcel
Published: January 2014

Vaccine immunity to the endemic mycoses of North America requires Th17 cells, but the pattern recognition receptors and signaling pathways that drive these protective responses have not been defined. We show that C-type lectin receptors exert divergent contributions to the development of antifungal Th17 cells and vaccine resistance against Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides posadasii. Acquired immunity to B. dermatitidis requires Dectin-2, whereas vaccination against H. capsulatum and C. posadasii infection depends on innate sensing by Dectin-1 and Dectin-2, but not Mincle. Tracking Ag-specific T cells in vivo established that the Card9 signaling pathway acts indispensably and exclusively on differentiation of Th17 cells, while leaving intact their activation, proliferation, survival, and migration. Whereas Card9 signaling is essential, C-type lectin receptors offer distinct and divergent contributions to vaccine immunity against these endemic fungal pathogens. Our work provides new insight into innate immune mechanisms that drive vaccine immunity and Th17 cells.
Antibodies VRC01 and 10E8 Neutralize HIV-1 with High Breadth and Potency Even with Ig-Framework Regions Substantially Reverted to Germline
Authors: Georgiev Ivelin S. , Rudicell Rebecca S. , Saunders Kevin O. , Shi Wei , Kirys Tatsiana , McKee Krisha , O’Dell Sijy , Chuang Gwo-Yu , Yang Zhi-Yong , Ofek Gilad , Connors Mark , Mascola John R. , Nabel Gary J. , Kwong Peter D.
Published: January 2014

Abs capable of effectively neutralizing HIV-1 generally exhibit very high levels of somatic hypermutation, both in their CDR and framework-variable regions. In many cases, full reversion of the Ab-framework mutations back to germline results in substantial to complete loss of HIV-1–neutralizing activity. However, it has been unclear whether all or most of the observed framework mutations would be necessary or whether a small subset of these mutations might be sufficient for broad and potent neutralization. To address this issue and to explore the dependence of neutralization activity on the level of somatic hypermutation in the Ab framework, we applied a computationally guided framework-reversion procedure to two broadly neutralizing anti–HIV-1 Abs, VRC01 and 10E8, which target two different HIV-1 sites of vulnerability. Ab variants in which up to 78% (38 of 49 for VRC01) and 89% (31 of 35 for 10E8) of framework mutations were reverted to germline retained breadth and potency within 3-fold of the mature Abs when evaluated on a panel of 21 diverse viral strains. Further, a VRC01 variant with an ∼50% framework-reverted L chain showed a 2-fold improvement in potency over the mature Ab. Our results indicate that only a small number of Ab-framework mutations may be sufficient for high breadth and potency of HIV-1 neutralization by Abs VRC01 and 10E8. Partial framework revertants of HIV-1 broadly neutralizing Abs may present advantages over their highly mutated counterparts as Ab therapeutics and as targets for immunogen design.
Progression Routes and Attainment in Occupational Therapy Education: The Impact of Background Characteristics
Authors: Watson Jo
Published: January 2014

Introduction:

United Kingdom government agendas promoting widening participation in higher education and diversification of the health and social care workforce have contributed to changing student profiles in pre-registration occupational therapy education. Sixty-seven percent of the 2005 intake was mature, and students increasingly enter with a range of ‘non-traditional’ academic backgrounds. A small body of evidence suggests that final degree marks are indistinguishable for occupational therapy students holding traditional and non-traditional entry qualifications, but none of these studies considered students unable to complete or the potential influence of socioeconomic background or gender.

Method:

The progression routes and academic achievements of 239 consenting occupational therapy students from a single programme were analysed using inferential statistics and binary logistic regressions to explore the influence of entry qualifications, age at entry, gender, and socioeconomic background.

Findings:

None of these characteristics had a statistically significant impact on graduates' final degree marks. The regressions, however, highlighted male gender and less privileged socioeconomic backgrounds as significant predictors of poorer outcomes regarding passing at Level 4, 5, and 6, and achievement of a ‘good’ (upper second or first class) honours degree.

Conclusion:

The findings raise important questions about how a profession that promotes social justice supports diversity amongst its own ranks.
Developing Mental Health Occupational Therapy Practice to Meet the Needs of People with Mental Health Problems and Physical Disability
Authors: Miles Helen , Morley Mary
Published: January 2014

It is well documented and evidenced that individuals with serious mental illness have an increased risk of developing a range of physical illnesses and conditions. This practice analysis describes how an initial audit of mental health occupational therapists identified a lack of clarity and protocols around working with individuals with associated physical conditions. Local joint care pathways and a skills development programme were introduced, and a follow-up audit completed to assess progress to date. The advancement in practice and production of a clear physical care pathway has made a positive difference to service users.
The iron budget in ocean surface waters in the 20th and 21st centuries: projections by the Community Earth System Model version 1
Authors: Misumi K. , Lindsay K. , Moore J. K. , Doney S. C. , Bryan F. O. , Tsumune D. , Yoshida Y.
Published: January 2014

Abstract. We investigated the simulated iron budget in ocean surface waters in the 1990s and 2090s using the Community Earth System Model version 1 and the Representative Concentration Pathway 8.5 future CO2 emission scenario. We assumed that exogenous iron inputs did not change during the whole simulation period; thus, iron budget changes were attributed solely to changes in ocean circulation and mixing in response to projected global warming, and the resulting impacts on marine biogeochemistry. The model simulated the major features of ocean circulation and dissolved iron distribution for the present climate. Detailed iron budget analysis revealed that roughly 70% of the iron supplied to surface waters in high-nutrient, low-chlorophyll (HNLC) regions is contributed by ocean circulation and mixing processes, but the dominant supply mechanism differed by region: upwelling in the eastern equatorial Pacific and vertical mixing in the Southern Ocean. For the 2090s, our model projected an increased iron supply to HNLC waters, even though enhanced stratification was predicted to reduce iron entrainment from deeper waters. This unexpected result is attributed largely to changes in gyre-scale circulations that intensified the advective supply of iron to HNLC waters. The simulated primary and export production in the 2090s decreased globally by 6 and 13%, respectively, whereas in the HNLC regions, they increased by 11 and 6%, respectively. Roughly half of the elevated production could be attributed to the intensified iron supply. The projected ocean circulation and mixing changes are consistent with recent observations of responses to the warming climate and with other Coupled Model Intercomparison Project model projections. We conclude that future ocean circulation has the potential to increase iron supply to HNLC waters and will potentially buffer future reductions in ocean productivity.
Lead‐Free Perovskites with Photochromism and Reversed Thermochromism for Repeatable Information Writing and Erasing
Authors: Sheng Yuhang , Gui Qingfeng , Zhang Yi , Yang Xingru , Xing Fangjian , Liu Cihui , Di Yunsong , Wei Shibiao , Cao Guiyuan , Yang Xifeng , Zhang Xiaowei , Liu Yushen , Gan Zhixing
Published: July 2024

Recently, novel optical information writing strategies have been developed based on fluorescent change of halide perovskites generated by light induced structural transformation. However, to date, the repeatable writing and erasing of fluorescent patterns are still a major challenge. Herein, lead‐free Cs3InCl6:Sb3+ perovskite with photochromism and reversed thermochromism is developed for repeatable information writing and erasing. The original Cs3InCl6:Sb3+ perovskite synthesized by a modified hot‐injection method exhibits green photoluminescence (PL), which is caused by recombination of self‐trapped excitons. After treating with ultrasonication and heating, the green PL gradually turns to blue emission, which is related to surficial Cl vacancies that are generated or exposed due to the desorption of surfactants. Under continuous UV light irradiation, due to the photo repairing effect, the blue emission gradually vanishes, the fluorescent color recovers to green. Based on this photochromic effect, fluorescent patterns are drawn by UV exposure with mask. Moreover, the green PL color can again return to blue by heating at 100 °C. Thus, the photochromism‐induced fluorescent patterns can be simply erased based on the reversed thermochromism effect. Therefore, repeatable optical information writing and thermal erasure are demonstrated based on reversible PL change of Cs3InCl6:Sb3+.
In Situ Triggered Self‐Contraction Bioactive Microgel Assembly Accelerates Diabetic Skin Wound Healing by Activating Mechanotransduction and Biochemical Pathway
Authors: Xie Qingqiao , Yan Chenchen , Liu Guohui , Bian Liming , Zhang Kunyu
Published: July 2024

Chronic nonhealing skin wounds, characterized by reduced tissue contractility and inhibited wound cell survival under hyperglycemia and hypoxia, present a significant challenge in diabetic care. Here, an advanced self‐contraction bioactive core‐shell microgel assembly with robust tissue‐adhesion (SMART‐EXO) is introduced to expedite diabetic wound healing. The SMART‐EXO dressing exhibits strong, reversible adhesion to damaged tissue due to abundant hydrogen and dynamic coordination bonds. Additionally, the core‐shell microgel components and dynamic coordination bonds provide moderate rigidity, customizable self‐contraction, and an interlinked porous architecture. The triggered in situ self‐contraction of the SMART‐EXO dressing enables active, tunable wound contraction, activating mechanotransduction in the skin and promoting the optimal fibroblast‐to‐myofibroblast conversion, collagen synthesis, and angiogenesis. Concurrently, the triggered contraction of SMART‐EXO facilitates efficient loading and on‐demand release of bioactive exosomes, contributing to re‐epithelialization and wound microenvironment regulation in diabetic mice. RNA‐seq results reveal the activation of critical signaling pathways associated with mechanosensing and exosome regulation, highlighting the combined biomechanical and biochemical mechanisms. These findings underscore SMART‐EXO as a versatile, adaptable solution to the complex challenges of diabetic wound care.
Ionic Photovoltaics‐in‐Memory in van der Waals Material
Authors: Li Dongyan , Li Zexin , Pan Chen , Sun Yan , Zhou Jian , Yangdong Xingjian , Xu Xiang , Liu Lixin , Wang Haoyun , Chen Yunxin , Song Xingyu , Liu Pengbin , Zhou Xing , Liang Shi‐Jun , Miao Feng , Zhai Tianyou
Published: July 2024

The photovoltaic effect is gaining growing attention in the optoelectronics field due to its low power consumption, sustainable nature, and high efficiency. However, the photovoltaic effects hitherto reported are hindered by the stringent band‐alignment requirement or inversion symmetry‐breaking, and are challenging for achieving multifunctional photovoltaic properties (such as reconfiguration, nonvolatility, and so on). Here, a novel ionic photovoltaic effect in centrosymmetric CdSb2Se3Br2 that can overcome these limitations is demonstrated. The photovoltaic effect displays significant anisotropy, with the photocurrent being most apparent along the CdBr2 chains while absent perpendicular to them. Additionally, the device shows electrically‐induced nonvolatile photocurrent switching characteristics. The photovoltaic effect is attributed to the modulation of the built‐in electric field through the migration of Br ions. Using these unique photovoltaic properties, a highly secure circuit with electrical and optical keys is successfully implemented. The findings not only broaden the understanding of the photovoltaic mechanism, but also provide a new material platform for the development of in‐memory sensing and computing devices.
Mitochondrial Transplantation Promotes Protective Effector and Memory CD4+ T Cell Response During Mycobacterium Tuberculosis Infection and Diminishes Exhaustion and Senescence in Elderly CD4+ T cells
Authors: Headley Colwyn A. , Gautam Shalini , Olmo‐Fontanez Angelica , Garcia‐Vilanova Andreu , Dwivedi Varun , Schami Alyssa , Weintraub Susan , Tsao Philip S. , Torrelles Jordi B. , Turner Joanne
Published: July 2024

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is a major global health concern, particularly affecting those with weakened immune systems, including the elderly. CD4+ T cell response is crucial for immunity against M.tb, but chronic infections and aging can lead to T cell exhaustion and senescence, worsening TB disease. Mitochondrial dysfunction, prevalent in aging and chronic diseases, disrupts cellular metabolism, increases oxidative stress, and impairs T‐cell functions. This study investigates the effect of mitochondrial transplantation (mito‐transfer) on CD4+ T cell differentiation and function in aged mouse models and human CD4+ T cells from elderly individuals. Mito‐transfer in naïve CD4+ T cells is found to promote protective effector and memory T cell generation during M.tb infection in mice. Additionally, it improves elderly human T cell function by increasing mitochondrial mass and altering cytokine production, thereby reducing markers of exhaustion and senescence. These findings suggest mito‐transfer as a novel approach to enhance aged CD4+ T cell functionality, potentially benefiting immune responses in the elderly and chronic TB patients. This has broader implications for diseases where mitochondrial dysfunction contributes to T‐cell exhaustion and senescence.
Tunable Intracavity Coherent Up‐Conversion with Giant Nonlinearity in a Polar Fluidic Medium
Authors: Okada Daichi , Nishikawa Hiroya , Araoka Fumito
Published: July 2024

The study has demonstrated a novel microcavity‐based flexible photon up‐conversion system using second harmonic generation (SHG) from a polar nematic fluidic medium doped with a laser dye. The idea is based on coherent light generation via stimulated emission (lasing) and simultaneous frequency doubling inside a microcavity. The polar nematic fluid equips very high even‐order optical nonlinearity due to its polar symmetry and large dipole moment along the molecular long axis. At the same time, its inherent fluidic nature allows to easily functionalize the media just by doping, in the present case, with an emissive laser dye. The demonstrated system exhibits a giant nonlinear optical response to input light, while enabling spectral narrowing and multiple‐signal output of up‐converted light, which is not attainable through the simple SH‐conversion of input light. Furthermore, the susceptibility of the liquid crystal offers dynamic modulation capabilities by an external stimulus, such as signal switching by the application of electric field or wavelength tuning through temperature variation. Such a brand‐new type of simple coherent flexible up‐conversion system must be promising as a new principle for easily accessible and down‐scalable wavelength conversion devices.
Two one‐dimensional cuprous iodide coordination polymers: Efficient and robust electrocatalysts for hydrogen evolution and glucose‐sensing
Authors: Gao Wei , Xie Yueyue , Liu Zhaolong , Dou Zilin , Huang Nannan , Wu Huilu
Published: July 2024

Development of efficient, low‐cost, robust, and structure tunability electrocatalysts for hydrogen evolution reaction (HER) is one of the main subjects of present study in renewable energies. In this work, two new cuprous iodide coordination polymers (Cu‐CPs) containing bisbenzimidazole‐derived ligand, namely, {[Cu2(L1)(μ2‐I)2]·DMF}n (1) and {[Cu(L2)0.5(μ2‐I)]·DMF} (2) (L1 = (2,2′‐(1,3‐propanediyl)‐6,6′‐bis(3‐methylpyridine)bis‐1,3‐benzimidazole); L2 = (2,2′‐(1,4‐butanediyl)‐7,7′‐bis(3‐methylpyridine)bis‐1,3‐benzimidazole); DMF = dimethyl formamide), were prepared under solvothermal conditions and structurally characterized. Single‐crystal structural analysis showed that although two Cu‐CPs have a one‐dimensional (1D) chain backbone structure, the coordination environment of cuprous is different. It is found that different coordination modes of ligands L1 and L2 lead to different coordination environments of central ions in two cuprous CPs. Electrocatalytic HER of modified electrodes (CP‐1~2/glassy carbon electrode [GCE]) prepared by coating the mixed solution of acetylene black, CPs 1–2, and Nafion on the surface of GCE was investigated in 0.5 M H2SO4 electrolyte. The HER measurements show that the overpotential η10293K of CP‐1~2/GCE positively shifted 113 and 74 mV compared with bare GCE (blank electrode, −930 mV), and the Tafel slope of bare/GCE and CP‐1~2/GCE were 298, 101, and 138 mV dec−1, respectively. The results indicate that CP‐1~2/GCE could effectively catalyze and accelerate the HER behavior, with electrocatalytic activity order being CP‐1/GCE > CP‐2/GCE > bare/GCE. The higher HER activity of the CP‐1/GCE can be attributed to that the coordination deformability of cuprous ion in CP 1 is greater. Furthermore, the recognition performance of CP‐1~2/GCE for glucose was further studied by chronoamperometry in 0.1 M NaOH. The two sensors can detect glucose in a linear range from 1 μM to 4 mM with sensitivities of 13.736 and 18.945 μA mM−1, and also revealed long‐term stability and good selectivity. These results indicate that cuprous CPs deserve further investigation as potential electrocatalyst candidates.
Research Progress of Cyanine‐Based Near‐Infrared Fluorescent Probes for Biological Application
Authors: Xuan Jigao , Yu Jiajun , Huang Chusen
Published: July 2024

Cyanine‐based near‐infrared (NIR) fluorescent probes have played vital roles in biological application due to their low interference from background fluorescence, deep tissue penetration, high sensitivity, and minimal photodamage to biological samples. They are widely utilized in molecular recognition, medical diagnosis, biomolecular detection, and biological imaging. Herein, we provide a review of recent advancements in cyanine‐based NIR fluorescent probes for the detection of pH, cells, tumor as well as their application in photothermal therapy (PTT) and photodynamic therapy (PDT).
Evaluating the thermal stability of chemicals and systems: A review
Authors: Andriani Giuseppe , Pio Gianmaria , Salzano Ernesto , Vianello Chiara , Mocellin Paolo
Published: July 2024

In the realm of chemical processing, particularly at the industrial scale, safety is of utmost importance. A predominant factor causing accidents within the chemical industry is runaway phenomena, primarily initiated by uncontrolled exothermic reactions. This review critically examines the often‐overlooked decomposition mechanisms as a significant contributor to thermal energy release, necessitating a comprehensive revision and understanding of both experimental and theoretical strategies for assessing thermal degradation. Key to this discourse is the explication of calorimetry as the principal experimental technique, alongside ab initio quantum chemistry simulations as a robust theoretical framework for quantifying the most relevant properties. However, more than mere cognisance of these methodologies is required for a meticulous thermal stability assessment. The review emphasizes identifying and quantifying fundamental parameters through experimental and theoretical investigations. Only upon acquiring these parameters, including kinetic, thermodynamic, onset, and peak characteristics of the exothermic decomposition reactions, can one effectively mitigate risks and hazards in designing and optimizing chemical processes and apparatus. Furthermore, this review delineates qualitative and quantitative methodologies for hazard assessment, proffering strategies for estimating safe operational conditions and sizing relief devices. The paper culminates in exploring future trajectories in thermal stability assessments, focusing on emerging applications in lithium‐ion batteries, electrolyzers, electrified reactors, ionic liquids, artificial intelligence and machine learning approaches. Thus, the paper underlines the evolving landscape of thermal risk management in contemporary and future chemical industries.
The emergence of neoadjuvant immune‐ over BRAF therapy in melanoma
Authors: Rozeman Elisa A. , Luke Jason J.
Published: July 2024

Neoadjuvant therapy has emerged in high‐risk stage III melanoma with immunotherapy improving long‐term outcomes when compared with BRAF and MEK inhibition. Unmet needs remain surrounding optimal immunotherapy combinations, selection biomarkers, and deintensification of treatment.
Association of enlarged perivascular spaces with cognitive function in dementia‐free older adults: A population‐based study
Authors: Zhao Mingqing , Li Yuanjing , Han Xiaodong , Li Chunyan , Wang Pin , Wang Jiafeng , Hou Tingting , Wang Yongxiang , Cong Lin , Wardlaw Joanna M. , Launer Lenore J. , Song Lin , Du Yifeng , Qiu Chengxuan
Published: July 2024

Introduction

We sought to characterize cognitive profiles associated with enlarged perivascular spaces (EPVS) among Chinese older adults.

Methods

This population‐based study included 1191 dementia‐free participants (age ≥60 years) in the MIND‐China MRI Substudy (2018–2020). We visually evaluated EPVS in basal ganglia (BG) and centrum semiovale (CSO), white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and cortical superficial siderosis. We used a neuropsychological test battery to assess cognitive function. Data were analyzed using general linear models.

Results

Greater BG‐EPVS load was associated with lower z‐scores in memory, verbal fluency, and global cognition (p < 0.05); these associations became non‐significant when controlling for other cerebral small vessel disease (CSVD) markers (e.g., WMHs, lacunes, and mixed CMBs). Overall, CSO‐EPVS load was not associated with cognitive z‐scores (p > 0.05); among apolipoprotein E (APOE) ‐ε4 carriers, greater CSO‐EPVS load was associated with lower verbal fluency z‐score, even when controlling for other CSVD markers (p < 0.05).

Discussion

The associations of BG‐EPVS with poor cognitive function in older adults are largely attributable to other CSVD markers.

HIGHLIGHTS

The association of enlarged perivascular spaces (EPVS) with cognitive function in older people is poorly defined.

The association of basal ganglia (BG)‐EPVS with poor cognition is attributed to other cerebral small vessel disease (CSVD) markers.

In apolipoprotein E (APOE) ε4 carriers, a higher centrum semiovale (CSO)‐EPVS load is associated with poorer verbal fluency.
In vitro metabolism study of ADB‐P‐5Br‐INACA and ADB‐4en‐P‐5Br‐INACA using human hepatocytes, liver microsomes, and in‐house synthesized references
Authors: Rautio Tobias , Obrist Robin , Krebs Lucas , Klingstedt Therése , Dahlén Johan , Wu Xiongyu , Gréen Henrik
Published: July 2024

Synthetic cannabinoids (SCs) remain a major public health concern, as they continuously are linked to severe intoxications and drug‐related deaths worldwide. As new SCs continue to emerge on the illicit drug market, an understanding of SC metabolism is needed to identify formed metabolites that may serve as biomarkers in forensic toxicology screening and for understanding the pharmacokinetics of the drugs. In this work, the metabolism of ADB‐4en‐P‐5Br‐INACA and ADB‐P‐5Br‐INACA ((S)‐N‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐5‐bromo‐1‐(pent‐4‐en‐1‐yl)‐1H‐indazole‐3‐carboxamide, (S)‐N‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐5‐bromo‐1‐pentyl‐1H‐indazole‐3‐carboxamide respectively) were investigated using human hepatocytes in vitro and in‐house synthesized references. Both SCs were incubated with pooled human hepatocytes over 3 h, with the aim to identify unique and abundant metabolites using liquid chromatography–quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS). In total nine metabolites were identified for ADB‐4en‐P‐5Br‐INACA and 10 metabolites for ADB‐P‐5Br‐INACA. The observed biotransformations included dihydrodiol formation, terminal amide hydrolysis, hydroxylation, dehydrogenation, carbonyl formation, glucuronidation, and combinations thereof. The major metabolites were confirmed by in‐house synthesized references. Recommended biomarkers for ADB‐P‐5Br‐INACA and ADB‐4en‐P‐5Br‐INACA are the terminal hydroxy and dihydrodiol metabolite respectively.
Targeting erythroid progenitor cells for cancer immunotherapy
Authors: Li Su‐Ran , Wu Zhi‐Zhong , Yu Hai‐Jun , Sun Zhi‐Jun
Published: July 2024

Immunotherapy, especially immune checkpoint blockade therapy, represents a major milestone in the history of cancer therapy. However, the current response rate to immunotherapy among cancer patients must be improved; thus, new strategies for sensitizing patients to immunotherapy are urgently needed. Erythroid progenitor cells (EPCs), a population of immature erythroid cells, exert potent immunosuppressive functions. As a newly recognized immunosuppressive population, EPCs have not yet been effectively targeted. In this review, we summarize the immunoregulatory mechanisms of EPCs, especially for CD45+ EPCs. Moreover, in view of the regulatory effects of EPCs on the tumor microenvironment, we propose the concept of EPC‐immunity, present existing strategies for targeting EPCs, and discuss the challenges encountered in both basic research and clinical applications. In particular, the impact of existing cancer treatments on EPCs is discussed, laying the foundation for combination therapies. The aim of this review is to provide new avenues for improving the efficacy of cancer immunotherapy by targeting EPCs.
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Authors: Hou Chongyang , Zhang Shuye , Liu Rui , Gemming Thomas , Bachmatiuk Alicja , Zhao Hongbin , Jia Hao , Huang Shirong , Zhou Weijia , Xu Jian‐Bin , Pang Jinbo , Rümmeli Mark H. , Bi Jinshun , Liu Hong , Cuniberti Gianaurelio
Published: July 2024

The blending of 2D materials and polymers promote the heterosis in flexible electronics, including senses, computing, memory and logic circuits.

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Enhanced CO2 capture and stability of MgO modified with alkali metal nitrates and carbonates at moderate temperature
Authors: Li Shuaipeng , Guo Neng , Zhu Dongdong , Jiang Dazhan , Chen Zhenting , Chen Shengwen , Sun Zhiguo , Wang Jifen
Published: July 2024

BACKGROUND

Magnesium oxide (MgO) is favored for solid‐state carbon dioxide (CO2) capture due to its high theoretical adsorption capacity, abundant reserves, low cost, and environmental friendliness. However, its practical application in industry is hindered by low CO2 adsorption capacity under moderate operating conditions. In this work, MgO was modified by a deposition method using LiNO3, NaNO3, KNO3, Na2CO3 and K2CO3 as additives.

RESULTS

The study determines optimal ratios within the [(Li, Na, K)x − (Na, K)]y/MgO system, specifically identifying x = 0.5 and y = 0.15 as most effective. At 275 °C under pure CO2 conditions, the adsorption capacity peaks at 0.631 g CO2 g−1 adsorbent. Effective regeneration of the adsorbent occurs at 400 °C under 100% N2 for 15 min. Under Integrated Gasification Combined Cycle (IGCC) conditions, the adsorption capacity stabilizes at 0.462 g g−1 after 20 cycles, representing a 25% decrease from initial capacity.

CONCLUSION

Experimental findings demonstrate that the inclusion of alkali metal salts in MgO precursors enhances the adsorbent's microstructure, thereby improving its CO2 capture efficiency and bolstering cycling stability. This research enhances our understanding of the factors influencing CO2 adsorption and cyclic stability in alkali metal salt‐promoted MgO, providing valuable insights for further refinement in the formulation and synthesis protocols of MgO‐based CO2 adsorbents. © 2024 Society of Chemical Industry (SCI).