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The synchronicity of rain and heat in the summer of China’s monsoon region provides sufficient water and heat resources for maize growth. However, the intra-annual distribution of precipitation and the probability of extreme precipitation have been inevitably altered by the ongoing climate change, thus affecting the matching degree between precipitation and crop water requirements (MDPCWR). Evaluating the extent to which the MDPCWR will change in the future is of great importance for food security and the sustainable management of water resources. In this study, considering that different growth stages of crops have different sensitivities to water stress, the AquaCrop model was used to calculate the MDPCWR more accurately. In addition, a cumulative distribution function-transform (CDF-t) method was used to remove the bias of 11 global climate models (GCMs) under two typical emission scenarios (SSP2-4.5 and SSP5-8.5) from phase six of the Coupled Model Intercomparison Project (CMIP6). A comprehensive investigation was conducted on how maize growth, water consumption, and the MDPCWR will respond to future climate change with CO2 concentration enrichment in the Huang–Huai–Hai (3H) region in China by driving a well-tested AquaCrop model with the bias-corrected GCMs outputs. The results indicate the following: (1) The CDF-t method can effectively remove seasonal bias, and it also performs well in eliminating the bias of extreme climate events. (2) Under the SSP2-4.5 scenario, the average maximum temperature will increase by 1.31 °C and 2.44 °C in 2021–2050 and 2051–2080, respectively. The average annual precipitation will increase up to 96.8 mm/year, but it will mainly occur in the form of heavy rain. (3) The increased maize evapotranspiration rate does not compensate for the decreased crop water requirement (up to −32 mm/year), due to a shorter growth cycle. (4) The farmland cultivation layer is not able to hold a significant amount of precipitation, due to the increased frequency of heavy rains, resulting in increased irrigation water requirements for maize over the next two periods, with the maximum value of 12 mm/year. (5) Under different scenarios, the projected future MDPCWR will decrease by 9.3–11.6% due to changes in precipitation patterns and crop water requirements, indicating that it will be more difficult for precipitation to meet the water demand of maize growing in the 3H region. The results can provide comprehensive information to understand the impact of climate change on the agricultural water balance and improve the regional strategy for water resource utilization in the 3H region.

Summary: Persistent Fusobacterium nucleatum infection is associated with the development of human colorectal cancer (CRC) and promotes tumorigenicity, but the underlying mechanisms remain unclear. Here, we reported that F. nucleatum promoted the tumorigenicity of CRC, which was associated with F. nucleatum-induced microRNA-31 (miR-31) expression in CRC tissues and cells. F. nucleatum infection inhibited autophagic flux by miR-31 through inhibiting syntaxin-12 (STX12) and was associated with the increased intracellular survival of F. nucleatum. Overexpression of miR-31 in CRC cells promoted their tumorigenicity by targeting eukaryotic initiation factor 4F-binding protein 1/2 (eIF4EBP1/2), whereas miR-31 knockout mice were resistant to the formation of colorectal tumors. In conclusion, F. nucleatum, miR-31, and STX12 form a closed loop in the autophagy pathway, and continuous F. nucleatum-induced miR-31 expression promotes the tumorigenicity of CRC cells by targeting eIF4EBP1/2. These findings reveal miR-31 as a potential diagnostic biomarker and therapeutic target in CRC patients with F. nucleatum infection.

Non-invasive prenatal diagnosis for single-gene disorders (NIPD) is still in development and deserves further study. The advent of next-generation sequencing technology significantly improved the detection of multiple mutations for non-invasive prenatal diagnosis for single-gene disorder purposes. However, bespoke amplicon-based NGS assays are costly. In this study, we developed a new strategy for non-invasive prenatal screening for single-gene disorders based on a capillary electrophoresis (CE) platform using an amplification refractory mutation system (ARMS)-PCR technique. Allele-specific primers for several disease-correlated mutations were designed, and subsequently, sensitivity and specificity assays were conducted. Assays on simulated two-person DNA mixtures showed that three primers targeting the mutant allele could detect minor DNA components in 1:500 mixtures. All primers showed positive results at 0.01 ng of the template DNA. Cell-free fetal DNA was extracted from a pregnant woman’s peripheral blood for the detection of paternally inherited mutations. Our results showed that one primer successfully amplified the mutant allele of fetal DNA in maternal plasma, which was confirmed by genotyping the genomic DNA extracted from amniotic fluid. This study suggested that the ARMS-PCR technique, a fast and cost-effective method, might be a promising method used to target de novo or paternally inherited pathogenic mutations in maternal plasma.

In this article, under investigation is a (2+1)-dimensional Zakharov–Kuznetsov equation with a general power law nonlinearity arising from magnetized quantum plasmas model. The analytical periodic wave, bright soliton and bright–dark soliton solutions are computed for the equation via the F-expansion method. Furthermore, the impacts of the general power law parameter on the soliton is examined in details. It is interesting that the general power law can be used to control the amplitude and propagation speed, which can determine partly the kinetic energy. Particularly, as the general power law parameter increases, the soliton’ energy will decrease.

Abstract Background School bullying victimization is associated with increased risk of anxiety in children and adolescents. However, little is known about the role of resilience in this association. The purpose of this study was to investigate the possible mediation by resilience in this association in a large group of Chinese children and adolescents. Methods A population-based cross-sectional study adopting two-stage simple random cluster sampling was implemented in Yunnan province, southwestern China. A comprehensive questionnaire was used to collect information from the participants. Among all the participants, 4624 were included in the final analysis. Descriptive statistics were used to present general characteristics of the study participants. Univariate and multivariate logistic regression models were adopted to estimate crude and adjusted associations among bullying victimization, anxiety, and resilience. A path model was used to analyze the hypothesized mediation by resilience in the association between bullying victimization and anxiety. Results Analytical results of multivariate logistic regression models suggested that bullying victimization was significantly associated with anxiety in Chinese children and adolescents; compared with individuals who had not been bullied, victims of bullying were more likely to experience anxiety symptoms, with an adjusted odds ratio (OR) of 3.02 (95% CI 2.46–3.71). Path analysis revealed a prominent mediating effect of resilience in the association between bullying victimization and anxiety, accounting for 31.89% of the total association. Further analysis indicated that, among the five dimensions of resilience, emotional regulation, interpersonal assistance, and family support were significant mediators, accounting for 30.34%, 10.79%, and 8.35% of the total association. Conclusions Our major findings highlighted the promising role of resilience-based intervention measures in reducing the risk of anxiety associated with school bullying victimization in Chinese children and adolescents.

Abstract Background Oculocutaneous albinism (OCA) is a group of heterogeneous genetic diseases characterized by a reduction or complete lack of pigmentation in the hair, skin, and eyes. It is associated with reduced visual acuity, nystagmus, photophobia, and strabismus. OCA type 1 (OCA1) and type 2 (OCA2) are caused by mutations in the tyrosinase (TYR) and OCA2 genes, which are responsible for most cases of OCA. The present study aimed to identify the mutational spectra of 18 southwest Chinese probands with OCA. Results We used a skin disease-targeted panel to sequence more than 400 genes, including 23 genes (TYR, OCA2, AP3B1, BLOC1S3, BLOC1S6, C10orf11, DTNBP1, FRMD7, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, MC1R, MITF, MLPH, MYO5A, RAB27A, SLC24A5, SLC45A2, TYRP1) associated with syndromic and non-syndromic albinism. The targeted panel was applied to 18 patients from southwest China, nine (50%) patients were diagnosed with OCA1, and nine (50%) were diagnosed with OCA2. Our data indicate that OCA1 and OCA2, the most common subtypes, probably have the same prevalence in southwest China. In total, we identified 26 variants in TYR and OCA2 from 18 OCA cases using the NGS technology, including 24 variants presented in the Human Gene Mutation Database Professional (HGMD) and two novel variants, c.559_560insCATTATTATGTGTCAAATTATCCCC in TYR and c.1514 T > C in OCA2, which have not been previously reported. According to the American College of Medical Genetics and Genomics (ACMG) classification, c.559_560insCATTATTATGTGTCAAATTATCCCC (p.G190Cfs*12) is classified as a pathogenic variant, and c.1514 T > C (p.F505S) is evaluated as a likely pathogenic variant. Conclusions Two novel variants were identified which will expand the mutational spectra of TYR and OCA2. The results of the present study may have implications for genetic counseling, carrier screening, and clinical management of the disease.

The selenization of natural products refers to the chemical modification method of artificially introducing selenium atoms into natural products to interact with the functional groups in the target molecule to form selenides. Nowadays, even though scientists in fields involving organic selenium compounds have achieved numerous results due to their continuous investment, few comprehensive and systematic summaries relating to their research results can be found. The present paper summarizes the selenization modification methods of several kinds of important natural products, such as polysaccharides, proteins/polypeptides, polyphenols, lipids, and cyclic compounds, as well as the basic principles or mechanisms of the selenizing methods. On this basis, this paper explored the future development trend of the research field relating to selenized natural products, and it is hoped to provide some suggestions for directional selenization modification and the application of natural active ingredients.

Abstract Background Familial exudative vitreoretinopathy (FEVR) is a complex form of blindness-causing retinal degeneration. This study investigated the potential disease-causing variants in 20 Chinese families with FEVR. Methods All available family members underwent detailed ophthalmological examinations, including best-corrected visual acuity and fundus examination. All probands and most family members underwent fluorescein fundus angiography. Twenty probands underwent whole exome sequencing; 16 of them also underwent copy number variant and mitochondrial genome analysis. Bioinformatics analysis and Sanger sequencing of available family members were used to confirm the disease-causing gene variant. Results Twenty families were diagnosed with FEVR based on clinical symptoms, fundus manifestations, and fundus fluorescein angiography. Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes among the 13 families. These variants were predicted to be damaging or deleterious according to multiple lines of prediction algorithms; they were not frequently found in multiple population databases. Seven variants had not previously been reported to cause FEVR: c.1039T>G p.(Phe347Val) in the FZD4 gene; c.1612C>T p.(Arg538Trp) and c.3237-2A>C in the LRP5 gene; and c.77T>A p.(Ile26Asn), c.170dupT p.(Leu57Phe fsTer60), c.236T>G p.(Met79Arg) and c.550dupA p.(Arg184Lys fsTer16) in the TSPAN12 gene. We did not detect any variants in the remaining seven families. Conclusions These results expand the spectrum of variants in the NDP, FZD4, LRP5, and TSPAN12 genes and provide insights regarding accurate diagnosis, family genetic counseling, and future gene therapy for FEVR.

Abstract Background and purpose This study assessed the predictive factors for symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) after receiving intravenous thrombolysis (IVT) within 6 h in northern China. Methods We retrospectively analyzed ischemic stroke patients who were treated with IVT between November 2016 and December 2018 in 19 hospitals in Shandong Province, China. Potential predictors of sICH were investigated using univariate and multivariate analyses. Results Of the 1293 enrolled patients (845 men, aged 62 ± 11 years), 33 (2.6%) developed sICH. The patients with sICH had increased coronary heart disease (36.4% vs. 13.7%, P = 0.001), more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score on admission of 14 vs.7, P 50 min, and a white blood cell count ≥9000/mm3 were independent risk factors for sICH in Chinese patients within 6 h after IVT for AIS.

Abstract Background Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients. Methods A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients. Results The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67–0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR

Objective. To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods. Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results. Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion. The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes.

As a tectonic block of the Qinling Orogenic Belt, Central China, the South Qinling Orogen is generally believed to have had a tight affinity with the Yangtze Block during the Precambrian. Knowledge on the South Qinling Orogen is important to constrain the tectonic evolution of the northern margin of the Yangtze Block basement. Previous studies mainly focused on the east segment of the South Qinling Orogen. This paper presented petrological, geochronological, and geochemical studies on the amphibolite-facies rocks newly discovered in the middle section of the South Qinling Orogen. Geochemical studies indicate that the protolith of these amphibolites is calc-alkaline island arc basalt, which was formed during the reconstruction of the Paleo-Middle Archean crust on the northern margin of the Yangtze Block 2,362 ± 100 Ma ago (equivalent to metamorphic rocks of the Yudongzi group). Later, these arc basalts experienced amphibolite-facies metamorphism at 1,500–1,800 Ma, which is consistent with the metamorphism identified in the Yangtze Block, confirming the association of the South Qinling Orogen with the Yangtze Block basement. Subsequently, these amphibolite-facies rocks further experienced three stages of metamorphism at c. 800 Ma, 440 Ma, and 200 Ma in the context of the northward subduction of the Yangtze Block.

Abstract Background A significant association between self-harm (SH) and suicide ideation (SI) has been found in Chinese left-behind children (LBC). Existing literature suggests that resilience might be a mediator in this association. However, this hypothesis has not been effectively discussed. The major aim of our study is to analyze the possible mediation of resilience in SH-SI association in Chinese LBC. Methods A population-based clustering sampling survey of 2619 LBC was conducted in southwestern China Yunnan province. Self-developed structured questionnaire was used to collect relevant information. Univariate and multivariate Logistic regression models were applied to estimate the associations between SH and SI, resilience and SI, and SH and resilience. Path analysis was adopted to measure the mediation of resilience, as well as its 5 dimensions, in the association between SH and SI. A subgroup analysis was further done to explore the mediation of resilience in the associations between SH severity and SI, SH repetition and SI, among self-harmed LBC. Results Compared with LBC who reported no SH behaviors, the odds ratio (OR) for SI was 3.37 (95% CI: 2.63–4.31) among self-harmed LBC. Based on the path model, resilience significantly mediated a quarter of the total association between SH and SI. Among the 5 dimensions of resilience, emotion regulation, interpersonal assistance, and family support were the strongest mediators. Subgroup analysis revealed that, the mediation of resilience was only significant for SH severity and SI. Conclusions Resilience played as a prominent mediator in SH-SI association among Chinese LBC. Resilience-centered intervention measures could be considered to reduce suicidal risk of this disadvantageous group.

BackgroundStudies indicated that bullying victimization (BV) is an important risk factor for self-harm in children and adolescents. However, it is unclear whether perceived social support significantly mediates this association. This study aimed to examine the association between BV and self-harm, with a particular focus on the mediating role of perceived social support.MethodsA population-based cross-sectional study of 4,627 Chinese students aged from 10 to 17 years was conducted in southwestern China Yunnan province. A two-stage simple random cluster sampling method was used to choose study subjects. The adjusted associations between school BV, perceived social support, and self-harm were examined by using the multivariate logistic regression models. The mediation of perceived social support in the association between BV and self-harm was evaluated by using a path model.ResultsAfter controlling potential covariates, BV was associated with a prevalence of increased self-harm, with an adjusted odds ratio of 1.90 (95% CI: 1.57, 2.32). Among all sources of perceived social support, only parental support played a prominent mediating role in the association between BV and self-harm, accounting for 20.73% of the explained variance. The mediation of parental support was comparable between boys and girls. As for different types of bullying victimization, path analyses indicated that only the association between physical victimization and self-harm was significantly mediated by parental support.ConclusionOur study results highlighted the promising interventional benefit of parental support in BV-associated self-harm risk for children and adolescents. For victims of bullying, especially physical bullying, promoting parental support might be effective in reducing self-harm risk. Longitudinal studies are warranted to further corroborate these findings.

The liver has unique regeneration potential, which ensures the continuous dependence of the human body on hepatic functions. As the composition and function of gut microbiota has been gradually elucidated, the vital role of gut microbiota in liver regeneration through gut-liver axis has recently been accepted. In the process of liver regeneration, gut microbiota composition is changed. Moreover, gut microbiota can contribute to the regulation of the liver immune microenvironment, thereby modulating the release of inflammatory factors including IL-6, TNF-α, HGF, IFN-γ and TGF-β, which involve in different phases of liver regeneration. And previous research have demonstrated that through enterohepatic circulation, bile acids (BAs), lipopolysaccharide, short-chain fatty acids and other metabolites of gut microbiota associate with liver and may promote liver regeneration through various pathways. In this perspective, by summarizing gut microbiota-derived signaling pathways that promote liver regeneration, we unveil the role of gut microbiota in liver regeneration and provide feasible strategies to promote liver regeneration by altering gut microbiota composition.

Background Non-suicidal self-injury (NSSI) has recently widely discussed. Independently, mobile phone addiction (MPA) has also attracted academic attention. A few research have examined the correlation between the two. However, there is inadequate knowledge to characterize this relationship altogether. This study further explores the correlation between MPA and NSSI, specifically repeated and severe NSSI. Method A population-based cross-sectional survey was conducted among 2,719 adolescents in Lincang, Yunnan. The mobile phone addiction index (MPAI) and the Modified Adolescents Self-Harm Survey (MASHS) were administered in combination. The connection between the MPAI and NSSI, as well as both repeated and severe NSSI, was studied using univariate and multivariate logistic regression models. (The copyright holders have permitted the authors to use the MPAI and the MASHS). Results The prevalence of NSSI was 47.11% (95% CI [36.2–58.0%]), and the detection rate of MPA was 11.11% (95% CI [6.7–18.0%]). The prevalence of NSSI among those with MPA was 4.280 times (95% CI [3.480–5.266]) that of respondents not exhibiting MPA. In addition, all subscales of the MPAI, except for the feeling anxious and lost subscale (FALS), were positively correlated with NSSI. Risk factors, represented by odds ratios, of repeated NSSI with the inability to control cravings subscale (ICCS), the FALS, and the withdrawal and escape subscale (WES) was 1.052 (95% CI [1.032–1.072]), 1.028 (95% CI [1.006–1.051]), and 1.048 (95% CI [1.019–1.078]) respectively. Risk factors of these same three subscales for severe NSSI, had odds ratios of 1.048 (95% CI [1.029–1.068]), 1.033 (95% CI [1.009–1.057]), and 1.045 (95% CI [1.018–1.073]). Conclusion MPA was shown to be a risk factor for NSSI in adolescents. Individuals with high scores on the ICCS, the WES, and the FALS were more prone to experience repeated and severe NSSI. As a result, early assessment using the MPAI to determine the need for intervention can contribute to the prediction and prevention of NSSI.

In the seepage-stress-damage coupled process, the mechanical properties and seepage characteristics of coal are distinctly different between pre-peak stage and post-peak stage. This difference is mainly caused by damage of coal. Therefore, in the process of seepage and stress analysis of coal under the influence of excavation or mining, we need to consider the weakening of mechanical properties and the development of fractures of damaged coal. Based on this understanding, this paper analyzes the influence of damage on mechanics and seepage behavior of coal. A coupled model is established to analyze the seepage-stress-damage coupled process of coal. This model implemented into COMSOL and MATLAB software to realize the numerical solving. Two examples are adopted to verify the correctness of the model and some useful conclusions are obtained. The numerical model establishes the relationship between microcosmic damage evolution and macroscopical fracture and simulates the whole process of coal from microcosmic damage to macroscopical fracture, and the dynamic simulation of fluid flow in this process. It provides a numerical tool for further research on the seepage-stress-damage analysis. [ABSTRACT FROM AUTHOR]

Climate change can exacerbate the occurrence of extreme precipitation events, thereby affecting both the frequency and intensity of rainfall-induced landslides. It is important to study the threat of rainfall-induced landslides under future climate conditions for the formulation of disaster prevention and mitigation policies. Due to the complexity of the climate system, there is great uncertainty in the climate variables simulated by a global climate model (GCM), which will be further propagated in landslide prediction. In this study, we investigate the spatial and temporal trends of future landslide hazards in China under climate change, using data from a multi-model ensemble of GCMs based on two scenarios, RCP4.5 and RCP8.5. The uncertainty characteristics are then estimated based on signal-to-noise ratios (SNRs) and the ratio of agreement in sign (RAS). The results show that the uncertainty of landslide prediction is mainly dominated by the GCM ensemble and the RCP scenario settings. Spatially, the uncertainty of landslide prediction is high in the western areas of China and low in the eastern areas of China. Temporally, the uncertainty of landslide prediction is evolving, with characteristics of high uncertainty in the near future and characteristics of low uncertainty in the distant future. The annual average SNRs in the 21st century are 0.44 and 0.50 in RCP4.5 and RCP8.5, respectively, and the RAS of landslide prediction in Southeastern China is only 50–60%. This indicates that more than half of the patterns show trends that are opposite to those of the ensemble, suggesting that their landslide change trends are not universally recognized in the pattern ensemble. Considering the uncertainty of climate change in landslide prediction can enable studies to provide a more comprehensive picture of the possible range of future landslide changes, effectively improving the reliability of landslide hazard prediction and disaster prevention.

Abstract Background Usher syndrome (USH) is the most common cause of inherited deaf-blindness. The current study aimed to identify pathogenic variants in a Chinese patient with hearing loss and to report the identification of a novel p.(Phe1583Leufs*10) variant in USH2A, which met the needs of prenatal diagnosis of the patient's mother. Case presentation Genomic DNA obtained from a five-year-old girl with hearing loss was analyzed via the hearing loss-targeted gene panels. We identified the compound heterozygous variants c.8559-2A>G and c.4749delT in Usher syndrome type 2A (USH2A) gene as the underlying cause of the patient; the former variation has been reported in the literature, but not the latter. The parents of the girl were heterozygous carriers. The two variants were classified as pathogenic. Based on these findings, amniotic fluid samples were used for prenatal diagnosis of the couple's fetus, which was found to carry c.4749delT but not c.8559-2A>G variation. During the follow-up period of more than 9 months after the birth of the fetus, it was confirmed that the infant was healthy. Conclusions The results of the present study identified two compound heterozygous USH2A variants in a patient with hearing loss and reported a novel USH2A variant which expands the spectrum of USH2A variants in USH.

Abstract Background Published studies examining the association between childhood maltreatment (CM) and self-harm (SH) among adolescents have been accumulated. It is possible that resilience serves as a moderator or mediator in CM-SH association, nevertheless, this topic has never been thoroughly investigated. Methods In this population-based cross-sectional study, we surveyed 3146 students aged 10–17 in southwest China. The Childhood Trauma Questionnaire (CTQ), the Modified version of Adolescents Self-Harm Scale (MASHS), and the Resilience Scale for Chinese Adolescents (RSCA) were used to measure CM, SH, and resilience. Correlational analyses, hierarchical multivariate linear regression, and structural equation modeling (SEM) were performed to test the moderation and mediation of resilience in CM-SH association. Results Findings revealed that, resilience with its five dimensions, CM, and SH were significantly correlated with each other. Resilience partially moderated and mediated the association between CM and SH. Besides, among all dimensions of resilience, emotion regulation, interpersonal assistance, and family support presented the strongest mediation in CM-SH association. Conclusions Our results highlight the importance of resilience in CM related SH among Chinese teenagers. Resilience-oriented intervention could be considered in SH intervention measures for adolescents who had experienced CM.

Background: The study aimed to report a boy with familial exudative vitreoretinopathy and amblyopia harboring a new mutation of the LRP5 and OPA1 gene abnormality.Case presentation: A 9-year-old boy presented with a 2-year history of deteriorating visual acuity in the right eye. His best-corrected visual acuity was −7.00/−1.75 × 100 = 0.3 in the right eye and −2.50/−1.50 × 170 = 0.8 in the left eye. Two autosomal dominant gene mutation sites were identified in the patient: LRP5 (c.2551C > T, p.His851Tyr) from his father and OPA1 (c.565G > A, p.Glu189Lys) from his mother. Interestingly, his fraternal twin brother harbored no abnormal gene mutations, and his eye tests were normal.Conclusion: This case expands the spectrum of LRP5 gene mutations among Chinese patients with familial exudative vitreoretinopathy, and it is the first time to report a patient harboring both LRP5 and OPA1 gene mutations having anisometropic amblyopia and strabismus as the primary manifestations. These four family members exhibited individual heterogeneity of phenotypes and genotypes associated with hereditary ophthalmopathy. A comprehensive analysis of clinical phenotypes and genotypes provides clinical clues for improving the level of clinical and genetic diagnoses and a deeper understanding of the disease.

Liver cancer is a major public health challenge. Few published studies reported temporal trend and geographical distribution of liver cancer mortality in China, especially in less developed southwest regions with higher liver cancer incidence. In the current study, we obtained liver cancer mortality data from population-based death surveillance system in Yunnan province in 2015–2019. The mortality of liver cancer was analyzed by using the joinpoint regression model. The space distribution of liver cancer mortality in 129 counties and districts in Yunnan province was illustrated by using the ArcGIS software. Moran's I method was used to estimate the global and local spatial autocorrelation of liver cancer mortality. Analytical results revealed that from 2015 to 2019, the average mortality rate of liver cancer in Yunnan province was 12.96/100,000, with an average annual growth rate of 6.26% (p < 0.05). Higher liver cancer mortality was found in rural areas and in males. Moreover, people aged 45–50 years experienced a steep increase in liver cancer mortality rate. High-high cluster was mainly consisted of areas with higher hepatitis virus infection rate or severe intravenous drug use problem. Our study results suggest a heavy burden of liver cancer in southwest China Yunnan province. Comprehensive intervention measures need to be developed and implemented.

Whey acidic protein four-disulfide core domain protein 12 (WFDC12) has been implicated in the pathogenesis of psoriasis but the specific molecular mechanism is not clearly defined. In this study, we found the expression of WFDC12 protein closely correlated with psoriasis. WFDC12 in keratinocyte might increase infiltration of Langerhans cells (LCs) and monocyte-derived dendritic cells (moDDCs), up-regulating the co-stimulation molecular CD40/CD86. Th1 cells in lymph nodes were higher in K14-WFDC12 transgenic psoiasis-like mice. Meanwhile, the mRNA of IL-12 and IFN-γ in the lesion skin was significantly increased in transgenic mice. Moreover, we found that the expression of the proteins that participated in the retinoic acid–related pathway and immune signaling pathway was more changed in the lesion skin of K14-WFDC12 transgenic psoriasis-like mice. Collectively, the results implied that WFDC12 might affect the activation of the retinoic acid signaling pathway and regulate the infiltration of DC cells in the skin lesions and lymph nodes, thereby inducing Th1 cells differentiation and increasing the secretion of IFN-γ to exacerbate psoriasis in mice.

Alzheimer’s disease (AD) is a serious public health crisis with only one current modifying treatment. The reduction of amyloid load by targeting γ-secretase (GS) has been a leading approach in AD drug discovery and development. Despite the focus on GS inhibition, multiple GS inhibitors (GSIs) have failed in clinical trials as a result of side effects including exacerbated cognitive decline. These side effects are largely attributable to inhibition of normal GS function. Standard enzyme inhibitors target catalytic or allosteric sites of the enzyme, including the active site presenilin, as previous GSIs did. To avoid issues observed from broad-spectrum GSIs we discovered that fragment 6H8 that covalently binds to the substrate of GS, the transmembrane domain of amyloid precursor protein (APPTM). Nuclear Magnetic Resonance (NMR) Spectroscopy combined with MALDI-TOF-MS established 6H8 covalently binds to APPTM. 6H8 acts as a Michael acceptor and covalently links to the side chain amines of lysine residues, specifically targeting a cluster of C-terminal lysines K53–K55. Through this modification, 6H8 can inhibit intramembrane proteolysis of an archaeal homolog of presenilin (the active subunit of GS) via substrate binding with a 2–4 μM IC50, determined by a gel-based cleavage assay. 6H8, while too small to be an effective drug candidate, can be combined with a specific non-covalent partner and function as an effective covalent warhead of a targeted covalent inhibitor (TCI). The future development of the 6H8 fragment into the covalent warhead of a TCI is, to our knowledge, a novel approach to AD drug discovery.

Bipolar disorder (BD) is associated with a higher risk of self-harm (SH) when compared with depression. Therefore, it is reasonable to suspect that the state of mania or hypomania may independently contribute to increased SH risk. However, for hypomania, its association with SH remains less known. We intend to investigate this hypothesis in a large sample of Chinese children and adolescents with depressive symptoms. Based on a two-stage simple random cluster sampling method with probability proportionate to sample size (PPS) design, a total of 4,858 children and adolescents aged between 10 and 17 years were surveyed in southwestern China, Yunnan Province, by using self-administered questionnaires. Among them, 1,577 respondents with depressive symptoms were screened out and included in the final analysis. Descriptive statistics were calculated to illustrate the major characteristics of the study subjects. Multivariate logistic regression models were fitted to evaluate the adjusted association between hypomanic symptoms and SH. The prevalence of SH in children and adolescents with depressive symptoms was 63.92% (95% CI: 58.70–69.00%). The two hypomanic factors, which measure “active/elated” (factor I) and “risk-taking/irritable” (factor II), were significantly and discordantly associated with SH: after adjustment, every one-point increase in factor I and factor II scores was associated with 0.94-fold (95% CI: 0.91–0.97) and 1.25-fold (95% CI: 1.15–1.36) of odds ratio (OR) in SH prevalence. Further analyses based on quartiles of the two factors revealed a more prominent dose–response relationship between factor II and SH prevalence, SH repetition, and SH severity. The results of this study may suggest that, for hypomanic children and adolescents, individuals with elevated factor II score are probably of greater urgency for SH intervention. Major limitations of this study include inability of causal inference, risk of information bias, and limited results extrapolation.

BackgroundPublished studies in comparing pre and post the COVID-19 pandemic depression and anxiety levels among children and adolescents yielded incongruent results. Therefore, there is a necessity to perform a timely meta-analysis to synthesize existing evidence.MethodsA total of 10 digital databases (PubMed, Web of Science, PsycINFO, the Cochrane Library, Embase, Scopus, ScienceDirect, CNKI, WanFang, CQVIP) were fully searched for eligible studies published before November 6, 2021. Based on quality assessment results, relevant data were extracted for eligible studies of higher quality. We combined standardized mean difference (SMD) or prevalence ratio (RR) for anxiety and depression pre and post the COVID-19 pandemic by using random-effects models. Sensitivity analysis was further performed to evaluate heterogeneity of included studies.Results14,508 articles were preliminarily identified, and after stepwise screening process, 8 articles were included eventually. The results showed that the SMD for post COVID-19 anxiety score measured by GAD-7 was 0.12 (95% CI: 0.08, 0.17), an significant increase compared with pre COVID-19 period; the SMDs and 95% CIs for post COVID-18 depression scores measured by PHQ-9, PHQ-8, and MFQ were 0.17 (95% CI: 0.10, 0.24), 0.23 (95% CI: 0.08, 0.38), and 0.11 (95% CI: 0.06, 0.17), respectively, also significantly increased compared with pre COVID-19 period. The RR for depression was 2.54 (95% CI: 2.48, 2.60) in post COVID-19 period when compared with pre-pandemic.ConclusionsChildren and adolescents reported deteriorated anxiety and depression levels after the COVID-19 pandemic. More attention should be paid to this vulnerable group. Effective, expedient, and practical intervention measures which are compatible with COVID-19 prevention and control policies should be developed and implemented to maintain mental health wellbeing of the youths.

Abstract Background Parenting styles are significantly associated with self-harm (SH) in adolescents. Nevertheless, little is known about the mechanism underlying this association. This study primarily aimed to evaluate the potential mediating role of impulsivity in the association between parenting styles and SH in Chinese adolescents. Methods Self-administered questionnaires were used to conduct a survey among a sample population consisting of 3146 adolescents in southwest China. Logistic regression analyses were performed to evaluate the association between parenting styles, impulsivity, and SH. A path model investigation further examined the mediating role of impulsivity in terms of the association between parenting styles and SH. Results The age range of participants was 10 to 17 years old. The prevalence of SH was 47.0% (95% CI: 36.3–58.0%). Impulsivity, less paternal emotional warmth, maternal over-protection, and rejection were significantly associated with SH. The path model identified impulsivity as a salient mediator, accounting for 23.4% of the total association between parenting styles and SH. The hypothesized path model indicated differences in the parenting styles of fathers and mothers: Impulsivity played a significant mediating role, though only in respect to the maternal over-protection and rejection paths. Conclusions For Chinese children and adolescents who experience a harsher maternal parenting style, impulsivity-centered intervention measures might be effective in reducing SH related to parenting styles.

Epigallocatechin gallate (EGCG) is a catechin flavonoid which induces apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Here authors use an interdisciplinary approach to show a direct interaction between EGCG and the tumor suppressor p53 and demonstrate that EGCG inhibits ubiquitination of p53 by MDM2.

A positive connection has been established between personality traits and suicidal ideation (SI). However, the possible mediation of resilience within this association has never been thoroughly discussed. In this study, we aimed to investigate this topic by using population-based cross-sectional survey data of 4,489 Chinese children and adolescents. A self-administered questionnaire was used to collect information from the participants. Univariate and multivariate logistic regression models were adopted to measure the crude and adjusted associations between personality traits, SI, and resilience. Path analysis was performed to evaluate the mediation of resilience in the association between personality traits and SI. For 4,489 study subjects, the mean age was 13.4 years, ethnic minorities accounted for 71.8%, and over a half (54.6%) were middle school students. The reported prevalence rates for 1-week, 1-year, and lifetime SI were 27.6% (95% CI: 24.9%, 30.0%), 35.5% (95% CI: 30.8%, 41.0%), and 56.7% (95% CI: 52.3%, 61.0%), respectively. Girls reported a significantly higher prevalence of SI than boys. Path analysis results revealed a prominent mediation of resilience; moreover, for different dimensions of personality traits, the proportion of mediation by resilience varied. Our major findings suggest that resilience-based intervention measures could be considered in preventing personality traits related to suicidal risk among youngsters. For children and adolescents, the measuring of personality dimensions may also be helpful in targeting key subpopulations of intervention priority.

Clostridium difficile (C.difficile) is an exclusively anaerobic, spore-forming, and Gram-positive pathogen that is the most common cause of nosocomial diarrhea and is becoming increasingly prevalent in the community. Because C. difficile is strictly anaerobic, spores that can survive for months in the external environment contribute to the persistence and diffusion of C. difficile within the healthcare environment and community. Antimicrobial therapy disrupts the natural intestinal flora, allowing spores to develop into propagules that colonize the colon and produce toxins, thus leading to antibiotic-associated diarrhea and pseudomembranous enteritis. However, there is no licensed vaccine to prevent Clostridium difficile infection (CDI). In this study, a multi-epitope vaccine was designed using modern computer methods. Two target proteins, CdeC, affecting spore germination, and fliD, affecting propagule colonization, were chosen to construct the vaccine so that it could simultaneously induce the immune response against two different forms (spore and propagule) of C. difficile. We obtained the protein sequences from the National Center for Biotechnology Information (NCBI) database. After the layers of filtration, 5 cytotoxic T-cell lymphocyte (CTL) epitopes, 5 helper T lymphocyte (HTL) epitopes, and 7 B-cell linear epitopes were finally selected for vaccine construction. Then, to enhance the immunogenicity of the designed vaccine, an adjuvant was added to construct the vaccine. The Prabi and RaptorX servers were used to predict the vaccine’s two- and three-dimensional (3D) structures, respectively. Additionally, we refined and validated the structures of the vaccine construct. Molecular docking and molecular dynamics (MD) simulation were performed to check the interaction model of the vaccine–Toll-like receptor (TLR) complexes, vaccine–major histocompatibility complex (MHC) complexes, and vaccine–B-cell receptor (BCR) complex. Furthermore, immune stimulation, population coverage, and in silico molecular cloning were also conducted. The foregoing findings suggest that the final formulated vaccine is promising against the pathogen, but more researchers are needed to verify it.

A trial was conducted to investigate the effects of different Se sources, including sodium selenite (S-Se) and selenium yeast (Y-Se) and different effective microorganism (EM) addition levels on growth performance, meat quality, and muscle fiber characteristics of three-yellow chickens and its potential mechanism. A total of 400 birds were randomly distributed into 4 groups (S-Se, S-Se + EM, Y-Se, and Y-Se + EM groups) consisting of a 2 × 2 factorial arrangement. The main factors were the source of Se (ISe = inorganic Se: 0.2 mg/kg S-Se; OSe = organic Se: 0.2 mg/kg Y-Se) and the level of EM (HEMB = high EM: 0.5% EM; ZEMB = low EM: 0% EM). Each treatment had 5 replicates and each replicate consisted of 20 broiler chickens. The trial lasted for 70 days. The results showed that, in breast muscle, the broiler chickens fed OSe source decreased the pH24h, drip loss, shear force, perimeter, cross-sectional area, and diameter, but increased the a24h* and density compared with the broiler chickens fed ISe source (p < 0.05); broiler chickens supplied with HEMB level decreased the cross-sectional area and diameter, but increased the pH24h, a24h,* and density compared with the broiler chickens supplied with ZEMB level (p < 0.05). In thigh muscle, OSe source and HEMB level also could improve the meat quality and change muscle fiber characteristics of broiler chickens (p < 0.05). Meat quality was correlated with the muscle fiber characteristics (p < 0.05). OSe source and HEMB level could regulate the expression levels of muscle fiber-relative genes in the breast and thigh muscles (p < 0.05). In conclusion, OSe source and HEMB level could improve the meat quality of the breast and thigh muscles of three-yellow chickens by changing the muscle fiber characteristics, and they changed the muscle fiber characteristics by regulating the expression levels of muscle fiber-relative genes.

Anewfunctional biopolymerwas synthesized through an ionic liquid-mediated homogeneous grafting of cinnamic anhydride to xylans. The ionic liquid used was 1-allyl-3-methylimidazolium chloride (AMIMCl) ionic liquid. Xylans with degrees of substitution (DS) between 0.11 and 0.57 were accessible in a completely homogeneous system by changing catalysts (NaOH, KOH and LiOH), time, reaction temperature, and cinnamic anhydride/xylan molar ratio. The chemical structure and the thermal stability of the derivatives were characterized by Fourier transform infrared spectroscopy (FT-IR), 13C-NMR spectroscopy, and thermogravimetry. The thermal stability of the derivatives was reduced compared with the original xylan. Possible applications of the cinnamic anhydride-acylated xylan derivatives include wet-end papermaking, organic-inorganic composite films, and hydrogels. [ABSTRACT FROM AUTHOR]

Ketamine is used for sedation and treatment of depression, but is also a drug of abuse. Here the authors show that ketamine modulates the endocannabinoid system in mice, and that this may contribute to its psychoactive effects.