bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the pilot construction of new-energy cities promote particulate matter 2.5 (PM2.5) reduction? Evidence from China
Authors: Yang Mingwei , Yang Wenju , Wang Zheng , Liu Jun
Published: January 2023

Introduction: In recent years, China has paid high attention on urban energy innovation, trying to achieve a win–win situation between environmental protection and urban development, and it has formulated a series of policies to promote urban energy innovation.

Methods: Taking China’s new energy demonstration city (NEDC) policy as an example, this paper empirically investigates the impact of China’s urban energy policy on PM2.5 by using a difference-in-differences (DID) model.

Results/Discussion: (1) NEDC policy has reduced PM2.5 concentrations by 4.84% in pilot cities. Moreover, this policy can continue to reduce PM2.5 concentrations for at least 5 years, and the policy effect increases year by year. (2) NEDC policy has spatial spillover effect, which significantly reduces PM2.5 of surrounding cities within 150 km. (3) The PM2.5 reducing effect of NEDC policy is primarily the result of technological effect and allocation effect generated by promoting innovation and industrial upgrading. (4) The PM2.5 control effect of NEDC policy presents an inverted U-shape with the expansion of city size, and is better in cities with low levels of financial support, high levels of human capital and information infrastructure. The conclusions of this paper have important theoretical value for understanding the ecological effect of innovation policy and provide experience for developing countries to implement an experimentalist governance model.
Toxicity of per- and polyfluoroalkyl substances to aquatic vertebrates
Authors: Ma Tingting , Wu Peng , Wang Lisha , Li Quanguo , Li Xiuhua , Luo Yongming
Published: January 2023

Rapid industrial development and extensive use of chemicals have resulted in elevated concentrations of emerging contaminants worldwide, posing a substantial threat to the ecological environment and human health. Per- and polyfluoroalkyl substances (PFASs) have been recognized as emerging pollutants that are widely distributed and accumulated in the environment and they have drawn the attention of scholars for several decades. The variety, long-term use, and long-distance transmission of PFASs have resulted in the ubiquitous contamination of global ecosystems, especially in aquatic environments. Ever since perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were added to the Stockholm Convention on Persistent Organic Pollutants (POPs), they have become the most typical, eye-catching, and frequently investigated PFASs. Owing to the high stability and bioaccumulation of PFASs, as well as the adverse impact on the endocrine, immune, and nervous systems, investigating their contamination levels, risk of transfer along the food chain, and ecotoxicity should be prioritized. In addition to the important evolutionary significance as primitive vertebrates and the main consumers of aquatic environment, fishes generally exist in various aquatic food chains from the bottom to the top and occupy a critical position in terms of aquatic ecology protection; while amphibians, as the key link from aquatic to terrestrial organisms, are highly sensitive to different environmental pollutants. This review is a comprehensive summary of the toxic effects and toxicity-related factors of PFASs on aquatic vertebrates, mainly Pisces and Amphilla organisms, the characteristics of different aquatic vertebrates in toxicity investigations, and the evaluation of the feasibility of PFASs substitute applications.
Evolution of sexually selected traits across animals
Authors: Tuschhoff E. , Wiens John J.
Published: January 2023

Sexual selection is thought to be a major driver of phenotypic diversity and diversification in animals, but large-scale evolutionary patterns in sexually selected (SS) traits remain largely unknown. Here, we survey and analyze the evolution of these traits across animal phylogeny. We find that female mate choice appears to be the most widespread mechanism of sexual selection, but male-male competition appears to be almost as frequent in chordates and male mate choice is also common in arthropods. Among sensory types, tactile traits appear to be most widespread whereas auditory traits are relatively uncommon. Rather than being ubiquitous or randomly distributed across animals, most of these different types of SS traits are confined to clades in arthropods and chordates, which form “hotspots” for the evolution of these diverse trait types. Thus, different sensory types show accelerated rates of evolution in these clades. Moreover, different types of SS traits are strongly correlated with each other in their evolution across animals. Finally, despite the intensive interest in the role of sexual selection in speciation, we find only limited support for the idea that SS traits drive large-scale patterns of diversification and species richness across all animals.
Temperature, nutrient availability, and species traits interact to shape elevation responses of Australian tropical trees
Authors: Singh Ramesh Arun , Cheesman Alexander W. , Flores-Moreno Habacuc , Preece Noel D. , Crayn Darren M. , Cernusak Lucas A.
Published: January 2023

Elevation gradients provide natural laboratories for investigating tropical tree ecophysiology in the context of climate warming. Previously observed trends with increasing elevation include decreasing stem diameter growth rates (GR), increasing leaf mass per area (LMA), higher root-to-shoot ratios (R:S), increasing leaf δ13C, and decreasing leaf δ15N. These patterns could be driven by decreases in temperature, lower soil nutrient availability, changes in species composition, or a combination thereof. We investigated whether these patterns hold within the genus Flindersia (Rutaceae) along an elevation gradient (0–1,600 m) in the Australian Wet Tropics. Flindersia species are relatively abundant and are important contributors to biomass in these forests. Next, we conducted a glasshouse experiment to better understand the effects of temperature, soil nutrient availability, and species on growth, biomass allocation, and leaf isotopic composition. In the field, GR and δ15N decreased, whereas LMA and δ13C increased with elevation, consistent with observations on other continents. Soil C:N ratio also increased and soil δ15N decreased with increasing elevation, consistent with decreasing nutrient availability. In the glasshouse, relative growth rates (RGR) of the two lowland Flindersia species responded more strongly to temperature than did those of the two upland species. Interestingly, leaf δ13C displayed an opposite relationship with temperature in the glasshouse compared with that observed in the field, indicating the importance of covarying drivers in the field. Leaf δ15N increased in nutrient-rich compared to nutrient-poor soil in the glasshouse, like the trend in the field. There was a significant interaction for δ15N between temperature and species; upland species showed a steeper increase in leaf δ15N with temperature than lowland species. This could indicate more flexibility in nitrogen acquisition in lowland compared to upland species with warming. The distinguishing feature of a mountaintop restricted Flindersia species in the glasshouse was a very high R:S ratio in nutrient-poor soil at low temperatures, conditions approximating the mountaintop environment. Our results suggest that species traits interact with temperature and nutrient availability to drive observed elevation patterns. Capturing this complexity in models will be challenging but is important for making realistic predictions of tropical tree responses to global warming.
Investigating nicotine pathway-related long non-coding RNAs in tobacco
Authors: Xie Xiaodong , Jin Jingjing , Wang Chen , Lu Peng , Li Zefeng , Tao Jiemeng , Cao Peijian , Xu Yalong
Published: January 2023

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with low or no protein-coding ability, which play essential roles in various biological processes in plants. Tobacco is an ideal model plant for studying nicotine biosynthesis and metabolism, and there is little research on lncRNAs in this field. Therefore, how to take advantage of the mature tobacco system to profoundly investigate the lncRNAs involved in the nicotine pathway is intriguing. By exploiting 549 public RNA-Seq datasets of tobacco, 30,212 lncRNA candidates were identified, including 24,084 large intervening non-coding RNAs (lincRNAs), 5,778 natural antisense transcripts (NATs) and 350 intronic non-coding RNAs (incRNAs). Compared with protein-coding genes, lncRNAs have distinct properties in terms of exon number, sequence length, A/U content, and tissue-specific expression pattern. lincRNAs showed an asymmetric evolutionary pattern, with a higher proportion (68.71%) expressed from the Nicotiana sylvestris (S) subgenome. We predicted the potential cis/trans-regulatory effects on protein-coding genes. One hundred four lncRNAs were detected as precursors of 30 known microRNA (miRNA) family members, and 110 lncRNAs were expected to be the potential endogenous target mimics for 39 miRNAs. By combining the results of weighted gene co-expression network analysis with the differentially expressed gene analysis of topping RNA-seq data, we constructed a sub-network containing eight lncRNAs and 25 nicotine-related coding genes. We confirmed that the expression of seven lncRNAs could be affected by MeJA treatment and may be controlled by the transcription factor NtMYC2 using a quantitative PCR assay and gene editing. The results suggested that lncRNAs are involved in the nicotine pathway. Our findings further deepened the understanding of the features and functions of lncRNAs and provided new candidates for regulating nicotine biosynthesis in tobacco.
Identification and functional analysis of Dmrt1 gene and the SoxE gene in the sexual development of sea cucumber, Apostichopus japonicus
Authors: Liu Bing-Zheng , Cong Jing-Jing , Su Wei-Yi , Hao Zhen-Lin , Sun Zhi-Hui , Chang Ya-Qing
Published: January 2023

Members of the Doublesex and Mab-3-related transcription factor (Dmrt) gene family handle various vital functions in several biological processes, including sex determination/differentiation and gonad development. Dmrt1 and Sox9 (SoxE in invertebrates) exhibit a very conserved interaction function during testis formation in vertebrates. However, the dynamic expression pattern and functional roles of the Dmrt gene family and SoxE have not yet been identified in any echinoderm species. Herein, five members of the Dmrt gene family (Dmrt1, 2, 3a, 3b and 5) and the ancestor SoxE gene were identified from the genome of Apostichopus japonicus. Expression studies of Dmrt family genes and SoxE in different tissues of adult males and females revealed different expression patterns of each gene. Transcription of Dmrt2, Dmrt3a and Dmrt3b was higher expressed in the tube feet and coelomocytes instead of in gonadal tissues. The expression of Dmrt1 was found to be sustained throughout spermatogenesis. Knocking-down of Dmrt1 by means of RNA interference (RNAi) led to the downregulation of SoxE and upregulation of the ovarian regulator foxl2 in the testes. This indicates that Dmrt1 may be a positive regulator of SoxE and may play a role in the development of the testes in the sea cucumber. The expression level of SoxE was higher in the ovaries than in the testes, and knocking down of SoxE by RNAi reduced SoxE and Dmrt1 expression but conversely increased the expression of foxl2 in the testes. In summary, this study indicates that Dmrt1 and SoxE are indispensable for testicular differentiation, and SoxE might play a functional role during ovary differentiation in the sea cucumber.
Identifying colon cancer stage related genes and their cellular pathways
Authors: Chen Bolin , Chakrobortty Nandita , Saha Apu Kumar , Shang Xuequn
Published: January 2023

In the world, colon cancer is regarded as one of the most common deadly cancer. Due to the lack of a better understanding of its prognosis system, this prevailing cancer has the second-highest morbidity and mortality rate compared with other cancers. A variety of genes are responsible to participate in colon cancer and the molecular mechanism is almost unsure. In addition, various studies have been done to identify the differentially expressed genes to investigate the dysfunctions of the genes but most of them did it individually. In this study, we constructed a functional interaction network for identifying the group of genes that conduct cellular functions and Protein-Protein Interaction network, which aims to better understanding protein functions and their biological relationships. A functional evolution network was also generated to analyze the dysfunctions from initial stage to later stage of colon cancer by investigating the gene modules and their molecular functions. The results show that the proposed evolution network is able to detect the significant cellular functions, which can be used to explore the evolution process of colon cancer. Moreover, a total of 10 core genes associated with colon cancer were identified, which were INS, SNAP25, GRIA2, SST, GCG, PVALB, SLC17A7, SLC32A1, SLC17A6, and NPY, respectively. The responsible candidate genes and corresponding pathways presented in this study could be used to develop new tumor indicators and novel therapeutic targets for the prevention and treatment of colon cancer.
Cassane diterpenoid ameliorates dextran sulfate sodium-induced experimental colitis by regulating gut microbiota and suppressing tryptophan metabolism
Authors: Liu Ting , Ning Zunxi , Liu Pengyu , Gao Huiyuan
Published: January 2023

Ulcerative colitis (UC) is one form of inflammatory bowel disease (IBD), characterized by chronic relapsing intestinal inflammation. As increasing morbidity of UC and deficiency of conventional therapies, there is an urgent need for attractive treatment. Cassane diterpenoids, the characteristic chemical constituents of Caesalpinia genus plants, have been studied extensively owing to various and prominent biological activities. This study attempted to investigate the bioactivity of caesaldekarin e (CA), a cassane diterpenoid isolated from C. bonduc in our previous work, on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the function mechanism. The results indicated that CA ameliorated mice colitis by relieving disease symptoms, suppressing inflammatory infiltration and maintaining intestinal barrier integrity. Furthermore, 16S rRNA gene sequencing analysis indicated that CA could improve the gut microbiota imbalance disrupted by DSS and especially restored abundance of Lactobacillus. In addition, untargeted metabolomics analysis suggested that CA regulated metabolism and particularly the tryptophan metabolism by inhibiting the upregulation of indoleamine 2,3-dioxygenase 1 (IDO-1). It also been proved in IFN-γ induced RAW264.7 cells. Overall, this study suggests that CA exhibits anti-UC effect through restoring gut microbiota and regulating tryptophan metabolism and has the potential to be a treatment option for UC.
Protective effects of dietary grape against atopic dermatitis-like skin lesions in NC/NgaTndCrlj mice
Authors: Singh Chandra K. , Mintie Charlotte A. , Ndiaye Mary A. , Chhabra Gagan , Roy Sushmita , Sullivan Ruth , Longley B. Jack , Schieke Stefan M. , Ahmad Nihal
Published: January 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant health/economic burdens. Existing therapies are not fully effective, necessitating development of new approaches for AD management. Here, we report that dietary grape powder (GP) mitigates AD-like symptoms in 2,4-dinitrofluorobenzene (DNFB)-induced AD in NC/NgaTndCrlj mice. Using prevention and intervention protocols, we tested the efficacy of 3% and 5% GP-fortified diet in a 13-weeks study. We found that GP feeding markedly inhibited development and progression of AD-like skin lesions, and caused reduction in i) epidermal thickness, mast cell infiltration, ulceration, excoriation and acanthosis in dorsal skin, ii) spleen weight, extramedullary hematopoiesis and lymph nodes sizes, and iii) ear weight and IgE levels. We also found significant modulations in 15 AD-associated serum cytokines/chemokines. Next, using quantitative global proteomics, we identified 714 proteins. Of these, 68 (normal control) and 21 (5% GP-prevention) were significantly modulated (≥2-fold) vs AD control (DNFB-treated) group, with many GP-modulated proteins reverting to normal levels. Ingenuity pathway analysis of GP-modulated proteins followed by validation using ProteinSimple identified changes in acute phase response signaling (FGA, FGB, FGG, HP, HPX, LRG1). Overall, GP supplementation inhibited DNFB-induced AD in NC/NgaTndCrlj mice in both prevention and intervention trials, and should be explored further.
IFNα and 5-Aza-2’-deoxycytidine combined with a dendritic-cell targeting DNA vaccine alter tumor immune cell infiltration in the B16F10 melanoma model
Authors: Gordy James T. , Sandhu Avinaash K. , Fessler Kaitlyn , Luo Kun , Kapoor Aakanksha R. , Ayeh Samuel K. , Hui Yinan , Schill Courtney , Chen Fengyixin , Wang Tianyin , Karanika Styliani , Sunshine Joel C. , Karakousis Petros C. , Markham Richard B.
Published: January 2023

Introduction

DNA vaccines containing a fusion of the gene encoding chemokine MIP-3α (CCL20), the ligand for CCR6 on immature dendritic cells (DCs), to melanoma-associated antigen genes have enhanced anti-tumor immunity and efficacy compared to those lacking the chemokine gene. Previous work has shown that type-I interferon (IFNα or IFN) and 5-Aza-2’-deoxycytidine (5Aza) significantly enhance the therapeutic benefit of DNA vaccines as measured by reduced tumor burden and improved mouse survival.

Methods

Here, we explored mouse intratumoral immune correlates underlying the therapeutic benefit of this combination regimen (vaccine, IFN, and 5Aza) as compared to vaccine alone and IFN and 5Aza without vaccine, focusing on chemokine mRNA expression by qRT-PCR and inflammatory cellular infiltration into the tumor microenvironment (TME) by flow cytometry and immunohistochemistry (IHC).

Results

The combination group significantly upregulated intratumoral mRNA expression of key immune infiltration chemokines XCL1 and CXCL10. Flow cytometric analyses of tumor suspensions exhibited greater tumor infiltration of CD8+ DCs, CCR7+ DCs, and NK cells in the combination group, as well as reduced levels of myeloid-derived suppressor cells (MDSCs) in vaccinated groups. The mice receiving combination therapy also had greater proportions of effector/memory T-cells (Tem), in addition to showing an enhanced infiltration of Tem and central memory CD8+ T-cells, (Tcm). Tem and Tcm populations both correlated with smaller tumor size. Immunohistochemical analysis of tumors confirmed that CD8+ cells were more abundant overall and especially in the tumor parenchyma with combination therapy.

Discussion

Efficient targeting of antigen to immature DCs with a chemokine-fusion vaccine offers a potential alternative approach to classic and dendritic cell-based vaccines. Combining this approach with IFNα and 5Aza treatments significantly improved vaccine efficacy. This treatment creates an environment of increased inflammatory chemokines that facilitates the trafficking of CD8+ DCs, NK cells, and CD8+ T-cells, especially memory cells, while reducing the number of MDSCs. Importantly, in the combination group, CD8+ cells were more able to penetrate the tumor mass in addition to being more numerous. Further analysis of the pathways engaged by our combination therapy is expected to provide additional insights into melanoma pathogenesis and facilitate the development of novel treatment strategies.
The role of major immune cells in myocardial infarction
Authors: Feng Qiang , Li Qirong , Zhou Hengzong , Sun Liqun , Lin Chao , Jin Ye , Wang Dongxu , Guo Gongliang
Published: January 2023

Myocardial infarction (MI) is a cardiovascular disease (CVD) with high morbidity and mortality worldwide, often leading to adverse cardiac remodeling and heart failure, which is a serious threat to human life and health. The immune system makes an important contribution to the maintenance of normal cardiac function. In the disease process of MI, necrotic cardiomyocytes release signals that activate nonspecific immunity and trigger the action of specific immunity. Complex immune cells play an important role in all stages of MI progression by removing necrotic cardiomyocytes and tissue and promoting the healing of damaged tissue cells. With the development of biomaterials, cardiac patches have become an emerging method of repairing MI, and the development of engineered cardiac patches through the construction of multiple animal models of MI can help treat MI. This review introduces immune cells involved in the development of MI, summarizes the commonly used animal models of MI and the newly developed cardiac patch, so as to provide scientific reference for the accurate diagnosis and effective treatment of MI.
Staining of activated ß2-integrins in combination with CD137 and CD154 for sensitive identification of functional antigen-specific CD4+ and CD8+ T cells
Authors: Schöllhorn Anna , Maia Ana , Kimmerle Felix , Born Jan , Rammensee Hans-Georg , Dimitrov Stoyan , Gouttefangeas Cécile
Published: January 2023

Common flow cytometry-based methods used for functional assessment of antigen-specific T cells rely on de novo expression of intracellular cytokines or cell surface activation induced markers. They come with some limitations such as complex experimental setting, loss of cell viability and often high unspecific background which impairs assay sensitivity. We have previously shown that staining of activated ß2-integrins either with multimers of their ligand ICAM-1 or with a monoclonal antibody can serve as a functional marker detectable on T cells after minutes (CD8+) or few hours (CD4+) of activation. Here, we present a simple method for detection of activated ß2-integrins in combination with established cell surface activation induced markers. We observed that activated ß2-integrins were still detectable after 14 hours of stimulation, allowing their detection together with CD137 and CD154. Combinatorial gating of cells expressing activated ß2-integrins and CD137 or CD154 reduced background in unstimulated samples, increasing the signal-to-noise ratio and allowing improved assessment of low-frequency T cell responses. Extracellular staining of these markers highly correlated with production of intracellular cytokines IL-2, TNF or IFNγ in CD4+ and CD8+ T cells. As an exemplary application, SARS-CoV-2 spike-specific T cell responses were assessed in individuals after COVID-19 vaccination. This method should be useful for epitope discovery projects and for the simultaneous monitoring of low-frequency antigen-specific CD4+ and CD8+ T cell responses in various physiological situations.
Airway epithelial cell-specific deletion of HMGB1 exaggerates inflammatory responses in mice with muco-obstructive airway disease
Authors: Mao Yun , Patial Sonika , Saini Yogesh
Published: January 2023

High mobility group box 1 (HMGB1), a ubiquitous chromatin-binding protein required for gene transcription regulation, is released into the extracellular microenvironment by various structural and immune cells, where it is known to act as an alarmin. Here, we investigated the role of airway epithelium-specific HMGB1 in the pathogenesis of muco-obstructive lung disease in Scnn1b-transgenic (Tg+) mouse, a model of human cystic fibrosis (CF)-like lung disease. We hypothesized that airway epithelium-derived HMGB1 modulates muco-inflammatory lung responses in the Tg+ mice. The airway epithelium-specific HMGB1-deficient mice were generated and the effects of HMGB1 deletion on immune cell recruitment, airway epithelial cell composition, mucous cell metaplasia, and bacterial clearance were determined. The airway epithelium-specific deletion of HMGB1 in wild-type (WT) mice did not result in any morphological alterations in the airway epithelium. The deficiency of HMGB1 in airway epithelial cells in the Tg+ mice, however, resulted in significantly increased infiltration of macrophages, neutrophils, and eosinophils which was associated with significantly higher levels of inflammatory mediators, including G-CSF, KC, MIP-2, MCP-1, MIP-1α, MIP-1β, IP-10, and TNF-α in the airspaces. Furthermore, as compared to the HMGB1-sufficient Tg+ mice, the airway epithelial cell-specific HMGB1-deficient Tg+ mice exhibited poor resolution of spontaneous bacterial infection. The HMGB1 deficiency in the airway epithelial cells of Tg+ mice did not alter airway epithelial cell-specific responses including epithelial cell proliferation, mucous cell metaplasia, and mucus obstruction. Collectively, our findings provide novel insights into the role of airway epithelial cell-derived HMGB1 in the pathogenesis of CF-like lung disease in Tg+ mice.
Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells
Authors: Thelen Benedikt , Schipperges Vincent , Knörlein Paulina , Hummel Jonas F. , Arnold Frederic , Kupferschmid Laurence , Klose Christoph S. N. , Arnold Sebastian J. , Boerries Melanie , Tanriver Yakup
Published: January 2023

The T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is widely expressed in the immune system but was initially identified as the lineage-specifying transcription factor of Th1 CD4+ T cells, where it governs expression of the signature cytokine IFN- γ and represses alternative cell fates like Th2 and Th17. T-bet’s paralog Eomes is less abundantly expressed and Eomes+ CD4+ T cells are mostly found in the context of persistent antigen exposure, like bone marrow transplantation, chronic infection or inflammation as well as malignant disorders. However, it has remained unresolved whether Eomes executes similar transcriptional activities as T-bet in CD4+ T cells. Here we use a novel genetic approach to show that Eomes expression in CD4+ T cells drives a distinct transcriptional program that shows only partial overlap with T-bet. We found that Eomes is sufficient to induce the expression of the immunoregulatory cytokine IL-10 and, together with T-bet, promotes a cytotoxic effector profile, including Prf1, Gzmb, Gzmk, Nkg7 and Ccl5, while repressing alternative cell fates. Our results demonstrate that Eomes+ CD4+ T cells, which are often found in the context of chronic antigen stimulation, are likely to be a unique CD4+ T cell subset that limits inflammation and immunopathology as well as eliminates antigen-presenting and malignant cells.
A review of TSHR- and IGF-1R-related pathogenesis and treatment of Graves’ orbitopathy
Authors: Cui Xuejiao , Wang Futao , Liu Cong
Published: January 2023

Graves’ orbitopathy (GO) is an organ-specific autoimmune disease, but its pathogenesis remains unclear. There are few review articles on GO research from the perspective of target cells and target antigens. A systematic search of PubMed was performed, focusing mainly on studies published after 2015 that involve the role of target cells, orbital fibroblasts (OFs) and orbital adipocytes (OAs), target antigens, thyrotropin receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R), and their corresponding antibodies, TSHR antibodies (TRAbs) and IGF-1R antibodies (IGF-1R Abs), in GO pathogenesis and the potentially effective therapies that target TSHR and IGF-1R. Based on the results, OFs may be derived from bone marrow-derived CD34+ fibrocytes. In addition to CD34+ OFs, CD34- OFs are important in the pathogenesis of GO and may be involved in hyaluronan formation. CD34- OFs expressing Slit2 suppress the phenotype of CD34+ OFs. β-arrestin 1 can be involved in TSHR/IGF-1R crosstalk as a scaffold. Research on TRAbs has gradually shifted to TSAbs, TBAbs and the titre of TRAbs. However, the existence and role of IGF-1R Abs are still unknown and deserve further study. Basic and clinical trials of TSHR-inhibiting therapies are increasing, and TSHR is an expected therapeutic target. Teprotumumab has become the latest second-line treatment for GO. This review aims to effectively describe the pathogenesis of GO from the perspective of target cells and target antigens and provide ideas for its fundamental treatment.
Comprehensive analysis of the immune pattern of T cell subsets in chronic myeloid leukemia before and after TKI treatment
Authors: Yao Danlin , Lai Jing , Lu Yuhong , Zhong Jun , Zha Xianfeng , Huang Xin , Liu Lian , Zeng Xiangbo , Chen Shaohua , Weng Jianyu , Du Xin , Li Yangqiu , Xu Ling
Published: January 2023

Background

Immunological phenotypes and differentiation statuses commonly decide the T cell function and anti-tumor ability. However, little is known about these alterations in CML patients.

Method

Here, we investigated the immunologic phenotypes (CD38/CD69/HLA-DR/CD28/CD57/BTLA/TIGIT/PD-1) of T subsets (TN, TCM, TEM, and TEMRA) in peripheral blood (PB) and bone marrow (BM) from de novo CML patients (DN-CML), patients who achieved a molecular response (MR) and those who failed to achieve an MR (TKI-F) after tyrosine kinase inhibitor (TKI) treatment using multicolor flow cytometry.

Results

CD38 or HLA-DR positive PB CD8+TN and TCM cells decreased in the DN-CML patients and this was further decreased in TKI-F patients. Meanwhile, the level of PD-1 elevated in CD8+ TEM and TEMRA cells from PB in all groups. Among BM sample, the level of HLA-DR+CD8+TCM cells significantly decreased in all groups and CD8+TEMRA cells from TKI-F patients exhibited increased level of TIGIT and CD8+ tissue-residual T cells (TRM) from DN-CML patients expressed a higher level of PD-1 and TIGIT. Lastly, we found a significantly decreased proportion of CD86+ dendritic cells (DCs) and an imbalanced CD80/CD86 in the PB and BM of DN-CML patients, which may impair the activation of T cells.

Conclusion

In summary, early differentiated TN and TCM cells from CML patients may remain in an inadequate activation state, particularly for TKI-F patients. And effector T cells (TEM, TEMRA and TRM) may be dysfunctional due to the expression of PD-1 and TIGIT in CML patients. Meanwhile, DCs cells exhibited the impairment of costimulatory molecule expression in DN-CML patients. Those factors may jointly contribute to the immune escape in CML patients.
Age-adjusted impact of prior COVID-19 on SARS-CoV-2 mRNA vaccine response
Authors: Nakagama Sachie , Nakagama Yu , Komase Yuko , Kudo Masaharu , Imai Takumi , Tshibangu-Kabamba Evariste , Nitahara Yuko , Kaku Natsuko , Kido Yasutoshi
Published: January 2023

More people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the level of protection granted by ‘hybrid immunity’, the combined response of infection- and vaccine-induced immunity, may impact vaccination strategies through tailored dosing. A total of 36 infected (‘prior infection’) and 33 SARS-CoV-2 ‘naïve’ individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody measurements and the receptor binding domain-ACE2 binding inhibition assays. The relationships between antibody titer, groups and age were explored. Anti-spike antibody titers at 6 months post-vaccination were significantly higher, reaching 13- to 17-fold, in the ‘prior infection’ group. Semi-log regression models showed that participants with ‘prior infection’ demonstrated higher antibody titer compared with the ‘naïve’ even after adjusting for age. The enhancement in antibody titer attributable to positive infection history increased from 8.9- to 9.4- fold at age 30 to 19- to 32-fold at age 60. Sera from the ‘prior infection’ group showed higher inhibition capacity against all six analyzed strains, including the Omicron variant. Prior COVID-19 led to establishing enhanced humoral immunity at 6 months after vaccination. Antibody fold-difference attributed to positive COVID-19 history increased with age, possibly because older individuals are prone to symptomatic infection accompanied by potentiated immune responses. While still pending any modifications of dosing recommendations (i.e. reduced doses for individuals with prior infection), our observation adds to the series of real-world data demonstrating the enhanced and more durable immune response evoked by booster vaccinations following prior infection.
The impact of host plant species on instar duration and body weight of nymphal Lycorma delicatula
Authors: Kreitman Devin , Keena Melody A. , Nielsen Anne L. , Hamilton George
Published: January 2023

The spotted lanternfly, Lycorma delicatula (White) (Hemiptera: Fulgoridae), is an invasive species of planthopper that was introduced to North America and is a threat to multiple industries. Nymphs and egg masses were collected to assess each instar’s rate of development at a constant temperature of 25°C on the following hosts: Ailanthus altissima (Miller) (Sapindales: Simaroubaceae), Vitis labrusca (L.) (Vitales: Vitaceae), Salix babylonica (L.) (Malpighiales: Salicaceae), Acer rubrum (L.) (Sapindales: Sapindaceae), Celastrus orbiculata (Thunberg) (Celastrales: Celastraceae), Ocimum basilicum (L.) (Lamiales: Lamiaceae), and Rosa multiflora (Thunberg) (Rosales: Rosaceae). Host plant species was found to have a significant effect on developmental time for nymphs in the first through third instars, as well as on nymphal survival. Nymphs failed to develop through the second instar on O. basilicum and the third and fourth instars on A. rubrum. Host plant species also had a significant effect on the mean weight of nymphs in the first, second, and fourth instars (but not in the third instar), and on the hind tibia length and forewing width of adult nymphs. This variability in L. delicatula developmental time by host plant species can potentially impact phenology models, which should be updated to reflect these new insights. Rearing practices should also be refined to account for host plant influences on the physiology of L. delicatula.
United States Gulf of Mexico Waters provide important nursery habitat for Mexico’s Green turtle nesting populations
Authors: Shamblin Brian M. , Hart Kristen M. , Lamont Margaret M. , Shaver Donna J. , Dutton Peter H. , LaCasella Erin L. , Nairn Campbell J.
Published: January 2023

Resolving natal populations for juvenile green turtles is challenging given their potential for extensive dispersal during the oceanic stage and ontogenetic shifts among nursery habitats. Mitochondrial DNA markers have elucidated patterns of connectivity between green turtle nesting populations (rookeries) and juvenile foraging aggregations. However, missing rookery baseline data and haplotype sharing among populations have often impeded inferences, including estimating origins of Gulf of Mexico juveniles. Here, we assessed genetic structure among seven foraging aggregations spanning southern Texas (TX) to southwestern Florida (SWFL), including Port Fourchon, Louisiana (LA); a surface-pelagic aggregation (SP) offshore of Louisiana and Florida; Santa Rosa Island, Florida (SRI); St. Joseph Bay, Florida (SJB); and the Big Bend region, Florida (BB). We estimated source contributions to aggregations with novel genetic data (excluding SP and BB) using a Bayesian many-to-one mixed stock analysis (MSA) approach. Haplotype frequencies for western (TX, LA, SP, SRI) and eastern (SJB, BB, SWFL) aggregations were significantly differentiated. The largest shift in haplotype frequencies between proximal nursery sites occurred between SRI and SJB, separated by only 150 km, highlighting the lack of a geographic yardstick for predicting genetic structure. In contrast to previous MSA results, there was no signal of Florida juveniles at any foraging site. Mexican contributions dominated in all aggregations, with strong connectivity between western Bay of Campeche (Tamaulipas/Veracruz) rookeries and western foraging aggregations. MSA indicated more diverse Mexican origins for eastern aggregations, with larger inputs from the eastern Bay of Campeche (Campeche/Yucatán), Campeche Bank, and Quintana Roo rookeries. These results demonstrate the significance of the Gulf of Mexico coast and offshore waters of the United States as important nursery habitat for green turtles of Mexican origin and highlight the need for international coordination for management of these populations.
Coral restoration patents are disconnected from academic research and restoration practitioners
Authors: Roch Cassandra , Schmidt-Roach Sebastian , Duarte Carlos M.
Published: January 2023

Global warming and other anthropogenic impacts have driven coral reef degradation on a global scale to unprecedented levels of decline, with further dramatic deterioration predicted by the end of this century. Along with a drastic reduction in carbon emissions, we face an imperative to restore and maintain marine habitats to secure the ecosystem services they provide. While terrestrial systems have benefited from the agricultural revolution that provided industrial tools for effective habitat restoration, limited access to marine environments has inhibited similar levels of innovation resulting in a lack of cost-effective and scalable solutions. Commercial off-the-shelf technologies to cater to this growing industry are still absent. Here we conducted a systematic analysis of patent and scientific literature data as indicators of research and development (R&D) output in the field of coral restoration. We identify technology growth trends, key areas of technological development, and their geographical distribution. While the number of inventions filed for coral restoration is on the rise, similar to the published academic literature, the stakeholders leading both fields are unrelated. Academic research appears to lack translation into inventions for commercialization. Intellectual property protection further seems to be spearheaded by a few countries and is often limited in its application to national jurisdictions, with China dominating this sector. This does not mirror the distribution of current and need for coral restoration efforts globally. Here we discuss potential differences in cultural, socio-economic, and philosophical ideologies that drive these divergences and their impact as inhibitors or promoters of innovations targeting coral restoration solutions.
Antimicrobial peptides from marine animals: Sources, structures, mechanisms and the potential for drug development
Authors: Wang Shuocun , Fan Liming , Pan Hanyu , Li Yingying , Qiu Yan , Lu Yiming
Published: January 2023

The emergence of antibiotic-resistant bacteria has become a major challenge in current clinical treatment. As essential natural molecules involved in innate immunity, antimicrobial peptides (AMPs) have the potential to break the limits of antibiotic resistance. While AMPs are widely presented in various organisms on this planet, the marine environment is unique in generating a large number of AMPs that exhibit characteristic structures and functions. This review summarizes the structures and mechanisms of action of AMPs derived from invertebrates, fish, amphibians, reptiles, and mammals in the ocean. The comparison of AMPs from organisms in different habitats demonstrates the preference of Arg (arginine) and Leu (leucine) in marine AMPs, which might be associated with the adaptation to the unique features of bacterial membranes in marine environments. In addition, the potential and applications of marine AMPs for the development of novel antibiotics are also described. These summaries are expected to provide a reference for the development and utilization of marine resources in drug development or aquiculture.
New science, drug regulation, and emergent public health issues: The work of FDA’s division of applied regulatory science
Authors: Chiu Kimberly , Racz Rebecca , Burkhart Keith , Florian Jeffry , Ford Kevin , Iveth Garcia M. , Geiger Robert M. , Howard Kristina E. , Hyland Paula L. , Ismaiel Omnia A. , Kruhlak Naomi L. , Li Zhihua , Matta Murali K. , Prentice Kristin W. , Shah Aanchal , Stavitskaya Lidiya , Volpe Donna A. , Weaver James L. , Wu Wendy W. , Rouse Rodney , Strauss David G.
Published: January 2023

The U.S. Food and Drug Administration (FDA) Division of Applied Regulatory Science (DARS) moves new science into the drug review process and addresses emergent regulatory and public health questions for the Agency. By forming interdisciplinary teams, DARS conducts mission-critical research to provide answers to scientific questions and solutions to regulatory challenges. Staffed by experts across the translational research spectrum, DARS forms synergies by pulling together scientists and experts from diverse backgrounds to collaborate in tackling some of the most complex challenges facing FDA. This includes (but is not limited to) assessing the systemic absorption of sunscreens, evaluating whether certain drugs can convert to carcinogens in people, studying drug interactions with opioids, optimizing opioid antagonist dosing in community settings, removing barriers to biosimilar and generic drug development, and advancing therapeutic development for rare diseases. FDA tasks DARS with wide ranging issues that encompass regulatory science; DARS, in turn, helps the Agency solve these challenges. The impact of DARS research is felt by patients, the pharmaceutical industry, and fellow regulators. This article reviews applied research projects and initiatives led by DARS and conducts a deeper dive into select examples illustrating the impactful work of the Division.
Diagnostic efficacy of sonographic measurement of laryngeal air column width difference for predicting the risk of post-extubation stridor: A meta-analysis of observational studies
Authors: Tsai Wen-Wen , Hung Kuo-Chuan , Huang Yen-Ta , Yu Chia-Hung , Lin Chien-Hung , Chen I-Wen , Sun Cheuk-Kwan
Published: January 2023

Background

This meta-analysis aimed at assessing the diagnostic accuracy of ultrasound-measured laryngeal air column width difference (ACWD) in predicting post-extubation stridor (PES) in intubated adult patients.

Methods

We searched the Medline, Cochrane Library, EMBASE, and Google scholar databases from inception to October, 2022 to identify studies that examined the diagnostic accuracy of ACWD for PES. The primary outcome was the diagnostic performance by calculating the pooled sensitivity, specificity, and area under the curve (AUC). The secondary outcomes were the differences in ACWD and duration of intubation between patients with and without PES.

Results

Following literature search, 11 prospective studies (intensive care setting, n = 10; operating room setting, n = 1) involving 1,322 extubations were included. The incidence of PES among the studies was 4–25%. All studies were mixed-gender (females: 24.1–68.5%) with sample sizes ranging between 41 and 432. The cut-off values of ACWD for prediction of PES varied from 0.45 to 1.6 mm. The pooled sensitivity and specificity of ACWD for PES were 0.8 (95% CI = 0.69–0.88, I2: 37.26%, eight studies) and 0.81 (95% CI = 0.72–0.88, I2: 89.51%, eight studies), respectively. The pooled AUC was 0.87 (95% CI = 0.84–0.90). Patients with PES had a smaller ACWD compared to those without PES (mean difference = −0.54, 95% CI = −0.79 to −0.28, I2: 97%, eight studies). Moreover, patients with PES had a longer duration of tracheal intubation than that in those without (mean difference = 2.75 days, 95% CI = 0.92, 4.57, I2: 90%, seven studies).

Conclusion

Ultrasound-measured laryngeal ACWD showed satisfactory sensitivity and specificity for predicting PES. Because of the limited number of studies available, further investigations are needed to support our findings.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022375772.
Black Lycium barbarum polysaccharide attenuates LPS-induced intestine damage via regulation gut microbiota
Authors: Yan An , Ding Houkang , Liu Junjun , Bi Chongliang , Han Zhaoqing , Wang Zhennan , Nawaz Shah , Shen Yizhao , Liu Shudong
Published: January 2023

Lycium barbarums are traditionally used as a homology of medicinal plants in China with a potent role in metabolism and immunomodulation. The current study was performed to explore the attenuation effect and microbiota regulation of Lycium barbarum polysaccharide (BLBP) on lipopolysaccharide (LPS)-induced intestine damage in mice. A total of 70 mice were randomly divided into five groups; negative control (GA), LPS (GB), both treated with an equal volume of normal saline, and BLBP treatment groups GC (100 mg/kg), GD (200 mg/kg), and GE (400 mg/kg) via gavage for 19 days. On Day 19, mice in groups GB, GC, GD, and GE were treated with 10 mg/kg LPS for 24 h and euthanized to collect intestine samples for pathological examination and microbiota sequencing. The results showed a non-significant difference in body weight gain among the five mouse groups; however, mice in the GC and GE groups showed decreased weight gain. An H&E examination revealed that the integrity of intestinal villi was destroyed by LPS, while BLBP supplement alleviated intestinal damage with an increase in villus height and a decrease in crypt depth. A total of over 59,000, 40,000, 50,000, 45,000, and 55,000 raw sequences were found in groups GA, GB, GC, GD, and GE, respectively. LPS challenge decreased alpha diversity indexes significantly (p < 0.05), while a non-significant difference was found between different BLBP treatment groups and the GA group. A total of 8 phyla and 13 genera were found among five mouse groups, and BLBP partly restored the bacterial abundance in mice. LPS changed 282 metabolic pathways in KEGG L2, 77 metabolic pathways in KEGG L3, and 205 metabolic pathways in MetaCyc, respectively. The BLBP-supplemented groups, especially GE, showed reverse effects on those metabolic pathways. The current study revealed that BLBP can effectively decrease intestinal damage through the regulation of intestinal microbiota, which may provide new insights for the prevention of intestinal disease using food and medicine homologous of Lycium ruthenicum.
Long non-coding RNA SNHG9 regulates viral replication in rhabdomyosarcoma cells infected with enterovirus D68 via miR-150-5p/c-Fos axis
Authors: Fu Huichao , Si Junzhuo , Xu Lei , Tang Xia , He Yonglin , Lu Nan , Li Huayi , Li Anlong , Gao Sijia , Yang Chun
Published: January 2023

Background

The Enterovirus D68 (EV-D68) epidemic has increased knowledge of the virus as a pathogen capable of causing serious respiratory and neurological illnesses. It has been shown that long noncoding RNAs (lncRNAs) regulate viral replication and infection via multiple mechanisms or signaling pathways. However, the precise function of lncRNAs in EV-D68 infection remains unknown.

Methods

The differential expression profiles of lncRNA in EV-D68-infected and uninfected rhabdomyosarcoma (RD) cells were studied using high-throughput sequencing technology. The knockdown through small interfering RNA (siRNA) and overexpression of lncRNA SNHG9 (small ribonucleic acid host gene 9) were applied to investigate how lncRNA SNHG9 regulates EV-D68 propagation. The targeted interactions of lncRNA SNHG9 with miR-150-5p and miR-150-5p with c-Fos were validated using dual luciferase reporter system. LncRNA SNHG9 knockdown and miR-150-5p inhibitor were co-transfected with RD cells. QRT-PCR and western blot were used to detect RNA and protein levels, of c-Fos and VP1, respectively. Median tissue culture infectious dose (TCID50) was applied to detect viral titers.

Results

The results demonstrated that a total of 375 lncRNAs were highly dysregulated in the EV-D68 infection model. In the EV-D68 infection model, lncRNA SNHG9 and c-Fos were increased in EV-D68-infected RD cells. However, the expression level of miR-150-5p was downregulated. In addition, overexpression of SNHG9 in RD cells resulted in decreased viral replication levels and viral titers following infection with EV-D68, and further experiments revealed that overexpression of SNHG9 inhibited the viral replication by targeting increased miR-150-5p binding and significantly increased c-Fos expression in RD cells.

Conclusion

Our findings indicate that the SNHG9/miR-150-5p/c-Fos axis influences EV-D68 replication in host cells and that SNHG9 may be a possible target for anti-EV-D68 infection therapies.