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Abstract The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

ABSTRACT The tumor suppressor p53, primarily functioning as a transcription factor, has exhibited antiviral capabilities against various viruses in chickens, including infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). Nevertheless, the existence of a universal antiviral mechanism employed by chicken p53 (chp53) against these viruses remains uncertain. This study conducted a comprehensive comparison of molecular networks involved in chp53’s antiviral function against IBDV, ALV-J, and ILTV. This was achieved through an integrated analysis of ChIP-seq data, examining chp53’s genome-wide chromatin occupancy, and RNA-seq data from chicken cells infected with these viruses. The consistent observation of chp53 target gene enrichment in metabolic pathways, confirmed via ChIP-qPCR, suggests a ubiquitous regulation of host cellular metabolism by chp53 across different viruses. Further genome binding motif conservation analysis and transcriptional co-factor prediction suggest conserved transcriptional regulation mechanism by which chp53 regulates host cellular metabolism during viral infection. These findings offer novel insights into the antiviral role of chp53 and propose that targeting the virus-host metabolic interaction through regulating p53 could serve as a universal strategy for antiviral therapies in chickens.IMPORTANCEThe current study conducted a comprehensive analysis, comparing molecular networks underlying chp53’s antiviral role against infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). This was achieved through a combined assessment of ChIP-seq and RNA-seq data obtained from infected chicken cells. Notably, enrichment of chp53 target genes in metabolic pathways was consistently observed across viral infections, indicating a universal role of chp53 in regulating cellular metabolism during diverse viral infections. These findings offer novel insights into the antiviral capabilities of chicken p53, laying a foundation for the potential development of broad-spectrum antiviral therapies in chickens.

Abstract Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well‐characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A‐driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.

ObjectiveDespite the fact that China amounts to one-fifth of the world’s population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men.MethodsBuilding upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant.ResultsA diet rich in “carnivorous”, “vegetarian”, “dairy, fruit, and egg” was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1–4 (L1–4). Yet, a diet rich in “beverage and fried food” was associated with a lower BMD at the FN and L1–4. High quartiles of the carnivorous diet were associated with 34%–39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures.ConclusionsOur study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1–4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

Abstract Background Team-based care is an essential part of primary health care (PHC), and its team service delivery process is a systematic one involving multiple and complex influences. Research on the formation mechanism can help improve the effectiveness of primary health care teams (PHCTs). Methods First, based on the Donabedian model, we explored the theoretical framework of a PHC team’s effectiveness formation mechanism. Semi-structured interviews were conducted with 23primary health care team members in Hangzhou, Zhejiang Province, China. A total of seven factors were then included as conditional variables using the crisp set qualitative comparative analysis (csQCA) to explore the complex influences between them and the outcome variable through univariate necessity analysis and path configuration analysis. Results Univariate necessity analysis showed that only “Clear Goals” in the structural dimension were necessary for team effectiveness perception. Six pathways to good primary health care team perception of effectiveness were identified. Two of these paths were more typical. Conclusion “Clear Goals” was the core variable that should be emphasized when exploring the mechanism of PHCT formation. The results suggest that human resources in the management team should be rationally allocated, goal-oriented, and given good attention. Future studies should explore complex combinations of PHCT factors to improve the effectiveness of PHCTs.

Abstract The α‐amylase inhibition and binding behaviors of shikimic acid and its structural analogues were studied. Uncompetitive inhibition characteristic of shikimic acid was identified through several linear transformation equations of enzymatic data considering the good linearity. Interestingly, the change in concentrations of starch would not decrease the inhibitory effects of shikimic acid with various concentrations used in present study. The inhibitory effect reduced greatly after the ethyl esterification of shikimic acid. Gallic acid was distinguished from shikimic acid by a benzene ring and exhibited lower inhibition than shikimic acid. Shikimic acid affected the α‐amylase structure by binding to the non‐active site but did not quench the α‐amylase fluorescent intensity. However, gallic acid anchored with a subsite containing some fluorescent residues at the entrance of active pocket, quenching the fluorescence intensity of α‐amylase strongly. The difference in shikimic acid and gallic acid made the changes in their binding sites as well as the binding behavior. Conclusively, the carboxyl and hexatomic ring with one double‐bond played an important role in binding of shikimic acid with the non‐active sites of α‐amylase. Shikimic acid has potentials as a functional‐factor in α‐amylase inhibition for controlling the postprandial blood sugar level.

Asthma is a heterogeneous respiratory disease characterized by airway inflammation occurring in the bronchus. Direct delivery of targeted treatments to the bronchus for asthma has the potential to optimize therapeutic efficacy. Inhaled corticosteroids are cornerstone therapy for persistent asthma, however, there remain challenges in designing effective formulations for the inhaled route and minimizing long-term corticosteroid side effects. Here, a nanogel delivery system with good bio-adhesion based on alginate crosslinked with zinc ions was designed. The prepared alginate nanogel particles (ALG-NPs) effectively delivered icariin (ICA) which possesses anti-inflammatory and antioxidant activities, to the bronchus through ultrasonic aerosol inhalation, thereby ameliorating asthmatic symptoms and attenuating bronchial inflammation. The ALG-NPs exhibited favorable biological safety and could be deposited in the bronchus to control the release of ICA, enabling targeted treatment of asthma. In addition, ICA loaded ALG-NPs significantly reduced airway inflammation by modulating key targets associated with asthm (Th1 transcription factor and Th2 transcription factor) while also inducing eosinophilic apoptosis by regulating the Bax/Bcl-2 ratio expression. This study suggests that the ultrasonic aerosol inhalation of ICA loaded ALG-NPs was a promising strategy of treating asthma.

Abstract Background Brain-derived neurotrophic factor (BDNF) with neuronic development and function is a promising therapeutic agent for treating depressive disorder, according to the neurotrophin hypothesis. However, the delivery of BDNF into the brain is not easy as these large protein molecules cannot efficiently cross the blood-brain barrier (BBB) and easily suffer oxidative damage in vivo. Therefore, the quercetin-based alginate nanogels (quercetin nanogels) loaded with BDNF have been developed, which could efficiently bypass the BBB via the nose-to-brain pathway and protect BDNF from oxidative damage, providing an effective route for the therapy of depressive disorders by intranasal delivery. Results Quercetin nanogels exhibited uniform size distribution, excellent biocompatibility, and potent antioxidant and anti-inflammatory activities. Quercetin nanogels in the thermosensitive gel achieved sustained and controlled release of BDNF with non-Fick’s diffusion, exhibited rapid brain distribution, and achieved nearly 50-fold enhanced bioavailability compared to oral quercetin. Quercetin nanogels as a therapeutic drug delivery carrier exerted antidepressant effects on reserpine-induced rats, effectively delivered BDNF to reverse despair behavior in stress-induced mice, and exhibited antidepressant effects on chronic mild unpredictable stimulation (CUMS) rats. These antidepressant effects of BDNF-Quercetin nanogels for CUMS rats are associated with the regulation of the glutamatergic system, PI3K-Akt, and BDNF-TrkB signaling pathway. Conclusions In this study, we provide a promising strategy for brain delivery of BDNF for treating depressive disorders, effectively achieved through combining quercetin nanogels and intranasal administration.

The life cycles of plants are characterized by significant alternations between the diploid sporophytic and the haploid gametophytic generations. Meiosis and fertilization are the prerequisites for achieving the alternation of generations. Diploid sporophytes undergo meiosis to produce haploid gametes, and male–female gametes fuse (double fertilization) to revert to the diploid sporophyte. The formation and development of male gametophytes are crucial for the alternation of generations in higher plants. During the long evolution of plants from aquatic to terrestrial, the way of sexual reproduction has undergone subversive innovations. From sperm swimming for fertilization to relying on the precise delivery of pollen tubes to female gametes for the fusion of the male–female gametes, higher requirements are placed on the male gametophytes’ development and fertilization process. The formation of male gametophytes has undergone significant changes to meet the needs for delivery and transportation of the male gametes. With the emergence of more and more evidence, the molecular mechanism underlying male gametophytes’ development, especially the initiation and specialization of germline cells has been better understood. Focusing on the latest studies, we reviewed and elucidated the critical proteins and factors involved in male gametophyte formation, highlighting the decisive role of auxin in archesporial cell specialization and the importance of microspore maturation in pre-mitosis, and analyzed the molecular mechanisms underlying male gametogenesis, with a view to providing insights for further exploration of male gametophytes formation in the future.

Background The prevalence of anti-myelin oligodendrocyte glycoprotein (MOG) -IgG associated disorders (MOGAD) is significantly higher in children than that in adults. The characteristics and associations of phenotypes and recurrence risk in children are still unclear. Objective To examine the phenotypic features and recurrence factors of MOG-IgG positivity in central nervous system inflammatory demyelinating diseases in children. Methods A follow-up study on 54 children with MOGAD diagnosed in Children's Hospital of Hebei Province from December 2017 to December 2021 was performed. Phenotypic features at each demyelinating attack, laboratory tests, imaging characteristics, MOG-IgG titers in serum/cerebrospinal fluid (CSF), efficacy, and high risk factors for recurrence were analyzed. The MOG-IgG was tested using cell-based immunofluorescence assay. All patients were followed up until March 31, 2022. Results In our study, the median age of onset was 6.0 (4.0, 8.0) years and the male to female ratio was 1∶1.07. Serum MOG-IgG titers were 1∶10-1∶320. Acute disseminated encephalomyelitis (ADEM) was the most common phenotype (44.4%, 24/54), followed by optic neuritis (ON) (25.9%, 14/54) and non-ADEM-like meninges /encephalitis (20.4%, 11/54). Ten cases (18.5%) were positive for MOG-IgG in serum and CSF, and 2 (3.7%) were positive for both NMDAR-IgG in CSF and MOG-IgG in serum. Brain MRI showed new lesions during the 76.9% (60/78) of the 78 attacks in total, and the most common locations were cortical white matter (66.7%, 40/60) and optic nerve (35.0%, 21/60). Forty patients (74.1%, 40/54) experienced one episode, the main phenotypes were ADEM (57.5%, 23/40) and non-ADEM-like meninges/encephalitis (25.0%, 10/40). Fourteen patients (25.9%, 14/54) had two or more episodes, and the initial phenotype of them was ADEM with ON (57.1%, 8/14) or ON (21.4%, 3/14). Compared with recrudescent cases, non-recrudescent cases had much lower prevalence of ON or ADEM with ON as the primary phenotype (P

Abstract Background To study the epidemiological characteristics of atypical Kashin–Beck disease cases without characteristic hand lesions such as interphalangeal joint enlargement and brachydactyly and the characteristics of ankle joint lesions. Methods We investigated Kashin–Beck in the endemic villages in Heilongjiang Province. The patients were judged according to the “Diagnosis of Kashin–Beck Disease” (WS/T 207–2010). The severity of foot lesions was judged based on the changes of X-ray images. Residents of non-Kashin–Beck disease area were selected as normal controls in Jilin Province. Results A total of 119 residents over 40 years old were surveyed in a natural village in the non-endemic area. A total of 1190 residents over 40 years old were surveyed in 38 endemic areas of Kashin–Beck disease. A total of 710 patients with Kashin–Beck disease were detected, including 245 patients with grade I, 175 patients with grade II, 25 patients with grade III, and 265 atypical patients. Among all investigated patients, 92.0% (653/710) had ankle joint changes, and it was 80.0% (196/245) in grade I patients and 95.4% (167/175) in grade II. Varying degrees of ankle joint changes were found in both grade III and atypical patients. The grade of Kashin–Beck disease was correlated with the degree of ankle joint change (P

Abstract Background Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population. Methods We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms. Results We identified 14 CNVRs (false discovery rate corrected P values

Context Acute lung injury (ALI) is a complex, severe inflammation disease with high mortality, and there is no specific and effective treatment for ALI. Qingfei Xiaoyan Wan (QFXYW) has been widely used to treat lung-related diseases for centuries.Objective This study evaluates the potential effects and elucidates the therapeutic mechanism of QFXYW against LPS induced ALI in mice.Materials and methods BALB/c Mice in each group were first orally administered medicines (0.9% saline solution for the control group, 0.5 mg/kg Dexamethasone, or 1.3, 2.6, 5.2 g/kg QFXYW), after 4 h, the groups were injected LPS (1.0 mg/kg) to induce ALI, then the same medicines were administered repeatedly. The transcriptomics-based system pharmacological analyses were applied to screen the hub genes, RT-PCR, ELISA, and protein array assay was applied to verify the predicted hub genes and key pathways.Results QFXYW significantly decreased the number of leukocytes from (6.34 ± 0.51) × 105/mL to (4.01 ± 0.11) × 105/mL, accompanied by the neutrophil from (1.41 ± 0.19) × 105/mL to (0.77 ± 0.10) × 105/mL in bronchoalveolar lavage fluid (BALF). Based on Degree of node connection (Degree) and BottleNeck (BN), important parameters of network topology, the protein-protein interaction (PPI) network screened hub genes, including IL-6, TNF-α, CCL2, TLR2, CXCL1, and MMP-9. The results of RT-PCR, ELISA, and protein chip assay revealed that QFXYW could effectively inhibit ALI via multiple key targets and the cytokine-cytokine signalling pathway.Conclusions This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.

Poultry farming is one of the pillar industries of global animal husbandry. In order to guarantee production, poultry are frequently vaccinated from the moment they are hatched. Even so, the initial immunity of chicks is still very poor as they are in the “window period” of immune protection. In ovo vaccination pushes the initial immunization time forward to the incubation period, thereby providing earlier immune protection for chicks. In ovo vaccination is currently a research hotspot of poultry disease prevention and control, which is in line with the intensification of poultry production. However, the vaccines currently available for in ovo vaccination are limited and cannot meet the needs of industrial development, so how to efficiently activate the adaptive immune response of chicken embryos becomes the key to restrict product development and technological progress of in ovo vaccination. Its breakthrough, to a large extent, depends on systematic illustration of the mechanism underlying the adaptive immune response post immunization. Clarification of this issue will provide us with theoretical support and potential solutions for the development of novel vaccines for in ovo vaccination, the augmentation of efficacy of current vaccines and the optimization of immune programs.

Plant development and pattern formation depend on diffusible signals and location cues. These developmental signals and cues activate intracellular downstream components through cell surface receptors that direct cells to adopt specific fates for optimal function and establish biological fitness. There may be a single-pole dual-control competing mode in controlling plant development and microbial infection. In plant development, paracrine signaling molecules compete with autocrine signaling molecules to bind receptors or receptor complexes, turn on antagonistic molecular mechanisms, and precisely regulate developmental processes. In the process of microbial infection, two different signaling molecules, competing receptors or receptor complexes, form their respective signaling complexes, trigger opposite signaling pathways, establish symbiosis or immunity, and achieve biological adaptation. We reviewed several “single-pole dual-control” competing modes, focusing on analyzing the competitive commonality and characterization of “single-pole dual-control” molecular mechanisms. We suggest it might be an economical protective mechanism for plants’ sequentially and iteratively programmed developmental events. This mechanism may also be a paradigm for reducing internal friction in the struggle and coexistence with microbes. It provides extraordinary insights into molecular recognition, cell-to-cell communication, and protein–protein interactions. A detailed understanding of the “single-pole dual-control” competing mode will contribute to the discovery of more receptors or antagonistic peptides, and lay the foundation for food, biofuel production, and crop improvement.

Highlights Quercetin (QU)-Nanogel shows a significant therapeutic effect on acute lung injury. Quercetin as an active substance, was also involved in the nanogel construction. The novel nanogel increase the bioavailability of quercetin. Inhalation of QU-Nanogel allows the drug to reach the lungs directly.

Sulodexide is a heparinoid compound with wide-ranging pharmacological activities. However, the effect of sulodexide on liver fibrogenesis has not been reported. In this study, we aim to evaluate the therapeutic potential of sulodexide in mouse model of liver fibrosis and explore the underlying antifibrotic mechanisms. We found that sulodexide treatment significantly attenuated thioacetamide (TAA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis in mice. Transcriptome analysis revealed that sulodexide treatment downregulated fibrosis-related genes and liver sinusoidal endothelial cells (LSECs) capillarization-associated genes in fibrotic livers. Immunohistochemistry confirmed that the increased expression of LSEC capillarization-related genes (CD34, CD31 and Laminin) in liver fibrotic tissues was reduced by sulodexide treatment. Scanning electron microscopy showed that LSECs fenestrations were preserved upon sulodexide treatment. Quantitative real-time PCR and immunofluorescence demonstrated that the expression of mesenchymal markers was downregulated by sulodexide administration, suggesting sulodexide inhibited endothelial-mesenchymal transition of LSECs during liver fibrosis. Furthermore, sulodexide administration protected primary LSECs from endothelial dysfunction in vitro. In conclusion, sulodexide attenuated liver fibrosis in mice by restoration of differentiated LSECs, indicating that sulodexide treatment may present as a potential therapy for patients with liver fibrosis.

Abstract. In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

MnO2@PCs (porous carbons) exhibiting high energy and power density are utilized as supercapacitor electrodes and prepared by impregnating porous carbons (PCs) derived from coal tar pitch (CTP) with KMnO4 as the manganese source. This study systematically investigates the impact of MnO2 loading on the microstructure and electrochemical performance in sample. It is found that the specific surface areas (SSA) of all MnO2@PCs significantly reduced compared to that of the PCs 2789 m2 g−1. The suggested mechanism might be a combination of the energy storage mechanism of dual layer capacitors with pseudo‐capacitance due to redox reactions of MnO2. Notably, MnO2@PCs‐0.0075 exhibits a maximum SSA of 1454.62 m2 g−1. Its specific capacitance reached 561 F g−1 at 0.5 A g−1, while the capacitance of the PCs increased by 81.5% to 309 F g−1. Remarkably, the Coulombic efficiency remained at 100%. The power density and energy density are determined in a two‐electrode test system to be 0.5 kW kg−1 and 58.01 Wh kg−1, respectively, at 0.5 A g−1. Concluding from these results and related literature, the MnO2 content significantly influences the electrochemical performance, suggesting that MnO2@PCs‐0.0075 could be a promising supercapacitor (SC) electrode material, provided its capacitance retention is enhanced. [ABSTRACT FROM AUTHOR]

Treatment options for herpesvirus infections that target the interactions between the virus and the host have been identified as promising. Our previous studies have shown that transcription factors p53 and Fos are essential host determinants of gallid alpha herpesvirus 1 (ILTV) infection. The impact of p53 and Fos on ILTV replication has ‘not been fully understood yet. Using the sole ILTV-permissive chicken cell line LMH as a model, we examined the effects of hosts p53 and Fos on all phases of ILTV replication, including viral gene transcription, viral genome replication, and infectious virion generation. We achieved this by manipulating the expression of p53 and Fos in LMH cells. Our results demonstrate that the overexpression of either p53 or Fos can promote viral gene transcription at all stages of the temporal cascade of ILTV gene expression, viral genome replication, and infectious virion production, as assessed through absolute quantitative real-time PCR, ILTV-specific RT-qPCR assays, and TCID50 assays. These findings are consistent with our previous analyses of the effects of Fos and p53 knockdowns on virus production and also suggest that both p53 and Fos may be dispensable for ILTV replication. Based on the synergistic effect of regulating ILTV, we further found that there is an interaction between p53 and Fos. Interestingly, we found that p53 also has targeted sites upstream of ICP4, and these sites are very close to the Fos sites. In conclusion, our research offers an in-depth understanding of how hosts p53 and Fos affect ILTV replication. Understanding the processes by which p53 and Fos regulate ILTV infection will be improved by this knowledge, potentially paving the way for the development of novel therapeutics targeting virus–host interactions as a means of treating herpesvirus infections.

Abstract Background The supracondylar humerus fractures are the most common fracture in children’s elbows. Generally, close reduction and percutaneous pinning can provide satisfactory outcomes after adequate reduction. Baumann angle is commonly used to evaluate reduction quality, however, it may fail to assess reduction well when the elbow is in flexion and/or when the patient is young. We conducted this study to evaluate the potential value of the humerus trochlear angle (HTa) for the reduction evaluation and compare it with the Baumann angle. Methods We retrospectively reviewed supracondylar humerus fractures in our trauma center from 2016 to 2019. Patients were grouped as followed: in the HTa group, an arthrogram was used to evaluate the HTa angle and reduction (HTa, defined by the intersection of the axis of the humerus shaft and the tangent of the articular surface of the trochlear); In the Baumann group, the Baumann angle was used to assess the reduction. Baumann angle ratio (BA of injured side/BA of contralateral side) was calculated to evaluate the reduction quality between groups. Flynn’s grading criteria were utilized to evaluate both function and cosmetic outcomes in two groups during the follow-up. Operation time, fluoroscopy shots, complications and Flynn’s grading scores were compared between groups. Results A total of 57 patients with an average age of 4.62 years and follow-up duration of 21.49 ± 5.40 months were included in the analysis. The gender and age distributions were similar in the two groups. Fluoroscopy shots in the HTa group were significantly less than in Baumann group (16.17 ± 0.73 vs. 21.85 ± 0.78, p

Autosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder which is associated with kidney and liver pathology, including liver fibrosis. Here the authors develop and characterize human liver organoids with a ARPKD mutation, and find that they show aspects of the pathology, including fibrosis.

P53, a well-known tumor suppressor, has been confirmed to regulate the infection of various viruses, including chicken viruses. Our previous study observed antiviral effect of p53 inhibitor Pifithrin-α (PFT-α) on the infection of avian infectious laryngotracheitis virus (ILTV), one of the major avian viruses economically significant to the poultry industry globally. However, the potential link between this antiviral effect of PFT-α and p53 remains unclear. Using chicken LMH cell line which is permissive for ILTV infection as model, we explore the effects of p53 on ILTV replication and its underlying molecular mechanism based on genome-wide transcriptome analysis of genes with p53 binding sites. The putative p53 target genes were validated by ChIP-qPCR and RT-qPCR. Results demonstrated that, consistent with the effects of PFT-α on ILTV replication we previously reported, knockdown of p53 repressed viral gene transcription and the genome replication of ILTV effectively. The production of infectious virions was also suppressed significantly by p53 knockdown. Further bioinformatic analysis of genes with p53 binding sites revealed extensive repression of these putative p53 target genes enriched in the metabolic processes, especially nucleotide metabolism and ATP synthesis, upon p53 repression by PFT-α in ILTV infected LMH cells. Among these genes, eighteen were involved in nucleotide metabolism and ATP synthesis. Then eight of the 18 genes were selected randomly for validations, all of which were successfully identified as p53 target genes. Our findings shed light on the mechanisms through which p53 controls ILTV infection, meanwhile expand our knowledge of chicken p53 target genes.

ABSTRACT: The tumor suppressor p53, which acts primarily as a transcription factor, can regulate infections from various viruses in chickens. However, the underlying mechanisms of the antiviral functions of chicken p53 (chp53) remain unclear due to the lack of detailed information on its transcriptional regulation. Here, to gain comprehensive insights into chp53 transcriptional regulatory function in a global and unbiased manner, we determined the genome-wide chromatin occupancy of chp53 by chromatin immunoprecipitation, which was followed by sequencing and chp53-mediated gene expression profile by RNA sequencing using chemically immortalized leghorn male hepatoma (LMH) cells with ectopic expression of chp53 as the model. The integrated parallel genome-wide chromatin occupancy and gene expression analysis characterized chp53 chromatin occupancy and identified 754 direct target genes of chp53. Furthermore, functional annotation and cross-species comparative biological analyses revealed the conserved key biological functions and DNA binding motifs of p53 between chickens and humans, which may be due to the consensus amino acid sequence and structure of p53 DNA-binding domains. The present study, to our knowledge, provides the first comprehensive characterization of the chp53 transcriptional regulatory network, and can possibly help to improve our understanding of p53 transcriptional regulatory mechanisms and their antiviral functions in chickens.