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IntroductionUnderstory removal is frequently used to relieve the renewal pressure on trees and promote the growth capability of trees for maintaining community stability, while the lack of previous study on temperate forests limits our assessment of the effectiveness of this essential management measurement.MethodsIn this study, we calculated the niche characteristics and interspecific association of main understory species and community stability in temperate forests [original broad-leaved Korean pine forest (BKF), Betula platyphylla secondary forest (BF), and Larix gmelinii plantation (LF)] after understory removal for characterizing the resource utilization capacity of the regeneration trees.ResultsDuring the restoration stage, the niche breadth of understory plants with similar habits varied across stands and layers; regeneration tree species with heliophile and semishade occupied a larger niche in BKF and LF, while it was the opposite in LF. Niche overlap among heliophile regeneration trees increased in both BKF and BF, but not in LF. The interspecific association among main species revealed that the distribution of each species was independent and the interspecific association was loose and it varied in different forests and different light-demanding species with regeneration trees. The stability of shrub communities in BF and LF improved whereas that of BKF declined, while that of the herb communities of corresponding forests showed the opposite state.DiscussionOur study demonstrated that the effectiveness of understory removal depends on species’ ecological habits, which enhances the renewal and resource utilization capacity of regeneration tree species in temperate forests and shrub community stability in BF and LF.

ObjectiveGiven the limited evidence on the relationship between the triglyceride-glucose (TyG) index and the risk of prediabetes among young adults, our study aimed to investigate the potential impact of the TyG index on the future development of prediabetes in young individuals.MethodsThis retrospective cohort study included 125,327 healthy adults aged 20 to 45 years. We utilized Cox proportional hazards regression models, combined with cubic spline functions and smooth curve fitting, to assess the relationship between baseline TyG index and the risk of prediabetes among young adults, exploring its non-linear association. A series of sensitivity analyses and subgroup analyses were conducted to ensure the robustness of our findings.ResultsAfter adjusting for covariates, the study found a positive correlation between the TyG index and the risk of prediabetes (HR=1.81, 95%CI: 1.54–2.13, p

BackgroundThe distant metastasis of lung cancer primarily occurs in the bones, liver, brain, and lungs, while the breast is an extremely rare site of metastasis. There is very limited literature on the occurrence of breast metastasis from lung cancer, and metastatic lesions in the breast are prone to being misdiagnosed as primary breast cancer, requiring careful attention and differentiation in the clinical diagnostic and treatment process.Case summaryThe patient, a 63-year-old female, initially presented with an EGFR exon 21 L858R mutated left lung adenocarcinoma in 2017, treated successfully with surgical resection and subsequent monitoring. The relapse of disease occurred in January 2020. Despite maintaining a prolonged progression-free survival (PFS) with first-generation EGFR-TKI Afatinib, disease progression occurred in 2022 without detectable resistance mutations. Transition to second-generation TKI Furmonertinib resulted in poor control, with rapid progression including unusual bilateral breast metastases that exhibited inflammatory breast cancer-like peau d’orange changes. Standard chemotherapy achieved only short-term stability. Upon detecting a MET amplification mutation, treatment with Savolitinib was initiated. Remarkably, this led to significant clinical and radiographic improvement, notably resolving the peau d’orange appearance and reducing multiple lesions across the body.ConclusionThis case underscores the importance of continuous genetic profiling and tailored treatment approaches in managing advanced lung adenocarcinoma, particularly when presenting with rare metastatic sites and complex genetic landscapes. The successful application of Savolitinib following the identification of a MET amplification mutation highlights its potential in overcoming resistance mechanisms in NSCLC, providing a significant therapeutic option for similarly challenging cases.

Metal-based nanoparticles have garnered significant usage across industries, spanning catalysis, optoelectronics, and drug delivery, owing to their diverse applications. However, their potential ecological toxicity remains a crucial area of research interest. This paper offers a comprehensive review of recent advancements in studying the ecotoxicity of these nanoparticles, encompassing exposure pathways, toxic effects, and toxicity mechanisms. Furthermore, it delves into the challenges and future prospects in this research domain. While some progress has been made in addressing this issue, there is still a need for more comprehensive assessments to fully understand the implications of metal-based nanoparticles on the environment and human well-being.

IntroductionUnderstory removal is a traditional practice in forest management to reduce fire risk and promote seedling regeneration. However, its effect on understory diversity, biomass and soil nutrients in temperate forest ecosystems is less known, which limits our assessment of the effectiveness of understory vegetation management.MethodsWe quantified the composition of the understory species, their diversity, and the biomass of the understory and factors driving changes in these parameters in primary mixed broad-leaved Pinus koraiensis forest (BKF), secondary Betula platyphylla forest (BF), and Larix gmelinii plantation (LF) in northeast China after a 5-year understory removal.ResultsAfter understory removal, the number of shrub and herb species in BKF and LF decreased, while the number of shrub species in BF increased significantly and that of herb species decreased; the species with strong light preference, Equisetum hyemale, Impatiens noli-tangere, and Filipendula Palmata, were dominant in the herb layer of the three forest types; Shannon–Wiener diversity, Pielou evenness, and Simpson diversity of the herb layer in LF increased significantly (P < 0.05), while those of the shrub and herb layers in BF and LF showed no significant changes (P > 0.05). The total understory biomass of understory of BKF and LF decreased by 0.94 t·hm−2 and 1.32 t·hm−2, respectively, while that of BF increased by 1.31 t·hm−2; soil NH4+-N and total phosphorus (TP) were the key factors regulating understory vegetation diversity and biomass, respectively.ConclusionThese results suggest that understory removal is a beneficial management strategy for increasing shrub biomass and diversity in secondary forests, while it should be avoided in primary forests and plantations to prevent the reduction of understory plant diversity and soil nutrient loss.

Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate, and the survival rate of HCC patients remains low. Animal medicines have been used as potential therapeutic tools throughout the long history due to their different structures of biologically active substances with high affinity to the human body. Here, we focus on the effects and the mechanism of action of animal-derived natural products against HCC, which were searched in databases encompassing Web of Science, PubMed, Embase, Science Direct, Springer Link, and EBSCO. A total of 24 natural products from 12 animals were summarized. Our study found that these natural products have potent anti-hepatocellular carcinoma effects. The mechanism of action involving apoptosis induction, autophagy induction, anti-proliferation, anti-migration, and anti-drug resistance via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Ras/extracellular signal regulated kinases (ERK)/mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Huachansu injection and sodium cantharidate have been used in clinical applications with good efficacy. We review the potential of animal-derived natural products and their derivatives in the treatment of HCC to date and summarize their application prospect and toxic side effects, hoping to provide a reference for drug development for HCC.

IntroductionHypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood.MethodsWe employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it.ResultsWe delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC.DiscussionOur research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.

BackgroundAcupuncture is a widely used clinical treatment method, and studies have confirmed its therapeutic effects on stroke patients. It can also reduce the burden on patients and society. Acupuncture treatment is a complementary and preventive treatment for stroke. However, there has yet to be a visual bibliometric analysis of the field of acupuncture for stroke rat models. This study explores future trends, research hotspots, and frontiers in acupuncture for stroke rat models over the past 20 years through investigation and visualization.MethodsWe collected literature data on acupuncture treatment of stroke in rats from the Web of Science Core Collection (WOSCC) database from January 1, 2004, to December 31, 2023. Import into CiteSpace (version 6.2.R4) and RStudio for analysis by author, country/region, affiliation, annual publication, keywords, and journal visualization.ResultsA total of 379 articles were retrieved, including articles from 16 countries, 258 research institutions, and 123 academic journals. The countries and institutions with the most publications were the People’s Republic of China (338) and the Fujian University of Traditional Chinese Medicine (43). Tao, Jing had the highest number of co-citations (144). The keywords and co-citation clustering show the main research directions in the field, including “artery occlusion,” “neural regeneration,” “stimulation,” “rapid tolerance,” “receptor,” “signaling pathway,” “apoptosis,” “oxidative stress,” “inflammatory response,” “endogenous neurogenesis,” “tolerance of local cerebral ischemic tissues,” “proliferation of reactive astrocytes” and “neuroprotective effect.” The intervention combines classical acupuncture treatment and modern technology (electricity) with electroacupuncture as a new intervention modality.ConclusionThis study demonstrates the increasing research on acupuncture for treating stroke in rat models. The country/region with the most publications is the People’s Republic of China. However, international cooperation still needs to be improved, and future researchers must strengthen international cooperation. In addition, in future studies, researchers should improve the overall quality of research results in this area and enhance research protocols.

AimBaseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is a more objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT.MethodsWe recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains.ResultsAs operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eye-movements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains.ConclusionEye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia.

Immersive 360° videos are of interest to educators because of their ability to provide immersive sensory experience and other features. This study examined the effects of four cue conditions on 360° video learning performance, attention, cognitive load, and mood using eye-tracking devices, brainwave meters, and subjective questionnaires. The randomly assigned participants (n = 62) did go to the experimental group (visual cues only, auditory cues only, and audiovisual cues) or the control group (no cues). The results showed that visual and audiovisual cues effectively guide learners’ attention to the related learning content, reduce cognitive load during learning, and improve retention performance but have no significant effect on knowledge transfer or long-term memory. Auditory cues increase the number of times learners look at the related learning content but do not affect gaze duration and distract their attention, hindering the acquisition of relevant learning content. The study also found that visual cues effectively increase the number of times learners looked at the content. However, they do not affect gaze duration. The study also revealed that visual cues effectively increase learners’ relaxation when viewing 360° videos. The study’s findings can provide a reference for the instructional processing of information related to 360° video design and its practical application in teaching.

Macrophages are the main component of the tumor microenvironment, which are differentiated from monocytes in the blood and play an important role in cancer development. Tumor-associated macrophages (TAMs) can promote tumor growth, invasion, metastasis, and resistance to anti–programmed death receptor 1 therapy by regulating programmed cell death ligand 1 expression and interacting with other immune cells in the tumor microenvironment. However, when activated properly, macrophages can also play an anti-tumor role by enhancing the phagocytosis and cytotoxicity of tumor cells. TAM is associated with poor prognosis and drug resistance in patients treated with immunotherapy, indicating that macrophages are attractive targets for combined therapy in cancer treatment. Combination of targeting TAMs and immunotherapy overcomes the drug resistance and achieved excellent results in some cancers, which may be a promising strategy for cancer treatment in the future. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis, and immunotherapy. We focus mainly on macrophage-centered therapy, including strategies to deplete and reprogram TAMs, which represent the potential targets for improving tumor immunotherapy efficacy.

Most of vaccinees and COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, which helps preventing infection and alleviating symptoms. However, breakthrough viral infections caused by emerging SARS-CoV-2 variants, especially Omicron subvariants, still pose a serious threat to global health. By monitoring the viral infections and the sera neutralization ability of a long-tracked cohort, we found out that the immune evasion of emerging Omicron subvariants and the decreasing neutralization led to the mini-wave of SARS-CoV-2 breakthrough infections. Meanwhile, no significant difference had been found in the infectivity of tested SARS-CoV-2 variants, even though the affinity between human angiotensin-converting enzyme 2 (hACE2) and receptor-binding domain (RBDs) of tested variants showed an increasing trend. Notably, the immune imprinting of inactivated COVID-19 vaccine can be relieved by infections of BA.5.2 and XBB.1.5 variants sequentially. Our data reveal the rising reinfection risk of immune evasion variants like Omicron JN.1 in China, suggesting the importance of booster with updated vaccines.

Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms.Methods: Rats with α-naphthylisothiocyanate (ANIT, 50 mg/kg)-induced cholestasis were administered low (0.3 g/kg) and high (0.6 g/kg) doses of CF, as well as CF combined with TR at doses of 0.6 g/kg and 0.9 g/kg, respectively. The anti-cholestatic effects of these treatments were assessed by determining their anti-inflammatory, hypolipidemic, and anti-oxidative stress properties. Additionally, fecal metabolomics and fecal microorganisms were analyzed.Results: Low dose CF had a more potent hypolipidemic effect than high dose CF, whereas high dose CF had more potent anti-inflammatory and anti-oxidative stress effects. Combination with TR enhanced the hypolipidemic effect, but antagonized the anti-inflammatory effect, of CF. Analyses of fecal metabolomics and fecal microorganisms showed differences in the regulation of lipid- and amino acid metabolism-related pathways, including pathways of linoleic acid, tyrosine, and arachidonic acid metabolism, and amino acid biosynthesis between different doses of CF as well as between different doses of CF in combination with TR. These differences may contribute to differences in the anti-cholestatic effects of these preparations.Conclusion: CF dose influences its anti-cholestatic efficacy. The combination with TR had synergistic or antagonistic effects on the properties of CF, perhaps by altering fecal metabolism and fecal microbial homeostasis.

IntroductionSalmonella is a major foodborne pathogen worldwide that causes severe morbidity and mortality. It is mainly caused by consuming contaminated food, with retail food considered the primary source.MethodsIn Guizhou, China, 102 Salmonella strains isolated from 2016 to 2021 underwent phenotypic antimicrobial resistance testing and whole-genome sequencing (WGS) to understand Salmonella diversity, including serotypes, sequencing types (STs), antimicrobial genes, virulence genes, plasmid types, multi-locus sequence types (MLST), and core genome MLST (cgMLST).Results and discussionS.Typhimurium was the dominant serotype, and O:4(B) was the leading serogroup. The most prevalent genotype was ST40. Phenotypic antimicrobial resistance identified 66.7% of the sampled isolates as multi-drug resistant (MDR). S.Enteritidis (n = 7), S.Typhimurium (n = 1), S.Indiana (n = 1), S.Kentucky (n = 1), S.Uganda (n = 1), all of which were MDR, were resistant to Colistin. Resistance rates varied significantly across different strains and food types, particularly meat products exhibiting higher resistance. Notably, significant increases in resistance were observed from 2016 to 2021 for the following: ≥ 1 resistant (P = 0.001), MDR (P = 0.001), ampicillin (P = 0.001), tetracycline (P

BackgroundDisorders associated with cognitive impairment impose a significant burden on both families and society. Previous studies have indicated that gait characteristics under dual-task as reliable markers of early cognitive impairment. Therefore, digital gait detection has great potential for future cognitive screening. However, research on digital biomarkers based on smart devices to identify cognitive impairment remains limited. The aim of this study is to explore digital gait biomarkers by utilizing intelligent wearable devices for discriminating mild cognitive impairment and dementia.MethodsThis study included 122 subjects (age: 74.7 ± 7.7 years) diagnosed with normal cognition (NC, n = 38), mild cognitive impairment (MCI, n = 42), or dementia (n = 42). All subjects underwent comprehensive neuropsychological assessments and cranial Magnetic Resonance Imaging (MRI). Gait parameters were collected using validated wearable devices in both single-task and dual-task (DT). We analyzed the ability of gait variables to predict MCI and dementia, and examined the correlations between specific DT-gait parameters and sub-cognitive functions as well as hippocampal atrophy.ResultsOur results demonstrated that dual-task could significantly improve the ability to predict cognitive impairment based on gait parameters such as gait speed (GS) and stride length (SL). Additionally, we discovered that turn velocity (TV and DT-TV) can be a valuable novel digital marker for predicting MCI and dementia, for identifying MCI (DT-TV: AUC = 0.801, sensitivity 0.738, specificity 0.842), and dementia (DT-TV: AUC = 0.923, sensitivity 0.857, specificity 0.842). The correlation analysis and linear regression analysis revealed a robust association between DT-TV and memory function, as well as the hippocampus atrophy.ConclusionThis study presents a novel finding that DT-TV could accurately identify varying degrees of cognitive impairment. DT-TV is strongly correlated with memory function and hippocampus shrinkage, suggests that it can accurately reflect changes in cognitive function. Therefore, DT-TV could serve as a novel and effective digital biomarker for discriminating cognitive impairment.

ObjectivesTo explore the preoperative high-risk clinical factors for contralateral medium-volume central lymph node metastasis (conMVCLNM) in unilateral papillary thyroid carcinoma (uPTC) and the indications for dissection of contralateral central lymph nodes (conCLN).MethodsClinical and pathological data of 204 uPTC patients who underwent thyroid surgery at the Hangzhou First People’s Hospital from September 2010 to October 2022 were collected. Univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors for contralateral central lymph node metastasis (conCLNM) and conMVCLNM in uPTC patients based on the preoperative clinical data. Predictive models for conCLNM and conMVCLNM were constructed using logistic regression analyses and validated using receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis (DCA).ResultsUnivariate and multivariate logistic regression analyses showed that gender (P < 0.001), age (P < 0.001), tumor diameter (P < 0.001), and multifocality (P = 0.008) were independent risk factors for conCLNM in uPTC patients. Gender(P= 0.026), age (P = 0.010), platelet-to-lymphocyte ratio (PLR) (P =0.003), and tumor diameter (P = 0.036) were independent risk factors for conMVCLNM in uPTC patients. A predictive model was established to assess the risk of conCLNM and conMVCLNM, with ROC curve areas of 0.836 and 0.845, respectively. The C-index, the calibration curve, and DCA demonstrated that the model had good diagnostic value.ConclusionGender, age, tumor diameter, and multifocality are high-risk factors for conCLNM in uPTC patients. Gender, age, tumor diameter, and PLR are high-risk factors for conMVCLNM in uPTC patients, and preventive conCLN dissection should be performed.

Panoramic video and virtual reality technologies create learning environments that provide learners with an “immersive” experience. In recent years, panoramic video design to create immersive learning environments, in particular, has become an increasingly popular topic in teacher education and educational research. However, few studies have explored the elements of panoramic virtual learning environment screens regarding the design of learning environments. Therefore, this experimental study uses eye-tracking technology to investigate how learners are guided by panoramic video elements in a panoramic virtual learning environment. Participants (n = 90) were randomly assigned to one of six conditions: (1) no caption + live interpretation, (2) no caption + AI interpretation, (3) 120-degree caption + live interpretation, (4) 120-degree caption + AI interpretation, (5) static follow caption + live interpretation, and (6) static follow caption + AI interpretation. The results of the study show that when learners experience a panoramic virtual learning environment with different narration methods, the live interpretation method is more likely to attract learners’ attention and bring better emotion and experience than the AI interpretation method. When experiencing a panoramic virtual learning environment with different caption presentation methods, the caption presentation methods induced learners’ attention, learning emotions, and experiences in the order of no caption >120-degree caption > static following caption. Finally, the rules for optimizing the design of panoramic virtual learning environment screens are given based on the findings of the study, which provide new ideas for designing and developing panoramic video teaching resources.

BackgroundRecent studies have shown that a higher intake of ascorbic acid was associated with a lower prevalence of depression. Nevertheless, the recall bias was common in dietary surveys in these studies, and it was ignored that there were differences in the absorption and utilization of ascorbic acid in the body. Hence, we aim to investigate the association between serum ascorbic acid levels and the prevalence of depression in US adults.MethodsA total of 3,404 participants from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) that underwent measurement of the Patient Health Questionnaire-9 (PHQ-9) scores and serum levels of ascorbic acid. Propensity Score Matching (PSM) successfully established a case–control study, comprising 299 participants diagnosed with depression and 1,107 as controls. We used binary logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to explore associated risk factors for depression. Restricted cubic splines (RCS) were used to show the nonlinear relationship between serum ascorbic acid levels and the prevalence of depression.ResultsThe prevalence of depression was approximately 8.8%, with a median serum ascorbic acid level of 49.9 (36.0, 67.0) μmol/L. Results revealed that the serum ascorbic acid levels of depressed patients were significantly lower than those of non-depressed individuals (42.97 VS 52.97 μmol/L). The baseline data indicated that as serum ascorbic acid levels increased from Quartile 1 (Q1) to Quartile 4 (Q4), the depression prevalence decreased from 12.0 to 5.4% (p

IntroductionBacillus cereus is a ubiquitous opportunistic human pathogen that causes food intoxications worldwide. However, the genomic characteristics and pathogenic mechanisms of B. cereus are still unclear.MethodsHere, we isolated and purified nine strains of B. cereus (LY01-LY09) that caused vomiting, diarrhea and other symptoms from four foodborne outbreaks happened in Guizhou Province in southwest China from June to September 2021. After colony observation, Gram staining, microscopic examination and biochemical test, they were identified as B. cereus. The genomic characteristics, phylogenetic relationships and virulence factors of the isolated strains were analyzed at the genome level. Genome sequencing, comparative genomic analysis, secondary metabolite analysis and quantitative PCR were utilized to give a thorough exploration of the strains.ResultsWe obtained the genome maps of LY01-LY09 and found that LY01-LY09 had a complex interspecific relationship with B. anthracis and B. thuringiensis. We also observed a contraction of gene families in LY01-LY09, and the contracted families were mainly associated with prophage, which contributed to the species diversity of B. cereus. The Hsp20 gene family underwent a rapid evolution in LY01-LY09, which facilitated the adaptation of the strains to adverse environmental conditions. Moreover, the LY01-LY09 strains exhibited a higher copy number in the non-ribosomal polypeptide synthetase (NRPS) genes and carried the complete cereulide synthetase (ces) gene cluster sequences. Considering that the NRPS system is a classical regulatory mechanism for emetic toxin synthesis, we hypothesized that LY01-LY09 could synthesize emetic toxins through the regulation of ces gene clusters by the NRPS system.DiscussionThese findings are important for further investigation into the evolutionary relationship between B. cereus and their related species, as well as the underlying mechanisms governing the synthesis and secretion of bacterial toxins.

Tumor-associated macrophages (TAMs) are critical in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Major vault protein (MVP) mediates multidrug resistance, cell growth and development, and viral immunity. However, the relationship between MVP and TAMs polarization has not been clarified in HCC. We found that MVP significantly increased M2-TAMs infiltration levels in tumor tissues of HCC patients. MVP promoted HCC proliferation, metastasis, and invasion by regulating M2 polarization in vivo and in vitro. Mechanistically, MVP associated with signal transducer and activator of transcription 6 (STAT6) and enhanced STAT6 phosphorylation. STAT6 translocated from the cytosol to the nucleus and regulated M2 macrophage-associated gene transcription. These findings suggest that MVP modulates the macrophage M2 transcriptional program, revealing its potential role in the TAMs of TME.

In recent years, the demand for advanced biomedical nanomaterials has seen a noticeable surge. Among the essential trace elements in the human body, selenium has gained recognition for its anti-cancer, antioxidant, and immune regulatory properties. However, traditional selenium-based semiconductor quantum dots (QDs) are often comprised of heavy metal elements that tend to be toxic, thereby limiting their usage in biomedical applications. Fortunately, the advent of elemental selenium quantum dots (SeQDs), a new kind of fluorescent nanomaterial with unique physicochemical properties, has provided a solution to this problem. These SeQDs are known for their low toxicity and good biocompatibility, making them a promising candidate for biomedical applications. In this mini-review, we delve into the synthesis methods of fluorescent SeQDs and the latest progress in their applications in bioimaging, biosensing, and diagnosis treatment. Finally, we identify the major challenges and future prospects in the field of SeQDs.

BackgroundCancer-associated fibroblasts (CAFs) represent the predominant stromal component within the tumour microenvironment (TME), exhibiting considerable heterogeneity and plasticity that significantly impact immune response and metabolic reprogramming within the TME, thereby influencing tumour progression. Consequently, investigating CAFs is of utmost importance. The objective of this study is to employ bibliometric analysis in order to evaluate the current state of research on CAFs and predict future areas of research and emerging trends.MethodsConduct a comprehensive search for scholarly publications within the Web of Science Core Collection database, encompassing the time period from January 1, 2001, to December 31, 2022. Apply VOSviewer, CiteSpace, R software and Microsoft Excel for bibliometric analysis and visualisation.ResultsThis study involved a comprehensive analysis of 5,925 publications authored by 33,628 individuals affiliated with 4,978 institutions across 79 countries/regions. These publications were published in 908 journals, covering 14,495 keywords and 203,947 references. Notably, there was a significant increase in articles published between 2019 and 2022. China had the highest count of articles, while the United States emerged as the most frequently cited country. The primary research institutions in this field were Shanghai Jiao Tong University, Harvard University, and the University of Texas MD Anderson Cancer Center. Sotgia, Federica and Lisanti, Michael P from the University of Manchester, and Martinet, Wim from the University of Antwerp were the most prolific and highly cited authors. The journal Cancers had the highest number of publications, while Cancer Research was the most frequently cited journal. Molecular, biology, immunology, medicine and genetics were the main research disciplines in the field of CAFs. Key directions in CAFs research encompassed the study of transforming growth factor-β, Fibroblast Activation Protein, breast cancer, as well as growth and metastasis. The findings from the analysis of keyword co-occurrence and literature co-citation have revealed several emerging hotspots and trends within the field of CAFs. These include STAT3, multidrug resistance, pancreatic ductal adenocarcinoma, pan-cancer analysis, preclinical evaluation, ionizing radiation, and gold nanoparticles.ConclusionTargeting CAFs is anticipated to be a novel and effective strategy for cancer treatment. This study provides a comprehensive overview of the existing research on CAFs from 2001 to 2022, utilizing bibliometric analysis. The study identified the prominent areas of investigation and anticipated future research directions, with the aim of providing valuable insights and recommendations for future studies in the field of CAFs.

Background and aimsEstimated pulse wave velocity (ePWV) and systemic inflammatory response index (SIRI) have been recently investigated as a marker of arterial stiffness and a novel systemic inflammatory indicator. This study aims to examine the independent and combined association of ePWV and SIRI with incident stroke and its subtypes.MethodsData of the Dongfeng-Tongji cohort study was analyzed for 9,154 middle-aged and older adults, who were free of cardiovascular disease and cancer and were followed up to document incident stroke. But their association with incident stroke events and its subtypes have not been well studied. Multivariable adjusted Cox regression models were used to determine the independent and combined association of ePWV and SIRI with incident stroke events.ResultsOver a 7.22-year follow-up, the cohort documented 491 stroke cases (387 ischemic stroke and 104 hemorrhagic stroke). The multivariate adjusted model showed that with each one-unit increase in the level of ePWV, the corresponding hazard ratios (HRs) (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.53 (95% CI, 1.23–1.90), 1.42 (95% CI, 1.11–1.83), and 1.92 (95% CI, 1.21–3.03), respectively. Similarly, with each one-unit increase in log-transformed levels of SIRI, the corresponding HRs (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.23 (95% CI,1.04–1.47), 1.16 (95% CI, 0.96–1.41), and 1.52 (95% CI, 1.05–2.20), respectively. There appeared to be a combined effect of ePWV and SIRI on stroke; Participants with high levels of both ePWV and SIRI had a higher risk of total stroke and hemorrhagic stroke, with multiple adjusted HR of 2.43 (95% CI, 1.09–5.42). Additionally, the incorporation of ePWV in addition to traditional cardiovascular risk factors significantly improved the predictive accuracy for total stroke with C statistic increased from 0.684 (95% CI, 0.661–0.707) to 0.687 (95% CI, 0.664–0.710; x2 = 6.65; p for difference = 0.010), and (suggestively) for ischemic stroke with C statistic increased from 0.684 (95% CI, 0.659–0.71) to 0.691(95% CI, 0.666–0.717; x2 = 3.13, p for difference = 0.077), respectively.ConclusionsThe presence of both high ePWV and SIRI individually, as well as together, was found to be associated with an increased incidence of stroke. The combined stroke risk assessment using these two indicators could potentially improve non-invasive assessment and treatment strategies for high-risk patients, as these indicators are easily accessible in clinical practice.

Bamboo forests, which have come to occupy large areas in recent years, naturally undergo the process of blooming. However, bamboo culms and rhizomes degenerate after the plants bloom, resulting in widespread loss of raw materials. Systematic research on the properties and physiology of bamboo culms after flowering is lacking, and whether flowering bamboo culms could be used as raw materials in industry is unclear. In this paper, we compared and measured the fiber morphology, chemical components, and sugar metabolism indexes of non-flowering and flowering Bambusa tuldoides culms at different ages. The results showed that the fibers in the middle internodes of both non-flowering and flowering B. tuldoides culms had the longest length. The fibers completed their elongation within 1 year, but the fiber walls were continually deposited with age. The levels of the chemical components in the nonflowering culms also continually increased with age. The nonstructural carbohydrate (NSC) content and sugar metabolism indexes showed the highest levels in the 2-year culms and then declined in the 3-year culms. Compared to young culms that had not yet flowered, the 3-month-old and 1-year-old flowering culms had a significant decrease in the fiber length and tangential diameter, and their holocellulose and lignin levels also decreased, while the levels of ash, SiO2, 1% NaOH extractives, and benzene-ethanol extractives increased. A correlation analysis showed that sugar catabolism was accelerated in the flowering cluster, which could lead to “starvation death” in bamboo and which had a significant negative impact on the anatomical and chemical properties of the bamboo culms. Generally, the flowering bamboo culms had shorter fibers, higher levels of extractives and ash, and lower holocellulose content, which indicated that bamboo flowering has an adverse effect on the application of such components in the production of pulp, in papermaking, and in other processing and utilization activities. This study revealed the physiological changes in flowering B. tuldoides culms and provided a theoretical basis to inform the utilization of culms in this species.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15–20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1–5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28–29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Background: HSK21542, a novel selective peripherally-restricted κ-opioid receptor agonist has been proven to be a safe and effective analgesic and antipruritic drug in both in vitro and in vivo studies. We aimed to evaluate its safety, pharmacokinetics and efficacy in hemodialysis patients over a 1-week treatment period, and to establish the optimal dosage for a further 12-week stage 2 trial.Methods: In this multiple ascending dose study, hemodialysis patients were randomly assigned to receive HSK21542 (0.05–0.80 μg/kg), or a placebo three times within 2.5 h at the end of each dialysis session for 1 week. Safety evaluations included reports of treatment-emergent adverse events (TEAEs); pharmacokinetics and efficacy outcomes were also assessed.Results: Among the 44 screened patients, 41 were enrolled and completed the trial. The overall incidence of TEAEs was higher in the HSK21542 group compared to the placebo group, with an incidence of 75.0%, 50.0%, 75.0%, and 88.9% in the range of 0.05–0.80 μg/kg. All TEAEs were grade 1 or 2 in severity. HSK21542 exhibited linear pharmacokinetics characteristics within the dose range 0.05–0.80 μg/kg, without drug accumulation after multiple-doses. Compared to the placebo, a significant decrease of the weekly mean Worst Itching Intensity Numerical Rating Scale was found in the HSK21542-0.30 μg/kg group (p = 0.046), but without significant improvement in the Skindex-16 score.Conclusion: HSK21542 was well tolerated in the dose range 0.05–0.80 μg/kg in hemodialysis patients. HSK21542-0.3 μg/kg exhibited promising efficacy in patients with moderate to severe pruritus and warrants a further Stage 2 trial.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT04470154.

BackgroundHypertension is a major public health problem, and its resulting other cardiovascular diseases are the leading cause of death worldwide. In this study, we constructed a convenient and high-performance hypertension risk prediction model to assist in clinical diagnosis and explore other important influencing factors.MethodsWe included 8,073 people from NHANES (2017—March 2020), using their 120 features to form the original dataset. After data pre-processing, we removed several redundant features through LASSO regression and correlation analysis. Thirteen commonly used machine learning methods were used to construct prediction models, and then, the methods with better performance were coupled with recursive feature elimination to determine the optimal feature subset. After data balancing through SMOTE, we integrated these better-performing learners to construct a fusion model based for predicting hypertension risk on stacking strategy. In addition, to explore the relationship between serum ferritin and the risk of hypertension, we performed a univariate analysis and divided it into four level groups (Q1 to Q4) by quartiles, with the lowest level group (Q1) as the reference, and performed multiple logistic regression analysis and trend analysis.ResultsThe optimal feature subsets were: age, BMI, waist, SBP, DBP, Cre, UACR, serum ferritin, HbA1C, and doctors recommend reducing salt intake. Compared to other machine learning models, the constructed fusion model showed better predictive performance with precision, accuracy, recall, F1 value and AUC of 0.871, 0.873, 0.871, 0.869 and 0.966, respectively. For the analysis of the relationship between serum ferritin and hypertension, after controlling for all co-variates, OR and 95% CI from Q2 to Q4, compared to Q1, were 1.396 (1.176–1.658), 1.499 (1.254–1.791), and 1.645 (1.360–1.989), respectively, with P

The growth of yield outputs is dwindling after the first green revolution, which cannot meet the demand for the projected population increase by the mid-century, especially with the constant threat from extreme climates. Cereal yield requires carbon (C) assimilation in the source for subsequent allocation and utilization in the sink. However, whether the source or sink limits yield improvement, a crucial question for strategic orientation in future breeding and cultivation, is still under debate. To narrow the knowledge gap and capture the progress, we focus on maize, rice, and wheat by briefly reviewing recent advances in yield improvement by modulation of i) leaf photosynthesis; ii) primary C allocation, phloem loading, and unloading; iii) C utilization and grain storage; and iv) systemic sugar signals (e.g., trehalose 6-phosphate). We highlight strategies for optimizing C allocation and utilization to coordinate the source–sink relationships and promote yields. Finally, based on the understanding of these physiological mechanisms, we envisage a future scenery of “smart crop” consisting of flexible coordination of plant C economy, with the goal of yield improvement and resilience in the field population of cereals crops.

Environmental pollution with potentially toxic elements (PTEs) has become one of the critical and pressing issues worldwide. Although these pollutants occur naturally in the environment, their concentrations are continuously increasing, probably as a consequence of anthropic activities. They are very toxic even at very low concentrations and hence cause undesirable ecological impacts. Thus, the cleanup of polluted soils and water has become an obligation to ensure the safe handling of the available natural resources. Several remediation technologies can be followed to attain successful remediation, i.e., chemical, physical, and biological procedures; yet many of these techniques are expensive and/or may have negative impacts on the surroundings. Recycling agricultural wastes still represents the most promising economical, safe, and successful approach to achieving a healthy and sustainable environment. Briefly, biochar acts as an efficient biosorbent for many PTEs in soils and waters. Furthermore, biochar can considerably reduce concentrations of herbicides in solutions. This review article explains the main reasons for the increasing levels of potentially toxic elements in the environment and their negative impacts on the ecosystem. Moreover, it briefly describes the advantages and disadvantages of using conventional methods for soil and water remediation then clarifies the reasons for using biochar in the clean-up practice of polluted soils and waters, either solely or in combination with other methods such as phytoremediation and soil washing technologies to attain more efficient remediation protocols for the removal of some PTEs, e.g., Cr and As from soils and water.

Background: Attention problems are one of the core symptoms of Attention-deficit/hyperactivity disorder (ADHD) in children. Previous studies have shown that physical activity intervention has a positive impact on executive function in children and adolescents with ADHD, but there is limited research on attention problems in school-aged children with ADHD. There are still uncertainties about the appropriate physical activity interventions to improve attention problems in this population. This study conducted a Meta-analysis of randomized controlled trials (RCTs) related to physical activity intervention for attention problems in school-aged children with ADHD, providing a certain reference for precise intervention in attention problems for this population.Methods: We systematically searched the following databases up to October 2022: PubMed, Embase, Web of Science, and Cochrane Library, to identify RCTs that investigated the effects of physical activity interventions on children with ADHD. Two investigators independently conducted literature screening, extraction, and quality assessment. We performed a meta-analysis using Stata 15.1.Results: In total, we included 10 studies in this meta-analysis. The results indicated that physical activity intervention had a moderate effect in improving attention problems in school-aged children with ADHD (SMD = −0.48, 95% CI: 0.85, −0.07, p < 0.05). Furthermore, subgroup analysis showed that the effect of physical activity intervention was moderated by intervention type, frequency, and period, rather than the physical activity environment or single intervention time.Conclusion: Our study suggests that cognitively engaging exercise is more effective in improving attention problems in school-aged children with ADHD. Specifically, when cognitive-engaging exercise is used as the type of physical activity and the intervention frequency is less than 3 times per week, with an intervention period of less than weeks, it is most beneficial for improving attention problems in school-aged children with ADHD. However, we should also consider individual differences in children with respect to their ADHD symptoms and accurately evaluate each child’s specific symptoms before intervention.Systematic Review Registration: identifier (CRD42022363255).

ObjectivesThe aim of this study was to explore the effects of a virtual reality (VR)-based motivational reinforcement + desensitization intervention program on psychological craving and addiction memory in female methamphetamine (MA)-dependent young adults.MethodsWe recruited 60 female MA-dependent young adults in a compulsory isolation drug rehabilitation facility in Sichuan Province, and randomly assigned them to intervention (mean age = 23.24 ± 2.06) and control groups (mean age = 23.33 ± 2.09). The intervention group received a VR-based motivational enhancement + desensitization intervention (total of eight sessions over a 4-week period), while the control group received regular detoxification management during the same period. Assessments were conducted before, immediately after, and 1 month after the intervention, with a visual analogue scale (VAS) being used to assess subjective craving, electronic sphygmomanometer employed to measure physiological parameters, and the Addiction Memory Intensity Scale (AMIS) applied to assess addiction memory intensity.ResultsGeneralized estimating equation analysis showed significant main effects of group on changes in heart rate difference, systolic blood pressure difference, VAS and AMIS scores (all p

ObjectiveSchisandra chinensis (Turcz.) Baill. (S. chinensis) is a Traditional Chinese medicinal herb that can be used both for medicinal purposes and as a food ingredient due to its beneficial properties, and it is enriched with a wide of natural plant nutrients, including flavonoids, phenolic acids, anthocyanins, lignans, triterpenes, organic acids, and sugars. At present, there is lack of comprehensive study or systemic characterization of nutritional and active ingredients of S. chinensis using innovative mass spectrometry techniques.MethodsThe comprehensive review was conducted by searching the PubMed databases for relevant literature of various mass spectrometry techniques employed in the analysis of nutritional components in S. chinensis, as well as their main nutritional effects. The literature search covered the past 5 years until March 15, 2023.ResultsThe potential nutritional effects of S. chinensis are discussed, including its ability to enhance immunity, function as an antioxidant, anti-allergen, antidepressant, and anti-anxiety agent, as well as its ability to act as a sedative-hypnotic and improve memory, cognitive function, and metabolic imbalances. Meanwhile, the use of advanced mass spectrometry detection technologies have the potential to enable the discovery of new nutritional components of S. chinensis, and to verify the effects of different extraction methods on these components. The contents of anthocyanins, lignans, organic acids, and polysaccharides, the main nutritional components in S. chinensis, are also closely associated to its quality.ConclusionThis review will provide guidelines for an in-depth study on the nutritional value of S. chinensis and for the development of healthy food products with effective components.

Transcranial magnetic stimulation (TMS) is a non-invasive brain neurostimulation technique that can be used as one of the adjunctive treatment techniques for neurological recovery after stroke. Animal studies have shown that TMS treatment of rats with middle cerebral artery occlusion (MCAO) model reduced cerebral infarct volume and improved neurological dysfunction in model rats. In addition, clinical case reports have also shown that TMS treatment has positive neuroprotective effects in stroke patients, improving a variety of post-stroke neurological deficits such as motor function, swallowing, cognitive function, speech function, central post-stroke pain, spasticity, and other post-stroke sequelae. However, even though numerous studies have shown a neuroprotective effect of TMS in stroke patients, its possible neuroprotective mechanism is not clear. Therefore, in this review, we describe the potential mechanisms of TMS to improve neurological function in terms of neurogenesis, angiogenesis, anti-inflammation, antioxidant, and anti-apoptosis, and provide insight into the current clinical application of TMS in multiple neurological dysfunctions in stroke. Finally, some of the current challenges faced by TMS are summarized and some suggestions for its future research directions are made.

ImportancePrimary insomnia (PI) has a high global incidence, and effective treatments with fewer side effects are needed. Acupuncture, a treatment used in traditional Chinese medicine, has become increasingly established as a treatment method for PI and is recognized by many physicians and patients. Some evidence has suggested that acupuncture was associated with improvements in objective sleep parameters and might induce changes in some brain regions. Individual studies with limited sample size and low detection thresholds may lead to false positives, and no systematic review of the effects of acupuncture has been conducted in PI.ObjectiveThe aim of this systematic review and coordinate-based meta-analysis was to summarize the literature on fMRI evaluation of patients with PI treated with acupuncture.DesignWe performed a methodical and comprehensive search of multiple publication databases (from inception to December 2022): Web of Science, PubMed, ScienceDirect, Embase, Wan Fang, China National Knowledge Infrastructure, and Chinese Scientific Journal Database. Bias and quality of studies were evaluated by three researchers. Furthermore, a seed-based D-mapping meta-analysis with permutation of subject images (SDM-PSI) was applied to investigate the central mechanisms behind acupuncture treatment at PI. The International Prospective Registry of Systematic Reviews received the protocol for this study. (PROSPERO: CRD42023400086).ResultsThe analysis included 305 patients with PI and 116 healthy controls from 11 studies. SDM-PSI analysis showed that patients with PI exhibited increased amplitudes of regional homogeneity and low-frequency fluctuations in the left superior frontal gyrus (1352 voxels, p = 0.0028), right angular gyrus (14 voxels, p = 0.0457), and cerebellum (12 voxels, p = 0.0446). Acupuncture improved the function of right superior frontal gyrus (1, 404 voxels, p = 0.0123), left inferior frontal gyrus (1068 voxels, p = 0.0088), left inferior temporal gyrus (903 voxels, p = 0.0074), left supramarginal gyrus (888 voxels, p = 0.0113), left precuneus (457 voxels, p = 0.0247), right precuneus (302 voxels, p = 0.0191), left supplementary motor area (82 voxels, p = 0.0354), and right parahippocampal gyrus (28 voxels, p = 0.0379). The brain regions affected by non-acupoint acupuncture were all located in the frontal lobe. The Cochrane risk-of bias tool and MINORS5 were used for quality assessment and the included articles had high performance bias and attrition bias.ConclusionThis coordinate-based meta-analysis found that acupuncture in patients with PI had significant effects on the default mode network, particularly on the frontal lobe and precuneus, and that non-acupoint acupuncture may provide some benefit to frontal brain region function.Systematic review registrationPROSPERO: CRD42023400086.

Granisetron patches are a prolonged delivery transdermal system that is used to prevent Chemotherapy-induced nausea and vomiting (CINV). To date, no pharmacokinetics comparison between Chinese and Caucasian populations has been conducted for granisetron patches. This study focused on the ethnic differences in pharmacokinetics (PK) of granisetron transdermal delivery system (GTDS) between Chinese and Caucasians and the influence of demographic covariates on pharmacokinetics (age, weight, height, body mass index, sex). To achieve this, blood concentration data were collected from 112 Caucasian healthy subjects participating in four clinical trials and 24 Chinese healthy subjects from one clinical trial, after a single application of the granisetron transdermal delivery system. A nonlinear mixed-effects model method of Phoenix NLME software was used to establish a population pharmacokinetic (Pop PK) model for Caucasian subjects. Bootstrap and visual predictive check (VPC) were used to validate the model. Based on the analysis a one-compartment model with first-order absorption and a first-order elimination well described the PK characteristics of GTDS. The apparent systemic clearance was determined to be 31316.3 mL/h and the central compartment volume of distribution was 6299.03 L. None of the five covariates (age, weight, height, body mass index, and sex) included in the Pop PK were significant covariates affecting PK. The final Pop PK model was used to simulate the Caucasian blood concentration by applying the dosing regimen used for the Chinese population. Comparison of the simulated Caucasian PK data with observed clinical PK data from Chinese healthy subjects revealed no significant differences in the main parameters, AUClast and Cavg, between the two groups. These findings suggested that no dose adjustment was required when applied to the Chinese population. In conclusion, this Pop PK study comparing the transdermal patch in Chinese and Caucasian healthy subjects provided valuable insights for optimizing dosage across ethnicities.

Understanding the effect of environmental factors on the net ecosystem CO2 exchange (NEE) and the response of NEE to rainfall events is of great significance for an accurate understanding of the carbon cycle for desert steppe ecosystems. Based on the long-term (2011–2018) eddy covariance flux data of a temperate desert steppe in Inner Mongolia, China, this study used path analysis to analyze the combined impact of the environmental factors on NEE. The results showed that during the growing season, vapor pressure deficit (VPD) and soil water content (SWC) was the most prominent environmental factor for the daytime NEE and nighttime NEE, respectively. NEE responds differently to individual environmental factors among multi-year climatic conditions. The size of rainfall event has significant impacts on NEE, it can effectively promote the CO2 uptake of the desert steppe ecosystem when rainfall event size is greater than 5 mm, and the NEE response increased with the rainfall event size. Moreover, NEE peaked approximately 1–3 days after a 5–10 mm rainfall event, while the rainfall event size >10 mm, it would take 3–5 days for NEE to reach a peak value; and yet, small rainfall events (< 5 mm) slightly increased CO2 emissions. During the growing season, carbon uptake increased with monthly rainfall, except in May. Our results are important for understanding the carbon cycle and its control mechanisms in the temperate desert steppe of Inner Mongolia.

IntroductionDeep-learn methods based on convolutional neural networks (CNNs) have demonstrated impressive performance in depression analysis. Nevertheless, some critical challenges need to be resolved in these methods: (1) It is still difficult for CNNs to learn long-range inductive biases in the low-level feature extraction of different facial regions because of the spatial locality. (2) It is difficult for a model with only a single attention head to concentrate on various parts of the face simultaneously, leading to less sensitivity to other important facial regions associated with depression. In the case of facial depression recognition, many of the clues come from a few areas of the face simultaneously, e.g., the mouth and eyes.MethodsTo address these issues, we present an end-to-end integrated framework called Hybrid Multi-head Cross Attention Network (HMHN), which includes two stages. The first stage consists of the Grid-Wise Attention block (GWA) and Deep Feature Fusion block (DFF) for the low-level visual depression feature learning. In the second stage, we obtain the global representation by encoding high-order interactions among local features with Multi-head Cross Attention block (MAB) and Attention Fusion block (AFB).ResultsWe experimented on AVEC2013 and AVEC2014 depression datasets. The results of AVEC 2013 (RMSE = 7.38, MAE = 6.05) and AVEC 2014 (RMSE = 7.60, MAE = 6.01) demonstrated the efficacy of our method and outperformed most of the state-of-the-art video-based depression recognition approaches.DiscussionWe proposed a deep learning hybrid model for depression recognition by capturing the higher-order interactions between the depression features of multiple facial regions, which can effectively reduce the error in depression recognition and gives great potential for clinical experiments.

A 22-year-old lady underwent penetrating keratoplasty for serious keratoconus. The following day, it was complicated by the development of infectious endophthalmitis. The source of infection was identified as carbapenem-resistant Klebsiella pneumoniae. The donor corneal button might be playing a role in infection transmission due to carbapenem-resistant Klebsiella pneumoniae in a sputum culture when the donor was still alive. Nosocomial infections were typically severe, rapidly progressive, and difficult to treat. Finally, the patient underwent therapeutic penetrating keratoplasty again with complete resolution of the infection.

BackgroundSarcopenia and osteoporosis are closely interconnected and associated with adverse health outcomes. Osteosarcopenia is the concurrent presence of the two conditions and has rarely been reported in hemodialysis patients. Whether hemodialysis patients with osteosarcopenia are at greater risk of mortality than those with either condition alone remains unknown. The aim of this study was to explore the prevalence of sarcopenia and its association with osteoporosis and to determine its impact on survival risk in hemodialysis patients.MethodsA total of 209 adults undergoing hemodialysis were enrolled from the dialysis center in the West China Hospital of Sichuan University, and our study was registered at the Chinese Clinical Trial Register (number: ChiCTR2100043932). Muscle mass, handgrip strength, bone mineral density (BMD), and biochemical parameters were assessed. All deaths were recorded during a follow-up of 35.15 ± 15.37 months.ResultsSeventy-eight patients were diagnosed with sarcopenia, with a prevalence of 37.3%. After adjustment for potential confounders, age (OR=1.094, P

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can manifest with abscesses, sinus tracts, and scarring in the intertriginous areas of the body. HS is characterized by immune dysregulation, featuring elevated levels of myeloid cells, T helper (Th) cells, and pro-inflammatory cytokines, particularly those involved in Th1- and Th17-mediated immunity. In most epidemiological studies, HS shows a strong female sex bias, with reported female-to-male ratios estimated at roughly 3:1, suggesting that sex-related factors contribute to HS pathophysiology. In this article, we review the role of intrinsic and extrinsic factors that contribute to immunological differences between the sexes and postulate their role in the female sex bias observed in HS. We discuss the effects of hormones, X chromosome dosage, genetics, the microbiome, and smoking on sex-related differences in immunity to postulate potential immunological mechanisms in HS pathophysiology. Future studies are required to better characterize sex-biased factors that contribute to HS disease presentations.

Background: Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia. In contrast, positive allosteric modulation of adenosine A2A receptors (A2ARs) leads to slow-wave sleep without cardiovascular side effects in contrast to A2AR agonists.Methods: We investigated the hypnotic effects of A2AR positive allosteric modulators (PAMs) in mice with mania-like behavior produced by ablating GABAergic neurons in the ventral medial midbrain/pons area and in a mouse model of schizophrenia by knocking out of microtubule-associated protein 6. We also compared the properties of sleep induced by A2AR PAMs in mice with mania-like behavior with those induced by DORA-22, a dual orexin receptor antagonist that improves sleep in pre-clinical models, and the benzodiazepine diazepam.Results: A2AR PAMs suppress insomnia associated with mania- or schizophrenia-like behaviors in mice. A2AR PAM-mediated suppression of insomnia in mice with mania-like behavior was similar to that mediated by DORA-22, and, unlike diazepam, did not result in abnormal sleep.Conclusion: A2AR allosteric modulation may represent a new therapeutic avenue for sleep disruption associated with bipolar disorder or psychosis.

ObjectiveTo determine the effectiveness of traditional Chinese mind–body exercises in improving cognition, memory, and executive function in older adults with cognitive impairment.Data sourcesRelevant English and Chinese language studies published until September 14th, 2022 were retrieved from PubMed, Web of Science, Cochrane Library, Embase, CINAHL, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases.Review methodsRandomized controlled trials assessing traditional Chinese mind–body exercises (Tai Chi, Baduanjin, Qigong, Mind–Body Therapies, and Yijinjing) in older adults with cognitive impairment were included. Two researchers independently identified eligible studies and extracted data. A risk-of-bias assessment was performed using the Cochrane Risk of Bias Tool.ResultsThis study included 15 randomized controlled trials (1,127 participants) from China, Thailand and American. Most studies had a high risk of bias in the blinding of participants and researchers, one study had a high risk of bias in the random sequence generation and two studies had a high risk of bias in the incomplete outcome data. Compared with conventional therapy alone, traditional Chinese mind–body exercises significantly improved global cognitive function (p

Introduction: Nanofat is an effective cell therapy for osteoarthritis (OA). However, it has clinical limitations due to its short half-life. We developed Nanofat lysate (NFL) to overcome the defect of Nanofat and explore its anti-OA efficacy and mechanism.Methods: Monoiodoacetate (MIA) was employed to establish rat OA model. For pain assessment, paw withdrawal latency (PWL) and thermal withdrawal latency (TWL) were evaluated. Degeneration of cartilage was observed by histopathological and immunohistochemical examination. Primary chondrocytes were treated with TNF-α to establish the cellular model of OA. MTT, wound healing, and transwell assays were performed to assess effects of NFL on chondrocytes. RNA-seq, qPCR and Western blot assays were conducted to clarify the mechanism of NFL.Results and Discussion: The animal data showed that PWL and TWL values, Mankin’s and OARSI scorings, and the Col2 expression in cartilage were significantly improved in the NFL-treated OA rats. The cellular data showed that NFL significantly improved the proliferation, wound healing, and migration of chondrocytes. The molecular data showed that NFL significantly restored the TNF-α-altered anabolic markers (Sox9, Col2 and ACAN) and catabolic markers (IL6 and Mmp13). The RNA-seq identified that TGF-β-Smad2/3 signaling pathway mediated the efficacy of NFL, which was verified by qPCR and Western blot that NFL significantly restored the abnormal expressions of TGFβR2, phosphorylated-Smad2, phosphorylated-Smad2/3, Col2, Mmp13 and Mmp3. After long-term storage, NFL exerted similar effects as its fresh type, indicating its advantage of storability. In sum, NFL was developed as a new therapeutic approach and its anti-OA efficacy and mechanism that mediated by TGF-β-Smad2/3 signaling was determined for the first time. Besides, the storability of NFL provided a substantial advantage than other living cell-based therapies.

Dodders (Cuscuta australis R. Br.) are holo-parasitic stem angiosperms with an extensive host range that have significant ecological and economic potential impact on the ecosystem and the agricultural system. However, how the host plant responds to this biotic stress remains mostly unexplored. To identify the defense-related genes and the pathways in white clover (Trifolium repens L.) induced by dodder parasitism, we performed a comparative transcriptome analysis of the leaf and root tissues from white clover with and without dodder infection by high throughput sequencing. We identified 1,329 and 3,271 differentially expressed genes (DEGs) in the leaf and root tissues, respectively. Functional enrichment analysis revealed that plant-pathogen interaction, plant hormone signal transduction, and phenylpropanoid biosynthesis pathways were significantly enriched. Eight WRKY, six AP2/ERF, four bHLH, three bZIP, three MYB, and three NAC transcription factors showed a close relationship with lignin synthesis-related genes, which defended white clover against dodder parasitism. Real-time quantitative PCR (RT-qPCR) for nine DEGs, further validated the data obtained from transcriptome sequencing. Our results provide new insights into understanding the complex regulatory network behind these parasite-host plant interactions.

IntroductionThe prevention and control of the COVID-19 pandemic has taken on a “New Normal” form, which necessitates a calm and peaceful social mentality. This study delves into the Chinese socioculturally oriented emotion construct of peace of mind (PoM) with regard to how it may affect employees’ work engagement in times of the pandemic. Based on the conversation of resource (COR) theory, we develop a model in which the relationship between PoM (i.e., a low-arousal positive affective state) and work engagement and the relationship between career calling (i.e., a high-arousal positive state) and work engagement are both mediated by social support.MethodsA total of 292 employees from 18 companies in Wuxi and Dalian, China, were surveyed at two different time points during the COVID-19 pandemic.ResultsThe results show that both relationships were mediated by social support; furthermore, after the mediating effect of social support on the relationship between PoM and work engagement was controlled for, the relationship between career calling and social support failed to reach significance.DiscussionThe findings attest to the unique advantages of PoM in boosting employees’ resource conservation and interpersonal communication in public crises. Possible implications on applying the incentive mechanism of PoM in the workplace are discussed.

BackgroundTo determine the reproducibility of measuring the gross total volume (GTV) of primary rectal tumor with manual and semi-automatic delineation on the diffusion-weighted image (DWI), examine the consistency of using the same delineation method on DWI images with different high b-values, and find the optimal delineation method to measure the GTV of rectal cancer.Methods41 patients who completed rectal MR examinations in our hospital from January 2020 to June 2020 were prospectively enrolled in this study. The post-operative pathology confirmed the lesions were rectal adenocarcinoma. The patients included 28 males and 13 females, with an average age of (63.3 ± 10.6) years old. Two radiologists used LIFEx software to manually delineate the lesion layer by layer on the DWI images (b=1000 s/mm2 and 1500 s/mm2) and used 10% to 90% of the highest signal intensity as thresholds to semi-automatically delineate the lesion and measure the GTV. After one month, Radiologist 1 performed the same delineation work again to obtain the corresponding GTV.ResultsThe inter- and intra-observer interclass correlation coefficients (ICC) of measuring GTV using semi-automatic delineation with 30% to 90% as thresholds were all >0.900. There was a positive correlation between manual delineation and semi-automatic delineation with 10% to 50% thresholds (P < 0.05). However, the manual delineation was not correlated with the semi-automatic delineation with 60%, 70%, 80%, and 90% thresholds. On the DWI images with b=1000 s/mm2 and 1500 s/mm2, the 95% limit of agreement (LOA%) of measuring GTV using semi-automatic delineation with 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% thresholds were -41.2~67.4, -17.8~51.5, -16.1~49.3, -26.2~50.1, -42.3~57.6, -57.1~65.4, -67.3~66.5, -101.6~91.1, -129.4~136.0, and -15.3~33.0, respectively. The time required for GTV measurement by semi-automatic delineation was significantly shorter than that of manual delineation (12.9 ± 3.6s vs 40.2 ± 13.1s).ConclusionsThe semi-automatic delineation of rectal cancer GTV with 30% threshold had high repeatability and consistency, and it was positively correlated with the GTV measured by manual delineation. Therefore, the semi-automatic delineation with 30% threshold could be a simple and feasible method for measuring rectal cancer GTV.

IntroductionInflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown.MethodsThe animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction.Results and conclusionsWe show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1β levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1β production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.

Pyrethrins, synthesized in the perennial plant Tanacetum cinerariifolium, are a class of terpene mixtures with high insecticidal activity and low human toxicity, which are widely used in plant-derived pesticides. Numerous studies have identified multiple pyrethrins biosynthesis enzymes, which can be enhanced by exogenous hormones such as methyl jasmonate (MeJA). However, the mechanism by which hormone signaling regulates pyrethrins biosynthesis and the potential involvement of certain transcription factors (TFs) remain unclear. In this study, we found that the expression level of a TF in T. cinerariifolium was significantly increased after treatment with plant hormones (MeJA, abscisic acid). Subsequent analysis identified this TF as a member of the basic region/leucine zipper (bZIP) family and was thus named TcbZIP60. TcbZIP60 was localized in the nucleus, suggesting that it is involved in the transcription process. The expression profiles of TcbZIP60 were similar to those of pyrethrins synthesis genes in different flower organs and at different flowering stages. Furthermore, TcbZIP60 could directly bind to the E-box/G-box motifs in the promoters of the pyrethrins synthesis genes TcCHS and TcAOC to activate their expression. Transient overexpression of TcbZIP60 increased the expression levels of pyrethrins biosynthesis genes, leading to the significant accumulation of pyrethrins. Silencing of TcbZIP60 significantly downregulated pyrethrins accumulation and the expression of related genes. Overall, our results reveal a novel TF, TcbZIP60, that regulates both the terpenoid and jasmonic acid pathways of pyrethrins biosynthesis in T. cinerariifolium.