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Abstract Objective To review the evidence for clinical adoption of clear cell likelihood score (ccLS) for identifying clear cell renal cell carcinoma (ccRCC) from small renal masses (SRMs). Methods We distinguished the literature on ccLS for identifying ccRCC via systematic search using PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data until 31 March, 2024. The risk of bias and concern on application was assessed using the modified quality assessment of diagnostic accuracy studies (QUADAS-2) tool. The level of evidence supporting the clinical adoption of ccLS for identifying ccRCC was determined based on meta-analyses. Results Eight MRI studies and three CT studies were included. The risk of bias and application were mainly related to the index test and flow and timing, due to incomplete imaging protocol, unclear rating process, and inappropriate interval between imaging and surgery. The diagnostic odds ratios (95% confidence intervals) of MRI and CT ccLS were 14.69 (9.71–22.22; 6 studies, 1429 SRM, 869 ccRCC), and 5.64 (3.34–9.54; 3 studies, 296 SRM, 147 ccRCC), respectively, for identifying ccRCC from SRM. The evidence level for clinical adoption of MRI and CT ccLS were both rated as weak. MRI ccLS version 2.0 potentially has better diagnostic performance than version 1.0 (1 study, 700 SRM, 509 ccRCC). Both T2-weighted-imaging with or without fat suppression might be suitable for MRI ccLS version 2.0 (1 study, 111 SRM, 82 ccRCC). Conclusion ccLS shows promising diagnostic performance for identifying ccRCC from SRM, but the evidence for its adoption in clinical routine remains weak. Critical relevance statement Although clear cell likelihood score (ccLS) demonstrates promising performance for detecting clear cell renal cell carcinoma, additional evidence is crucial to support its routine use as a tool for both initial diagnosis and active surveillance of small renal masses. Key Points Clear cell likelihood score is designed for the evaluation of small renal masses. Both CT and MRI clear cell likelihood scores are accurate and efficient. More evidence is necessary for the clinical adoption of a clear cell likelihood score. Graphical Abstract

Scientific and technological revolutions and industrial transformations have accelerated the rate of innovation in environmental engineering technologies. However, few researchers have evaluated the current status and future trends of technologies. This paper summarizes the current research status in eight major subfields of environmental engineering—water treatment, air pollution control, soil/solid waste management, environmental biotechnology, environmental engineering equipment, emerging contaminants, synergistic reduction of pollution and carbon emissions, and environmental risk and intelligent management—based on bibliometric analysis and future trends in greenization, low carbonization, and intelligentization. Disruptive technologies are further identified based on discontinuous transformation, and ten such technologies are proposed, covering general and specific fields, technical links, and value sources. Additionally, the background and key innovations in disruptive technologies are elucidated in detail. This study not only provides a scientific basis for strategic decision-making, planning, and implementation in the environmental engineering field but also offers methodological guidance for the research and determination of breakthrough technologies in other areas.

Abstract Objective To evaluate whether and how the radiological journals present their policies on the use of large language models (LLMs), and identify the journal characteristic variables that are associated with the presence. Methods In this meta-research study, we screened Journals from the Radiology, Nuclear Medicine and Medical Imaging Category, 2022 Journal Citation Reports, excluding journals in non-English languages and relevant documents unavailable. We assessed their LLM use policies: (1) whether the policy is present; (2) whether the policy for the authors, the reviewers, and the editors is present; and (3) whether the policy asks the author to report the usage of LLMs, the name of LLMs, the section that used LLMs, the role of LLMs, the verification of LLMs, and the potential influence of LLMs. The association between the presence of policies and journal characteristic variables was evaluated. Results The LLM use policies were presented in 43.9% (83/189) of journals, and those for the authors, the reviewers, and the editor were presented in 43.4% (82/189), 29.6% (56/189) and 25.9% (49/189) of journals, respectively. Many journals mentioned the aspects of the usage (43.4%, 82/189), the name (34.9%, 66/189), the verification (33.3%, 63/189), and the role (31.7%, 60/189) of LLMs, while the potential influence of LLMs (4.2%, 8/189), and the section that used LLMs (1.6%, 3/189) were seldomly touched. The publisher is related to the presence of LLM use policies (p

Sophora flavescens is a traditional Chinese medicinal herb rich in various bioactive secondary metabolites, such as alkaloids and flavonoids, and exhibits remarkable resistance to abiotic stress. The WRKY transcription factor (TF) family is one of the largest plant-specific TF families and plays a crucial role in plant growth, development, and responses to abiotic stress. However, a comprehensive genome-wide analysis of the WRKY gene family in S. flavescens has not yet been conducted. In this study, we identified 69 SfWRKY genes from the S. flavescens genome and classified them into seven distinct subfamilies based on phylogenetic analysis. Transposed duplications and dispersed duplications were found to be the primary driving forces behind the expansion of the SfWRKY family. Additionally, several cis-acting elements related to the stress response and hormone signaling were discovered within the promoter regions of SfWRKYs. Transcriptomic analyses across five tissues (leaves, flowers, pods, roots, and stems) revealed that genes exhibiting high expression levels in specific tissues generally showed high expression across all the examined tissues. Coexpression network constructed based on metabolomic and transcriptomic analyses of root and pod development indicated that SfWRKY29 may play a significant role in regulating the biosynthesis of secondary metabolites during tissue development. The RT-qPCR results of gene expression analysis revealed that several SfWRKY genes were significantly induced in response to the accumulation of secondary metabolites or salt stress. Our study systematically analyzed WRKY TFs in S. flavescens, which provides valuable reference data for further studies on the key roles of SfWRKY genes in growth development as well as their responses under salt stress conditions.

Epithelial-mesenchymal interactions (EMI) are fundamental mechanisms in regulating development and organogenesis. Here we summarized the signaling mechanisms involved in EMI in the major developmental events during craniofacial morphogenesis, including neural crest cell induction, facial primordial growth as well as fusion processes. Regional specificity/polarity are demonstrated in the expression of most signaling molecules that usually act in a mutually synergistic/antagonistic manner. The underlying mechanisms of pathogenesis due to disrupted EMI was also discussed in this review.

Abstract This paper is dedicated to proposing improved input‐to‐state stability (ISS) criteria for a class of continuous‐time time‐varying switched singular systems (CTSSS) under slow/fast/slow‐fast switching signals. Specifically, for a CTSSS with time‐varying singular matrices, the authors start with an improved sufficient condition for verifying its ISS under slow switching signals based on the average dwell time method and a relaxed multiple Lyapunov function. Then, considering several or all subsystems may destroy the overall ISS, relaxed sufficient conditions are presented to ensure the ISS of the CTSSS under fast switching signals and slow‐fast switching signals, respectively. Note that the improvement of the proposed ISS criteria is embodied in the derivative of the required multiple Lyapunov functions along with the state trajectories of CTSSS can be positive or negative. Finally, three numerical examples are provided to illustrate the feasibility of the obtained results.

ObjectiveAlthough guidelines support the efficacy of Modified Qing’ E Formula (MQEF) in treating postmenopausal osteoporosis (PMOP), its underlying mechanisms remain incompletely understood. This retrospective investigation aims to elucidate MQEF’s impact on serum exosomal miRNA expression in postmenopausal osteoporosis patients and to explore potential therapeutic mechanisms.MethodsFollowing ethical approval and registration, postmenopausal osteoporosis patients aged 50–85 years, meeting the diagnostic criteria were randomly selected and received MQEF decoction supplementary therapy. Serum samples were collected pre- and post-treatment, followed by isolation and sequencing of exosomal miRNAs. Differential miRNAs in serum exosomes were identified, and bioinformatics analysis was conducted to discern the principal exosomal miRNAs involved in MQEF’s effects on PMOP and the associated signaling pathways.ResultsEighteen clinical blood samples were collected. A total of 282,185 target genes were detected across the three groups. 306 miRNAs exhibited altered expression in serum exosomes of PMOP patients, while MQEF intervention resulted in changes in 328 miRNAs. GO enrichment analysis revealed the immune and endocrine systems was pertained. KEGG enrichment analysis indicated associations between PMOP occurrence and MQEF treatment with cytokine interactions, oxidative phosphorylation, and the renin-angiotensin system. Intersectional analysis identified 17 miRNAs, including 2 consistent trends. miR-3188 as a potentially pivotal miRNA implicated in both PMOP occurrence and MQEF treatment.ConclusionThis study constitutes the first randomized, retrospective clinical exploration confirming that MQEF demonstrates regulatory influence over exosomal miRNA expression in PMOP patients’ serum, its impact likely involves modulation of the immune and endocrine systems, as well as the renin-angiotensin system.

The basic helix-loop-helix (bHLH) transcription factors play crucial roles in various processes, such as plant development, secondary metabolism, and response to biotic/abiotic stresses. Sophora flavescens is a widely used traditional herbal medicine in clinical practice, known for its abundant flavonoids as the main active compounds. However, there has been no comprehensive analysis of S. flavescens bHLH (SfbHLH) gene family reported currently. In this study, we identified 167 SfbHLH genes and classified them into 23 subfamilies based on comparative genomics and phylogenetic analysis. Furthermore, widespread duplications significantly contributed to the expansion of SfbHLH family. Notably, SfbHLH042 was found to occupy a central position in the bHLH protein-protein interaction network. Transcriptome analysis of four tissues (leaf, stem, root and flower) revealed that most SfbHLH genes exhibited high expression levels exclusively in specific tissues of S. flavescens. The integrated analysis of transcriptomics and metabolomics during pod development stages revealed that SfbHLH042 may play a central role in connecting SfbHLH genes, flavonoids, and key enzymes involved in the biosynthesis pathway. Moreover, we also checked the expression of 8 SfbHLH genes using RT-qPCR analysis to realize the expression profiles of these genes among various tissues at different cultivated periods and root development. Our study would aid to understand the phylogeny and expression profile of SfbHLH family genes, and provide a promising candidate gene, SfbHLH042, for regulating the biosynthesis of flavonoids in S. flavescens.

Abstract Aloperine (ALO), a quinolizidine‐type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non‐small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome‐1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO‐induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti‐PD‐L1/TGF‐β bispecific antibody in inhibiting LLC‐derived subcutaneous tumor models. Thus, ALO is first identified as a novel late‐stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

Abstract Objective To appraise the quality of guidelines on intravenous iodinated contrast media (ICM) use in patients with kidney disease, and to compare the recommendations among them. Methods We searched four literature databases, eight guideline libraries, and ten homepages of radiological societies to identify English and Chinese guidelines on intravenous ICM use in patients with kidney disease published between January 2018 and June 2023. The quality of the guidelines was assessed with the Scientific, Transparent, and Applicable Rankings (STAR) tool. Results Ten guidelines were included, with a median STAR score of 46.0 (range 28.5–61.5). The guidelines performed well in “Recommendations” domain (31/40, 78%), while poor in “Registry” (0/20, 0%) and “Protocol” domains (0/20, 0%). Nine guidelines recommended estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as the cutoff for referring patients to discuss the risk-benefit balance of ICM administration. Three guidelines further suggested that patients with an eGFR < 45 mL/min/1.73 m2 and high-risk factors also need referring. Variable recommendations were seen in the acceptable time interval between renal function test and ICM administration, and that between scan and repeated scan. Nine guidelines recommended to use iso-osmolar or low-osmolar ICM, while no consensus has been reached for the dosing of ICM. Nine guidelines supported hydration after ICM use, but their protocols varied. Drugs or blood purification therapy were not recommended as preventative means. Conclusion Guidelines on intravenous ICM use in patients with kidney disease have heterogeneous quality. The scientific societies may consider joint statements on controversial recommendations for variable timing and protocols. Critical relevance statement The heterogeneous quality of guidelines, and their controversial recommendations, leave gaps in workflow timing, dosing, and post-administration hydration protocols of contrast-enhanced CT scans for patients with kidney diseases, calling for more evidence to establish a safer and more practicable workflow. Key points • Guidelines concerning iodinated contrast media use in kidney disease patients vary. • Controversy remains in workflow timing, contrast dosing, and post-administration hydration protocols. • Investigations are encouraged to establish a safer iodinated contrast media use workflow. Graphical Abstract

Abstract Background Sexual minority status is associated with face-to-face bullying and cyberbullying victimization. However, limited studies have investigated whether such a relationship differs by sex or grade in a nationally representative sample. Methods We concatenated the national high school data from the Youth Risk Behavior Surveillance System (YRBSS) chronologically from 2015 to 2019, resulting in a sample of 32,542 high school students. We constructed models with the interaction term between sexual minority status and biological sex assigned at birth to test the effect modification by sex on both the multiplicative and additive scales. A similar method was used to test the effect modification by grade. Results Among heterosexual students, females had a higher odds of being bullied than males, while among sexual minority students, males had a higher odds of being bullied. The effect modification by sex was significant on both the multiplicative and additive scales. We also found a decreasing trend of bullying victimization as the grade increased among both heterosexual and sexual minority students. The effect modification by the grade was significant on both the multiplicative and the additive scale. Conclusions Teachers and public health workers should consider the difference in sex and grade when designing prevention programs to help sexual minority students.

Abstract Background Complete reporting is essential for clinical research. However, the endorsement of reporting guidelines in radiological journals is still unclear. Further, as a field extensively utilizing artificial intelligence (AI), the adoption of both general and AI reporting guidelines would be necessary for enhancing quality and transparency of radiological research. This study aims to investigate the endorsement of general reporting guidelines and those for AI applications in medical imaging in radiological journals, and explore associated journal characteristic variables. Methods This meta-research study screened journals from the Radiology, Nuclear Medicine & Medical Imaging category, Science Citation Index Expanded of the 2022 Journal Citation Reports, and excluded journals not publishing original research, in non-English languages, and instructions for authors unavailable. The endorsement of fifteen general reporting guidelines and ten AI reporting guidelines was rated using a five-level tool: “active strong”, “active weak”, “passive moderate”, “passive weak”, and “none”. The association between endorsement and journal characteristic variables was evaluated by logistic regression analysis. Results We included 117 journals. The top-five endorsed reporting guidelines were CONSORT (Consolidated Standards of Reporting Trials, 58.1%, 68/117), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 54.7%, 64/117), STROBE (STrengthening the Reporting of Observational Studies in Epidemiology, 51.3%, 60/117), STARD (Standards for Reporting of Diagnostic Accuracy, 50.4%, 59/117), and ARRIVE (Animal Research Reporting of In Vivo Experiments, 35.9%, 42/117). The most implemented AI reporting guideline was CLAIM (Checklist for Artificial Intelligence in Medical Imaging, 1.7%, 2/117), while other nine AI reporting guidelines were not mentioned. The Journal Impact Factor quartile and publisher were associated with endorsement of reporting guidelines in radiological journals. Conclusions The general reporting guideline endorsement was suboptimal in radiological journals. The implementation of reporting guidelines for AI applications in medical imaging was extremely low. Their adoption should be strengthened to facilitate quality and transparency of radiological study reporting.

Abstract In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

The relationship between the local structures and the thermodynamic properties of metallic liquids has been a fundamental issue, which significantly impacts the comprehensive performances of metallic materials. The temperature-induced structure evolution in CoxBy alloy liquids, involving CoB, Co2B, Co3B, and Co23B6, was investigated using ab initio molecular dynamics simulations. The results show that the clusters of icosahedral-like polyhedrons are found predominantly in all alloys at low temperature, while the heating induces the decrease in ideal icosahedral and the increase in defected icosahedral. At high temperature, the polyhedron clusters decrease significantly and the ideal icosahedra transforms into smaller short-range polyhedrons, signifying the temperature-induced chemical structure change from long-range to short-range ordering. The aggregation of B atoms at high temperature is confirmed by atomic configuration, charge density, and B-centered Voronoi polyhedrons, and the α-Co single phase is observed below 1600 K. This study is helpful for understanding the local structure variability in eutectic Co-B alloys and guiding solidification path in theory.

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Based on data on the shear wave speed and physical properties of the shallow sediment samples collected in the northwest South China Sea, the hyperparameter selection and contribution of the characteristic factors of the machine learning model for predicting the shear wave speed of seafloor sediments were studied using the eXtreme Gradient Boosting (XGBoost) algorithm. An XGBoost model for predicting the shear wave speed of seafloor sediments was established based on four physical parameters of the sediments: porosity (n), water content (w), density (ρ), and average grain size (MZ). The result reveals that: (1) The shear wave speed has a good correlation with n, w, ρ, and MZ, and their Pearson correlation coefficients are all above 0.75, indicating that they can be used as the suitable characteristic parameters for predicting the shear wave speed based on the XGBoost model; (2) When the number of weak learners (n_estimators) is 115 and the maximum depth of the tree (max_depth) is 6, the XGBoost model has a very high goodness of fit (R2) of the validation data of 0.914, the very low mean absolute error (MAE) and mean absolute percentage error (MAPE) of the predicted shear wave speed are 3.366 m/s and 9.90%, respectively; (3) Compared with grain-shearing (GS) model and single- and dual-parameter regression equation prediction models, the XGBoost model for the shear wave speed of seafloor sediments has higher fitting goodness and lower prediction error.

Abstract Objective To conduct an overview of meta-analyses of radiomics studies assessing their study quality and evidence level. Methods A systematical search was updated via peer-reviewed electronic databases, preprint servers, and systematic review protocol registers until 15 November 2022. Systematic reviews with meta-analysis of primary radiomics studies were included. Their reporting transparency, methodological quality, and risk of bias were assessed by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 checklist, AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews, version 2) tool, and ROBIS (Risk Of Bias In Systematic reviews) tool, respectively. The evidence level supporting the radiomics for clinical use was rated. Results We identified 44 systematic reviews with meta-analyses on radiomics research. The mean ± standard deviation of PRISMA adherence rate was 65 ± 9%. The AMSTAR-2 tool rated 5 and 39 systematic reviews as low and critically low confidence, respectively. The ROBIS assessment resulted low, unclear and high risk in 5, 11, and 28 systematic reviews, respectively. We reperformed 53 meta-analyses in 38 included systematic reviews. There were 3, 7, and 43 meta-analyses rated as convincing, highly suggestive, and weak levels of evidence, respectively. The convincing level of evidence was rated in (1) T2-FLAIR radiomics for IDH-mutant vs IDH-wide type differentiation in low-grade glioma, (2) CT radiomics for COVID-19 vs other viral pneumonia differentiation, and (3) MRI radiomics for high-grade glioma vs brain metastasis differentiation. Conclusions The systematic reviews on radiomics were with suboptimal quality. A limited number of radiomics approaches were supported by convincing level of evidence. Clinical relevance statement The evidence supporting the clinical application of radiomics are insufficient, calling for researches translating radiomics from an academic tool to a practicable adjunct towards clinical deployment. Graphical Abstract

A renormalized group improved Schwarzschild black hole spacetime contains two quantum correction parameters. One parameter γ represents the identification of cutoff of the distance scale, and another parameter Ω stems from nonperturbative renormalization group theory. The two parameters are constrained by the data from the shadow of M87* central black hole. The dynamics of electrically charged test particles around the black hole are integrable. However, when the black hole is immersed in an external asymptotically uniform magnetic field, the dynamics are not integrable and may allow for the occurrence of chaos. Employing an explicit symplectic integrator, we survey the contributions of the two parameters to the chaotic dynamical behavior. It is found that a small change of the parameter γ constrained by the shadow of M87* black hole has an almost negligible effect on the dynamical transition of particles from order to chaos. However, a small decrease in the parameter Ω leads to an enhancement in the strength of chaos from the global phase space structure. A theoretical interpretation is given to the different contributions. The term with the parameter Ω dominates the term with the parameter γ, even if the two parameters have same values. In particular, the parameter Ω acts as a repulsive force, and its decrease means a weakening of the repulsive force or equivalently enhancing the attractive force from the black hole. On the other hand, there is a positive Lyapunov exponent that is universally given by the surface gravity of the black hole when Ω≥0 is small and the external magnetic field vanishes. In this case, the horizon would influence chaotic behavior in the motion of charged particles around the black hole surrounded by the external magnetic field. This point can explain why a smaller value of the renormalization group parameter would much easily induce chaos than a larger value.

Background: Adverse Childhood Experience (ACE) has been shown to have detrimental impact on amygdala structure. Prior research found that adaptive psychological changes after Mindfulness-Based Interventions (MBI) were associated with amygdala volumetric changes. The present study aims to further investigate whether such effects also occur among ACE survivors and whether the effects are unique to MBI. Methods: A total of 64 young adult childhood adversity survivors were randomized to an eight-week MBI or Stress Management Education (SME) as an active control condition. Anatomical MRI and questionnaires on mindfulness, stress and psychological health were collected at baseline and post-intervention. Due to subject dropout, the final sample included 39 subjects (MBI:20, SME:19). Results: Both groups showed increased mindfulness levels, reduced stress, and improved psychological symptoms (depression, anxiety, and somatization), with no significant group by time interaction effect. There was no significant group difference on amygdala volumetric changes. Within the MBI group, childhood maltreatment severity was a significant mediator between changes of mindfulness levels and right amygdala volumetric changes. Across pooled sample of both groups, childhood maltreatment was a significant moderator for the effect of trait anxiety level changes on left amygdala volumetric changes. Limitations: Modest sample size, relatively low retention rates, suboptimal monitoring of home practice. Conclusions: MBI did not demonstrate overall better clinical effects than SME. Psychological-change-dependent amygdala volumetric change was not specific to MBI. Childhood maltreatment severity modulated the relationships between adaptive psychological changes and amygdala volumetric changes.

BackgroundSuicidal and self-injurious-related behaviors (SSIRBs) are a serious public health challenge in China. However, a comprehensive systematic review of psychosocial interventions for SSIRBs among Chinese adolescents has not been performed. To fill this gap, this systematic review and meta-analysis aimed to examine psychosocial interventions for SSIRBs among Chinese adolescents.MethodsEight international (PubMed, EMBASE, Cochrane Library, ScienceDirect, Clinical Trial, CINAHL, PsycINFO, and Web of Science) and four Chinese (Wanfang, SinoMed, CEPS, and CNKI) databases were searched from inception to 31 January 2023. Data extraction and quality assessment were independently conducted by two groups of researchers. Qualitative synthesis and meta-analysis were both used.ResultsThe initial search yielded 16,872 titles. Of the 649 full texts reviewed, 19 intervention articles focusing on SSIRBs met the inclusion criteria. Thirteen out of the 19 included studies involved cognitive–behavioral therapy (CBT). Seven non-suicidal self-injury (NSSI) studies assessing self-injurious behaviors were included (six short-term studies and three long-term studies). Compared with long-term interventions [−1.30 (95% CI: –1.84, −0.76)], short-term psychosocial interventions had a higher standardized mean difference (SMD) value [1.86 (95% CI: –2.72, −0.99)]. Meta-regression showed an inverse relationship between the treatment response and sample size (slope = 0.068, Z = 2.914, p = 0.004) and proportion of females (slope = 1.096, Z = 5.848, p

Background: Losing an only child (Shidu) is a grievous traumatic event that may affect brain structure, even if it does not lead to psychiatric disorders. However, longitudinal changes in brain structure and their relationship to subclinical psychiatric symptoms (SPS) have not been well investigated in Shidu parents without any psychiatric disorders (SDNP). Objectives: This study aimed to investigate cross-sectional and longitudinal changes in cortical thickness and surface area in SDNP, and to explore their relationship with SPS. Methods: A total of 50 SDNP and 40 matched healthy controls (HC) were enrolled. All participants underwent structural MRI scans and clinical assessment at baseline and at the 5-year follow-up. Differences in brain structural phenotypes (cortical thickness, surface area, and their annual rate of change) between the SDNP and HC groups were compared using FreeSurfer. Correlations between significant brain structural phenotypes and SPS in the SDNP group were evaluated using multiple linear regressions. Results: The SDNP group showed a smaller surface area in the left inferior parietal cortex than the HC group at baseline and follow-up. The SDNP group showed slower rates of cortical thinning and surface area loss in several brain regions than the HC group from baseline to follow-up. Moreover, slower rates of cortical thinning in the left insula, superior frontal cortex, and superior temporal cortex were associated with greater reductions in avoidance, depression, and trauma re-experiencing symptoms scores over time in the SDNP group, respectively. Conclusions: Shidu trauma-induced structural abnormalities in the inferior parietal cortex may persist over time and be independent of the severity of psychiatric symptoms. The expansion of prefrontal, temporal, and insular cortex implicated in emotional regulation may contribute to improvements in psychiatric symptoms in Shidu parents.

Abstract Globally, air pollution is amongst the most significant causes of premature death. Nevertheless, studies on the relationship between fine particulate matter (PM2.5) exposure and blood lipids have typically not been population-based. In a large, community-based sample of residents in Yixing city, we assessed the relationship between short-term outdoor PM2.5 exposure and blood lipid concentrations. Participants who attended the physical examination were enrolled from Yixing People’s hospital from 2015 to 2020. We collected general characteristics of participants, including gender and age, as well as test results of indicators of blood lipids. Data on daily meteorological factors were collected from the National Meteorological Data Sharing Center ( http://data.cma.cn/ ) and air pollutant concentrations were collected from the China Air Quality Online Monitoring and Analysis Platform ( https://www.aqistudy.cn/ ) during this period. We applied generalized additive models to estimate short-term effects of ambient PM2.5 exposure on each measured blood lipid-related indicators and converted these indicators into dichotomous variables (non- hyperlipidemia and hyperlipidemia) to calculate risks of hyperlipidemia associated with PM2.5 exposure. A total of 197,957 participants were included in the analysis with mean age 47.90 years (± SD, 14.28). The increase in PM2.5 was significantly associated with hyperlipidemia (odds ratio (OR) 1.003, 95% CI 1.001–1.004), and it was still significant in subgroups of males and age

Abstract Background The breastfeeding rate in China is lower than that in many other countries and the extent of adoption of the “Feeding Recommendations for Preterm Infants and Low Birth Weight Infants” guideline in NICUs remains unclear. Method A web-based survey about the current status of human milk feeding and enteral feeding practices at NICUs was sent to all China Neonatal Network’s cooperation units on September 7, 2021, and the respondents were given a month to send their responses. Results All sixty NICUs responded to the survey, the reply rate was 100%. All units encouraged breastfeeding and provided regular breastfeeding education. Thirty-six units (60.0%) had a dedicated breastfeeding/pumping room, 55 (91.7%) provided kangaroo care, 20 (33.3%) had family rooms, and 33 (55.0%) routinely provided family integrated care. Twenty hospitals (33.3%) had their own human milk banks, and only 13 (21.7%) used donor human milk. Eight units (13.3%) did not have written standard nutrition management guidelines for infants with body weight

Abstract Background Sexual minorities are at a higher risk of suffering from depressive symptoms compared with heterosexual individuals. Only a few studies have examined the conditions of having depressive symptoms within different sexual minority groups, especially people with sexual orientation uncertainty in a nationally representative sample. Furthermore, few studies have explored whether the mean white blood count (WBC) is different between people with and without depressive symptoms among different sexual minority groups in a nationally representative sample. Methods We analyzed the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2014 with a sample of 14,090 subjects. We compared the prevalence of depressive symptoms in subpopulations stratified by sex, sexual minority status, and race. We also examined the difference in mean WBC count between depressed and non-depressed people among heterosexual individuals and different sexual minority groups. Additionally, two multivariable logistic regression models were used to explore the association between sexual minority status and depressive symptoms, treating sexual minority status as both a binary and categorical variable. Results Female sex (OR: 1.96, 95% CI: 1.72—2.22) and sexual minority status (OR: 1.79, 95% CI: 1.47—2.17) were both independently associated with depressive symptoms. Within the sexual minority population, subjects who were unsure about their sexual identities had the highest odds of having depressive symptoms (OR: 2.56, 95% CI: 1.40—4.68). In the subgroup analysis considering intersectionality, black sexual minority females had the highest rate of depressive symptoms (19.4%, 95% CI: 7.72—40.98). Finally, the mean WBC count differed significantly between people with and without depressive symptoms among male heterosexual individuals, female heterosexual individuals, and female sexual minorities, but not among male sexual minorities. Conclusions Based on sex, race, and sexual minority status, black females of sexual minority status had the highest rate of depressive symptoms. Within sexual minority groups, participants who were unsure about their sexual identities had the highest odds of having depressive symptoms. Finally, the mean WBC count was significantly higher among people with depressive symptoms than those without depressive symptoms only among male heterosexuals, female heterosexuals, and female sexual minorities, but not among male sexual minorities. Future research should investigate the social and biological mechanisms of the differences.

Abstract In September 2022, two destructive earthquakes of moment magnitude (M w) 6.6 (foreshock) and 7.1 (mainshock) occurred in Taitung County, south-eastern Taiwan. To understand their complex rupture processes, we analysed these earthquakes using the Potency Density Tensor Inversion method, which can stably estimate the rupture propagation process, including fault geometry, without overfitting the data. The analyses revealed that the major rupture of the foreshock propagated towards shallow depth, in a south–southwest direction, following an initial rupture that propagated towards the deeper part of the fault. The mainshock, with its epicentre on the north–northeast side of that of the foreshock, consists of two distinct episodes. During the first episode (0–10 s), the initial rupture propagated north–northeast, through a deep path, followed by the main rupture that propagated bilaterally in a north–northeast and south–southwest direction. The second rupture episode (10–16 s) started near the hypocentre of the mainshock, and the rupture propagated towards the shallow side of the fault. The results suggest that the stress concentration from both the foreshock and mainshock’s first rupture episode may have caused the second rupture episode in the high fracture surface energy area between the foreshock and the first rupture episode of the mainshock. The irregular rupture process of the foreshock and mainshock may reflect the heterogeneity of stress and structure in the source region.

Inner fracture zones play a decisive role in the formation of high-quality reservoirs in buried hill reservoirs in covered metamorphic rock. Based on core, sidewall core, thin section, seismic, logging and reservoir physical property data, the fracture development characteristics of the Bozhong 13-2 block buried hill reservoir are described in detail and the controlling factors and the influence on reservoir quality are discussed. The results showed: (1) three groups of tectonic fractures developed in the study area—near-EW-striking, ENE-striking and nearly N–S-striking fractures—were controlled by the early Indosinian thrusting, the late Indosinian to early Yanshanian sinistral strike-slipping and the late Yanshanian late dextral strike-slipping in the Bohai Bay Basin, respectively. The ENE- and nearly-E-W-striking fractures are the most common, and the dip angles of the fractures are mostly between 35° and 75° and thus oblique. (2) The Indosinian-early Yanshanian was the main fracture-forming period, and the dextral strike-slip action in the late Yanshanian was the key to maintaining effective fractures. Imaging logging shows that 97.87% of the fractures are effective fractures. Based on thin section observation, 14.47% of the fractures are unmodified open fractures and 80.37% of the fractures are effective fractures due to reactivation. (3) The late Yanshanian strike-slip fault transformed the deformation adjustment zone formed by the early Indosinian thrust faulting and the core of the fold structure was more conducive to fracture development. The fracture density of a single well located within the deformation adjustment zone and at the core of the fold is between 0.93–1.49 m−1, the fracture density of a single well located only at the core of the fold is between 0.67–0.75 m−1 and that of a single well located at the wing of the fold is between 0.35–0.59 m−1. Diabase dike intrusions promoted the development of local fractures. (4) Fractures promote the migration and accumulation of oil and gas, and the fracture density in the oil layer is between 0.81–2.19 m−1. That in the nonoil layer is between 0.25–1.12 m−1. In addition, fractures not only provide storage space but also effectively improve the reservoir capacity of the inner fracture zones of buried hill reservoirs by concentrating dissolution.

Mitosis mediates the accurate separation of daughter cells, and abnormalities are closely related to cancer progression. KIF11, a member of the kinesin family, plays a vital role in the formation and maintenance of the mitotic spindle. Recently, an increasing quantity of data have demonstrated the upregulated expression of KIF11 in various cancers, promoting the emergence and progression of cancers. This suggests the great potential of KIF11 as a prognostic biomarker and therapeutic target. However, the molecular mechanisms of KIF11 in cancers have not been systematically summarized. Therefore, we first discuss the functions of the protein encoded by KIF11 during mitosis and connect the abnormal expression of KIF11 with its clinical significance. Then, we elucidate the mechanism of KIF11 to promote various hallmarks of cancers. Finally, we provide an overview of KIF11 inhibitors and outline areas for future work.

Ion contamination considerably influences the properties of geopolymers. This study investigated the effects of magnesium chloride (MgCl2) and magnesium sulfate (MgSO4) concentrations on the microstructure and properties of metakaolinite-based geopolymers with Si/Al ratios of 1.3 (adding NaOH) and 1.6 (adding NaOH and Na2SiO3). The chemical structures and compositions of as-obtained geopolymers formed through the alkali activation of kaolinite were characterized through X-ray diffraction, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy, while the microstructure was characterised via scanning electron microscopy and mercury intrusion porosimetry.The salt-free geopolymer with a Si/Al ratio of 1.3 exhibited a loose microstructure and hence poor 28-day compressive strength (9.4 MPa). The addition of magnesium salt to the geopolymer did not considerably influence its microstructure and mechanical properties. Comparatively, the geopolymer with a Si/Al ratio of 1.6 exhibited a compact microstructure and high 28-day compressive strength (43.0 MPa). The geopolymer compressive strength gradually decreased with increasing salt concentration. MgCl2 addition induced halite formation, increased pore diameter and pore volume, and reduced Si incorporated into the geopolymer matrix. In contrast, MgSO4 addition resulted in relatively less change in the pore diameter and pore volume and based on NMR result, more Si was incorporated into the geopolymer matrix. Thus, MgCl2 was more detrimental to the mechanical properties of the kaolinite-based geopolymers than MgSO4.Overall, the results indicate that salt contamination considerably affects the chemical compositions, microstructural characteristics, and compressive strength of metakaolinite-based geopolymers at high Si/Al ratio (adding NaOH and Na2SiO3) and those chlorine ions are more detrimental to the properties of metakaolinite-based geopolymer than sulfate ions.

IntroductionThe bibliometric analysis aims to identify research trends in estrogen receptor (ERs) and progesterone receptor (PRs) in prostate cancer (PCa), and also discuss the hotspots and directions of this field.Methods835 publications were sourced from the Web of Science database (WOS) from 2003 to 2022. Citespace, VOSviewer, and Bibliometrix were used for the bibliometric analysis.ResultsThe number of published publications increased in early years, but declined in the last 5 years. The United States was the leading country in citations, publications, and top institutions. Prostate and Karolinska Institutet were the most publications of journal and institution, respectively. Jan-Ake Gustafsson was the most influential author based on the number of citations/publications. The most cited paper was “Estrogen receptors and human disease” by Deroo BJ, published in the Journal of Clinical Investigation. The most frequently used keywords were PCa (n = 499), gene-expression (n = 291), androgen receptor (AR) (n = 263), and ER (n = 341), while ERb (n = 219) and ERa (n = 215) further emphasized the importance of ER.ConclusionsThis study provides useful guidance that ERa antagonists, ERb agonists, and the combination of estrogen with androgen deprivation therapy (ADT) will potentially serve as a new treatment strategy for PCa. Another interesting topic is relationships between PCa and the function and mechanism of action of PRs subtypes. The outcome will assist scholars in gaining a comprehensive understanding of the current status and trends in the field, and provide inspiration for future research.

Hundreds of mutations in the gene CFTR lead to cystic fibrosis and represent a challenge to developing therapeutics. Here, authors demonstrate the ability of airway cells derived from human iPSCs to model genotype-specific CFTR function as well as pharmacologic rescue of disease causing mutations.

A dedicated test bench is employed to record acoustic emission signals from dry gas seals under various operating conditions. Time-domain and frequency-domain analysis methods are utilized to process and analyze the acoustic emission signals during start/stop, stable operation, and two common fault states (end-face defects and compensation spring failure). Furthermore, feature recognition research is conducted. A method for identifying the operational states of seals (low-speed friction, gradual detachment, stable operation) based on the root mean square (RMS) was established, with transition points at speeds of 100 and 1000 RPM, respectively. Additionally, spectral analysis is conducted using Fourier transform to determine the frequency band of acoustic emission signals (240–320 kHz) generated during contact wear of dry gas seals. Investigation into two typical faults of dry gas seals reveals that the RMS value of the acoustic emission signal gradually increases with the rotational speed during the operation of dry gas seal end-face defects. This is attributed to the insufficient dynamic pressure effect on the end face, resulting in long-term wear and tear. When the dry gas seal compensates for spring failure, the RMS value of the acoustic emission signal initially increases, then decreases, and finally increases again as the speed increases. It reaches the stable operating inflection point when the end-face speed is 800 r/min.

Based on the data of the acoustic and physical properties of seafloor sediments obtained on the continental shelf area of the East China Sea (ECS), prediction equations of the sediment sound speed based on single and dual parameters were established, and the correlation of the sound speed with physical parameters was discussed. The results show that the sediment sound speed (c) is strongly correlated with water content (w), density (ρ), void ratio (e), mean grain size (Mz) and median grain size (Md), and the coefficient of determination R2 of the empirical regression equation is generally greater than 0.80, while the empirical regression equation coefficient of determination R2 of the compression coefficient (a) and compression modulus (E) are slightly lower, with 0.79 and 0.73, respectively. The coefficients of determination of the dual parameter regression equations between sediment sound speed with physical property parameters are generally higher than those of the single parameter equations, which are all higher than 0.90 indicating better prediction performance. The sensitivity of the physical parameters to the sound speed was analyzed, and the result shows that the sequence of sensitivity from high to low influence on sediment sound speed is void ratio, density, compressibility coefficient, median grain size and mean grain size. The prediction equations established in this study are a good extension and supplement to marine geoacoustic models and is of great significance for obtaining the acoustic properties of the seafloor sediments on the shelf of the East China Sea.

Denosumab, a fully humanized monoclonal neutralizing antibody, inhibits activation of the RANK/RANKL/OPG signaling pathway through competitive binding with RANKL, thereby inhibiting osteoclast-mediated bone resorption. Denosumab inhibits bone loss; therefore, it is used to treat metabolic bone diseases (including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis), in clinical practice. Since then, multiple effects of denosumab have been discovered. A growing body of evidence suggests that denosumab has a variety of pharmacological activities and broad potential in clinical diseases such as osteoarthritis, bone tumors, and other autoimmune diseases. Currently, Denosumab is emerging as a treatment for patients with malignancy bone metastases, and it also shows direct or indirect anti-tumor effects in preclinical models and clinical applications. However, as an innovative drug, its clinical use for bone metastasis of malignant tumors is still insufficient, and its mechanism of action needs to be further investigated. This review systematically summarizes the pharmacological mechanism of action of denosumab and the current understanding and clinical practice of the use of denosumab for bone metastasis of malignant tumors to help clinicians and researchers deepen their understanding of denosumab.

Abstract Nanomaterials are promising carriers to improve the bioavailability and therapeutic efficiency of drugs by providing preferential drug accumulation at their sites of action, but their delivery efficacy is severely limited by a series of biological barriers, especially the mononuclear phagocytic system (MPS)—the first and major barrier encountered by systemically administered nanomaterials. Herein, the current strategies for evading the MPS clearance of nanomaterials are summarized. First, engineering nanomaterials methods including surface modification, cell hitchhiking, and physiological environment modulation to reduce the MPS clearance are explored. Second, MPS disabling methods including MPS blockade, suppression of macrophage phagocytosis, and macrophages depletion are examined. Last, challenges and opportunities in this field are further discussed.

Remote sensing image scene classification faces challenges, such as the difference in semantic granularity of different scene categories and the imbalance of the number of samples, which cause the wrong features learning for deep convolutional networks (DCNs). This article proposes a multiple granularity semantic learning network (MGSN), including multiple granularity semantic learning (MGSL) and nonuniform sampling augmentation (NUA) modules. Specifically, the MGSL module makes full use of different granularities of semantic information of scenes, guiding the network to learn global and local features simultaneously. And, the relationship between semantic features of different granularity has been explored, based on which the learning of coarse-grained features helps to improve the learning of fine-grained semantic features. It shows that learning fine-grain semantics can inhibit learning coarse-grain semantic features. The NUA module combines sampling and sample augmentation to balance the sample distribution, which can avoid overfitting caused by oversampling. The proposed MGSN achieved state-of-the-art classification accuracy on two large-scale remote sensing image scene classification datasets, Million-AID and NWPU-RESISC45. Under 10$\%$ and 20$\%$ training samples of the NWPU-RESISC45 dataset, MGSN achieves 91.92$\%$ and 94.33$\%$ top-1 accuracy, respectively. In experiments conducted on the Million-AID dataset, the proposed MGSN performed best among 18 DCNs. In comparison to the baseline, FixEfficientNet, MGSN improved the accuracy of top-1 and top-5 by 10.63$\%$ and 5.47$\%$, respectively, with low complexity costs.

Abstract Background Split fractures of the humeral greater tuberosity (HGT) are common injuries. Although there are numerous surgical treatments for these fractures, no classification system combining clinical and biomechanical characteristics has been presented to guide the choice of fixation method. Methods We created a standardised fracture of the HGT in 24 formalin-fixed cadavers. Six were left as single-fragment fractures (Group A), six were further prepared to create single-fragment with medium size full-thickness rotator cuff tear (FT-RCT) fractures (Group B), six were cut to create multi-fragment fractures (Group C), and six were cut to create multi-fragment with FT-RCT fractures (Group D). Each specimen was fixed with a shortened proximal humeral internal locking system (PHILOS) plate. The fixed fractures were subjected to load and load-to-failure tests and the differences between groups analysed. Results The mean load-to-failure values were significantly different between groups (Group A, 446.83 ± 38.98 N; Group B, 384.17 ± 36.15 N; Group C, 317.17 ± 23.32 N and Group D, 266.83 ± 37.65 N, P

The increasing demand for distributed energy and active load increases the risk of voltage violations in active distribution systems. This paper proposes a distributionally robust transactive control method for local energy trading and network operation management of active distribution systems with interconnected microgrids. In particular, the emerging SOP technology is used for the flexible connection of the multi-microgrids (MMGs). First, the local energy interactive market between distribution network operator (DNO) and regional microgrids is constructed to simultaneously solve the economic and security problems of distribution networks considering the energy trading scenarios and various operational constraints. Then, the dual relaxation technique is used to transform the two-layer structure model into a single-layer model. Furthermore, the single-layer game model is further transformed into a two-stage distributed robust problem considering the uncertainties of load demand and renewable power outputs, and the second stage of the problem is decomposed into multiple parallel subproblems without dual information. Finally, numerical simulations on IEEE-33 test system verify the advantages and effectiveness of the proposed method.

Guanine nucleotide-binding (G) proteins, namely, phosphate-binding (P) loop GTPases, play a critical role in life processes among different species. Based on the structural characteristics, G proteins can be divided into heterotrimeric G proteins, small G proteins and multiple unique unconventional G proteins. The highly conserved unconventional G protein YchF is composed of a core G domain, an inserted coiled-coil domain, and a TGS domain from the N-terminus to the C-terminus. In this review, we compared the structural characteristics of the G domain in rice OsYchF1 with those of Rattus norvegicus heterotrimeric G protein α-subunit and human small G protein Ras-related G protein C and analyzed the binding modes of these G proteins with GTP or ATP by performing molecular dynamics simulations. In summary, it will provide new insights into the enormous diversity of biological function of G proteins.

Rechargeable zinc-air batteries (ZABs) have gained a significant amount of attention as next-generation energy conversion and storage devices owing to their high energy density and environmental friendliness, as well as their safety and low cost. The performance of ZABs is dominated by oxygen electrocatalysis, which includes the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Therefore, it is crucial to develop effective bifunctional oxygen electrocatalysts that are both highly active and stable. Carbon-based materials are regarded as reliable candidates because of their superior electrical conductivity, low price, and high durability. In this Review, we briefly introduce the configuration of ZABs and the reaction mechanism of bifunctional ORR/OER catalysts. Then, the most recent developments in carbon-based bifunctional catalysts are summarized in terms of carbon-based metal composites, carbon-based metal oxide composites, and other carbon-based composites. In the final section, we go through the significant obstacles and potential future developments for carbon-based bifunctional oxygen catalysts for ZABs.

ObjectiveTo explore whether the modified Qing’ e Pills (MQEP) exerts anti-osteoporotic effects and prevents bone loss by enhancing angiogenesis.MethodsNetwork pharmacology was used to assess whether MQEP has a pro-angiogenic capacity and to predict its potential targets. Human umbilical vein endothelial cells were treated with glucocorticoids and MQEP to assess cell viability. The expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor, and angiotensin converting enzyme, which are associated with the activation of the renin-angiotensin-aldosterone system, and the expression of vascular endothelial growth factor and hypoxia-inducible factor 1 alpha, which are associated with the formation of type H blood vessels, were examined by western blot and RT-qPCR. Thereafter, the glucocorticoid-induced osteoporosis model was established and intervened with MQEP. Femur scanning was performed with micro-computed tomography; trabecular spacing, trabecular thickness, and trabecular number were observed and calculated; the expression of nuclear factor-kappa B ligand and osteoprotegerin was detected by ELISA, and the ratio was calculated to evaluate the degree of bone resorption. Finally, type H blood vessels that were highly coupled to osteogenic cells were identified by immunohistochemistry staining and flow cytometry.ResultsThis is the first study to reveal and confirm that MQEP could prevent bone loss in glucocorticoid-induced osteoporosis by promoting the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, which are highly associated with type H blood vessel formation. In vitro experiments confirmed that MQEP could effectively promote the proliferation of vascular endothelial cells and alleviate glucocorticoids-induced activation of the renin-angiotensin-aldosterone system, thereby reducing vascular injury.ConclusionMQEP exerts anti-osteoporosis effects and prevents bone loss by alleviating vascular injury caused by renin-angiotensin-aldosterone system activation and promoting type H blood vessel formation.

ObjectiveTo investigate the differential expression of exosomal miRNAs in the bone marrow tissue of Modified Qing’ E Formula (MQEF) on steroid-induced ischemic necrosis of the femoral head (INFH) model.MethodsSteroid hormones were used to establish the INFH model and treated with MQEF. After successful modeling, femoral tissue exosomes were isolated for miRNA sequencing to obtain femoral tissue exosomal differential miRNAs. By GO analysis and KEGG analysis of the differential genes in both groups, the major exosomal miRNAs of MQEF exerting anti-INFH as well as the major signaling pathways were identified. Next, a quantitative metabolomic validation of MQEF with broad targeting was performed to obtain the main active components of MQEF and to perform biological analysis and signaling pathway prediction of the active components by network pharmacology. Finally, the sequencing results were validated by using RT-qPCR. The results of miRNA sequencing were verified by double examination of network pharmacology and RT-qPCR, and the exosomal miRNAs regulated by the anti-INFH effect of MQEF and the specific signaling pathway of the effect were clarified.ResultsA total of 65,389 target genes were predicted in the exosomes of two groups of mice, and 18 significant differentially expressed miRNAs were obtained, of which 14 were up-regulated and 4 down-regulated. GO enrichment analysis showed that these predicted target genes were enriched in 12371 biological processes, 1727 cell components, and 4112 molecular functions. KEGG analysis showed that the predicted miRNA target genes were annotated to 342 signal pathways, in which the highly enriched pathways closely related to bone metabolism were PI3K-Akt signal pathway, MAPK signal pathway, and Wnt signal pathway. The most significantly up-regulated miRNAs were miR-185-3p and miR-1b-5p and the most significantly down-regulated miRNAs were miR-129b-5p and miR-223-5p, of which the targeted genes were closely related to the PI3K-Akt signal pathway. MQEF aqueous decoction extract targeted metabolomics quantitatively combined with network pharmacology predicted targets also closely related to PI3K-Akt signaling pathway. Real-time quantitative PCR validation showed that miR-185-3p was up-regulated 7.2-fold and miR-129b-5p was down-regulated 2.2-fold in the treatment group, and the difference was significant (P < 0.05).ConclusionsMQEF can regulate exosomal miRNA expression in steroid-induced INFH models, miR-185-3p or miR-129b-5p/PI3K-Akt signal axis may be part of the mechanism of MQEF against steroid-induced INFH.

Industrial oil and gas eruptions underwater have been found in the pyroclastic rocks of the Huoshiling Formation in the continental lacustrine basin of the Changling fault depression, Songliao Basin. This paper investigates the reservoir space characteristics, physical characteristics, and pore structure differences of subaqueous pyroclastic reservoirs in the Huoshiling Formation, and the causes of physical property differences of different types of reservoirs and their formation and evolution processes are analyzed. (1) The content of volcanic glass in tuff is higher, the reservoir space is dominated by devitrification pores and dissolution pores, and the coarser the grain size, the more favorable the physical properties, with larger pore sizes and higher porosities. The content of clay minerals in sedimentary tuff is high, the pores between clay minerals are the main pores, and the physical properties of sedimentary tuff are poor. The content of soluble components such as feldspar, debris, and laumontite is high in tuffaceous sandstone, which is dominated by dissolution pores. (2) Primary pores are not developed in the pyroclastic reservoirs in the study area, and the reservoirs are relatively dense, with an average porosity of 2.43% and an average permeability of 0.076 mD. The coarse-grained tuff has the highest porosity, followed by tuffaceous sandstone and fine-grained tuff, and the sedimentary tuff has the least favorable physical properties. (3) Devitrification was an important cause of the high-porosity and ultralow permeability of tuff reservoirs. Two oil and gas charges in the middle diagenetic stage led to the organic acid dissolution of rocks. In addition, fractures can provide migration channels for organic acids and deep hydrothermal fluids, leading to late dissolution, and can connect various scattered dissolution pores to improve the effectiveness of the reservoir space. (4) Coarse-grained tuff reservoirs that developed in the proximal facies are favorable targets for hydrocarbon exploration.

Abstract This paper is concerned with necessary and sufficient conditions for stabilisability of time‐varying discrete‐time switched systems. Starting with an asymptotically stable function, an exponentially stable function and a uniformly exponentially stable function, we successively propose necessary and sufficient conditions for asymptotic stabilisability, exponential stabilisability and uniform exponential stabilisability of time‐varying switched linear systems. Further, considering the broad applications of finite‐time stability in practical systems, based on an additionally introduced concept of finite‐time stable functions, we derive a necessary and sufficient condition for finite‐time stabilisability of time‐varying switched linear systems. Afterwards, three illustrative examples are given to show the applicability of our theoretical results. In the end, we further discuss the necessary and sufficient conditions for global exponential stabilisability and global uniform exponential stabilisability of time‐varying switched non‐linear systems. Compared to traditional difference Lyapunov inequalities, we release the requirement on negative definiteness of the time‐difference of Lyapunov functions.

Osteoporosis (OP) is known as a silent disease in which the loss of bone mass and bone density does not cause obvious symptoms, resulting in insufficient treatment and preventive measures. The losses of bone mass and bone density become more severe over time and an only small percentage of patients are diagnosed when OP-related fractures occur. The high disability and mortality rates of OP-related fractures cause great psychological and physical damage and impose a heavy economic burden on individuals and society. Therefore, early intervention and treatment must be emphasized to achieve the overall goal of reducing the fracture risk. Anti-OP drugs are currently divided into three classes: antiresorptive agents, anabolic agents, and drugs with other mechanisms. In this review, research progress related to common anti-OP drugs in these three classes as well as targeted therapies is summarized to help researchers and clinicians understand their mechanisms of action and to promote pharmacological research and novel drug development.

Quantum graphs are ideally suited to studying the spectral statistics of chaotic systems. Depending on the boundary conditions at the vertices, there are Neumann and Dirichlet graphs. The latter ones correspond to totally disassembled graphs with a spectrum being the superposition of the spectra of the individual bonds. According to the interlacing theorem, Neumann and Dirichlet eigenvalues on average alternate as a function of the wave number, with the consequence that the Neumann spectral statistics deviate from random matrix predictions. There is, e.g., a strict upper bound for the spacing of neighboring Neumann eigenvalues given by the number of bonds (in units of the mean level spacing). Here, we present analytic expressions for level spacing distribution and number variance for ensemble averaged spectra of Dirichlet graphs in dependence of the bond number, and compare them with numerical results. For a number of small Neumann graphs, numerical results for the same quantities are shown, and their deviations from random matrix predictions are discussed.

Extreme fluctuations in water temperature lead to significant economic losses for the aquaculture industry. Cyprinus carpio var qingtianensis (locally called Qingtian paddy field carp), is a local variety commonly found in Zhejiang province, China. Unlike traditional aquaculture environments, the water temperature range between day and night in the rice field environment is much larger, and the high temperature in summer may exceed the growth threshold of fish because there is no manual intervention; therefore, the study of how the Qingtian paddy field carp (PF carp) adapts to high-temperature conditions can shed light how the species adapt to the rice field environment. To investigate the molecular mechanisms of this fish under thermal stress, the liver metabolomics of Qiangtian paddy field carp (PF carp) were analyzed. In this study, metabolomics was used to examine the metabolic reaction of PF carp (102 days old, 104.69 ± 3.08 g in weight, 14.65 ± 0.46 cm in length) at water temperatures of 28 °C (control group, CG), 34 °C (experimental group (EG) 34), and 38 °C (EG38). The results show that 175 expression profile metabolites (DEMs), including 115 upregulated and 60 downregulated metabolites, were found in the CG vs. EG34. A total of 354 DEMs were inspected in CG vs. EG38, with 85 metabolites downregulated and 269 metabolites upregulated. According to the pathway enrichment study, various pathways were altered by thermal stress, including those of lipid, amino-acid, and carbohydrate metabolism. Our study presents a potential metabolic profile for PF carp under thermal stress. It also demonstrates how the host responds to thermal stress on a metabolic and molecular level.

Based on the acoustic and physical data of typical seafloor sediment samples collected in the East China Sea, this study on the super parameter selection and contribution of the characteristic factors of the machine learning model for predicting the sound speed of seafloor sediments was conducted using the eXtreme gradient boosting (XGBoost) algorithm. An XGBoost model for predicting the sound speed of seafloor sediments was established based on five physical parameters: density (ρ), water content (w), void ratio (e), sand content (S), and average grain size (Mz). The results demonstrated that the model had the highest accuracy when n_estimator was 75 and max_depth was 5. The model training goodness of fit (R2) was as high as 0.92, and the mean absolute error and mean absolute percent error of the model prediction were 7.99 m/s and 0.51%, respectively. The results demonstrated that, in the study area, the XGBoost prediction method for the sound speed of seafloor sediments was superior to the traditional single- and two-parameter regressional equation prediction methods, with higher prediction accuracy, thus providing a new approach to predict the sound speed of seafloor sediments.

Differentiation of human pluripotent stem cells towards definitive endoderm (DE) is the critical first step for generating cells comprising organs such as the gut, liver, pancreas and lung. This in-vitro differentiation process generates a heterogeneous population with a proportion of cells failing to differentiate properly and maintaining expression of pluripotency factors such as Oct4. RNA sequencing of single cells collected at four time points during a 4-day DE differentiation identified high expression of metallothionein genes in the residual Oct4-positive cells that failed to differentiate to DE. Using X-ray fluorescence microscopy and multi-isotope mass spectrometry, we discovered that high intracellular zinc level corresponds with persistent Oct4 expression and failure to differentiate. This study improves our understanding of the cellular heterogeneity during in-vitro directed differentiation and provides a valuable resource to improve DE differentiation efficiency. Keywords: hPSC, Differentiation, Definitive endoderm, Heterogeneity, Single cell, RNA sequencing

An M-O-L acid (mineral acid, organic acid, and Lewis acid)-catalyzed integrated process for furfural production from corncob was proposed to improve corncob conversion and furfural selectivity. First, the co-catalysts of sulfuric acid and acetic acid were investigated for their impact on furfural production. Sulfuric acid as a pretreatment catalyst was mixed with corncob before the experiment. Acetic acid, which is a byproduct of hemicellulose hydrolysis, was fed together with steam. The results showed that the cooperation of sulfuric acid and acetic acid decreased the total acid consumption dramatically. FeCl3·6H2O was also investigated as a co-catalyst in an effort to enhance the conversion of xylose to furfural and decrease furfural degradation. The integrated catalytic process achieved the highest furfural yield of 68.04% through the use of M-O-L acid under a reaction temperature of 180°C, 3v% acetic acid, 4.0 wt.% sulfuric acid of 0.6 mL/g liquid to solid ratio, and 5 g FeCl3·6H2O per 100 g of biomass.

Multiple states emerge in the fluid flow with certain or sudden external interference. In this paper, multiple solutions of the velocity and temperature distributions of power-law fluids are found when the fluid is flowing through a viscous sheet with suction or blowing. By coupling the sheet dynamics with the surrounding fluid equations by the stress balance, the investigation results shed some light on many engineering applications of flow on various soft surfaces, for example, the synthetic plastics. The present research considers the nonuniformity of the mass suction or blowing effects, which is connected with both the stretching velocity and the thickness of the sheet. A similar transformation is adopted to transform the boundary layer equations into a series of ordinary differential equations, and multiple solutions are obtained. The existence of similar solutions has some limitations. The multiple solutions of the friction coefficient and the generalized Nusselt number affected by the power-law index n and the suction/blowing rate fw are shown, and we also discuss the influence of the generalized Prandtl number Npr and the Eckert number Ec on the velocity and temperature distributions.