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Abstract Background Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. Methods We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan–Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. Results The TSR cutoff was identified to be − 6.6%. Median PFS and OS were longer in the group with a TSR − 6.6%. Brain metastasis-free survival was better in the group with a TSR

Abstract Over the last decade, a number of clinical trials have reported effects of chronic treatment with intranasal oxytocin on autistic symptoms but with inconsistent findings. Autism is a heterogeneous disorder and one factor which may influence treatment outcome is whether a subtype of individuals is more sensitive to oxytocin. In a recent cross-over trial on 41 young autistic children we reported that 44% showed a reliable improvement in clinical symptoms (Autism Diagnostic Observation Schedule, ADOS-2) after a placebo-controlled, 6-week intranasal oxytocin intervention where treatment was given every other day followed by a period of positive social interaction. In the current re-assessment of the data, we used an unsupervised data-driven cluster analysis approach to identify autism subtypes using 23 different demographic, social subtype, endocrine, eye-tracking and clinical symptom measures taken before treatment and this revealed an optimum of two different subtypes. We then assessed the proportion of identified responders to oxytocin and found that while 61.5% of one subtype included responders only 13.3% of the other did so. During the placebo phase there was no difference between the two subtypes for the small proportion of responders (19.2% vs 6.7%). This oxytocin-sensitive subtype also showed overall significant post-treatment clinical and eye-tracking measure changes. The oxytocin-sensitive subtype was primarily characterized at baseline by lower initial clinical severity (ADOS-2) and greater interest in the eye-region of emotional faces. These features alone were nearly as efficient in identifying the two subtypes as all 23 baseline measures and this easy-to-conduct approach may help rapidly and objectively screen for oxytocin responders. Future clinical trials using oxytocin interventions may therefore achieve greater success by focusing on children with this specific autism subtype and help develop individualized oxytocin intervention.

Abstract The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This differentiation process plays a crucial role in bone formation and homeostasis and is regulated by two intricate processes: cell signal transduction and transcriptional gene expression. Various essential cell signaling pathways, including Wnt, BMP, TGF-β, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, and Piezo1/2, play a critical role in facilitating osteoblast differentiation, bone formation, and bone homeostasis. Key transcriptional factors in this differentiation process include Runx2, Cbfβ, Runx1, Osterix, ATF4, SATB2, and TAZ/YAP. Furthermore, a diverse array of epigenetic factors also plays critical roles in osteoblast differentiation, bone formation, and homeostasis at the transcriptional level. This review provides an overview of the latest developments and current comprehension concerning the pathways of cell signaling, regulation of hormones, and transcriptional regulation of genes involved in the commitment and differentiation of osteoblast lineage, as well as in bone formation and maintenance of homeostasis. The paper also reviews epigenetic regulation of osteoblast differentiation via mechanisms, such as histone and DNA modifications. Additionally, we summarize the latest developments in osteoblast biology spurred by recent advancements in various modern technologies and bioinformatics. By synthesizing these insights into a comprehensive understanding of osteoblast differentiation, this review provides further clarification of the mechanisms underlying osteoblast lineage commitment, differentiation, and bone formation, and highlights potential new therapeutic applications for the treatment of bone diseases.

Abstract Background Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth. Method Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women’s history of spontaneous abortion and stillbirth were investigated by logistic regression. Results 7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% [CI, Confidence Interval] 1.10–2.10), 1.50 (95% CI 1.07–2.09) and 1.68 (95% CI 1.21–2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12–4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives’ history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01–3.26) and 1.83 (95% CI 1.03–3.25), respectively. Conclusion Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.

Abstract The TGF-β1/Smad3-signaling pathway and gender differences were investigated in alcoholic liver fibrosis. Mice were divided into female normal, female model, male normal, and male model groups. Liver injury and fibrosis were assessed using histopathology and serology. Western blotting was performed to analyze the expression of relevant factors. HSC-T6 cells were divided into estradiol + saline, estradiol + ethanol, testosterone + saline, and testosterone + ethanol groups, and similar assessments were conducted in vitro. Compared with the female model group, the male model group exhibited significantly increased GPT, GOT, TNF-α, IL-6, and testosterone levels, fibrosis rate, and TGF-β1, Smad3, and PCNA expression, and significantly decreased estradiol levels and Caspase-3 expression. The apoptosis rate was higher in the estradiol + ethanol group than in the testosterone + ethanol group, although the testosterone + ethanol group exhibited significantly increased TNF-α, IL-6, Collagen-I, α-SMA, TGF-β1, Smad3, and PCNA expression, and significantly decreased Caspase-3 expression. Alcoholic liver fibrosis showed significant gender differences associated with the TGF-β1/Smad3-signaling pathway.

As the most common degenerative joint disease, osteoarthritis (OA) contributes significantly to pain and disability during aging. Several genes of interest involved in articular cartilage damage in OA have been identified. However, the direct causes of OA are poorly understood. Evaluating the public human RNA-seq dataset showed that CBFB (subunit of a heterodimeric Cbfβ/Runx1, Runx2, or Runx3 complex) expression is decreased in the cartilage of patients with OA. Here, we found that the chondrocyte-specific deletion of Cbfb in tamoxifen-induced Cbfbf/f;Col2a1-CreERT mice caused a spontaneous OA phenotype, worn articular cartilage, increased inflammation, and osteophytes. RNA-sequencing analysis showed that Cbfβ deficiency in articular cartilage resulted in reduced cartilage regeneration, increased canonical Wnt signaling and inflammatory response, and decreased Hippo/Yap signaling and Tgfβ signaling. Immunostaining and western blot validated these RNA-seq analysis results. ACLT surgery-induced OA decreased Cbfβ and Yap expression and increased active β-catenin expression in articular cartilage, while local AAV-mediated Cbfb overexpression promoted Yap expression and diminished active β-catenin expression in OA lesions. Remarkably, AAV-mediated Cbfb overexpression in knee joints of mice with OA showed the significant protective effect of Cbfβ on articular cartilage in the ACLT OA mouse model. Overall, this study, using loss-of-function and gain-of-function approaches, uncovered that low expression of Cbfβ may be the cause of OA. Moreover, Local admission of Cbfb may rescue and protect OA through decreasing Wnt/β-catenin signaling, and increasing Hippo/Yap signaling and Tgfβ/Smad2/3 signaling in OA articular cartilage, indicating that local Cbfb overexpression could be an effective strategy for treatment of OA.

Abstract Outcomes of past decisions profoundly shape our behavior. However, choice-outcome associations can become volatile and adaption to such changes is of importance. The present study combines pharmaco-electroencephalography with computational modeling to examine whether intranasal oxytocin can modulate reinforcement learning under a volatile vs. a stable association. Results show that oxytocin increases choice accuracy independent of learning context, which is paralleled by a larger N2pc and a smaller P300. Model-based analyses reveal that while oxytocin promotes learning by accelerating value update of outcomes in the volatile context, in the stable context it does so by improving choice consistency. These findings suggest that oxytocin’s facilitatory effects on learning may be exerted via improving early attentional selection and late neural processing efficiency, although at the computational level oxytocin’s actions are highly adaptive between learning contexts. Our findings provide proof of concept for oxytocin’s therapeutic potential in mental disorders with adaptive learning dysfunction.

Abstract Preservatives are essential components in cosmetic products, but their safety issues have attracted widespread attention. There is an urgent need for safe and effective alternatives. Antimicrobial peptides (AMPs) are part of the innate immune system and have potent antimicrobial properties. Using machine learning-assisted rational design, we obtained a novel antibacterial peptide, IK-16-1, with significant antibacterial activity and maintaining safety based on β-defensins. IK-16-1 has broad-spectrum antimicrobial properties against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, and has no haemolytic activity. The use of IK-16-1 holds promise in the cosmetics industry, since it can serve as a preservative synergist to reduce the amount of other preservatives in cosmetics. This study verified the feasibility of combining computational design with artificial intelligence prediction to design AMPs, achieving rapid screening and reducing development costs.

BackgroundMobile phone addiction has adverse influences on the physical and mental health of college students. However, few studies shed light on the effect of fear of missing out on mobile phone addiction and the underlying mechanisms among college students.MethodsTo explore their associations, the present study used the Fear of Missing Out Scales (FoMOS), Loneliness Scale (USL-8), Mobile Phone Addiction Index Scale (MPAI), and Depression-Anxiety-Stress Questionnaire (DASS-21) to investigate 750 college students.ResultsThe results suggested that fear of missing out significantly positively predicted mobile phone addiction. This direct effect could be mediated by depression, and the indirect effect of fear of missing out on mobile phone addiction could be moderated by loneliness. Specifically, the indirect effect was stronger for students with high levels of loneliness.ConclusionThis study provides a theoretical basis for developing future interventions for mobile phone addiction in higher education students.

Parent-child shared experiences has an important influence on social development in children although contributions of mothers and fathers may differ. Neural synchronicity occurs between mothers and fathers and their children during social interactions but it is unclear whether they differ in this respect. We used data from simultaneous fNIRS hyperscanning in mothers (n = 33) and fathers (n = 29) and their children (3–4 years) to determine different patterns and strengths of neural synchronization in the frontal cortex during co-viewing of videos or free-play. Mothers showed greater synchrony with child than fathers during passive viewing of videos and the synchronization was positively associated with video complexity and negatively associated with parental stress. During play interactions, mothers showed more controlling behaviors over their child and greater evidence for joint gaze and joint imitation play with child whereas fathers spent more time gazing at other things. In addition, different aspects of child communication promoted neural synchrony between mothers and fathers and child during active play interactions. Overall, our findings indicate greater neural and behavioral synchrony between mothers than fathers and young children during passive or active shared experiences, although for both it was weakened by parental distress and child difficulty.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine carcinoma (HGNEC) accounting for 3% of primary lung cancer, and characterized by strong invasion, high heterogeneity, and extremely poor prognosis. At present, the diagnosis and treatment of LCNEC remains controversial and refer to therapeutic strategy of small cell lung cancer (SCLC), lacking precise therapy. Recently, the genetic analysis and clinical trials of LCNEC gradually emerged, providing more evidence for precise diagnosis and treatment. Here, we review the diagnosis, molecular characteristics, and treatment of LCNEC based on the existing research and frontier progress to provide a potential direction for future diagnosis and treatment of LCNEC.

Abstract Aim This study aimed to explore whether the addition of sarcopenia and visceral adiposity could improve the accuracy of model predicting progression-free survival (PFS) in hepatocellular carcinoma (HCC). Methods In total, 394 patients with HCC from five hospitals were divided into the training and external validation datasets. Patients were initially treated by liver resection or transarterial chemoembolization. We evaluated adipose and skeletal muscle using preoperative computed tomography imaging and then constructed three predictive models, including metabolic (ModelMA), clinical–imaging (ModelCI), and combined (ModelMA−CI) models. Their discrimination, calibration, and decision curves were compared, to identify the best model. Nomogram and subgroup analysis was performed for the best model. Results ModelMA−CI containing sarcopenia and visceral adiposity had good discrimination and calibrations (integrate area under the curve for PFS was 0.708 in the training dataset and 0.706 in the validation dataset). ModelMA−CI had better accuracy than ModelCI and ModelMA. The performance of ModelMA−CI was not affected by treatments or disease stages. The high-risk subgroup (scored > 198) had a significantly shorter PFS (p

Abstract Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.

BackgroundArylsulfatase D (ARSD) belongs to the sulfatase family and plays a crucial role in maintaining the proper structure of bone and cartilage matrix. Although several researches have revealed the functions of ARSD in tumor progression, the prognostic value of ARSD in glioma and the related mechanisms have not been fully investigated.MethodsWe performed a pan-cancer analysis of ARSD, and investigated the relationship between expression of ARSD and overall survival (OS) in multiple glioma datasets. ROC curves and nomograms were created to investigate the predictive capacity of ARSD. Immune and analysis were conducted to investigate the mechanisms underlying the roles of ARSD in glioma. Glioma tissue samples were collected to verify the expression of ARSD in glioma, while the functions of ARSD were explored using cell experiment. M2 macrophage infiltration assay was used to determine the relation between ARSD and tumor immune microenvironment.ResultsSurvival analysis indicated that individuals with high ARSD expression in glioma had a shorter survival time. Cox analysis showed that ARSD had a good ability for predicting prognosis in glioma. Immune analysis suggested that ARSD could regulate immune cell infiltration and affect the Cancer-Immunity Cycle to create an immunosuppressive environment. Combined with cell experiment and bioinformatic analysis, we found that ARSD can promote glioma progression through regulation of JAK2/STAT3 pathway and M2 macrophage infiltration.ConclusionOur study found that ARSD can promote glioma development by regulating immune microenvironment and JAK2/STAT3 signaling pathway, which provided a potential therapy target for glioma treatment.

OBJECTIVES This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.

Long intergenic non-protein coding RNA 1547 (LINC01547) presents a notable relationship with prognosis in patients with ovarian cancer. Herein, we examined the expression of LINC01547 in non-small cell lung cancer (NSCLC) to ascertain its clinical significance. We also explored the detailed functions of LINC01547 in regulating the aggressive phenotype of NSCLC and the molecular mechanism of action underlying its carcinogenic activities events in NSCLC. Furthermore, we applied the data acquired from the tissue specimens and the Cancer Genome Atlas (TCGA) database to analyze the level of LINC01547 in NSCLC and conducted functional assays to address the regulatory effect of LINC01547. Further, we examined the mechanistic interaction among LINC01547, microRNA-195-5p (miR-195-5p), and homeobox C8 (HOXC8) using bioinformatics prediction and luciferase reporter assay. LINC01547 was noticeably overexpressed, as affirmed by data from TCGA and our own cohort; moreover, poor prognosis was associated with increased LINC01547 levels in patients with NSCLC. LINC01547 regulates cell proliferation, colony-forming, migration, and invasion, and its absence produced tumor-repressing effects in NSCLC. Mechanistically, as a competitive endogenous RNA, LINC01547 decoyed miR-195-5p and consequently resulted in the overexpression of HOXC8 in NSCLC cells. Using rescue experiments, we found that the regulatory activities of LINC01547 deficient in repressing the malignant properties of NSCLC cells could be counteracted by hindering miR-195-5p or overexpressing HOXC8. Conclusively, LINC01547 serves as a crucial component to worsen the oncogenicity of NSCLC cells by controlling the miR-195-5p/HOXC8 axis. Thus, the newly identified competing endogenous RNA pathway may potentially be an attractive therapeutic for NSCLC management.

The mirror neuron system (MNS), including the inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and superior temporal sulcus (STS) plays an important role in action representation and imitation and may be dysfunctional in autism spectrum disorder (ASD). However, it's not clear how these three regions respond and interact during the imitation of different basic facial expressions and whether the pattern of responses is influenced by autistic traits. Thus, we conducted a natural facial expression (happiness, angry, sadness and fear) imitation task in 100 healthy male subjects where expression intensity was measured using facial emotion recognition software (FaceReader) and MNS responses were recorded using functional near-infrared spectroscopy (fNIRS). Autistic traits were measured using the Autism Spectrum Quotient questionnaire. Results showed that imitation of happy expressions produced the highest expression intensity but a small deactivation in MNS responses, suggesting a lower processing requirement compared to other expressions. A cosine similarity analysis indicated a distinct pattern of MNS responses during imitation of each facial expression with functional intra-hemispheric connectivity between the left IPL and left STS being significantly higher during happy compared to other expressions, while inter-hemispheric connectivity between the left and right IPL differed between imitation of fearful and sad expressions. Furthermore, functional connectivity changes during imitation of each different expression could reliably predict autistic trait scores. Overall, the results provide evidence for distinct patterns of functional connectivity changes between MNS regions during imitation of different emotions which are also associated with autistic traits.

Missing wind speed data are mainly caused by harsh weather, wind turbine failures, and data transmission errors, which have adverse effects on the performance of wind power forecasting, power curve modeling, and energy assessment. Inspired by context encoders (CE), this paper proposes an improved context encoder network (ICE) for missing wind speed data reconstruction. An auto-encoder architecture with multiple one-dimensional convolutional layers is established for data generation. During network training, a joint loss function that includes reconstruction loss and adversarial loss is presented to obtain the stable and near-real reconstructed wind speed data. We add an Inception layer to the generator network to automatically select the appropriate convolutional filters and then recalibrate the channel relationship between feature maps via the squeeze-and-excitation network. At last, this paper uses wind speed data collected from an on-shore wind farm to verify the effectiveness of the proposed network. The results show that the mean absolute error (MAE) and root mean square error (RMSE) of the ICE network in different data missing rates are 0.019–0.021 and 0.021–0.025, respectively. It has the lowest reconstruction errors compared with six typical data reconstruction methods.

The purpose of this study was to explore the intervention effects of mulberry polyphenols on neurobehavioral toxicity induced by nonylphenol (NP). 70 SPF male SD rats were randomly divided into seven groups: Blank control group (corn oil+saline), Mulberry control group [corn oil+mulberry crude extract (MCE)], NP exposure group (NP+saline), mulberry group (NP+MCE), anthocyanin group (NP+anthocyanin), resveratrol group (NP+resveratrol), combined group (NP+anthocyanin+resveratrol). The gavage amount of MCE was calculated according to 120 mg/kg·bw polyphenol content, and the anthocyanin and resveratrol content corresponded to the content in MCE. Open field test (OFT) and elevated plus maze (EPM) were used to evaluate the intervention effects of mulberry polyphenols on neurobehavioral toxicity of NP, and the levels of thyroxine (FT3, FT4), thyroid-stimulating hormone (TSH) and deiodinase (DIO1, DIO2, DIO3) were measured. The results showed that compared with NP group, all four intervention groups had varying degrees of intervention effects on the decrease of body weight growth rate, food utilization rate and organ coefficient of rats induced by NP (P

Abstract Background The prevalence of infectious diseases remains one of the major challenges faced by the Chinese health sector. Policymakers have a tremendous interest in investigating the spatiotemporal epidemiology of infectious diseases. We aimed to review the small-scale (city level, county level, or below) spatiotemporal epidemiology of notifiable infectious diseases in China through a systematic review, thus summarizing the evidence to facilitate more effective prevention and control of the diseases. Methods We searched four English language databases (PubMed, EMBASE, Cochrane Library, and Web of Science) and three Chinese databases (CNKI, WanFang, and SinoMed), for studies published between January 1, 2004 (the year in which China’s Internet-based disease reporting system was established) and December 31, 2021. Eligible works were small-scale spatial or spatiotemporal studies focusing on at least one notifiable infectious disease, with the entire territory of mainland China as the study area. Two independent reviewers completed the review process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results A total of 18,195 articles were identified, with 71 eligible for inclusion, focusing on 22 diseases. Thirty-one studies (43.66%) were analyzed using city-level data, 34 (47.89%) were analyzed using county-level data, and six (8.45%) used community or individual data. Approximately four-fifths (80.28%) of the studies visualized incidence using rate maps. Of these, 76.06% employed various spatial clustering methods to explore the spatial variations in the burden, with Moran’s I statistic being the most common. Of the studies, 40.85% explored risk factors, in which the geographically weighted regression model was the most commonly used method. Climate, socioeconomic factors, and population density were the three most considered factors. Conclusions Small-scale spatiotemporal epidemiology has been applied in studies on notifiable infectious diseases in China, involving spatiotemporal distribution and risk factors. Health authorities should improve prevention strategies and clarify the direction of future work in the field of infectious disease research in China.

BackgroundAdverse childhood experiences (ACEs) are associated with higher depressive risks in adulthood. Whether respondents’ ACEs are associated with their own depressive symptoms in adulthood and whether this association extends to their spouses’ depressive symptoms remain unexplored.MethodsData were from China Health and Retirement Longitudinal Study (CHARLS), the Health and Retirement Study (HRS), and the Survey of Health, Ageing and Retirement in Europe (SHARE). ACEs were categorized into overall, intra-familial, and extra-familial ACEs. Correlations of couples’ ACEs were calculated using Cramer’s V and partial Spearman’s correlation. Associations of respondents’ ACEs with spousal depressive symptoms were assessed using logistic regression, and mediation analyses were conducted to explore the mediating role of respondents’ depressive symptoms.ResultsSignificant associations between husbands’ ACEs and wives’ depressive symptoms, with odds ratios (ORs) and 95% confidence intervals (CIs) of 2.09 (1.36–3.22) for 4 or more ACEs in CHARLS, and 1.25 (1.06–1.48) and 1.38 (1.06–1.79) for 2 or more ACEs in HRS and SHARE. However, wives’ ACEs were associated with husbands’ depressive symptoms only in CHARLS and SHARE. Findings in intra-familial and extra-familial ACEs were consistent with our main results. Additionally, respondents’ depressive symptoms mediated more than 20% of the effect of respondents’ ACEs on spousal depressive symptoms.ConclusionWe found that ACEs were significantly correlated between couples. Respondents’ ACEs were associated with spousal depressive symptoms, with respondents’ depressive symptoms mediating the association. The bidirectional implications of ACEs on depressive symptoms should be considered within household and effective interventions are warranted.

Objectives: To assess the associations of the triglyceride and glucose (TyG) index with hypertension stages, phenotypes, and their progressions.Methods: The data originated from the China Health and Retirement Longitudinal Study. Multinomial logistic regression investigated the associations of the TyG index with hypertension stages (stage 1, stage 2), phenotypes (isolated systolic hypertension [ISH], isolated diastolic hypertension [IDH], systolic diastolic hypertension [SDH]), their progressions.Results: Compared with the lowest quartile of TyG index, the highest quartile was associated with increased risks of stage 1 hypertension (OR 1.71, 95% CI 1.38–2.13), stage 2 (1.74, 1.27–2.38), ISH (1.66, 1.31–2.11), IDH (2.52, 1.26–5.05), and SDH (1.65, 1.23–2.23). Similar results were found when TyG index was a continuous variable. From 2011 to 2015, a higher baseline TyG index was associated with normotension to stage 1 (per-unit: 1.39, 1.16–1.65), normotension to ISH (per-unit: 1.28, 1.04–1.56), and normotension to IDH (per-unit: 1.94, 1.27–2.97).Conclusion: The TyG index was associated with different hypertension stages, phenotypes, their progressions, and could be served as a surrogate indicator for early hypertension management.

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a newly developed technique involves stimulating the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear, with resulting activation of vagal connections to central and peripheral nervous systems. Increasing evidence indicates that maladaptive neural plasticity may underlie the pathology of several pediatric neurodevelopmental and psychiatric disorders, such as autism spectrum disorder, attention deficit hyperactivity disorder, disruptive behavioral disorder and stress-related disorder. Vagal stimulation may therefore provide a useful intervention for treating maladaptive neural plasticity. In the current review we summarize the current literature primarily on therapeutic use in adults and discuss the prospects of applying taVNS as a therapeutic intervention in specific pediatric neurodevelopmental and other psychiatric disorders. Furthermore, we also briefly discuss factors that would help optimize taVNS protocols in future clinical applications. We conclude from these initial findings that taVNS may be a promising alternative treatment for pediatric disorders which do not respond to other interventions.

BackgroundIn China, numerous people still rely on solid fuel for household use. To date, the association between household solid fuel use and functional disability, and what benefit reducing household solid fuel usage could bring at the population level to China remain unclear.MethodData were from the China Health and Retirement Longitudinal Study. Household fuel was classified as clean or solid for cooking or heating. Functional disability was defined as difficulties in any item of activities of daily living (ADL) or instrumental activities of daily living (IADL). The associations of household fuel use in 2011 and its transitions between 2011 and 2013 with subsequent ADL or IADL disability were assessed with Cox proportional-hazards models. The number of events prevented in a population (NEPP) was generated to estimate how many functionally disabled patients could be prevented by reducing solid fuel usage.ResultsA total of 6,216 and 9,716 participants without prior ADL or IADL disability in 2011 were included. Solid (vs. clean) fuel users were more likely to develop ADL and IADL disability, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.37 (1.28~1.45) and 1.38 (1.31~1.46) for using both solid cooking and heating fuel. Furthermore, participants that switched heating fuel from solid to clean (vs. keep solid) were about 20% less likely to develop functional disability. Cooking fuel use switching from solid to clean (vs. keep solid) was also negatively associated with IADL disability (HR = 0.84, 95% CI 0.74~0.96). Over the next 7 years, raising clean fuel usage to 80% could prevent about 4.9 million ADL disability and 2.6 million IADL disability among Chinese aged 45 and older.ConclusionHousehold solid fuel use was a risk factor for functional disability. Reducing solid fuel usage could help reduce the burden of functional disability in the current aging society of China.

Dentin regeneration is the preferred method used to preserve dental pulp vitality after pulp exposure due to caries. Red light-emitting diode irradiation (LEDI), which is based on photobiomodulation (PBM), has been used to promote hard-tissue regeneration. However, the underlying mechanism still needs elucidation. This study aimed to explore the mechanism involved in red LEDI affecting dentin regeneration. Alizarin red S (ARS) staining revealed that red LEDI induced mineralization of human dental pulp cells (HDPCs) in vitro. We further distinguished the cell proliferation (0–6 d), differentiation (6–12 d), and mineralization (12–18 d) of HDPCs in vitro and treated cells either with or without red LEDI in each stage. The results showed that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, increased mineralized nodule formation around HDPCs. Western blot also indicated that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, upregulated the expression of dentin matrix marker proteins (dentin sialophosphoprotein, DSPP; dentin matrix protein 1, DMP1; osteopontin, OPN) and an intracellular secretory vesicle marker protein (lysosomal-associated membrane protein 1, LAMP1). Therefore, the red LEDI might enhance the matrix vesicle secretion of HDPCs. On the molecular level, red LEDI enhanced mineralization by activating the mitogen-activated protein kinase (MAPK) signaling pathways (ERK and P38). ERK and P38 inhibition reduced mineralized nodule formation and the expression of relevant marker proteins. In summary, red LEDI enhanced the mineralization of HDPCs by functioning to produce a positive effect in the mineralization stage in vitro.

Human skeletal development is continuous and staged, and different stages have various morphological characteristics. Therefore, bone age assessment (BAA) can accurately reflect the individual’s growth and development level and maturity. Clinical BAA is time consuming, highly subjective, and lacks consistency. Deep learning has made considerable progress in BAA in recent years by effectively extracting deep features. Most studies use neural networks to extract global information from input images. However, clinical radiologists are highly concerned about the ossification degree in some specific regions of the hand bones. This paper proposes a two-stage convolutional transformer network to improve the accuracy of BAA. Combined with object detection and transformer, the first stage mimics the bone age reading process of the pediatrician, extracts the hand bone region of interest (ROI) in real time using YOLOv5, and proposes hand bone posture alignment. In addition, the previous information encoding of biological sex is integrated into the feature map to replace the position token in the transformer. The second stage extracts features within the ROI by window attention, interacts between different ROIs by shifting the window attention to extract hidden feature information, and penalizes the evaluation results using a hybrid loss function to ensure its stability and accuracy. The proposed method is evaluated on the data from the Pediatric Bone Age Challenge organized by the Radiological Society of North America (RSNA). The experimental results show that the proposed method achieves a mean absolute error (MAE) of 6.22 and 4.585 months on the validation and testing sets, respectively, and the cumulative accuracy within 6 and 12 months reach 71% and 96%, respectively, which is comparable to the state of the art, markedly reducing the clinical workload and realizing rapid, automatic, and high-precision assessment.

Osteoblasts must acquire a considerable capacity for folding unfolded and misfolded proteins (MPs) to produce large amounts of extracellular matrix proteins and maintain bone homeostasis. MP accumulation contributes to cellular apoptosis and bone disorders. Photobiomodulation therapy has been used to treat bone diseases, but the effects of decreasing MPs with photobiomodulation remain unclear. In this study, we explored the efficacy of 625 nm light-emitting diode irradiation (LEDI) to reduce MPs in tunicamycin (TM) induced-MC3T3-E1 cells. Binding immunoglobulin protein (BiP), an adenosine triphosphate (ATP)-dependent chaperone, is used to evaluate the capacity of folding MPs. The results revealed that pretreatment with 625 nm LEDI (Pre-IR) induced reactive oxygen species (ROS) production, leading to the increased chaperone BiP through the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1s (XBP-1s) pathway, and then restoration of collagen type I (COL-I) and osteopontin (OPN) expression relieving cell apoptosis. Furthermore, the translocation of BiP into the endoplasmic reticulum (ER) lumen might be followed by a high level of ATP production. Taken together, these results suggest that Pre-IR could be beneficial to prevent MP accumulation through ROS and ATP in TM-induced MC3T3-E1cells.

Oral surgery, such as tooth extractions and dental implantations, can cause inflammation in the surrounding tissue, especially in bones. Anti-inflammatory drugs are crucial for pain relief and wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) and light-emitting diode irradiation (LEDI) at 625 nm have been used as therapies to reduce inflammation, which ultimately promotes wound healing. The mechanism of these two methods, however, is different, which possibly makes the combined use of the two approaches effective. Therefore, the efficacy of 625 nm LEDI, NSAIDs, or a combination of both on anti-inflammatory and wound healing effects were analyzed in MC3T3-E1. In this study, piroxicam, ibuprofen, indomethacin, and celecoxib were selected as the NSAIDs. The effect of LEDI at 625 nm was investigated by cell viability, prostaglandin E2 (PGE2) release, and the expression of inflammation-related proteins and cell migration-related proteins were evaluated. Additionally, alkaline phosphatase staining with activity, cell migration assay and BrdU cell proliferation assays were performed. Both LEDI and NSAIDs reduced cyclooxygenase-2 (COX-2) and PGE2. Additionally, LEDI promoted cell migration, proliferation, and bone formation as well, but not by NSAIDs. Thus, a combination of LEDI and NSAIDs can benefits the cells in inflammation, which provides upturn strategies for bone healing after tooth extraction.

Abstract Power load parameters are one of the most important parameters for power system model. The load has the characteristics of time‐varying, diversity and non‐linearity. Therefore, obtaining the load parameters accurately is crucial to the safe and stable operation of the power system. The research in this paper is based on the synthesis load model which takes into account the impedance of distribution network. The multi‐fault curves identification method and chaos‐whale algorithm are adopted to improve the accuracy and practicability of load parameter identification. First, the algorithm proposed in this paper applies chaos algorithm to whale algorithm, and uses the randomness and ergodicity of chaos algorithm to make up for the shortcomings of the whale algorithm that the solution accuracy is not high and it is easy to fall into local optimum. Secondly, the identification method of multi‐fault curves is to select several different faults for parameter identification, and the average value of each group of results obtained is regarded as the final result. Then compared with single curve identification, the multi‐fault curves method is more superior. Finally, the accuracy of the results is verified by other faults. Simulation results show that the method is reliable to a certain extent.

BackgroundCA-125 is a clinical biomarker with predictive effect on the prognosis of different cancers. Numerous clinical trials have been conducted to investigate the possibility of using the pretreatment level of CA-125 to predict the prognosis of epithelial ovarian cancer (EOC). However, its value in predicting prognosis remains controversial. The purpose of this meta-analysis was to assess the predictive value of pretreatment CA-125 levels for prognosis in EOC patients.MethodsWe searched the EMBASE, Cochrane library, PubMed and Web of Science databases for studies published up to 3 December 2021, according to specific inclusion and exclusion criteria. The clinical studies that were included investigated the relationship between pretreatment CA-125 levels and ovarian cancer prognosis. Combined hazard ratios (HR) of overall survival (OS) and progression-free survival (PFS) reported in the studies were compared and analyzed using fixed-effects/random-effects models. Sensitivity analysis was used to assess study stability, while Egger’s and Begg’s tests were used to assess publication bias.ResultsThis meta-analysis included 23 studies published in 2004 - 2021 with a total of 10,594 EOC patients. Comprehensive analysis demonstrated that the serum level of CA-125 before treatment was significantly correlated with overall survival (OS: HR=1.62, 95%CI=1.270-2.060, p

Automatic segmentation of the cancerous esophagus in computed tomography (CT) images is a computer-assisted method that can improve the efficiency of the diagnosis and treatment. Due to the diversity of the cancer stage and location, the anatomical structure of the cancerous esophagus is various. Moreover, the low contrast against surrounding tissues leads to a blurry boundary of the cancerous esophagus. Therefore, existing segmentation networks cannot achieve satisfactory results in automatic segmentation of the cancerous esophagus. In this article, we propose a novel 2.5D segmentation network named Eso-Net for the cancerous esophagus based on an encoder-decoder architecture. A 3D enhancement filter called Multi-Structure Response Filter (MSRF) is designed to extract 3D structural information as prior knowledge. Furthermore, dilated convolutions and residual connections are employed in the convolutional blocks of Eso-Net for multi-scale feature learning. With 3D structural priors, Prior Attention Modules (PAM) are incorporated into the network to facilitate the transmission of relevant spatial information. The experiments are conducted on the dataset from 30 esophageal cancer patients, and we report an 84.839% dice similarity coefficient, an 85.955% precision, an 83.752% sensitivity, and a 2.583mm Hausdorff distance. The experimental results demonstrate that the proposed method outperforms other existing segmentation networks in this task and can effectively assist doctors in the diagnosis and treatment of esophageal cancer.

This paper focuses on domain adaptation in a semantic segmentation task. Traditional methods regard the source domain and the target domain as a whole, and the image matching is determined by random seeds, leading to a low degree of consistency matching between domains and interfering with the reduction in the domain gap. Therefore, we designed a two-step, three-level cascaded domain consistency matching strategy—co-occurrence-based consistency matching (COCM)—in which the two steps are: Step 1, in which we design a matching strategy from the perspective of category existence and filter the sub-image set with the highest degree of matching from the image of the whole source domain, and Step 2, in which, from the perspective of spatial existence, we propose a method of measuring the PIOU score to quantitatively evaluate the spatial matching of co-occurring categories in the sub-image set and select the best-matching source image. The three levels mean that in order to improve the importance of low-frequency categories in the matching process, we divide the categories into three levels according to the frequency of co-occurrences between domains; these three levels are the head, middle, and tail levels, and priority is given to matching tail categories. The proposed COCM maximizes the category-level consistency between the domains and has been proven to be effective in reducing the domain gap while being lightweight. The experimental results on general datasets can be compared with those of state-of-the-art (SOTA) methods.

The application of biochar can affect soil properties and retention of fertilizer nitrogen, but its effects and mechanism on the retention capacity of different forms of nitrogen in soils are still uncertain. In this study, an indoor soil column leaching experiment was conducted using vegetable soil samples with 3% rice husk biochar by mass prepared at 450 °C by pyrolysis and 150 mg N/kg 15N-labeled urea. Adding biochar increased the soil pH, thus alleviating soil acidification caused by fertilizer nitrogen application. It also increased the content of soil organic carbon, total nitrogen and available phosphorus while decreasing that of NH4+-N and NOX−-N(NO3−-Nand NO2−-N) in soils. NOX−-N was the predominant form in the leachate of all treatments, accounting for 63.15–87.90% of the total N loss. Compared to the urea-alone application (the N treatment), incorporating biochar and urea (the RBN treatment) significantly reduced total N and NOX−-N loss by 19.99% and 25.95%, respectively, while showing slight effects on NH4+-N loss. The 15N results show that fertilizer N retention in soil increased by 13.67%, while inorganic 15N leaching decreased by 25.97% after the biochar addition, compared to that in the N treatment. The RBN treatment increased fertilizer N losses in other ways (e.g., organic N leaching, ammonia and NOx volatilization) by 21.72%. Effects of biochar application on other N losses need to be further investigated. Biochar application can reduce the leaching of inorganic 15N and improve fertilizer N retention in the soil. Thus, the potential risk of fertilizer N on the quality of water bodies can be reduced.

Illumina is the leading sequencing platform in the next-generation sequencing (NGS) market globally. In recent years, MGI Tech has presented a series of new sequencers, including DNBSEQ-T7, MGISEQ-2000 and MGISEQ-200. As a complex application of NGS, cancer-detecting panels pose increasing demands for the high accuracy and sensitivity of sequencing and data analysis. In this study, we used the same capture DNA libraries constructed based on the Illumina protocol to evaluate the performance of the Illumina Nextseq500 and MGISEQ-2000 sequencing platforms. We found that the two platforms had high consistency in the results of hotspot mutation analysis; more importantly, we found that there was a significant loss of fragments in the 101–133 bp size range on the MGISEQ-2000 sequencing platform for Illumina libraries, but not for the capture DNA libraries prepared based on the MGISEQ protocol. This phenomenon may indicate fragment selection or low fragment ligation efficiency during the DNA circularization step, which is a unique step of the MGISEQ-2000 sequence platform. In conclusion, these different sequencing libraries and corresponding sequencing platforms are compatible with each other, but protocol and platform selection need to be carefully evaluated in combination with research purpose.

Dimethoxyethyl phthalate (DMEP) is an environmental endocrine disruptor. However, research into the underlying mechanisms of DMEP mitochondrial toxicity is still in its infancy. We therefore expect to understand whether DMEP induced mitochondrial damage in HepG2 cells and the associated signaling pathways. DMEP (0.125, 0.25, 0.5, 1 and 2 mM) exposure for 48 h induced a notable increment in reactive oxygen species (ROS), malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate transaminase (AST) and 8-hydroxydeoxyguanosine (8-OHdG) in hepG2 cells, resulting in cellular oxidative stress. Low doses of DMEP upregulated nuclear factor E2-related factor 2 (Nrf2) and downstream protein haeme oxygenase-1 (HO-1) levels and high doses down-regulated their levels. Nrf2 levels increased after ROS scavenging by N-acetyl-L-cysteine (NAC), which indicated that the Nrf2 pathway may be affected by oxidative stress. We also found that DMEP decreased ATP content, mitochondrial copy number (mtDNA), translocase of the outer membrane subunit 20 (TOM20) expression, mitochondria-encoded genes CO1, CO2, CO3, ATP6, ATP8 expression, inhibited mitochondrial biogenesis pathway, down-regulated sirtuin 1(SIRT1), PPAR gamma co-activator 1 alpha (PGC-1α), Nuclear respiratory factor 1(Nrf1), Mitochondrial transcription factor A (TFAM) content and activated PINK1/Parkin autophagy pathway. DMEP also activated the mitochondrial apoptotic pathway, causing cytochrome c cytoplasmic translocation and caspase 3 cleavage. What’s more, DMEP activated the Nuclear factor-κB (NF-κB) pathway and levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly upregulated, causing an inflammatory response. In summary, DMEP can cause inflammatory response and oxidative stress in HepG2 cells, inhibited the Nrf2 pathway and mitochondrial biogenesis, and induced autophagy and apoptosis. And oxidative stress at least partially affected the Nrf2 pathway and mitochondrial biogenesis SIRT1/PGC-1α pathway.

No consensus has yet been reached on the associations of lipid variability (LV) with cardiovascular diseases (CVDs) and all-cause mortality. We aimed to quantify the associations of different types and metrics of LV with CVDs and all-cause mortality. PubMed, Medline, and Embase databases were searched for eligible cohort studies published until 14 December 2021. Lipids included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Metrics of variability included standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM). The primary outcomes were CVDs and all-cause mortality. Random-effects meta-analysis was used to generate a summary of the relative risks (SRRs). Sources of heterogeneity were explored by subgroup analysis and meta-regression. A total of 11 articles based on seven cohorts were included. Participants in the top quartile of TC variability had an increased risk of CVDs (vs. bottom quartile: TC-CV: SRR 1.29, 95% CI 1.15-1.45; TC-SD: 1.28, 1.15–1.43; TC-VIM: 1.26, 1.13–1.41, respectively) and all-cause mortality (vs. bottom quartile: TC-CV: 1.28, 1.15–1.42; TC-SD: 1.32, 1.22–1.44; TC-VIM: 1.32, 1.25–1.40, respectively). Participants in the top quartile of HDL-C variability had an increased risk of CVDs (vs. bottom quartile: HDL-C-CV: 1.11, 1.07–1.15; HDL-C-SD: 1.18, 1.02–1.38; HDL-C-VIM: 1.18, 1.09–1.27, respectively) and all-cause mortality (vs. bottom quartile: HDL-C-CV: 1.29, 1.27–1.31; HDL-C-SD: 1.24, 1.09–1.41; HDL-C-VIM: 1.25, 1.22–1.27, respectively). LDL-C variability was also associated with an increased risk of CVDs (for top vs. bottom quartile; LDL-C-SD: 1.09, 1.02–1.17; LDL-C-VIM: 1.16, 1.02–1.32, respectively) and all-cause mortality (for top vs. bottom quartile; LDL-C-CV: 1.19, 1.04–1.36; LDL-C-SD: 1.17, 1.09–1.26, respectively). The relationships of TG variability with the risk of CVDs and all-cause mortality were inconclusive across different metrics. The effects of SRR became stronger when analyses were restricted to studies that adjusted for lipid-lowering medication and unadjusted for mean lipid levels. These findings indicate that the measurement and surveillance of lipid variability might have important clinical implications for risk assessment of CVDs and all-cause mortality.

The buffeting analysis of an uncertain long-span bridge deck was carried out in this paper. Due to the effect of strong spatial correlation of wind excitation, it should be assumed as partially coherent multiple excitations. The following includes a theoretical formula for the buffeting analysis of a long-span bridge deck with uncertain parameters, which was achieved mainly by a combination of the stochastic pseudo excitation method (SPEM) and response surface method (RSM). The SPEM-RSM was firstly applied to deal with the complicated spectral density function matrix of wind excitation. The buffeting response of the bridge deck was then calculated and verified by the results from the Monte Carlo simulation (MCS). The efficiency and applicability of the hybrid method for strong spatial correlation was proved. After the comparison, the effect of uncertain structural parameters and wind speed on the buffeting performance of the bridge deck were computed. The results showed that the whole uncertainties essentially affected the buffeting response of the deck. The uncertain wind speed played the most significant role in the vertical and lateral motion of the deck. The joint influences between structural uncertainties and uncertain wind speed further affect the random characteristics of the responses. Finally, the effects of different wind speed and wind angle of attack on the aerodynamic performance of the bridge are examined. The variance of the responses increased with the development of wind speed. The effect of different attack angles on the buffeting responses was significant.

Abstract Evaluation is necessary and informative for processing and applying the precipitation products. However, researchers mainly focus on the statistical indicators of satellite‐based precipitation evaluation over manually determined regions without further considering the geographical information. To reveal the potential connections between geographical features and the error patterns of satellite precipitation estimates, this study focuses on proposing a new perspective for charactering the spatiotemporal patterns of errors in the Integrated Multi‐satellitE Retrievals for global precipitation measurement (GPM; IMERG) based on China Merged Precipitation Analysis over mainland China in the period from 2012 to 2018. We applied a quantitative cluster analysis method to analyze the characteristics of the errors in GPM IMERG based on three geographical features including elevation (Ele), latitude (Lat), and the distance from seashore (DFS). Additionally, the analysis was conducted in both warm and cold seasons to capture the temporal error patterns in IMERG. The results show that: (1) IMERG has the ability to capture spatiotemporal precipitation patterns over mainland China, with relative overestimations mainly over southeastern region; (2) geographical features (Ele, Lat, and DFS) have strong linear relationships with the statistical error indexes (e.g., correlation coefficient) of IMERG; and (3) the spatial patterns of errors in IMERG were automatically determined and demonstrated significant geographical characteristics. Finally, results of this study would provide valuable references for improving the quality of the IMERG over land.

It is very extraordinary for the success of coal mine roadway grouting with the following factors of high early strength, good fluidity, and convenient pumping, but the existing grouting materials make it difficult to achieve the above characteristics at the same time. Therefore, a modified grouting material is developed, which is composed of two kinds of dry materials A and B, which are mixed with water and in equal amounts. The physical and mechanical properties of modified grouting materials under different ratios were tested by laboratory orthogonal test, and the optimal ratio of grouting materials and additives was obtained: (1) the water-cement ratio is 0.8 : 1; (2) base material: the mass ratio of cement, fly ash, bentonite, and water is 1 : 0.3 : 0.1 : 1.44; (3) admixture: the mass ratio of water reducer C, accelerator D, and retarder E is 1.5% : 0.05% : 0.3%. The basic properties of the modified grouting materials were studied from the aspects of slurry flow state, diffusion range, and grouting parameters by using the numerical simulation method, and the reinforcement mechanism of slurry to the broken surrounding rock properties of the roadway was revealed: (1) the grouting pressure is the main factor affecting the slurry diffusion radius; (2) the mechanical properties of the roadway surrounding rock are improved, the plastic zone and deformation of surrounding rock are reduced, and the active support function of the anchor and cable is enhanced through grouting reinforcement; (3) the control effect of the roadway is improved, and the balanced bearing with anchorage structure of the roadway surrounding rock is realized through grouting reinforcement. On this basis, the modified grouting material is applied to roadway repair and reinforcement engineering practice. The field monitoring data show that the production practices were guided by roadway repair and reinforcement technology with the modified grouting material, as the core of the roadway surrounding rock control effect is good, and the modified grouting material has a wide range of application prospects.

With the increase of mining intensity of coal resources, some coal mines in China have gradually entered the deep mining stage. The complexity of the stress environment of the deep rock stratum leads to the difficulty of coal mining. Among them, the control of the deep roadway is one of the bottlenecks restricting the safety mining of the deep coal resources in China. By means of statistical analysis, the factors affecting the stability of the deep roadway were summed up: roadway occurrence environment, driving disturbance, and support means. The mechanical model of the deep roadway was established with the theory of elastic-plastic mechanics, the distribution characteristics of the plastic zone of the roadway were revealed, and the influence laws of lateral pressure coefficient, vertical stress, and support strength on the stability of the roadway were analyzed. Through numerical simulation, the law of stress, displacement and the plastic zone distribution evolution of the deep roadway, the mechanism of horizontal stress, and the mechanism of bolt support on the roadway were studied. On this basis, the safety control strategies to ensure the stability of the deep roadway were put forward: improving the strength of the roof and floor, especially the bearing part of the top angle and the side angle, enhancing the stability of the two sides of the roadway and controlling the floor heave, and making the surrounding rock of the deep roadway release pressure moderately, so as to make the roadway easy to be maintained under the low stress environment. These meaningful references were provided for the exploitation of deep coal resources in China.

The Xiong’an New Area is abundant in geothermal resources due to its unique geological structure. To address whether large-scale deep geothermal exploitation will induce a fault slip, we first determined the initial in situ stress field using shallow (~4000 m) in situ stress measurements from the North China plain. After characterizing the in situ stress field, we analyzed the initial stability of the main active faults in the sedimentary strata of the Rongcheng deep geothermal reservoir based on the Mohr–Coulomb failure criteria. Assuming that this area will be subjected to forty years of continuous fluid injection, we calculated the excess pore pressure in the deep geothermal reservoir and, subsequently, estimated the fault slip potential of the main active faults in this region from 2021 to 2060. Our results indicated that both the in situ stress field in the shallow crust of the Xiong’an New Area and the Middle-Late Pleistocene active faults will initially maintain a stable state. With constant fluid injection for forty years at six geothermal wells in the Rongcheng deep geothermal reservoir, the maximum superposed excess pore pressure at a single well is 18 MPa; this excess pore pressure value impacts the stress state of faults within 8 km of the well location. These pore pressure perturbations heavily impact the F5-10, F5-11, and F9-2 segments of the Rongcheng uplift boundary fault, with FSP values of 92%, 23%, and 47% in 2060, respectively. Porosity exacts little impact on the fault slip potential on the boundary fault segments of F5-10 and F9-2 in the Rongcheng deep geothermal reservoir, while an enhanced permeability can weaken the FSP values for these faults. The predicted maximum moment magnitude of an induced earthquake due to continuous injection of forty years can be up to Mw 5.0 with a 5% fluid loss in the Rongcheng deep geothermal reservoir. Long-term water injection may increase the ambient thermoelastic stress to the point where faults in a critical (or subcritical) stress state become unstable. The results can provide a reference for geothermal development in terms of injection rate and locations of geothermal wells.

The pseudoexcitation method (PEM) can improve efficiency of random vibration analysis. However, for large-sized structures with wide frequency range of response, the workload of calculation is heavy if conventional integration methods, such as trapezoidal integration, are used to combine with the PEM to calculate structural response. In such case, self-adaptive technology is induced to combine with the PEM to form an efficient method for solving random vibration. During calculation, this method can realize the adaptability of random excitation to actual structural response, identify automatically critical frequency intervals of random excitation, and process intelligently the identified critical frequency intervals and noncritical frequency intervals. Based on the identified frequency intervals, Gauss integration is carried out to obtain response results with random characteristics. The computational efficiency and accuracy of PEM-SGI are verified by wind-induced performance of the slender bridge tower. Finally, the influence of damping ratio of the bridge structure and train marshalling on vehicle-bridge coupled system is investigated to further verify the application of the proposed method. Results show that the efficiency of solving random vibration can be improved by the present method.

Particle mixing process is critical for the design and quality control of concrete and composite production. This paper develops an algorithm to simulate the high-shear mixing process of a granular flow containing a high proportion of solid particles mixed in a liquid. DEM is employed to simulate solid particle interactions; whereas SPH is implemented to simulate the liquid particles. The two-way coupling force between SPH and DEM particles is used to evaluate the solid-liquid interaction of a multi-phase flow. Using Darcy’s Law, this paper evaluates the coupling force as a function of local mixture porosity. After the model is verified by two benchmark case studies, i.e., a solid particle moving in a liquid and fluid flowing through a porous medium, this method is applied to a high shear mixing problem of two types of solid particles mixed in a viscous liquid by a four-bladed mixer. A homogeneity metric is introduced to characterize the mixing quality of the particulate mixture. The virtual experiments with the present algorithm show that adding more liquid or increasing liquid viscosity slows down the mixing process for a high solid load mix. Although the solid particles can be mixed well eventually, the liquid distribution is not homogeneous, especially when the viscosity of liquid is low. The present SPH-DEM model is versatile and suitable for virtual experiments of particle mixing process with different blades, solid particle densities and sizes, and liquid binders, and thus can expedite the design and development of concrete materials and particulate composites.

The Integrated Multi-satellitE Retrievals for the Global Precipitation Measurement mission (IMERG) has been widely evaluated. However, most of these studies focus on the ultimate merged satellite-gauge precipitation estimate and neglect the valuable intermediate estimates which directly guide the improvement of the IMERG product. This research aims to identify the error sources of the latest IMERG version 6 by evaluating the intermediate and ultimate precipitation estimates, and further examine the influences of regional topography and surface type on these errors. Results show that among six passive microwave (PMW) sensors, the Microwave Humidity Sounder (MHS) has outstanding comprehensive behavior, and Special Sensor Microwave Imager/Sounder (SSMIS) operates advanced at precipitation detection, while the Sounder for Atmospheric Profiling of Humidity in the Intertropics by Radiometry (SAPHIR) has the worst performance. More precipitation events are detected with larger quantitative uncertainty in low-lying places than in highlands, in urban and water body areas than in other places, and more in coastal areas than in inland regions. Infrared (IR) estimate has worse performance than PMW, and the precipitation detectability of IR is more sensitive to the factors of elevation and the distance to the coast, as larger critical successful index (CSI) over lowlands and coastal areas. PMW morphing and the mixing of PMW and IR algorithms partly reverse the conservative feature of the precipitation detection of PMW and IR estimates, resulting in higher probability of detection (POD) and false alert ratio (FAR). Finally, monthly gauge calibration improves most of the statistical indicators and reduces the influence of elevation and surface type factor on these errors.

Summary: The growth plate (GP) comprising sequentially differentiated cell layers is a critical structure for bone elongation and regeneration. Although several key regulators in GP development have been identified using genetic perturbation, systematic understanding is still limited. Here, we used single-cell RNA-sequencing (RNA-seq) to determine the gene expression profiles of 217 single cells from GPs and developed a bioinformatics pipeline named Sinova to de novo reconstruct physiological GP development in both temporal and spatial high resolution. Our unsupervised model not only confirmed prior knowledge, but also enabled the systematic discovery of genes, potential signal pathways, and surface markers CD9/CD200 to precisely depict development. Sinova further identified the effective combination of transcriptional factors (TFs) that regulates GP maturation, and the result was validated using an in vitro EGFP-Col10a screening system. Our case systematically reconstructed molecular cascades in GP development through single-cell profiling, and the bioinformatics pipeline is applicable to other developmental processes. Video Abstract: : Li et al. have developed an unsupervised clustering approach called Sinova to analyze single-cell RNA-seq data. By using this pipeline to analyze single-cell RNA-seq data from developing GPs in mice, they have generated a spatial and temporal map of the GP and identified molecular networks involved in GP development.

This study investigated heterogeneity in language skills of children with autism and their relationship with different autistic social subtypes. Data from 90 autistic and 30 typically developing children were analyzed. Results showed that autistic social subtypes varied in language skill problems (aloof > passive > active-but-odd). There was a negative association between aloof dimension scores and language performance but positive for the active-but-odd dimension and no association in the passive one. Moreover, aloof dimension score was the main contributor to language performance. A receiver operating characteristic analysis suggested language vocabulary as an additional component in differentiating autistic social subtypes. These findings demonstrate that variations in language skills in autistic children provide additional information for discriminating their social subtype.

Reading self-beliefs, comprising self-concept and self-efficacy, play a pivotal role in shaping students' learning engagement and learning outcomes. However, existing literature on the self-beliefs of school-entry students primarily originates from Western contexts, and the exploration of differences in self-beliefs, engagement in learning, and their impact on reading performance among L1 and L2 learners remains uncharted territory. This dearth of knowledge leaves us questioning whether self-concept and self-efficacy function uniquely in shaping the reading development of L1 and L2 children. Research Findings: By conducting multigroup SEM analysis, this study found no significant differences in self-efficacy or self-concept between L1 and L2 Chinese first-grade students. However, it did reveal distinct patterns in their impact: In L1 students, self-efficacy and self-concept predict learning engagement, with self-concept having a stronger influence on reading performance. Conversely, for L2 students, self-efficacy primarily affects their learning engagement, which indirectly impacts reading performance. Practice or Policy: This study enhances our understanding of different roles of self-beliefs in L1 and L2 learning and offers pedagogical insights for language teaching in countries with both ethnic minority and local populations.

The interaction of SDF-1α (also known as CXCL12) with the CXCR4 receptor plays a critical role in the retention of hematopoietic stem cells (HSCs) in bone marrow. The viral macrophage inflammatory protein-II (vMIP-II), a human herpesvirus-8 (HHV-8)-encoded viral chemokine, can bind the CXCR4 receptor and inhibit endogenous ligand-induced calcium responses and cell migration. Previously, we used the bivalent ligand approach to link synthetically two unnatural D-amino acid peptides derived from the N-terminus of vMIP-II (DV1 and DV3, respectively) to generate a dimeric peptide, DV1-K-(DV3) (also named HC4319), which shows very high affinity for CXCR4. Here, we studied the biological effects of this dimeric peptide, HC4319, and its monomeric counterpart, DV1, on SDF-1α-induced signaling in CXCR4- or CXCR7-transfected Chinese hamster ovary cells and mobilization of hematopoietic progenitor cells (HPCs) in C3H/HeJ mice using an HPC assay. HC4319 and DV1 inhibited significantly the phosphorylation of Akt and Erk, known to be downstream signaling events of CXCR4. This in vivo study in C3H/HeJ mice showed that HC4319 and DV-1 strongly induced rapid mobilization of granulocyte–macrophage colony-forming units (CFUs), erythrocyte burst-forming units, and granulocyte–erythrocyte–monocyte–megakaryocyte CFUs from the bone marrow to the blood. These results provide the first reported experimental evidence that bivalent and D-amino acid peptides derived from the N-terminus of vMIP-II are potent mobilizers of HPCs in C3H/HeJ mice and support the further development of such agents for clinical application.

Root-induced channels are the primary controlling factors for rapid movement of water and solute in forest soils. To explore the effects of root distribution on preferential flow during rainfall events, deciduous (Quercus variabilis BI.) and coniferous forest (Platycladus orientalis (L.) Franco) sites were selected to conduct dual-tracer experiments (Brilliant Blue FCF and Bromide [Br−]). Each plot (1.30 × 1.30 m) was divided into two subplots (0.65 × 1.30 m), and two rainfall simulations (40 mm, large rainfall and 70 mm, extreme rainfall) were conducted in these. Vertical soil profiles (1.00 m × 0.40 m) were excavated, and preferential flow path features were quantified based on digital image analysis. Root (fine and coarse) abundance and Br− concentration were investigated for each soil profile. In deciduous forest, accumulated roots in the upper soil layer induce larger lateral preferential flow as compared to the coniferous forest soil during large rainfall events. Compared with deciduous forest, coniferous forest soil, with higher (horizontal and vertical) spatial variability of preferential flow paths, promotes higher percolation and solute leaching to deeper soil layers during extreme rainfall events. Fine roots, accounting for a larger proportion of total roots (compared to coarse roots), facilitate preferential flow in the 0−40 cm forest soil layer. Overall, our results indicate that the root distribution pattern of different tree species can exert diverse effects on preferential flow in forest soils.