bluuebunny/crossref_metadata_2025 huggingface dataset:
M2 macrophage-derived extracellular vesicles facilitate CD8+T cell exhaustion in hepatocellular carcinoma via the miR-21-5p/YOD1/YAP/β-catenin pathway
Authors: Pu Jian , Xu Zuoming , Nian Jiahui , Fang Quan , Yang Meng , Huang Youguan , Li Wenchuan , Ge Bin , Wang Jianchu , Wei Huamei
Published: July 2021

Hepatocellular carcinoma (HCC) is a common malignancy. CD8+ T cell-mediated immune response is critical for the inhibition of HCC progression. M2 macrophages participate in HCC progression. This study set out to investigate the effect of M2 macrophage-derived extracellular vesicles (EVs) on CD8+ T cell exhaustion in HCC. M2 macrophage-derived EVs were isolated and identified. The murine model of primary HCC was established through DEN/CCl4 induction, and model mice were injected with EVs. Peripheral blood mononuclear cells (PBMCs) were isolated from the mouse liver and CD8+ T cells were sorted. The expressions of immune checkpoint inhibitory receptors and effector cytokines on CD8+ T cells were detected, followed by the evaluation of CD8+ T cell proliferation and killing function. miR-21-5p expression in M2 macrophage-derived EVs was detected. The binding relationship between miR-21-5p and YOD1 was verified. The activation of the YAP/β-catenin pathway was detected. Consequently, M2 macrophage-derived EVs promoted CD8+ T cell exhaustion in HCC mice. miR-21-5p expression was upregulated in M2 macrophage-derived EVs, and EVs carried miR-21-5p into HCC tissues. miR-21-5p targeted YOD1. Inhibition of miR-21-5p or overexpression of YOD1 annulled the promoting effect of EVs on CD8+ T cell exhaustion. YOD1 inactivated the YAP/β-catenin pathway. In conclusion, M2 macrophage-derived EVs facilitated CD8+ T cell exhaustion via the miR-21-5p/YOD1/YAP/β-catenin axis. This study may confer novel insights into the immunotherapy of HCC.
What can visual electrophysiology tell about possible visual-field defects in paediatric patients
Authors: Handley Siân E. , Šuštar Maja , Tekavčič Pompe Manca
Published: July 2021

Recognising a potential visual-field (VF) defect in paediatric patients might be challenging, especially in children before the age of 5 years and those with developmental delay or intellectual disability. Visual electrophysiological testing is an objective and non-invasive technique for evaluation of visual function in paediatric patients, which can characterise the location of dysfunction and differentiate between disorders of the retina, optic nerve and visual pathway. The recording of electroretinography (ERG) and visual-evoked potentials (VEP) is possible from early days of life and requires no subjective input from the patient. As the origins of ERG and VEP tests are known, the pattern of electrophysiological changes can provide information about the VF of a child unable to perform accurate perimetry. This review summarises previously published electrophysiological findings in several common types of VF defects that can be found in paediatric patients (generalised VF defect, peripheral VF loss, central scotoma, bi-temporal hemianopia, altitudinal VF defect, quadrantanopia and homonymous hemianopia). It also shares experience on using electrophysiological testing as additional functional evidence to other tests in the clinical challenge of diagnosing or excluding VF defects in complex paediatric patients. Each type of VF defect is illustrated with one or two clinical cases.
Insulin protects acinar cells during pancreatitis by preserving glycolytic ATP supply to calcium pumps
Authors: Bruce Jason I. E. , Sánchez-Alvarez Rosa , Sans Maria Dolors , Sugden Sarah A. , Qi Nathan , James Andrew D. , Williams John A.
Published: July 2021

Acute pancreatitis (AP) is serious inflammatory disease of the pancreas. Accumulating evidence links diabetes with severity of AP, suggesting that endogenous insulin may be protective. We investigated this putative protective effect of insulin during cellular and in vivo models of AP in diabetic mice (Ins2Akita) and Pancreatic Acinar cell-specific Conditional Insulin Receptor Knock Out mice (PACIRKO). Caerulein and palmitoleic acid (POA)/ethanol-induced pancreatitis was more severe in both Ins2Akita and PACIRKO vs control mice, suggesting that endogenous insulin directly protects acinar cells in vivo. In isolated pancreatic acinar cells, insulin induced Akt-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) which upregulated glycolysis thereby preventing POA-induced ATP depletion, inhibition of the ATP-dependent plasma membrane Ca2+ ATPase (PMCA) and cytotoxic Ca2+ overload. These data provide the first mechanistic link between diabetes and severity of AP and suggest that phosphorylation of PFKFB2 may represent a potential therapeutic strategy for treatment of AP.
Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway
Authors: Zhang Dali , Huang Junlan , Sun Xianding , Chen Hangang , Huang Shuo , Yang Jing , Du Xiaolan , Tan Qiaoyan , Luo Fengtao , Zhang Ruobin , Zhou Siru , Jiang Wanling , Ni Zhenhong , Wang Zuqiang , Jin Min , Xu Meng , Li Fangfang , Chen Liang , Liu Mi , Su Nan , Luo Xiaoqing , Yin Liangjun , Zhu Ying , Feng Jerry Q. , Chen Di , Qi Huabing , Chen Lin , Xie Yangli
Published: July 2021

Acquired heterotopic ossification (HO) is the extraskeletal bone formation after trauma. Various mesenchymal progenitors are reported to participate in ectopic bone formation. Here we induce acquired HO in mice by Achilles tenotomy and observe that conditional knockout (cKO) offibroblast growth factor receptor 3(FGFR3) in Col2+cells promote acquired HO development. Lineage tracing studies reveal that Col2+cells adopt fate of lymphatic endothelial cells (LECs) instead of chondrocytes or osteoblasts during HO development.FGFR3cKO in Prox1+LECs causes even more aggravated HO formation. We further demonstrate thatFGFR3deficiency in LECs leads to decreased local lymphatic formation in a BMPR1a-pSmad1/5-dependent manner, which exacerbates inflammatory levels in the repaired tendon. Local administration of FGF9 in Matrigel inhibits heterotopic bone formation, which is dependent on FGFR3 expression in LECs. Here we uncover Col2+lineage cells as an origin of lymphatic endothelium, which regulates local inflammatory microenvironment after trauma and thus influences HO development via FGFR3-BMPR1a pathway. Activation of FGFR3 in LECs may be a therapeutic strategy to inhibit acquired HO formation via increasing local lymphangiogenesis.
Molecular classification of blood and bleeding disorder genes
Authors: Baz Batoul , Abouelhoda Mohamed , Owaidah Tarek , Dasouki Majed , Monies Dorota , Al Tassan Nada
Published: July 2021

The advances and development of sequencing techniques and data analysis resulted in a pool of informative genetic data, that can be analyzed for informing decision making in designing national screening, prevention programs, and molecular diagnostic tests. The accumulation of molecular data from different populations widen the scope of utilization of this information. Bleeding disorders are a heterogeneous group of clinically overlapping disorders. We analyzed the targeted sequencing data from ~1285 Saudi individuals in 17 blood and bleeding disorders genes, to determine the frequency of mutations and variants. We used a replication set of ~5000 local exomes to validate pathogenicity and determine allele frequencies. We identified a total of 821 variants, of these 98 were listed in HGMD as disease related variants and 140 were novel variants. The majority of variants were present in VWF, followed by F5, F8, and G6PD genes, while FGG, FGB, and HBA1 had the lowest number of variants. Our analysis generated a priority list of genes, mutations and novel variants. This data will have an impact on informing decisions for screening and prevention programs and in management of vulnerable patients admitted to emergency, surgery, or interventions with bleeding side effects.
Abnormal interhemispheric resting state functional connectivity in Parkinson’s disease patients with impulse control disorders
Authors: Gan Caiting , Wang Lina , Ji Min , Ma Kewei , Sun Huimin , Zhang Kezhong , Yuan Yongsheng
Published: July 2021

Impulse control disorders (ICD) in Parkinson’s disease (PD) might be attributed to misestimate of rewards or the failure to curb inappropriate choices. The mechanisms underlying ICD were reported to involve the lateralization of monoamine network. Our objective was to probe the significant role of lateralization in the pathogenesis of ICD. Twenty-one PD patients with ICD (PD-ICD), thirty-three without ICD (PD-no ICD), and thirty-seven healthy controls (HCs) were recruited and performed T1-weighted, diffusion tensor imaging (DTI) scans and resting state functional magnetic resonance imaging (rs-fMRI). By applying the Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer, we evaluated participants’ synchronicity of functional connectivity and structural changes between hemispheres. Also, tract-based spatial statistics (TBSS) was applied to compare fiber tracts differences. Relative to PD-no ICD group, PD-ICD group demonstrated reduced VMHC values in middle frontal gyrus (MFG). Compared to HCs, PD-ICD group mainly showed decreased VMHC values in MFG, middle and superior orbital frontal gyrus (OFG), inferior frontal gyrus (IFG) and caudate, which were related to reward processing and inhibitory control. The severity of impulsivity was negatively correlated with the mean VMHC values of MFG in PD-ICD group. Receiver operating characteristic (ROC) curves analyses uncovered that the mean VMHC values of MFG might be a potential marker identifying PD-ICD patients. However, we found no corresponding asymmetrical alteration in cortical thickness and no significant differences in fractional anisotropy (FA) and mean diffusivity (MD). Our results provided further evidence for asymmetry of functional connectivity in mesolimbic reward and response inhibition network in ICD.
Obstetric hemorrhage risk assessment tool predicts composite maternal morbidity
Authors: Colalillo Emer L. , Sparks Andrew D. , Phillips Jaclyn M. , Onyilofor Chinelo L. , Ahmadzia Homa K.
Published: July 2021

Obstetric hemorrhage is one of the leading preventable causes of maternal mortality in the United States. Although hemorrhage risk-prediction models exist, there remains a gap in literature describing if these risk-prediction tools can identify composite maternal morbidity. We investigate how well an established obstetric hemorrhage risk-assessment tool predicts composite hemorrhage-associated morbidity. We conducted a retrospective cohort analysis of a multicenter database including women admitted to Labor and Delivery from 2016 to 2018, at centers implementing the Association of Women’s Health, Obstetric, and Neonatal Nurses risk assessment tool on admission. A composite morbidity score incorporated factors including obstetric hemorrhage (estimated blood loss ≥ 1000 mL), blood transfusion, or ICU admission. Out of 56,903 women, 14,803 (26%) were categorized as low-risk, 26,163 (46%) as medium-risk and 15,937 (28%) as high-risk for obstetric hemorrhage. Composite morbidity occurred at a rate of 2.2%, 8.0% and 11.9% within these groups, respectively. Medium- and high-risk groups had an increased combined risk of composite morbidity (diagnostic OR 4.58; 4.09–5.13) compared to the low-risk group. This established hemorrhage risk-assessment tool predicts clinically-relevant composite morbidity. Future randomized trials in obstetric hemorrhage can incorporate these tools for screening patients at highest risk for composite morbidity.
TRPV1 activation and internalization is part of the LPS-induced inflammation in human iPSC-derived cardiomyocytes
Authors: Sattler Katherine , El-Battrawy Ibrahim , Cyganek Lukas , Lang Siegfried , Lan Huan , Li Xin , Zhao Zhihan , Utikal Jochen , Wieland Thomas , Borggrefe Martin , Zhou Xiaobo , Akin Ibrahim
Published: July 2021

The non-selective cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed throughout the cardiovascular system. Recent evidence shows a role for TRPV1 in inflammatory processes. The role of TRPV1 for myocardial inflammation has not been established yet. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (hiPSC-CM) from 4 healthy donors were incubated with lipopolysaccharides (LPS, 6 h), TRPV1 agonist capsaicin (CAP, 20 min) or the antagonist capsazepine (CPZ, 20 min). TRPV1 expression was studied by PCR and western blotting. TRPV1 internalization was analyzed by immunofluorescence. Interleukin-6 (IL-6) secretion and phosphorylation of JNK, p38 and ERK were determined by ELISA. TRPV1-associated ion channel current was measured by patch clamp. TRPV1-mRNA and -protein were expressed in hiPSC-CM. TRPV1 was localized in the plasma membrane. LPS significantly increased secretion of IL-6 by 2.3-fold, which was prevented by pre-incubation with CPZ. LPS induced TRPV1 internalization. Phosphorylation levels of ERK, p38 or JNK were not altered by TRPV1 stimulation or inhibition. LPS and IL-6 significantly lowered TRPV1-mediated ion channel current. TRPV1 mediates the LPS-induced inflammation in cardiomyocytes, associated with changes of cellular electrophysiology. LPS-induced inflammation results in TRPV1 internalization. Further studies have to examine the underlying pathways and the clinical relevance of these findings.
Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells
Authors: Liang Ya-Han , Wu Jiann-Ming , Teng Jui-Wen , Hung Eric , Wang Hwai-Shi
Published: July 2021

Breast cancer is the leading cause of cancer-related death for women. In breast cancer treatment, targeted therapy would be more effective and less harmful than radiotherapy or systemic chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in cancer cells but not in normal cells. Mesenchymal stem cells have shown great therapeutic potential in cancer therapy owing to their ability of homing to tumor sites and secreting many kinds of anti-tumor proteins including TRAIL. In this study, we found that IL-1β-stimulated human umbilical cord-derived mesenchymal stem cells (hUCMSCs) enhance the expression of membrane-bound and soluble TRAIL. Cellular FADD-like IL-1β-converting enzyme inhibitory protein (cFLIP) is an important regulator in TRAIL-mediated apoptosis and relates to TRAIL resistance in cancer cells. Previous studies have shown that embelin, which is extracted from Embelia ribes, can increase the TRAIL sensitivity of cancer cells by reducing cFLIP expression. Here we have demonstrated that cFLIPL is correlated with TRAIL-resistance and that embelin effectively downregulates cFLIPL in breast cancer cells. Moreover, co-culture of IL-1β-stimulated hUCMSCs with embelin-treated breast cancer cells could effectively induce apoptosis in breast cancer cells. The combined effects of embelin and IL-1β-stimulated hUCMSCs may provide a new therapeutic strategy for breast cancer therapy.
Evidence for use of both capital and income breeding strategies in the mangrove tree crab, Aratus pisonii
Authors: Carver Jade , Meidell Morgan , Cannizzo Zachary J. , Griffen Blaine D.
Published: July 2021

Two common strategies organisms use to finance reproduction are capital breeding (using energy stored prior to reproduction) and income breeding (using energy gathered during the reproductive period). Understanding which of these two strategies a species uses can help in predicting its population dynamics and how it will respond to environmental change. Brachyuran crabs have historically been considered capital breeders as a group, but recent evidence has challenged this assumption. Here, we focus on the mangrove tree crab, Aratus pisonii, and examine its breeding strategy on the Atlantic Florida coast. We collected crabs during and after their breeding season (March–October) and dissected them to discern how energy was stored and utilized for reproduction. We found patterns of reproduction and energy storage that are consistent with both the use of stored energy (capital) and energy acquired (income) during the breeding season. We also found that energy acquisition and storage patterns that supported reproduction were influenced by unequal tidal patterns associated with the syzygy tide inequality cycle. Contrary to previous assumptions for crabs, we suggest that species of crab that produce multiple clutches of eggs during long breeding seasons (many tropical and subtropical species) may commonly use income breeding strategies.
Combined prognostic nutritional index and albumin-bilirubin grade to predict the postoperative prognosis of HBV-associated hepatocellular carcinoma patients
Authors: Liang Xie , Liangliang Xu , Peng Wang , Tao Yan , Jinfu Zhang , Ming Zhang , Mingqing Xu
Published: July 2021

This study aims to evaluate the predictive value of the prognostic nutritional index (PNI) and albumin-bilirubin grade (ALBI) for the postoperative prognosis of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) patients undergoing radical hepatectomy (RH). Besides, we seek to identify novel prognosis indicators for HBV-HCC patients. Between April 2009 and March 2015, this work enrolled 868 patients diagnosed with HBV-HCC and undergoing RH in the Liver Surgery Department, West China Hospital, Sichuan University (WCHSU). The basic information, laboratory examination indicators, pathological reports, and follow-up data of patients were included. SPSS 22.0 statistical software was used for statistical data analyses. Platelet (PLT), alpha-fetoprotein (AFP), maximum diameter (max-D), number of tumors (Number), degree of differentiation (DD), Microvascular invasion situation (MVI), satellite focus situation (SF), PNI, and ALBI were the independent risk factors for both overall survival (OS) and disease-free survival (DFS) of HBV-HCC patients undergoing RH. Taking PNI = 46 and ALBI = − 2.80 as cut-off values, the OS and DFS of the PNI-high group were significantly higher than those of the PNI-low group. Meanwhile, the OS and DFS of the ALBI-low group were significantly higher than those of the ALBI-high group; the OS and DFS of the PNI-high + ALBI-low group were significantly higher than those of the PNI-low + ALBI-high group. Xie prognostic index (XPI) was the independent risk factor for both OS and DFS of HBV-HCC patients undergoing RH. The OS and DFS of the XPI-high group were significantly higher than those of the XPI-low group. This paper reveals that preoperative PNI and ALBI can predict the OS and DFS of HBV-HCC patients undergoing RH. Their impact on the prognosis of HBV-HCC patients is insignificant, however, it cannot be ignored. XPI can precisely predict the prognosis of HBV-HCC patients undergoing RH, nonetheless, its effect requires additional research for validation.
A general theory of polymer ejection tested in a quasi two-dimensional space
Authors: Hsiao Pai-Yi , Chen Wei-Yei
Published: July 2021

A general ejection theory of polymer is developed in a two- and three-dimensional space. A polymer is confined initially in a cavity and ejects spontaneously to the outer space through a nanopore channel without the help of any external stimulus. A reflective wall boundary is set at the pore entrance to prevent the falling of the head monomer of chain into the cavity. Three stages are distinguished in a process: (1) an entering stage, in which the head monomer enters the pore to search for a way to traverse the pore channel, (2) a main ejection stage, in which the chain body is transported from the cavity to the outer space, (3) a leaving stage, in which the tail monomer passes through and leaves the pore channel. Depending on the number of the monomers remaining in the cavity, the main ejection stage can be divided into the confined and the non-confined stages. The non-confined stage can be further split into the thermal escape and the entropic pulling stages. The Onsager’s variational principle is applied to derive the kinetics equation of ejection. The escape time is calculated from the corresponding Kramers’ escape problem. Extensive molecular dynamics simulations are then performed in a quasi two-dimensional space to verify the theory. The variation of the ejection speed is carefully examined. The decreasing behavior of the number of monomers in the cavity is studied in details. The scaling properties of the spending time at each processing stage are investigated systematically by varying the chain length, the cavity diameter, and the initial volume fraction of chain. The results of simulation support firmly the predictions of the theory, cross-checked in the studies of various topics. In combining with the previous investigations in the three-dimensional space, the generalized theory is very robust, able to explain the two seemly different phenomena, polymer ejection and polymer translocation, together under the same theoretical framework in the two space dimensions.
No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
Authors: Nexoe Anders B. , Pedersen Andreas A. , von Huth Sebastian , Sorensen Grith L. , Holmskov Uffe , Jiang Ping-Ping , Detlefsen Sönke , Husby Steffen , Rathe Mathias
Published: July 2021

Mucositis is a serious adverse effect of chemotherapeutic treatment. During intestinal mucositis, the mucosal barrier is compromised, increasing the risk of severe infections. Mucositis necessitates dose reduction or pauses in treatment, which affect the outcome of the treatment. Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger protein with effects on innate immunity and epithelial regeneration. We have previously shown that jejunal DMBT1 expression is increased in piglets during chemotherapeutic treatment. We hypothesized that DMBT1 ameliorates doxorubicin-induced mucositis. Individually-caged Dmbt1+/+ (WT) and Dmbt1−/− (KO) female mouse littermates received intraperitoneal injections of either doxorubicin or saline. They were euthanized after three (D3) or seven days (D7). Weight loss was monitored every day, and serum citrulline levels were measured at termination. Intestinal tissue was analyzed for the expression of DMBT1 and proinflammatory cytokines (IL-1β, IL-6, and TNF). Specimens from the small intestines and colon were scored for inflammation and epithelial and mucosal architecture changes. We detected no effect of DMBT1 on weight loss, serum citrulline levels, expression of proinflammatory cytokines, or histologic damage. We detected a significant increase in crypt depth in WT mice compared to that in KO mice on D3. In conclusion, DMBT1 does not affect doxorubicin-induced mucositis in mice.
Effect of shock wave power spectrum on the inner ear pathophysiology in blast-induced hearing loss
Authors: Kimura Eiko , Mizutari Kunio , Kurioka Takaomi , Kawauchi Satoko , Satoh Yasushi , Sato Shunichi , Shiotani Akihiro
Published: July 2021

Blast exposure can induce various types of hearing impairment, including permanent hearing loss, tinnitus, and hyperacusis. Herein, we conducted a detailed investigation of the cochlear pathophysiology in blast-induced hearing loss in mice using two blasts with different characteristics: a low-frequency dominant blast generated by a shock tube and a high-frequency dominant shock wave generated by laser irradiation (laser-induced shock wave). The pattern of sensorineural hearing loss (SNHL) was low-frequency- and high-frequency-dominant in response to the low- and high-frequency blasts, respectively. Pathological examination revealed that cochlear synaptopathy was the most frequent cochlear pathology after blast exposure, which involved synapse loss in the inner hair cells without hair cell loss, depending on the power spectrum of the blast. This pathological change completely reflected the physiological analysis of wave I amplitude using auditory brainstem responses. Stereociliary bundle disruption in the outer hair cells was also dependent on the blast’s power spectrum. Therefore, we demonstrated that the dominant frequency of the blast power spectrum was the principal factor determining the region of cochlear damage. We believe that the presenting models would be valuable both in blast research and the investigation of various types of hearing loss whose pathogenesis involves cochlear synaptopathy.
Altered social cognition in a community sample of women with disordered eating behaviours: a multi-method approach
Authors: Heath Devon S. , Jhinjar Nimrit , Hayward Dana A.
Published: July 2021

Prior work suggests that individuals with an eating disorder demonstrate task-based and overall differences in sociocognitive functioning. However, the majority of studies assessed specifically anorexia nervosa and often employed a single experimental paradigm, providing a piecemeal understanding of the applicability of various lab tasks in denoting meaningful differences across diverse individuals. The current study was designed to address these outstanding issues. Participants were undergraduate females who self-identified as having an official (n = 18) eating disorder diagnosis or disordered eating behaviours with no diagnosis (n = 18), along with a control group (n = 32). Participants completed three social tasks of increasing complexity with different outcome measures, namely a gaze cueing task, passive video-watching using eyetracking, and a task to measure preferred social distance. Results diverged as a function of group across tasks; only the control group produced typical social attention effects, the disordered eating group looked significantly more at faces, and the eating disorder group demonstrated a significantly larger preferred social distance. These results suggest variations in task efficacy and demonstrate that altered sociocognitive functioning extends beyond official eating disorder diagnosis.
Long-term observation of mortality among inpatients evacuated from psychiatric hospitals in Fukushima prefecture following the Fukushima nuclear disaster
Authors: Terui Toshihiro , Kunii Yasuto , Hoshino Hiroshi , Kakamu Takeyasu , Hidaka Tomoo , Fukushima Tetsuhito , Anzai Nobuo , Gotoh Daisuke , Miura Itaru , Yabe Hirooki
Published: July 2021

The debate regarding the need for hospital evacuation and the evacuation distance remains rather chaotic. Furthermore, the relationship between hospital evacuation and the prognoses of psychiatric inpatients has not yet been investigated. We aimed to reveal the association between the long-term prognosis of psychiatric inpatients evacuated immediately following the Fukushima Daiichi Nuclear Power Plant accident and their backgrounds. In this retrospective cohort study, 777 psychiatric inpatients who were immediately evacuated from their hospitals following the accident were included for analysis. Survival time was the primary outcome. We conducted univariable and multivariable analyses to examine the associations between mortality and linear distance of evacuation and different backgrounds, including psychiatric/physical traits. Univariable analysis showed that the estimated survival time among patients was significantly associated with their evacuation distance. A multivariable analysis showed that a longer evacuation distance had a significantly lower hazard ratio (HR) and resulted in lower mortality. In contrast, older patients with physical complications of respiratory disease (International Statistical Classification of Diseases and Related Health Problems 10th revision, J00–99) and genitourinary disease (N00–99) showed a significantly higher HR and had a higher mortality than patients without these complications. To prevent death among elderly psychiatric inpatients with physical comorbidities during disasters, the evacuation destination should be determined taking into consideration the evacuees’ tolerance for long-distance transportation and the availability of post-evacuation care in the destination hospitals.
Laboratory model test study of the hydrological effect on granite residual soil slopes considering different vegetation types
Authors: Chen Jie , Lei Xue-wen , Zhang Han-lin , Lin Zhi , Wang Hui , Hu Wei
Published: July 2021

The problems caused by the interaction between slopes and hydrologic environment in traffic civil engineering are very serious in the granite residual soil area of China, especially in Guangdong Province. Against the background of two heavy rainfall events occurring during a short period due to a typhoon making landfall twice or even two typhoons consecutively making landfall, laboratory model tests were carried out on the hydrological effects of the granite residual soil slope considering three vegetation types under artificial rainfall. The variation in slope surface runoff, soil moisture content and rain seepage over time was recorded during the tests. The results indicate that surface vegetation first effectively reduces the splash erosion impact of rainwater on slopes and then influences the slope hydrological effect through rainwater forms adjustment. (1) The exposed slope has weak resistance to two consecutive heavy rains, the degree of slope scouring and soil erosion damage will increase greatly during the second rainfall. (2) The multiple hindrances of the stem leaf ofZoysia japonicaplays a leading role in regulating the hydrological effect of slope, the root system has little effect on the permeability and water storage capacity of slope soil, but improves the erosion resistance of it. (3) Both the stem leaf and root system ofNephrolepis cordifoliahave important roles on the hydrological effect. The stem leaf can stabilize the infiltration of rainwater, and successfully inhibit the surface runoff under continuous secondary heavy rainfall. The root system significantly enhances the water storage capacity of the slope, and greatly increases the permeability of the slope soil in the second rainfall, which is totally different from that of the exposed andZoysia japonicaslopes. (4) Zoysia is a suitable vegetation species in terms of slope protection because of its comprehensive slope protection effect.Nephrolepis cordifoliashould be cautiously planted as slope protection vegetation. Only on slopes with no stability issues shouldNephrolepis cordifoliabe considered to preserve soil and water.
Comparison of two simulators for individual based models in HIV epidemiology in a population with HSV 2 in Yaoundé (Cameroon)
Authors: Hendrickx Diana M. , Sousa João Dinis , Libin Pieter J. K. , Delva Wim , Liesenborgs Jori , Hens Niel , Müller Viktor , Vandamme Anne-Mieke
Published: July 2021

Model comparisons have been widely used to guide intervention strategies to control infectious diseases. Agreement between different models is crucial for providing robust evidence for policy-makers because differences in model properties can influence their predictions. In this study, we compared models implemented by two individual-based model simulators for HIV epidemiology in a heterosexual population with Herpes simplex virus type-2 (HSV-2). For each model simulator, we constructed four models, starting from a simplified basic model and stepwise including more model complexity. For the resulting eight models, the predictions of the impact of behavioural interventions on the HIV epidemic in Yaoundé-Cameroon were compared. The results show that differences in model assumptions and model complexity can influence the size of the predicted impact of the intervention, as well as the predicted qualitative behaviour of the HIV epidemic after the intervention. These differences in predictions of an intervention were also observed for two models that agreed in their predictions of the HIV epidemic in the absence of that intervention. Without additional data, it is impossible to determine which of these two models is the most reliable. These findings highlight the importance of making more data available for the calibration and validation of epidemiological models.
Enhancing the cooling potential of photoluminescent materials through evaluation of thermal and transmission loss mechanisms
Authors: Garshasbi Samira , Huang Shujuan , Valenta Jan , Santamouris Mat
Published: July 2021

Photoluminescent materials are advanced cutting-edge heat-rejecting materials capable of reemitting a part of the absorbed light through radiative/non-thermal recombination of excited electrons to their ground energy state. Photoluminescent materials have recently been developed and tested as advanced non-white heat-rejecting materials for urban heat mitigation application. Photoluminescent materials has shown promising cooling potential for urban heat mitigation application, but further developments should be made to achieve optimal photoluminescence cooling potential. In this paper, an advanced mathematical model is developed to explore the most efficient methods to enhance the photoluminescence cooling potential through estimation of contribution of non-radiative mechanisms. The non-radiative recombination mechanisms include: (1) Transmission loss and (2) Thermal losses including thermalization, quenching, and Stokes shift. The results on transmission and thermal loss mechanisms could be used for systems solely relying on photoluminescence cooling, while the thermal loss estimations can be helpful to minimize the non-radiative losses of both integrated photoluminescent-near infrared (NIR) reflective and stand-alone photoluminescent systems. As per our results, the transmission loss is higher than thermal loss in photoluminescent materials with an absorption edge wavelength (λAE) shorter than 794 nm and quantum yield (QY) of 50%. Our predictions show that thermalization loss overtakes quenching in photoluminescent materials with λAE longer than 834 nm and QY of 50%. The results also show that thermalization, quenching, and Stokes shift constitute around 56.8%, 35%, and 8.2% of the overall thermal loss. Results of this research can be used as a guide for the future research to enhance the photoluminescence cooling potential for urban heat mitigation application.
Cytosine and adenine deaminase base-editors induce broad and nonspecific changes in gene expression and splicing
Authors: Fan Jiao , Ding Yige , Ren Chao , Song Ziguo , Yuan Jie , Chen Qiuzhen , Du Chenchen , Li Chao , Wang Xiaolong , Shu Wenjie
Published: July 2021

Cytosine or adenine base editors (CBEs or ABEs) hold great promise in therapeutic applications because they enable the precise conversion of targeted base changes without generating of double-strand breaks. However, both CBEs and ABEs induce substantial off-target DNA editing, and extensive off-target RNA single nucleotide variations in transfected cells. Therefore, the potential effects of deaminases induced by DNA base editors are of great importance for their clinical applicability. Here, the transcriptome-wide deaminase effects on gene expression and splicing is examined. Differentially expressed genes (DEGs) and differential alternative splicing (DAS) events, induced by base editors, are identified. Both CBEs and ABEs generated thousands of DEGs and hundreds of DAS events. For engineered CBEs or ABEs, base editor-induced variants had little effect on the elimination of DEGs and DAS events. Interestingly, more DEGs and DAS events are observed as a result of over expressions of cytosine and adenine deaminases. This study reveals a previously overlooked aspect of deaminase effects in transcriptome-wide gene expression and splicing, and underscores the need to fully characterize such effects of deaminase enzymes in base editor platforms.
PEGylated cationic nanoassemblies based on triblock copolymers to combine siRNA therapeutics with anticancer drugs
Authors: Conte Claudia , Dal Poggetto Giovanni , Schiano Di Cola Viola , Russo Annapina , Ungaro Francesca , Russo Giulia , Laurienzo Paola , Quaglia Fabiana
Published: July 2021

PEGylated cationic NPs based on PEG–pDMAEMA–PCL triblock copolymers are able to condense a therapeutic siRNA and simultaneously entrap the anticancer drug DTX, thus exerting in cancer cells high silencing efficacy and a combined anticancer effect.
Space-confined construction of two-dimensional nitrogen-doped carbon with encapsulated bimetallic nanoparticles as oxygen electrocatalysts
Authors: Wang Fang , Xu Yang , Wang Yanzhi , Liang Zuozhong , Zhang Ru , Wang Yaru , Zhang Hang , Zhang Wei , Cao Rui , Zheng Haoquan
Published: July 2021

A space-confined strategy has been used to control the pyrolysis of two-dimensional (2D) NiCo-MOF@ZIF-L(Zn).
SARS-CoV-2 Mproinhibition by a zinc ion: structural features and hints for drug design
Authors: Grifagni Deborah , Calderone Vito , Giuntini Stefano , Cantini Francesca , Fragai Marco , Banci Lucia
Published: July 2021

The first structure of the SARS-CoV-2 main protease in complex with an isolated zinc ion provides solid ground for the design of potent and selective metal-conjugated inhibitors.
Advances in photochemical and electrochemical incorporation of sulfur dioxide for the synthesis of value-added compounds
Authors: Blum Stephan P. , Hofman Kamil , Manolikakes Georg , Waldvogel Siegfried R.
Published: July 2021

Photosynthesis and electrosynthesis enable the “green” upcycling of SO2to value-added products.
The effect of SO2 on the structural evolution of a supported Mn2V2O7 catalyst and its DeNOx performance
Authors: Huangfu Lin , Zhao Shuying , Li Jianling , Yao Zhiliang , Li Changming , Gao Shiqiu , Yu Jian
Published: July 2021

Mn2V2O7/TiO2 can decompose to form sulfated VOx and MnSO4 on TiO2 in the presence of SO2, and the corresponding DeNOx efficiency increases above 250 °C but it decreases below 250 °C.
Enhanced toughness of hydroxyapatite–poly(ethylene terephthalate) composites by immersion in water
Authors: Okuda Yui , Hirota Ken , Mizutani Tadashi , Numamoto Yusuke
Published: July 2021

Composites of hydroxyapatite and poly(ethylene terephthalate) bearing carboxylate groups were prepared by coprecipitation in water. The fracture energy of the compact was four times larger after immersion in water at 37 °C for 1 week.
Analysis of pancreatic extracellular matrix protein post-translational modifications via electrostatic repulsion-hydrophilic interaction chromatography coupled with mass spectrometry
Authors: Tabang Dylan Nicholas , Cui Yusi , Tremmel Daniel M. , Ford Megan , Li Zihui , Sackett Sara Dutton , Odorico Jon S. , Li Lingjun
Published: July 2021

Glycosylation and phosphorylation in extracellular matrix proteins from human pancreas tissues were analyzed using a chromatographic simultaneous enrichment strategy followed by mass spectrometry.
The effects of MoO3 impregnation order on the catalytic activity for propane combustion over Pt/ZrO2 catalysts: the crucial roles of Pt–MoO3 interfacial sites density
Authors: Zhao Peipei , Wang Weiyue , Wang Xufang , Liu Chufeng , Lu Jiqing , Luo Mengfei , Chen Jian
Published: July 2021

MoO3 promoted Pt/ZrO2 catalysts were prepared by co-impregnation (Pt–Mo/ZrO2) or stepwise impregnation (Pt/Mo/ZrO2 and Mo/Pt/ZrO2) for propane combustion.
Ag2S monolayer: an ultrasoft inorganic Lieb lattice
Authors: Yang Tong , Luo Yong Zheng , Wang Zishen , Zhu Tao , Pan Hui , Wang Shijie , Lau Shu Ping , Feng Yuan Ping , Yang Ming
Published: July 2021

Ag2S monolayer is revealed as an inorganic electronic Lieb lattice. Its ultrasoft nature enables its properties to be finely tuned by strains. This work expands the search scope of electronic Lieb lattices to the vast inorganic material domain.
Continuous production of ultrathin organic–inorganic Ruddlesden–Popper perovskite nanoplatelets via a flow reactor
Authors: Biesold Gill M. , Liang Shuang , Wagner Brent K. , Kang Zhitao , Lin Zhiqun
Published: July 2021

Continuous production of ultrathin Ruddlesden–Popper perovskite nanoplatelets using a flow reactor.
Y(OTf)3-catalyzed phosphorylation of 2H-chromene hemiacetals with P(O)–H compounds to 2-phosphorylated 2H-chromenes
Authors: Zheng Shi-Lu , Zou Yun-Xiang , Wen Zhong , Lin Jia-Fu , Gu Ling-Hui , Chen Long
Published: July 2021

A highly efficient dehydrative phosphorylation of 2H-chromene hemiacetals with P(O)–H compounds was reported, which provides 2-phosphorylated 2H-chromenes in rich diversity with up to 98% yield.
Tailorable MOF architectures for high-efficiency electromagnetic functions
Authors: Zhu Si-Qi , Shu Jin-Cheng , Cao Mao-Sheng
Published: July 2021

Adjustable microstructures and components of MOF architectures for high-efficiency electromagnetic functions.
Towards controlled bubble nucleation in microreactors for enhanced mass transport
Authors: Ripken Renée M. , Wood Jeffery A. , Schlautmann Stefan , Günther Axel , Gardeniers Han J. G. E. , Le Gac Séverine
Published: July 2021

The exact location of bubbles with respect to the catalytic layer impacts the microreactor performance. In this work, we propose to control bubble nucleation using micropits to maximize the microreactor efficiency.
Dynamics of phase transitions in Na2TiO3 and its possible utilization as a CO2 sorbent: a critical analysis
Authors: Blanco Maria Valeria , Abdala Paula Macarena , Gennari Fabiana , Cova Federico
Published: July 2021

Thermally-driven structural changes of Na2TiO3 and their effect on its carbonation behaviour.
In silico design to enhance the barrier height for magnetization reversal in Dy(iii) sandwich complexes by stitching them under the umbrella of corannulene
Authors: Sharma Tanu , Singh Mukesh Kumar , Gupta Radhika , Khatua Munmun , Rajaraman Gopalan
Published: July 2021

Bringing half-sandwich Dy(iii) SIMs under the umbrella of corannulene was found to offer stability, greater barrier height and may offer higher blocking temperatures.
Resolving electron injection from singlet fission-borne triplets into mesoporous transparent conducting oxides
Authors: Gish Melissa K. , Raulerson Emily K. , Pekarek Ryan T. , Greenaway Ann L. , Thorley Karl J. , Neale Nathan R. , Anthony John E. , Johnson Justin C.
Published: July 2021

The rate of photoinduced electron transfer from triplet excited states after singlet fission in molecules adsorbed to mesoporous oxide substrates is shown through transient absorption studies to depend systematically on applied bias.
Roughness-dependent clogging of particle suspensions flowing into a constriction
Authors: Hsu Chiao-Peng , Baysal Hasan Emre , Wirenborn Görel , Mårtensson Gustaf , Prahl Wittberg Lisa , Isa Lucio
Published: July 2021

Surface roughness plays a key role in the clogging of dense suspensions.
Triggered interactions between nanoparticles and lipid membranes: design principles for gel formation or disruption-and-release
Authors: Cao Rui , Gao Jingjing , Thayumanavan S. , Dinsmore Anthony D.
Published: July 2021

A light-responsive system, composed of lipid vesicles and particles self-assembled from amphiphilic polymers, leads to gelation or disruption and release.
Tailoring the cationic and anionic sites of LaFeO3-based perovskite generates multiple vacancies for efficient water oxidation
Authors: Selvadurai A. Paul Blessington , Xiong Tuzhi , Huang Peng , Tan Qirong , Huang Yongchao , Yang Hao , Balogun M.-Sadeeq (Jie Tang)
Published: July 2021

A simple strategy involving Cr and Mo tailoring and post-reduction process to generate multivacancies in LaFeO3 is reported, which substantially accelerates the OER electroactivity of LaFeO3 with overpotential of 263 mV at 10 mA cm−2.
A reverse-design-strategy for C@Li3VO4 nanoflakes toward superb high-rate Li-ion storage
Authors: Xu Jie , Liang Pei , Zhang Dongmei , Pei Cunyuan , Zhang Zongping , Yang Shuyue , Ni Shibing
Published: July 2021

C@LVO nanoflakes with tailored crystallographic planes of LVO were reversely designed and prepared for the first time via a water-etching strategy, showing outstanding high-rate and long-life performance outperforming most of the LVO-based electrodes.
Inhibitory feedback control of NF-κB signalling in health and disease
Authors: Prescott Jack A. , Mitchell Jennifer P. , Cook Simon J.
Published: July 2021

Cells must adapt to changes in their environment to maintain cell, tissue and organismal integrity in the face of mechanical, chemical or microbiological stress. Nuclear factor-κB (NF-κB) is one of the most important transcription factors that controls inducible gene expression as cells attempt to restore homeostasis. It plays critical roles in the immune system, from acute inflammation to the development of secondary lymphoid organs, and also has roles in cell survival, proliferation and differentiation. Given its role in such critical processes, NF-κB signalling must be subject to strict spatiotemporal control to ensure measured and context-specific cellular responses. Indeed, deregulation of NF-κB signalling can result in debilitating and even lethal inflammation and also underpins some forms of cancer. In this review, we describe the homeostatic feedback mechanisms that limit and ‘re-set’ inducible activation of NF-κB. We first describe the key components of the signalling pathways leading to activation of NF-κB, including the prominent role of protein phosphorylation and protein ubiquitylation, before briefly introducing the key features of feedback control mechanisms. We then describe the array of negative feedback loops targeting different components of the NF-κB signalling cascade including controls at the receptor level, post-receptor signalosome complexes, direct regulation of the critical ‘inhibitor of κB kinases’ (IKKs) and inhibitory feedforward regulation of NF-κB-dependent transcriptional responses. We also review post-transcriptional feedback controls affecting RNA stability and translation. Finally, we describe the deregulation of these feedback controls in human disease and consider how feedback may be a challenge to the efficacy of inhibitors.
Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis
Authors: da Silva Josiane Fernandes , Alves Juliano V. , Silva-Neto Julio A. , Costa Rafael M. , Neves Karla B. , Alves-Lopes Rheure , Carmargo Livia L. , Rios Francisco J. , Montezano Augusto C. , Touyz Rhian M. , Tostes Rita C.
Published: July 2021

Objective: The mechanisms involved in NOX5 activation in atherosclerotic processes are not completely understood. The present study tested the hypothesis that lysophosphatidylcholine (LPC), a proatherogenic component of oxLDL, induces endothelial calcium influx, which drives NOX5-dependent reactive oxygen species (ROS) production, oxidative stress, and endothelial cell dysfunction. Approach: Human aortic endothelial cells (HAEC) were stimulated with LPC (10−5 M, for different time points). Pharmacological inhibition of NOX5 (Melittin, 10−7 M) and NOX5 gene silencing (siRNA) was used to determine the role of NOX5-dependent ROS production in endothelial oxidative stress induced by LPC. ROS production was determined by lucigenin assay and electron paramagnetic spectroscopy (EPR), calcium transients by Fluo4 fluorimetry, and NOX5 activity and protein expression by pharmacological assays and immunoblotting, respectively. Results: LPC increased ROS generation in endothelial cells at short (15 min) and long (4 h) stimulation times. LPC-induced ROS was abolished by a selective NOX5 inhibitor and by NOX5 siRNA. NOX1/4 dual inhibition and selective NOX1 inhibition only decreased ROS generation at 4 h. LPC increased HAEC intracellular calcium, important for NOX5 activation, and this was blocked by nifedipine and thapsigargin. Bapta-AM, selective Ca2+ chelator, prevented LPC-induced ROS production. NOX5 knockdown decreased LPC-induced ICAM-1 mRNA expression and monocyte adhesion to endothelial cells. Conclusion: These results suggest that NOX5, by mechanisms linked to increased intracellular calcium, is key to early LPC-induced endothelial oxidative stress and pro-inflammatory processes. Since these are essential events in the formation and progression of atherosclerotic lesions, the present study highlights an important role for NOX5 in atherosclerosis.