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Electric signal accelerates full‐thickness wound healing in the clinic, which is usually generated by a large power generation system and requires delicate control by authorized personnel. Here, a self‐powered flexible and biocompatible thermoelectric device with exceptionally high power generation efficiency is developed. It generates 10 mV voltage at a temperature gradient of 10 K, outperforming all reported flexible thermoelectric devices. Accordingly, it can directly and efficiently convert the omnipresent heat in the skin to electricity at the microvolt level. The output electricity activates and upregulates the expression of Piezo1‐mediated pathways that are associated with tissue regeneration, accelerating the cell migration and proliferation in vitro and healing the wound 4 days faster in vivo. Importantly, the thermoelectric device fast‐heals the wound without involving any additional electric circuit such as an amplifier. These advantages will revolutionize the designing of self‐powered wearable bioelectronics for diagnosing, monitoring, and treating various pathological conditions employing the skin heat. [ABSTRACT FROM AUTHOR]

2D covalent organic frameworks (COFs) are attractive for fluorescence sensing due to their lightweight, robust, and highly ordered porous structures. However, the highly conjugated structures between adjacent layers of covalent organic frameworks can often result in aggregation‐caused quenching (ACQ) properties. Here, the study designs two flexible hydrazone‐linked COFs to suppress ACQ effects, thereby enhancing their luminescent activities. Furthermore, the high density of nitrogen and oxygen atoms on these flexible walls serves as binding sites for hydrogen bonding interactions, indicating sensitivity and selectivity towards 2,4,6‐trinitrophenol detection. [ABSTRACT FROM AUTHOR]

Aim: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose–response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose–response meta‐analyses to fill this gap. Methods: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose–response relationship was evaluated using a one‐stage random‐effects dose–response meta‐analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety). Results: The dose–response meta‐analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near‐maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose‐efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups. Conclusions: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk. [ABSTRACT FROM AUTHOR]

Background: Tertiary lymphoid structures (TLSs) have prognostic value in intrahepatic cholangiocarcinoma (ICC) patients. Noninvasive tool to preoperatively evaluate TLSs is still lacking. Purpose: To explore the association between TLSs status of ICC and preoperative MRI radiomics analysis. Study Type: Retrospective. Subjects: One hundred and ninety‐two patients with ICC, divided into training (T = 105), internal validation groups (V1 = 46), and external validation group (V2 = 41). Sequence: Coronal and axial single‐shot fast spin‐echo T2‐weighted, diffusion‐weighted imaging, T1‐weighted, and T1WI fat‐suppressed spoiled gradient‐recall echo LAVA sequence at 3.0 T. Assessment: The VOIs were drawn manually within the visible borders of the tumors using ITK‐SNAP version 3.8.0 software in the axial T2WI, DWI, and portal vein phase sequences. Radiomics features were subjected to least absolute shrinkage and selection operator regression to select the associated features of TLSs and construct the radiomics model. Univariate and multivariate analyses were used to identify the clinical radiological variables associated with TLSs. The performances were evaluated by the area under the receiver operator characteristic curve (AUC). Statistical Tests: Logistic regression analysis, ROC and AUC, Hosmer–Lemeshow test, Kaplan–Meier method with the log‐rank test, calibration curves, and decision curve analysis. P < 0.05 was considered statistically significant. Results: The AUCs of arterial phase diffuse hyperenhancement were 0.59 (95% confidence interval [CI], 0.50–0.67), 0.52 (95% CI, 0.43–0.61), and 0.66 (95% CI, 0.52–0.80) in the T, V1, and V2 cohorts. The AUCs of Rad‐score were 0.85 (95% CI, 0.77–0.92), 0.81 (95% CI, 0.67–0.94), and 0.84 (95% CI, 0.71–0.96) in the T, V1, and V2 cohorts, respectively. In cohort T, low‐risk group showed significantly better median recurrence‐free survival (RFS) than that of the high‐risk group, which was also confirmed in cohort V1 and V2. Data Conclusion: A preoperative MRI radiomics signature is associated with the intratumoral TLSs status of ICC patients and correlate significantly with RFS. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Objective Materials and methods Results Conclusions To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines.In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts.A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle–Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls.Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Two studies were conducted to investigate the relationship between Early Life Adversity and Malevolent Creativity as well as its underlying mechanism. Study 1 established a moderated mediation model to explore the mediating role of Belief in a Just World (BJW) and the moderating role of Dark Triad. A total of 353 college students (Mage = 21.25, SDage = 2.21, 58.9% women) were recruited to fill out questionnaires. The results showed that Early Life Adversity positively predicted Malevolent Creativity behavior and indirectly predicted Malevolent Creativity behavior through BJW. Dark Triad reduced the effects of Early Life Adversity on BJW and intensified the effects of Early Life Adversity on Malevolent Creativity behavior. Study 2 explored the effect of threatening BJW on Malevolent Creativity potential. A total of 180 participants (Mage = 20.53, SDage = 1.7, 64.4% women) were investigated with questionnaires and a Malevolent Creativity Problem‐Solving Task. Study 2 validated study 1 and illustrated that the Malevolent Creativity potential (including fluency, originality, and malevolence) was enhanced when Belief in a Just World was threatened. However, greater fluency was only observed in men. As a whole, these finding emphasizes the important linking role of BJW between Early Life Adversity and Malevolent Creativity, and Dark Triad and gender influence the expression of Malevolent Creativity as well. [ABSTRACT FROM AUTHOR]

Most existing path following control approaches for underactuated Autonomous underwater vehicles (AUVs) assumed that the roll angle can be passively stabilized at zero, and simplified the problem to the 5‐degree‐of‐freedom model. However, in practice, the roll motion suffers from undesirable oscillations induced by environmental disturbances, unbalanced propeller torque, etc. To preserve the stability of the system under nonzero roll dynamics, this paper proposes a novel line‐of‐sight‐ (LOS) guided path following control approach. Firstly, the spatial path following error dynamics model is derived to comprehensively reveal the negative effect of roll dynamics. Secondly, an improved LOS guidance law is designed to compensate for the nonzero roll angle. A salient feature is that the proposed guidance law can be applied to the underwater vehicle no matter it is underactuated in the roll motion or not. Thirdly, by assigning the guidance angles to the desired attitude angles, a robust attitude tracking controller is developed, in which the adaptive estimation technique is employed to handle the lumped uncertainties. The tanh‐based saturation function is incorporated such that the resultant control signals are inherently bounded. The closed‐loop path following and attitude tracking errors are proved to be globally asymptotically stable at the origin. Comparative simulation results are provided to substantiate the effectiveness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

For bulk‐heterojunction organic solar cells (OSCs), molecular structure design to control molecular stacking is crucial to obtain ideally phase‐separated morphology and high device performance. Herein, the investigation focuses on two polythiophene‐quinoxaline (PTQ) derivatives (PTQ8 and PTQ10) blended with Y6, utilizing coarse‐grained molecular dynamics simulations based on the Lennard–Jones static potential (LJSP) method. The study reveals that the diminished photovoltaic efficiencies of PTQ8:Y6 blends, compared to PTQ10:Y6 blends, are not solely attributed to reduced driving forces. The introduction of fluorine‐substituted sites in the thiophene group of PTQ polymer is identified as a significant factor. This alteration causes PTQ polymers in PTQ8:Y6 blends to coil, compromising the crystalline structure. PTQ8's bifluorine group induces a repulsive effect on the quinoxaline group, leading to a coiled‐chain structure that hinders chain stacking. Conversely, PTQ10 exhibits a straighter chain conformation. Additionally, PTQ8's high solubility in chloroform prevents effective aggregation, further impeding suitable morphology formation. Coarse‐grained simulations employing LJSP prove effective in precisely exploring the morphology of OSCs, offering crucial insights for materials in this field. [ABSTRACT FROM AUTHOR]

This paper proposes a fault‐tolerant control strategy for the air path system of a turbocharged diesel engine, considering the simultaneous presence of matched and mismatched external disturbances, additive and loss of effectiveness fault modes in the EGR and VGT subsystems. Firstly, a disturbance observer based on H∞$$ {H}_{\infty } $$ theory is designed for estimating additive faults and external disturbances, and the upper bound of observation error is obtained. Based on the observation information, an integral sliding mode surface is designed, and the effectiveness of the sliding mode surface is analyzed. For the loss of effectiveness faults in the actuators, a novel adaptive update sliding mode controller is designed. The proposed control algorithm can get the fault information of the system and achieve fault‐tolerant control of through controller reconstruction. Ultimately, the effectiveness of the proposed method is validated through simulations and comparative analysis. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) represent a new type of crystalline porous polymers that possess pre‐designed skeletons, uniform nanopores, and ordered π structure. These attributes make them well‐suited for the design of light‐emitting materials. However, the majority of COFs exhibits poor luminescence due to aggregation‐caused quenching (ACQ), resulting from the strong interaction between adjacent layers. To break the limitation, the building units with three methoxy groups on the walls are used to construct TM‐OMe‐EBTHz‐COF, which suppresses the ACQ effects to improve light‐emitting activity of COF. The TM‐OMe‐EBTHz‐COF exhibits a notable emission of yellow‐green luminescence in the solid state, with a remarkably high absolute quantum yield of 21.1%. The methoxy groups and hydrazine linkage form three coordination sites, contributing to excellent performance in metal ions sensing. The TM‐OMe‐EBTHz‐COF demonstrates high sensitivity and selectivity to Fe3+ ion. Importantly, the low detection limit is below 150 nanomolar, ranking it among the best‐performing Fe3+ sensor systems. [ABSTRACT FROM AUTHOR]

Shrub expansion is increasing in grasslands worldwide and has profound effects on biodiversity and ecosystem functions. Shrub expansion has primarily been explained by extrinsic factors such as climate change and human activities, yet the roles of intrinsic shrub demographic population dynamic and shrub–grass interaction remain poorly understood. With a paired mown and exclosure comparison experiment and baseline levels of shrub abundance in a semiarid grassland, we confirmed that long‐term livestock exclusion promotes expansion of two native shrubs, Artemisia sacrorum and Caragana brachypoda. Shrub abundance increased during the livestock exclusion period. Shrub biomass in fenced plots was about 5‐ to 10‐fold greater than in mown plots. Both increase in population density and individual size (especially height) contributed to shrub increase. The mechanism behind this was the divergent effects of litter accumulation on shrubs and grasses. Litter accumulation suppressed grass production, while facilitating shrub recruitment and growth. Our findings highlight the potential role of litter accumulation‐mediated shifts in shrub–grass interactions, which should be incorporated into grazing top‐down control to better predict the restoration outcomes of grassland management changes. The identified internal biotic mechanism raises the possibility that removal of accumulated litter by grazing or mowing may be an alternative way to maintain or restore a grass‐dominated state in shrub expansion areas. [ABSTRACT FROM AUTHOR]

Alveolar bone injury under diabetic conditions can severely impede many oral disease treatments. Rebuilding diabetic alveolar bone in clinics is currently challenging due to persistent infection and inflammatory response. Here, an antibacterial DNA‐based hydrogel named Agantigel is developed by integrating silver nanoclusters (AgNCs) and tumor necrosis factor‐alpha (TNF‐α) antibody into DNA hydrogel to promote diabetic alveolar bone regeneration. Agantigel can effectively inhibit bacterial growth through AgNCs while exhibiting negligible cytotoxicity in vitro. The sustained release of TNF‐α antibody from Agantigel effectively blocks TNF‐α and promotes M2 polarization of macrophages, ultimately accelerating diabetic alveolar bone regeneration in vivo. After 21 days of treatment, Agantigel significantly accelerates the defect healing rate of diabetic alveolar bone up to 82.58 ± 8.58% and improves trabecular architectures compared to free TNF‐α (42.52 ± 15.85%). The results imply that DNA hydrogels are potential bio‐scaffolds helping the sustained release of multidrug for treating DABI or other oral diseases. [ABSTRACT FROM AUTHOR]

Analysis of T‐cell receptor (TCR) repertoires in different stages of hepatocellular carcinoma (HCC) might help to elucidate its pathogenesis and progression. This study aimed to investigate TCR profiles in liver biopsies and peripheral blood mononuclear cells (PBMCs) in different Barcelona Clinic liver cancer (BCLC) stages of HCC. Ten patients in early stage (BCLC_A), 10 patients in middle stage (BCLC_B), and 10 patients in late stage (BCLC_C) cancer were prospectively enrolled. The liver tumor tissues, adjacent tissues, and PBMCs of each patient were collected and examined by TCR β sequencing. Based on the ImMunoGeneTics (IMGT) database, we aligned the V, D, J, and C gene segments and identified the frequency of CDR3 sequences and amino acids sequence. Diversity of TCR in PBMCs was higher than in both tumor tissues and adjacent tissues, regardless of BCLC stage and postoperative recurrence. TCR clonality was increased in T cells from peripheral blood in advanced HCC, compared with the early and middle stages. No statistical differences were observed between different BCLC stages, either in tumors or adjacent tissues. TCR clonality revealed no significant difference between recurrent tumor and non‐recurrent tumor, therefore PBMCs was better to be representative of TCR characteristics in different stages of HCC compared to tumor tissues. Clonal expansion of T cells was associated with low risk of recurrence in HCC patients. [ABSTRACT FROM AUTHOR]

Kaempferol is the active ingredient of Er‐Xian decoction (EXD), a traditional Chinese medicine formula used clinically to treat ovarian dysfunction, but the mechanism of kaempferol relieving age‐related diminished ovarian reserve (AR‐DOR) is still unclear. In this study, 36 volunteers and 78 DOR patients (37 patients with EXD treatment) were enrolled in the clinical research. Meanwhile, 32‐week‐old female mice were used to establish the AR‐DOR model, and these model mice were intragastrically administered with 100 mg/kg kaempferol in the presence or absence of 200 mg/kg geranylgeranylacetone (GGA) or 1 mg/kg geldanamycin (GDA). The effects of kaempferol on serum hormone levels and oxidative stress‐related indexes were detected by enzyme‐linked immunosorbent assay. Antral follicle count (AFC) was determined by hematoxylin–eosin staining. The protein levels of HSP90 and nuclear factor erythroid 2‐related factor 2 (NRF2) were assayed by Western blot. This study displayed that the serum anti‐Mullerian hormone (AMH) level in DOR patients with EXD treatment was higher than that in DOR patients without EXD treatment. Kaempferol treatment reversed the low levels of AMH, estradiol (E2), AFC, superoxide dismutase (SOD), and catalase (CAT), as well as the high levels of follicle‐stimulating hormone (FSH), reactive oxygen species (ROS), and malonaldehyde (MDA). The results showed that HSP90 was predicted to have high affinity with kaempferol, and its expression was inhibited by kaempferol, while the expression of NRF2, the target of HSP90, was up‐regulated by kaempferol. However, the above effects of kaempferol were reversed by GGA. On the contrary, GDA enhanced the therapeutic effects of kaempferol on AR‐DOR mice. Moreover, the treatment of kaempferol resulted in a reduction in the phosphorylation level of heat shock factor 1 (HSF1), the transcription factor associated with HSP90, and an increase in the phosphorylation level of Src, a client protein of HSP90. In summary, kaempferol exerts an antioxidant effect on AR‐DOR by inhibiting HSP90 expression to up‐regulate NRF2 expression. This study provides a theoretical basis for the clinical application of kaempferol in AR‐DOR. [ABSTRACT FROM AUTHOR]

PRDM16 (PR domain containing protein 16) serves as a dominant activator of brown and beige adipocyte. However, mechanisms underlying the regulation of PRDM16 expression are incompletely understood. A Prdm16 luciferase knockin reporter mouse model is generated, enabling high throughput monitoring of Prdm16 transcription. Single clonal analysis reveals high heterogeneity of Prdm16 expression in the inguinal white adipose tissue (iWAT) cells. Amongst all transcription factors, androgen receptor (Ar) shows the strongest negative correlation with Prdm16. A sex dimorphism for PRDM16 mRNA expression is present in human WAT, with female individuals exhibiting increased expression than males. Androgen‐AR signaling mobilization suppresses Prdm16 expression, accompanied by attenuated beiging in beige adipocytes, but not in brown adipose tissue. The suppressive effect of androgens on beiging is abolished upon overexpression of Prdm16. Cleavage under targets and tagmentation mapping reveals direct binding of AR within the intronic region of Prdm16 locus, whereas no direct binding is detected on Ucp1 and other browning‐related genes. Adipocyte‐selective deletion of Ar potentiates beige cell biogenesis whereas adipocyte‐specific overexpression of AR attenuates white adipose beiging. This study highlights an essential role of AR in negative regulation of PRDM16 in WAT and provides an explanation for the observed sex difference in adipose beiging. [ABSTRACT FROM AUTHOR]

Radioactive iodine waste in the nuclear field is harmful to the environment and human health. Covalent organic frameworks (COFs) are a novel kind of porous organic material with a well‐fine and unformal structure, which is an excellent candidate as a solid adsorbent for iodine adsorption. Herein, a linkage design is proposed for effective iodine adsorption. Imine‐linkage COF (I‐COF) and hydrazone‐linked COF (H‐COF) are constructed under solvothermal conditions. The Brunauer–Emmett–Teller surface area of H‐COF is as high as 1747 m2 g−1. Furthermore, the H‐COF shows high porosity, stability, and rich atoms in the linkage. As a result, the work outperforms most of the previous reports in iodine capture with a high capture value at 5.72 g g−1. [ABSTRACT FROM AUTHOR]

In dermatology, photodynamic therapy (PDT) is widely used in skin tumors, infections, etc., because of the killing effect triggered by toxic reactive oxygen species (ROS). However, the ROS concentration is determined by various photosensitizer concentrations and formulations, as well as various irradiation parameters. Low‐dose PDT leads to sufficiently low ROS level, which results in biological effects that are the exact opposite of the killing potency. Therefore, in recent years, low‐dose PDT has been exploited in improving aging and wound. Low‐dose ALA/MAL PDT might improve aging through promoting the proliferation of fibroblasts, blocking DNA damage, counteracting oxidative stress, inhibiting melanogenesis, and remodeling lymphatic vessels in aged skin. Promoting fibroblasts and epidermal stem cells proliferation and migration, promoting granulation tissue formation and angiogenesis and regulating the inflammatory process might be the mechanisms of low‐dose ALA/MAL PDT in wound healing. Nevertheless, the positive effects of low‐dose PDT have not been thoroughly investigated in dermatology, and high‐quality studies are still needed to fill the relevant vacancy. [ABSTRACT FROM AUTHOR]

Overnutrition is a risk factor for various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. Therefore, targeting overnutrition represents a simple but attractive strategy for the treatment of these increasing public health threats. Fasting as a dietary intervention for combating overnutrition has been extensively studied. Fasting has been practiced for millennia, but only recently have its roles in the molecular clock, gut microbiome, and tissue homeostasis and function emerged. Fasting can slow aging in most species and protect against various human diseases, including neurodegenerative diseases, metabolic disorders, and cancers. These centuried and unfading adventures and explorations suggest that fasting has the potential to delay aging and help prevent and treat diseases while minimizing side effects caused by chronic dietary interventions. In this review, recent animal and human studies concerning the role and underlying mechanism of fasting in physiology and pathology are summarized, the therapeutic potential of fasting is highlighted, and the combination of pharmacological intervention and fasting is discussed as a new treatment regimen for human diseases. [ABSTRACT FROM AUTHOR]

Unveiling the principles governing embryonic stem cell (ESC) differentiation into specific lineages is critical for understanding embryonic development and for stem cell applications in regenerative medicine. Here, we establish an intersection between LIF‐Stat3 signaling that is essential for maintaining murine (m) ESCs pluripotency, and the glycolytic enzyme, the platelet isoform of phosphofructokinase (Pfkp). In the pluripotent state, Stat3 transcriptionally suppresses Pfkp in mESCs while manipulating the cells to lift this repression results in differentiation towards the ectodermal lineage. Pfkp exhibits substrate specificity changes to act as a protein kinase, catalyzing serine phosphorylation of the developmental regulator Lin41. Such phosphorylation stabilizes Lin41 by impeding its autoubiquitination and proteasomal degradation, permitting Lin41‐mediated binding and destabilization of mRNAs encoding ectodermal specification markers to favor the expression of endodermal specification genes. This provides new insights into the wiring of pluripotency‐differentiation circuitry where Pfkp plays a role in germ layer specification during mESC differentiation. Synopsis: Pfkp has a non‐glycolytic activity in mESC differentiation, where it catalyzes Lin41 phosphorylation, protecting Lin41 from proteasomal destruction. In turn, Lin41 promotes endodermal differentiation of mESCs by binding to and destabilizing mRNAs encoding ectodermal specification markers. Pfkp is transcriptionally repressed in mESCs through LIF‐Stat3 signaling.Lifting Stat3 repression promotes Pfkp expression and its phosphorylation of Lin41.Stabilized Lin41 disrupts expression of ectodermal mRNAs during differentiation. [ABSTRACT FROM AUTHOR]

Objective: Fear of progression (FoP) is a common psychosocial problem among adult cancer patients, but data on parents of children undergoing cancer treatment are scarce. This study aimed to determine the prevalence of FoP in parents of children undergoing cancer treatment and explore the associated factors.Methods: Overall, 285 parents of children undergoing cancer treatment were recruited from three general hospitals in China. FoP in the parents was assessed using the Chinese version of the Fear of Progression Questionnaire-parent version (FoP-Q-SF/PR). Other questionnaires included the Self-Compassion Scale, Pittsburgh Sleep Quality Index, Posttraumatic Stress Disorder Checklist-Civilian Version, and items on socio-demographic and medical characteristics. Pearson correlation and multiple linear regression analysis were used to identify factors associated with FoP.Results: A total of 75.1% of the participants showed dysfunctional levels of FoP. The mean FoP-Q-SF/PR score was 39.98 (standard deviation = 9.18). Parental FoP was significantly associated with a shorter time since diagnosis, lower levels of self-compassion, poor sleep quality, and severe posttraumatic stress symptoms (Adjusted R Squared = 0.369, F = 12.838, p < 0.01).Conclusions: FoP is a frequently reported problem among parents of children undergoing cancer treatment. In this cohort, parents of children with a shorter time since cancer diagnosis were at higher risk of suffering from FoP. Interventions to enhance self-compassion, improve sleep quality, and mitigate posttraumatic stress symptoms may help with the psychological adjustment and well-being of parents whose children are undergoing cancer treatment. [ABSTRACT FROM AUTHOR]

This study examines whether enterprises can obtain abnormal returns through philanthropic giving during public health emergencies, such as the COVID‐19 crisis, by using an event study approach to conduct an empirical analysis. The results show that if enterprises participate in philanthropic giving during the COVID‐19 crisis, they can obtain abnormal returns in the stock market. The extent of this market reaction is directly proportional to the level of philanthropic giving, and it is more significant for private enterprises, enterprises in regions that are more affected by the epidemic, enterprises in social responsibility sensitive industries, and enterprises with more timely donations. [ABSTRACT FROM AUTHOR]

Hypokalemia is a common disorder in clinical settings; however, nonmolecular diagnostic testing cannot explain some causes of hypokalemia. To determine the etiology of clinically unexplained hypokalemia without hypertension (CUHypoNH) and to obtain a diagnostic yield of monogenic hypokalemia without hypertension in adults (MHNHA), we enrolled 82 patients with CUHypoNH for whole‐exome sequencing or targeted gene sequencing of genes associated with 4000 monogenic disorders. Through molecular diagnosis, 25 patients were diagnosed with monogenic hypokalemia, and a diagnostic yield of 30.5% was obtained. Among patients with MHNHA, 18 patients (18/82, 22.0% and 72% of MHNHA) with Gitelman syndrome accounted for the largest proportion. Among the 29 diagnostic variants found, eight mutations have not been reported previously; these include three point mutations, one frameshift mutation, and four exon deletions. Based on the clinical presentation of patients with CUHypoNH, the diagnostic yield of monogenic hypokalemia was the highest for chronic asymptomatic hypokalemia (8/11, 72.7%). Twenty‐one patients had concomitant hypomagnesemia, when accompanied with hypocalciuria, the molecular diagnostic yield of Gitelman syndrome increased to 88.2%. Overall, this study on hospitalized adult patients explored the etiology of CUHypoNH using high‐throughput sequencing. Molecular diagnosis of CUHypoNH is clinically significant in guiding precision treatment and improving disease prognosis. [ABSTRACT FROM AUTHOR]

Background & Aims: The DEAD (Asp‐Glu‐Ala‐Asp)‐box helicase family member DDX3x has been proven to involve in hepatic lipid disruption during HCV infection. However, the role of DDX3x in non‐alcoholic fatty liver disease (NAFLD), in which lipid homeostasis is severely disrupted, remains unclear. Here, we aimed to illustrate the potential role of DDX3x in NAFLD. Methods: DDX3x protein levels were evaluated in NAFLD patients and NAFLD models via immunohistochemistry or western blotting. In vivo ubiquitin assay was performed to identify the ubiquitination levels of DDX3x in the progression of steatosis. DDX3x protein levels in mice livers were manipulated by adeno‐associated virus‐containing DDX3x short hairpin RNA or DDX3x overexpression plasmid. Hepatic or serum triglyceride and total cholesterol were evaluated and hepatic steatosis was confirmed by haematoxylin and eosin staining and oil red o staining. Western blotting was performed to identify the underlying mechanisms of DDX3x involving in the progression of NAFLD. Results: DDX3x protein levels were significantly decreased in NAFLD patients and NAFLD models. DDX3x protein might be degraded via ubiquitin–proteasome system in the progression of steatosis. Knockdown of hepatic DDX3x exacerbated HFD‐induced hepatic steatosis in mice, while overexpression of hepatic DDX3x alleviated HFD‐induced hepatic steatosis in mice. Further explorative experiments revealed that knockdown of DDX3x could lead to the overactivation of mTORC1 signalling pathway which exacerbates NAFLD. Conclusions: DDX3x involved in the progression of NAFLD via affecting the mTORC1 signalling pathway. DDX3x might be a potential target for NAFLD treatment. [ABSTRACT FROM AUTHOR]

By applying innovative culture methods for newly isolated microbes or adopting activity-oriented experimental discovery processes, scores of natural products with antibacterial activity have been identified from the human microbiota, for example ribosomally synthesized and post-translationally modified peptides including salivaricin,1 and non-ribosomal peptide lugdunin2 (Figure 1). Bioactive synthetic-bioinformatic natural product cyclic peptides inspired by nonribosomal peptide synthetase gene clusters from the human microbiome. [Extracted from the article]

Hailstones and extreme precipitation generate substantial economic losses across the United States (US) and the globe. Their strong association with short‐lived, intense convective storms poses a great challenge in predicting their future changes. Here, we conducted model simulations at 1.2 km grid spacing for severe convective storms with large hail and heavy precipitation that occurred in two typical types of synoptic‐scale environments in spring seasons over the central US under both current and future climate conditions. We find that the responses of large hail (diameters >2.5 cm) to anthropogenic climate change (ACC) are markedly different between the hailstorms developed in the two types of synoptic‐scale environments, with over 110% increase in large hail occurrences for the frontal systems, whereas less than 30% increase for the Great Plains low‐level jet (GPLLJ) systems. This is explained by the larger increase in convective intensity and updraft width and a smaller increase in warm cloud depth in the frontal storms compared with the GPLLJ storms. Interestingly, the occurrences and intensity of heavy precipitation (rain rate >20 mm hr−1) in both types of systems are similarly sensitive to ACC (e.g., 40% and 33% increases in the occurrences for the frontal and GPLLJ systems, respectively). These results advance our knowledge of hail projection and have important implications for managing risks for future hail. Plain Language Summary: Severe convective storms (SCSs) and associated weather hazards have caused significant property damage and economic losses worldwide. In a warming climate, how storms that presently produce hazardous weather will change and how anthropogenic warming will affect particular hazard types (e.g., hail) remain highly uncertain. Through high‐resolution (1.2‐km grid spacing) simulations of hailstorms in spring over the central United States for both current and future climate, we show that the hailstorms developed in the two typical types of synoptic environments have a contrasting response to climate warming. The hailstorms developed in the frontal environment are sensitive to future warming and produce much more occurrences of large hail, whereas those developed in the GPLLJ environment are not sensitive to climate warming. This study presents an important concept to study and understand the impacts of climate warming on hailstorms based on the synoptic weather systems for a specific region. Key Points: Synoptic‐scale environments regulate the response of hail to anthropogenic climate change (ACC)The occurrence of large hail is sensitive to ACC in the frontal storms while they are not in the GPLLJ stormsAn enhanced trough and a small increase in warm cloud depth in the future climate explain the large impact on frontal storms [ABSTRACT FROM AUTHOR]

Autophagy represents a fundamental mechanism for maintaining cell survival and tissue homeostasis in response to physiological and pathological stress. Autophagy initiation converges on the FIP200‐ATG13‐ULK1 complex wherein the serine/threonine kinase ULK1 plays a central role. Here, we reveal that the E3 ubiquitin ligase TRIM27 functions as a negative regulatory component of the FIP200‐ATG13‐ULK1 complex. TRIM27 directly polyubiquitinates ULK1 at K568 and K571 sites with K48‐linked ubiquitin chains, with proteasomal turnover maintaining control over basal ULK1 levels. However, during starvation‐induced autophagy, TRIM27 catalyzes non‐degradative K6‐ and K11‐linked ubiquitination of the serine/threonine kinase 38‐like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27‐mediated hyper‐ubiquitination of ULK1. This cooperative mechanism serves to restrain the amplitude and duration of autophagy. Further evidence from mouse models shows that basal autophagy levels are increased in Trim27 knockout mice and that Trim27 differentially regulates tumorigenesis and metastasis. Our study identifies a key role of STK38L‐TRIM27‐ULK1 signaling axis in negatively controlling autophagy with relevance established in human breast cancer. Synopsis: While ULK1 is essential for autophagy initiation, the mechanisms controlling its expression levels and function remain unclear. This report discloses how E3 ubiquitin ligase TRIM27 suppresses ULK1 protein expression to restrain autophagy through dual ubiquitination events, differentially impacting tumorigenesis. E3 ligase TRIM27 negatively regulates autophagy flux under basal and starvation conditions.TRIM27 mediates ubiquitination of ULK1 via K48‐linked chains, inducing its proteasomal degradation.Starvation induces TRIM27 ubiquitination and activation of STK38L kinase via K6‐linked chains.STK38L phosphorylates ULK1, providing a permissive state for increased ULK1 ubiquitination by TRIM27.Ablation of TRIM27 in the PyMT model inhibits murine mammary tumor initiation but promotes metastasis. [ABSTRACT FROM AUTHOR]

Since it is difficult for clinicians to make a decision among the various types of antidiabetic medications due to their great discrepancy in mechanisms, pharmacological properties, and cardiovascular/renal protection, a relatively "precision" or personalized hypoglycemic treatment suggestion is practical for type 2 diabetes (T2D) management in adults. This expert consensus makes some recommendations based on the characteristics of adult T2D patients without clinical cardiovascular disease (CVD) or chronic kidney disease (CKD) by evidence from large‐scale clinical trials. The main consideration for initiating antidiabetic medications is the safety and benefits for prevention of target organ damage, such as CVD and CKD. The choice of personalized glucose‐lowering therapy regarding target organ protection is based on the various effects of antidiabetic medications, patients' clinical characteristics and their key risks, as well as the sociological factors. According to the effects on glucose reduction, cardiovascular protection, renal benefit, body weight change, hypoglycemic risk, and liver function impact, the antidiabetic medications are recategorized in this consensus. Combined with the glucose control target and the different effects of hypoglycemic agents, a significant body of recommendations have been developed for optimal T2D management according to the risk factors for atherosclerotic CVD, heart failure, CKD, primary fatty liver, and hypoglycemia. This consensus gives detailed guidance on personalized antidiabetic therapy initiation in newly diagnosed T2D adults, which attaches great importance to both glucose control and target organ protection. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate whether soy isoflavone supplementation is effective in preventing periodontal destruction exacerbated by estrogen deficiency (ED) and its potential mechanism. Background: The progression of periodontitis is affected by host factors, such as smoking, diabetes mellitus, and steroid use. Bone loss in periodontitis can be aggravated by ED. Methods: A rat model of experimental periodontitis (EP) with ED was established by silk ligature and inoculation with Porphyromonas gingivalis, and some EP rats were subjected to bilateral ovariectomy (OVX). The treatment groups received an intravenous injection of 17‐β‐estradiol (E2B) or soy isoflavones (SI) by gavage. The rats were euthanized, and the maxillary jaws, gingiva, and serum were harvested. Tight junction protein and interleukin (IL)‐17 expression, reactive oxygen species (ROS) level, and periodontal destruction were assessed. In addition, we determined whether grainyhead‐like 2 (GRHL2) is required for enhancing the epithelial barrier by SI in an in vitro P. gingivalis infection model. Results: Estrogen deficiency impaired the expression of genes encoding tight junction proteins in the gingiva, increased IL‐17 level, and accelerated alveolar bone resorption. SI treatment alleviated tight junction protein expression, decreased IL‐17 and ROS levels, and prevented the absorption of alveolar bone. Furthermore, GRHL2 expression was significantly induced by SI in human oral keratinocytes‐1 (HOK‐1) cells; GRHL2 knockdown impaired the expression of OCLN and ZO‐1 induced by SI treatment. Conclusion: Soy isoflavones alleviates periodontitis in OVX rats, as observed by the increased expression of tight junction proteins, and reduced IL‐17 level and alveolar bone loss. The in vitro studies suggested that the enhancement of oral epithelial barrier by SI treatment was partially dependent on GRHL2. [ABSTRACT FROM AUTHOR]

Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient's hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are novel biomarkers of various cancers. CircRNAs can sponge miRNAs and regulate target mRNAs, which was called competing endogenous RNAs (ceRNA). This study was designed to identify circRNAs related to patients with clear cell renal cell carcinoma (ccRCC) and the first to select three independent Gene Expression Omnibus microarrays covering circRNAs, miRNAs, and mRNAs for multiple analyses. The data of clinical cases applied in our study were obtained from The Cancer Genome Atlas. We successfully conducted a circRNA/miRNA/mRNA ceRNA network related to ccRCC patients via R software and Cytoscape including 8 circRNAs, 6 miRNAs, and 49 mRNAs. The prognosis‐associated subnet covered 8 circRNAs, 6 miRNAs, and 22 mRNAs. Quantitative real‐time PCR was applied to measure our prediction in three renal cell lines and 23 pairs of tissues. Small interfering RNA targeting the back‐splice region of hsa_circ_0001167 was further implied to confirm the regulation. Ultimately, hsa_circ_0001167/hsa‐miR‐595/CCDC8 regulatory axis was identified in this study, which may serve as prognostic indicators. Lower levels of hsa_circ_0001167 and CCDC8 were potentially correlated with worse patient survival. [ABSTRACT FROM AUTHOR]

Conjugated organic polymers (COPs) have been excellent candidates because the conjugated structure occupied π structure that is useful to develop light‐emitting materials. However, most COPs emitt weak luminescence owing to the H‐aggregation effect. Light‐emitting conjugated organic polymers (LCOP‐1) possess rich butyl groups anchored in the skeleton to enhance light‐emitting activity via reducing the H‐aggregation effect. Owing to abundant hydroxyl and nitrogen atoms, LCOP‐1 exhibits high sensitivity, selectivity, and fast response to Cu2+ ions within 1 min in comparison with the cations of Na+, Mg2+, Al3+, Zn2+, Cd2+, Ni2+, Cr3+, Hg2+, Fe3+, Fe2+, Pb2+, Co2+, etc. The detection limit can be down to nanomolar. Moreover, the sensor exhibits detection toward Cu2+ ions via a naked eye colorful change from pale‐yellow to yellowish‐brown. Furthermore, the light‐emitting probe also successfully achieves the detection of Cu2+ ions in cells without cytotoxicity, indicating its great potentials in biological function. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Material and Methods: This multicentre phase 3 trial included a 24‐week randomized, double‐blind, placebo‐controlled period, followed by a 28‐week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once‐daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28‐week treatment, and patients on henagliflozin during 24‐week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24. Results: At Week 24, the least squares mean HbA1c changes versus placebo from baseline were − 0.76% (−8.3 mmol/mol) and − 0.80% (−8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2‐hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported. Conclusions: Henagliflozin 5 mg or 10 mg as add‐on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated. [ABSTRACT FROM AUTHOR]

The insufficient active site density and poor stability of iron and nitrogen co‐doped carbon (Fe‐N‐C) catalyst remain as great challenges for advanced oxygen reduction reaction (ORR). Surface N‐doping together with Fe species is considered as an efficient strategy to enhance the catalytic activity and stability of Fe‐N‐C. Here, we report a facile preparation of high performing Fe‐N‐C catalysts derived from Fe/melamine‐decorated polyaniline. The optimal catalyst displays much better ORR onset and half‐wave potentials (1.00 and 0.86 V) than that of the melamine‐free catalyst (0.97 and 0.83 V) and even the commercial Pt/C (0.99 and 0.83 V), respectively. It also shows a decent stability during 20 000 cycles of accelerated durability test (ADT) with only 15 mV loss in the half‐wave potential. Physical and electrochemical characterizations demonstrate that introduction of melamine could increase the percentage of surface pyrrolic N species and non‐crystalline Fe species, which would be responsible for the significant improvement in the catalytic performance toward ORR. [ABSTRACT FROM AUTHOR]

Qianliexin capsule (QLX) is a standardized traditional Chinese herbal preparation that has long been used to treat chronic non‐bacterial prostatitis (CNP) and benign prostatic hyperplasia (BPH). This study investigated the anti‐inflammatory activity of QLX in improving lower urinary tract symptoms (LUTS) associated with CNP and BPH. Rat models of CNP and BPH were induced by oestradiol or testosterone (hormonal imbalance) or chemical inflammation (carrageenan). QLX significantly relieved LUTS in CNP and BPH rat model by reducing prostate enlargement, epithelial thickness, pain response time, urine volume and bleeding time, and by improving prostatic blood flow. The expression of the pro‐inflammatory cytokines interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α, the pro‐inflammatory transcription factor nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and inflammasome components (NLRP3, caspase‐1 and ASC) in CNP and BPH tissues was reduced by QLX addition. QLX treatment was followed by reduced cellular malondialdehyde and increased superoxide dismutase, catalase and glutathione peroxidase activity, consistent with antioxidant activity. Increases in Beclin‐1 expression and the LC3II/I ratio following QLX treatment indicated that autophagy had been induced. QLX relieved LUTS in CNP and BPH rat models by inhibiting inflammation. The underlying mechanisms included inhibition of inflammasome activation, NF‐κB activation, oxidant stress and autophagy. [ABSTRACT FROM AUTHOR]

This article presents a pattern‐and frequency‐reconfigurable antenna based on movable liquid metal. The proposed antenna mainly consists of a printed three‐element Yagi‐Uda structure whose two parasitic elements are loaded with slots in the middle. Six movable liquid metal poles are filled in the microfluidic channels, which adhered to the surface of the three radiating arms of the Yagi‐Uda antenna. By moving these liquid metal poles, the slots can be shorted or opened and the equivalent electrical lengths of the director and fed‐dipole can be changed, thus adjusting the antenna in radiation pattern and frequency. As a result, this antenna can work at different states, which are mainly classified into five modes. To verify this design concept, a prototype of the proposed antenna is fabricated and measured. The measured results indicate that the antenna can operate in the frequency range from 1.52 to 3.2 GHz, and the peak gain can reach 7.3 dBi. [ABSTRACT FROM AUTHOR]

Aim: To evaluate henagliflozin, a novel sodium‐glucose co‐transporter‐2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise. Materials and Methods: This multicentre trial included a 24‐week, randomized, double‐blind, placebo‐controlled period, followed by a 28‐week extension period. Four hundred and sixty‐eight patients with an HbA1c of 7.0%–10.5% were randomly assigned (1:1:1) to receive once‐daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks. Results: At Week 24, the placebo‐adjusted least squares (LS) mean changes from baseline in HbA1c were −0.91% (95% CI: −1.11% to −0.72%; P <.001) and −0.94% (−1.13% to −0.75%; P <.001) with henagliflozin 5 and 10 mg, respectively; the placebo‐adjusted LS mean changes were −1.3 (−1.8 to −0.9) and −1.5 (−2.0 to −1.1) kg in body weight, and −5.1 (−7.2 to −3.0) and −4.4 (−6.5 to −2.3) mmHg in systolic blood pressure (all P <.05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred. Conclusions: Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated. [ABSTRACT FROM AUTHOR]

Background: The emergence of COVID‐19 has become a global health emergency. The transmissibility of the disease is of great interest to healthcare workers and scientists alike. The primary route of transmission is via respiratory droplets, but viral RNA has also been found in feces and body fluids such as urine, serum, and semen. So far, there has been no report on whether SARS‐CoV‐2 is present in the exudates of cutaneous lesions. This study was designed to investigate whether SARS‐CoV‐2 can be found in the pressure injury exudates in patients with severe COVID‐19 infections. Methods: 46 critically ill COVID‐19 patients who were admitted to the ICU of the Sino‐French New City Branch of Tongji Hospital in Wuhan between February 4 and April 12 developed pressure injuries. 22 patients with pressure injuries had wound exudates. Wound and pharyngeal swabs of the 22 patients were collected and RT‐PCRs were conducted to detect SARS‐CoV‐2 viral RNA. Results: At the time of pressure injury, 5 patients still tested positive by pharyngeal swabs, the rest of the 17 patients tested negative. However, none of the wound exudate swabs from the participants tested positive for SARS‐CoV‐2 by RT‐PCR. Conclusion: Our study suggests that it is rather unlikely that COVID‐19 can be transmitted via pressure injury exudates, but we still recommend standardized personal protective equipment, face shield and an additional pair of gloves when treating pressure injuries. [ABSTRACT FROM AUTHOR]

Designing and synthesizing a stable compound with a planar tetracoordinate silicon (ptSi) center is a challenging goal for chemists. Here, a series of potential aromatic ptSi compounds composed of four conjugated rings shared by a centrally embedded Si atom are theoretically designed and computationally verified. Both Born–Oppenheimer molecular dynamics (BOMD) simulations and potential energy surface scannings verify the high stability and likely existence of these compounds, particularly Si‐16‐5555 (SiN4C8H8) with 16 π electrons, under standard ambient temperature and pressure. Notably, the Hückel aromaticity rule, which works well for single rings, is inconsistent with the high stability of Si‐16‐5555 where the 16 p electrons are spread over four five‐membered rings fused together. Bonding analyses show that the strong electron donation from the peripheral 12‐membered conjugated ring with 16 π electrons to the vacant central atomic orbital Si 3pz leads to the stabilization for both the ptSi coordination and planar aromaticity. The partial occupation of Si 3pz results in the peculiar carbenoid‐type behaviors for the amphoteric center. By modulating the electron density on the ring with substituent groups, we can regulate the nucleophilic and electrophilic properties of the central Si. [ABSTRACT FROM AUTHOR]

The hepatic stellate cells (HSCs) play a significant role in the onset of liver fibrosis, which can be treated by the inhibition and reversal of HSC activation. The RNA interference‐mediated TLR4 gene silencing might be a potential therapeutic approach for liver fibrosis. The crucial challenge in this method is the absence of an efficient delivery system for the RNAi introduction in the target cells. HSCs have an enhanced capacity of vitamin A intake as they contain retinoic acid receptors (RARs). In the current study, we developed cationic liposomes modified with vitamin A to improve the specificity of delivery vehicles for HSCs. The outcome of this study revealed that the VitA‐coupled cationic liposomes delivered the TLR4 shRNA to aHSCs more efficiently, as compared to the uncoupled cationic liposomes, both in the in vitro and in vivo conditions. Besides, as evident from the outcome of this study, the TLR4 gene silencing inhibited the HSCs activation and attenuated the liver fibrosis via the NF‐κB transcriptional inactivation, pro‐inflammatory cytokines secretion and reactive oxygen species (ROS) synthesis. Thus, the VitA‐coupled liposomes encapsulated with the TLR4‐shRNA might prove as an efficient therapeutic agent for liver fibrosis. [ABSTRACT FROM AUTHOR]

Cardiomyocyte apoptosis induced by hypoxia and ischemia plays important roles in heart dysfunction after acute myocardial infarction (AMI). However, the mechanism of apoptosis induction remains unclear. A previous study reported that Y‐box protein 1 (YB1) is upregulated after myocardial hypoxia/reoxygenation or ischemia/reperfusion (H/R or I/R, respectively) injury; however, whether YB1 is associated with H/R‐induced cardiomyocyte apoptosis is completely unknown. In the present study, we investigated the roles of YB1 in H/R‐induced cardiomyocyte apoptosis and the possible underlying molecular mechanisms. In vitro, H/R treatment upregulated the YB1 expression in H9C2 cells, whereas YB1 knockdown inhibited H/R‐induced cardiomyocyte apoptosis and induced H9C2 cell proliferation via Src homology region 2 domain‐containing phosphatase 1 (SHP‐1)‐mediated activation of signal transducer and activator of transcription 3 (STAT3). In vivo, YB1 knockdown ameliorated AMI, reducing infarct size, cardiomyocyte apoptosis, and oxidative stress, via SHP‐1‐mediated inactivation of STAT3. Additionally, YB1 knockdown inhibited H/R‐ or I/R‐induced oxidative stress in vitro and in vivo. H/R and I/R increase YB1 expression, and YB1 knockdown ameliorates AMI injury via SHP‐1‐dependent STAT3 inactivation. [ABSTRACT FROM AUTHOR]

A piezoresistive flexible pressure sensor with high sensitivity as well as ultra‐large sensing range up to MPa is proposed based on inelastic metallic microstructures and flat elastic polymer films. During the pressure loading process, the metallic microstructures continuously penetrate into the polymer film due to the rigid characteristic, resulting in continuous contact area variation and ultra‐large pressure sensing range of the pressure sensor. Polydimethylsiloxane (PDMS) and polyvinylidene difluoride (PVDF) are introduced to construct flexible pressure sensors, achieving elastic modulus tunable sensing performance. The pressure sensors exhibit high sensitivity, superior sensing range (300 kPa for PDMS, 1.4 MPa for PVDF), ultra‐fast response time (≈3.5 ms) as well as high stability (>10 000 cycles), enabling potential applications in monitoring human vital signs, such as wrist pulse, human movements, and gait recognition. In addition, an acceleration sensor is constructed based on the as‐fabricated pressure sensor, which is utilized for extensive applications in action identification, virtual reality, and vehicle safety systems. This work provides an alternative strategy to construct high performance pressure sensors. [ABSTRACT FROM AUTHOR]

Objectives: Bone marrow edema is a universal manifestation of rheumatoid arthritis (RA), and its pathological essence is a bone marrow lesion (BML) formed by various bone marrow (BM) immune cells. Neutrophils play an important role in inflammatory arthritis, but the role and mechanism of neutrophils in BML are not clear. Materials and methods: Granulocyte colony‐stimulating factor (G‐CSF) −/− mice and wild type (WT) C57BL/6 mice were immunized for collagen‐induced arthritis (CIA). Histological scores of arthritis were evaluated. Immunohistochemistry staining with anti‐Ly6G was conducted. Neutrophil extracellular traps (NETs) in joint sections were determined by immunofluorescence staining. BM neutrophils were isolated for flow cytometry and NETosis induction in vitro. Results: Histological study showed significant neutrophil infiltrations in BML of CIA mice. Inhibition of BM neutrophil production by G‐CSF knock out can obstruct the induction of BML and CIA. In addition to abundant infiltrated NETs intra‐articular, remarkable NETosis primed BM neutrophils were infiltrated in BML of CIA mice, which was positively related to bone erosion. Neutrophils derived from G‐CSF−/− mice have diminished ability of NETs formation in vitro, while G‐CSF induction can enhance its capacity of NETs formation. Conclusions: We propose for the first time that the overproduced BM neutrophils in CIA mice are primed for NETosis in a G‐CSF dependent manner, and these pathogenic cells may have an important role in inflammatory arthritis. Blocking this pathological process could be a potential strategy for the treatment of RA. [ABSTRACT FROM AUTHOR]