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Abstract Background Catheter-related bladder discomfort (CRBD) commonly occurs in patients who have indwelling urinary catheters while under general anesthesia. And moderate-to-severe CRBD can lead to significant adverse events and negatively impact patient health outcomes. However, current screening studies for patients experiencing moderate-to-severe CRBD after waking from general anesthesia are insufficient. Constructing predictive models with higher accuracy using multiple machine learning techniques for early identification of patients at risk of experiencing moderate-to-severe CRBD during general anesthesia resuscitation. Methods Eight hundred forty-six patients with indwelling urinary catheters who were resuscitated in a post-anesthesia care unit (PACU). Trained researchers used the CRBD 4-level assessment method to evaluate the severity of a patient’s CRBD. They then inputted 24 predictors into six different machine learning algorithms. The performance of the models was evaluated using metrics like the area under the curve (AUC). Results The AUCs of the six models ranged from 0.82 to 0.89. Among them, the RF model displayed the highest predictive ability, with an AUC of 0.89 (95%CI: 0.87, 0.91). Additionally, it achieved an accuracy of 0.93 (95%CI: 0.91, 0.95), 0.80 sensitivity, 0.98 specificity, 0.94 positive predictive value (PPV), 0.92 negative predictive value (NPV), 0.87 F1 score, and 0.07 Brier score. The logistic regression (LR) model has achieved good results (AUC:0.87) and converted into a nomogram. Conclusions The study has successfully developed a machine learning prediction model that exhibits excellent predictive capabilities in identifying patients who may develop moderate-to-severe CRBD after undergoing general anesthesia. Furthermore, the study also presents a nomogram, which serves as a valuable tool for clinical healthcare professionals, enabling them to intervene at an early stage for better patient outcomes.

Abstract Background Alterations in DNA methylation (DNAm) have been observed in patients with fatty liver, but whether they are cause or consequence remains unknown. The study aimed to investigate longitudinal association of epigenome-wide DNAm with liver fat content (LFC) in Chinese participants, and explore their temporal relationships. Methods Data were obtained from 2 waves over a four-year time period of the Shanghai Changfeng Study (discovery, n = 407 and replication, n = 126). LFC and peripheral blood DNAm were repeatedly measured using quantitative hepatic ultrasonography and the 850 K Illumina EPIC BeadChip, respectively. Longitudinal and cross-sectional epigenome-wide association studies (EWASs) were conducted with linear mixed model and linear regression model, respectively. Meta-analysis was performed using METAL. Cross-lagged panel analysis (CLPA) was carried out to infer temporal relationships between the significant CpGs and LFC. Results Longitudinal EWAS identified cg11024682 (SREBF1), cg06500161 (ABCG1), cg16740586 (ABCG1), cg15659943 (ABCA1) and cg00163198 (SNX19) significantly associated with LFC with P

Abstract The members of the classic B7 family regulate the immune microenvironment of several malignant tumors. However, the potential relationship between the B7 family and the breast cancer (BrCa) tumor immune microenvironment has remained elusive. In the present study, we provide a comprehensive explanation of the expression, clinical significance, mutation, and immune cell infiltration of B7 family molecules in BrCa. First, we recruited 10 patients with BrCa surgery from the Wuxi Maternal and Child Health Hospital and performed single-cell RNA sequencing (scRNA-seq) analysis to investigate the distribution of B7 family members in multiple immune cell subsets. We focused on B7-2, B7-H3, and B7-H5 molecules of the B7 family and constructed tumor microarrays by self-recruiting patients to perform multiple immunohistochemical (mIHC) analyses and study tumor expression of B7-2, B7-H3, B7-H5 and CD8+ immune cell infiltration. B7-H5 displayed a strong correlation with CD8+ immune cell infiltration. In summary, B7-H5 provides a new perspective for the identification of immunothermal subtypes of BrCa and could function as a switch to reverse BrCa from an “immunologically cold” state to an “immunologically hot” state. Graphical abstract

Abstract Fokienia hodginsii (F. hodginsii), belonging to the genus Fokienia of the Cupressaceae. F. hodginsii has significant application value due to its wood properties and great research value in evolutionary studies as a gymnosperm. However, the genome of F. hodginsii remains unknown due to the large size of gymnosperms genome. Pacific Bioscience sequencing, Hi‐C mapping, whole‐genome Bisulfite Sequencing (BS‐Seq), long‐read isoform sequencing (Iso‐Seq), direct RNA sequencing (DRS), quantitative proteomics, and metabonomics analysis are employed to facilitate genome assembly, gene annotation, and investigation into epigenetic mechanisms. In this study, the 10G F. hodginsii genome is assembled into 11 chromosomes. Furthermore, 50 521 protein‐coding genes are annotated and determined that 65% of F. hodginsii genome comprises repetitive sequences. It is discovered that transposable element (TE)‐including introns is associated with higher expression. The DNA methylome of F. hodginsii reveals that xylem has a higher DNA methylation level compared to callus. Moreover, DRS reveals the significant alterations in RNA full‐length ratio, which potentially associated with poly(A) length (PAL) and alternative polyadenylation (APA). Finally, the morphology measurement and metabonomics analysis revealed the difference of 14 cultivars. In summary, the genomes and epigenetics datasets provide a molecular basis for callus formation in the gymnosperm family.

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

The benign coupling coordination between electricity (EL) and economy (EC) contributes to a better environment and sustainability. This study explores whether EL and EC can coordinate theoretically, how to evaluate their coordination, what the statuses are, and how to enhance coupling coordination levels (CCL). Specifically, we select the data from 2011 to 2020 of the 31 provincial regions of China, use information entropy weight and the technique for order preference by similarity to an ideal solution method, establish the theoretical coupling coordination mechanism and the evaluation index system to measure CCL temporally-spatially and propose policy implications based on prediction tendencies. We find that most regions' CCLs fluctuate temporally with mild upward trends, indicating the much more benign coupling coordination status; the spatial distributions are uneven with narrowing gaps. However, future CCL gaps may increase; therefore, differentiated policy implications are needed, such as encouraging balanced-coordination policies, innovating for higher-quality coordination, and cooperating for intelligence and wealth transfer. This study is conducive to theoretically describing the coupling coordination mechanism between EL and EC, providing new insights for CCL evaluation and the coordination practice for different regions.

Abstract Background This study aimed to investigate the actual application, knowledge, and training needs of comprehensive geriatric assessment (CGA) among geriatric practitioners in China. Methods A total of 225 geriatric practitioners attending the geriatric medicine or geriatric nursing training were recruited for this cross-sectional study. The questionnaire included demographics, healthcare institution characteristics, the actual application, knowledge, training needs, and barriers to CGA and geriatric syndromes (GS). Results Physicians and nurses were 57.3% and 42.7%, respectively. 71.1% were female, with a median age was 35 years. Almost two-thirds (140/225) of geriatric practitioners reported exposure to CGA in their clinical practice. The top five CGA evaluation items currently used were malnutrition risk (49.8%), fall risk (49.8%), activity of daily living (48.0%), pain (44.4%), and cognitive function (42.7%). Median knowledge scores for the management procedures of GS ranged from 2 to 6. Physicians identified medical insurance payment issues (29.5%) and a lack of systematic specialist knowledge and technology (21.7%) as the two biggest barriers to practicing geriatrics. Nurses cited a lack of systematic specialist knowledge and technology (52.1%) as the primary barrier. In addition, physicians and nurses exhibited significant differences in their knowledge of CGA-specific evaluation items and management procedures for GS (all P

Abstract Background Early water intake has gained widespread attention considering enhanced recovery after surgery (ERAS). In the present systematic evaluation and meta-analysis, we assessed the effects of early water intake on the incidence of vomiting and aspiration in adult patients who received general anaesthesia on regaining consciousness during the resuscitation period. Objective To systematically analyse the results of randomised controlled trials on early postoperative water intake in patients who underwent different types of surgery under general anaesthesia, both at home and abroad, to further explore the safety and application of early water intake and provide an evidence-based foundation for clinical application. Design Systematic review and meta-analysis. Methods To perform the systematic evaluation and meta-analysis, we searched the Web of Science, CINAHL, Embase, PubMed, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI), Wanfang, and Vipshop databases to identify randomised controlled trial studies on early water intake in adult patients who received general anaesthesia. Results Herein, we included 10 publications with a total sample size of 5131 patients. Based on statistical analysis, there was no statistically significant difference in the incidence of vomiting (odds ratio [OR] = 0.81; 95% confidence interval [CI] [0.58–1.12]; p = 0.20; I-squared [I2] = 0%) and aspiration (OR = 0.78; 95%CI [0.45–1.37]; p = 0.40; I2 = 0%) between the two groups of patients on regaining consciousness post-general anaesthesia. Conclusion Based on the available evidence, early water intake after regaining consciousness post-anaesthesia did not increase the incidence of adverse complications when compared with traditional postoperative water abstinence. Early water intake could effectively improve patient thirst and facilitate the recovery of gastrointestinal function.

Programmed cell death is intricately linked to various physiological phenomena such as growth, development, and metabolism, as well as the proper function of the pancreatic β cell and the migration and invasion of trophoblast cells in the placenta during pregnancy. Traditional and recently identified programmed cell death include apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition to cancer and degenerative diseases, abnormal activation of cell death has also been implicated in pregnancy related diseases like preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, fetal growth restriction, and recurrent miscarriage. Excessive or insufficient cell death and pregnancy related diseases may be mutually determined, ultimately resulting in adverse pregnancy outcomes. In this review, we systematically describe the characteristics and mechanisms underlying several types of cell death and their roles in pregnancy related diseases. Moreover, we discuss potential therapeutic strategies that target cell death signaling pathways for pregnancy related diseases, hoping that more meaningful treatments will be applied in clinical practice in the future.

Abstract Breast cancer (BC) is the second-leading factor of mortality for women globally and is brought on by a variety of genetic and environmental causes. The conventional treatments for this disease have limitations, making it difficult to improve the lifespan of breast cancer patients. As a result, extensive research has been conducted over the past decade to find innovative solutions to these challenges. Targeting of the antitumor immune response through the immunomodulatory checkpoint protein B7 family has revolutionized cancer treatment and led to intermittent patient responses. B7-H3 has recently received attention because of its significant demodulation and its immunomodulatory effects in many cancers. Uncontrolled B7-H3 expression and a bad outlook are strongly associated, according to a substantial body of cancer research. Numerous studies have shown that BC has significant B7-H3 expression, and B7-H3 induces an immune evasion phenotype, consequently enhancing the survival, proliferation, metastasis, and drug resistance of BC cells. Thus, an innovative target for immunotherapy against BC may be the B7-H3 checkpoint. In this review, we discuss the structure and regulation of B7-H3 and its double costimulatory/coinhibitory function within the framework of cancer and normal physiology. Then we expound the malignant behavior of B7-H3 in BC and its role in the tumor microenvironment (TME) and finally focus on targeted drugs against B7-H3 that have opened new therapeutic opportunities in BC.

Abstract Hypoxia, which activates a variety of signaling pathways to enhance tumor cell growth and metabolism, is among the primary features of tumor cells. Hypoxia-inducible factors (HIFs) have a substantial impact on a variety of facets of tumor biology, such as epithelial-mesenchymal transition, metabolic reprogramming, angiogenesis, and improved radiation resistance. HIFs induce hypoxia-adaptive responses in tumor cells. Many academics have presented preclinical and clinical research targeting HIFs in tumor therapy, highlighting the potential applicability of targeted HIFs. In recent years, the discovery of numerous pharmacological drugs targeting the regulatory mechanisms of HIFs has garnered substantial attention. Additionally, HIF inhibitors have attained positive results when used in conjunction with traditional oncology radiation and/or chemotherapy, as well as with the very promising addition of tumor immunotherapy. Immune checkpoint inhibitors (CPIs), which are employed in a range of cancer treatments over the past decades, are essential in tumor immunotherapy. Nevertheless, the use of immunotherapy has been severely hampered by tumor resistance and treatment-related toxicity. According to research, HIF inhibitors paired with CPIs may be game changers for multiple malignancies, decreasing malignant cell plasticity and cancer therapy resistance, among other things, and opening up substantial new pathways for immunotherapy drug development. The structure, activation mechanisms, and pharmacological sites of action of the HIF family are briefly reviewed in this work. This review further explores the interactions between HIF inhibitors and other tumor immunotherapy components and covers the potential clinical use of HIF inhibitors in combination with CPIs.

Abstract Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancers, but exhibits higher chemotherapeutic and immunotherapeutic responses due to its unique immunogenicity. Thus, appropriate discrimination of subtypes is critical for guiding therapeutic options in clinical practice. In this research, using multiple in-house and public cohorts, we investigated the expression features and immuno-correlations of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in a mouse model. We also developed a novel classifier combining B7-H3 and PD-L1 expression in TNBC. B7-H3 was revealed to be related to immuno-cold features and accumulated collagen in TNBC. In addition, targeting B7-H3 using the monoclonal antibody significantly suppressed mouse TNBC growth, reversed the armored-cold phenotype, and also boosted anti-PD-1 immunotherapy. In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.

Abstract Introduction Elevated urinary albumin‐to‐creatinine ratio (UACR) was associated with increased mortality in general population and diabetic patients. However, whether the association remains similar in the subjects with different status of glucose metabolism was unclear. The optimal level of UACR in predicting mortality also remained unknown. This study aims to investigate the relationship between UACR with all‐cause and cardiovascular mortality in population with different status of glucose metabolism and explore the predictive cutoff point of UACR. Methods Six thousand three hundred and eighty‐six community‐dwelling individuals aged ≥45 years were enrolled and followed for an average of 5.3 years. Cox proportional hazards model was performed to analysis the association of baseline UACR and all‐cause as well as cardiovascular mortality according to the status of glucose metabolism. Receiver operating characteristic curve was plotted to explore the optimal predictive cutoff point of UACR. Results With UACR increasing, both the prevalence of all‐cause and cardiovascular death increased. Cox analyses showed baseline UACR independently predicted the risk of all‐cause and cardiovascular mortality in the patients with prediabetes mellitus (pre‐DM) and diabetes mellitus (DM) but not in subjects with normal glucose tolerance (NGT). When divided by quartiles of UACR, the cumulative survival rate decreased acrossing the quartiles. Compared to the subjects with lowest quartile of UACR, participants with UACR ≥7.40 mg/gCr had a higher risk of all‐cause mortality, and participants with UACR ≥16.60 mg/gCr had an increased risk of cardiovascular mortality in all hyperglycemia subjects. The optimal predictive cutoff point of UACR was about 17 mg/gCr. Conclusion UACR was an independent predictor of all‐cause and cardiovascular mortality in population with pre‐DM and DM but not in the subjects with NGT. The optimal predictive cutoff point of UACR is about 17 mg/gCr, which was far below the diagnostic cutoff point of microalbuminuria. Earlier interventions of albuminuria should be initiated from very early stage of hyperglycemia to reduce the burden of death in all patients whose glucose metabolism are impaired.

IntroductionThe escalation of urbanization correlates with rising rates of inflammatory bowel disease (IBD), necessitating research into new etiological factors. This study aims to elucidate the gut microbiota profiles in IBD patients and compare them with healthy controls in a western city of China.MethodsWe conducted a multicenter case-control study from the end of 2020, using 16S rRNA gene sequencing (n = 36) and metagenomic sequencing (n = 12) to analyze the gut microbiota of newly diagnosed IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC).ResultsOur results demonstrated a significant enrichment of the phylum Proteobacteria, particularly the genus Escherichia-Shigella, in CD patients. Conversely, the genus Enterococcus was markedly increased in UC patients. The core gut microbiota, such as the Christensenellaceae R-7 group, Fusicatenibacter, and Holdemanella, were primarily identified in healthy subjects. Additionally, significant interactions between the microbiome and virulence factors were observed.DiscussionThe findings suggest that oxidative stress may play a pivotal role in the pathology of IBD. This study contributes to the growing dialogue about the impact of gut microbiota on the development of IBD and its variations across different geographies, highlighting potential avenues for further research.

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is a prevalent pregnancy-specific complication that presents with maternal itching and elevated serum bile acid levels. ICP is associated with unfavorable pregnancy outcomes, severely decreasing the pregnant woman’s quality of life. Timely identification of ICP is crucial for effective management and improved outcomes. Methods We collected urine samples from 8 patients with ICP and 8 healthy individuals. We used Liquid Chromatography-Mass Spectrometry (LC-MS) to detect metabolite expression levels, then conducted a series of bioinformatic analyses to explore the potential biological meanings of differentially expressed metabolites, and preliminarily discovered several candidate biomarkers. To validate these candidate biomarkers, we performed Gas Chromatography-Mass Spectrometry (GC-MS) detection and analyzed their diagnostic values using receiver operating characteristic (ROC) curve. Results Untargeted metabolomics data showed that 6129 positive peaks and 6218 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory capability in discriminating ICP specimens from controls. Subsequent analysis extracted 64 significantly differentially expressed metabolites, which could be potential biomarkers for diagnosis of ICP. Based on the KEGG enrichment analyses, six candidate biomarkers were preliminarily identified. Two most promising biomarkers (3-hydroxypropionic acid and uracil) were validated by targeted metabolomics analyses with the area under the curve (AUC) of 0.920 and 0.850 respectively. Conclusion Based on preliminary screening from untargeted metabolomics and subsequent validation through targeted metabolomics, 3-hydroxypropionic acid and uracil were identified as promising diagnostic biomarkers for ICP.

Sesuvium portulacastrum L. is a dicotyledonous halophyte belonging to the family Aizoaceae. Its young leaves are highly nutritious, and many ecotypes are used as leafy vegetable and medicinal crops. Additionally, due to their tolerance to soil salinity, flooding, and high temperatures, some ecotypes are used for the remediation of saline soils. As a result, there is an increasing need for a large number of disease-free S. portulacastrum propagules. This study developed an efficient protocol for the regeneration of S. portulacastrum through indirect shoot organogenesis. Leaf explants were cultured on Murashige and Skoog basal medium supplemented with different concentrations of zeatin (ZT) and indole-3-acetic acid (IAA). Callus was induced in all explants cultured with 1.5 mg/L ZT only or 1.5 mg/L ZT with 0.5 mg/L IAA. The callus was cut into small pieces and cultured on the same medium on which it was initially induced. ZT at 1.5 mg/L induced 73.7% of callus pieces to produce adventitious shoots, and the shoot numbers per callus piece were up to 20. To improve the in vitro rooting of adventitious shoots, commonly known as microshoots or microcuttings, an endophytic fungus, Cladosporium ‘BF-F’, was inoculated onto the rooting medium. ‘BF-F’ substantially enhanced rooting and plantlet growth, as the root numbers were three times more and plantlet heights were 70% greater than those without ‘BF-F’ inoculation. To detect the genes involved in the enhanced rooting and plantlet growth, qRT-PCR analysis was performed. Results showed that genes related to auxin responses and nitrogen uptake and metabolism were highly upregulated in ‘BF-F’-inoculated plantlets. Plants inoculated with ‘BF-F’ grew vigorously after being transplanted into a sand–soil substrate. Thus, this study not only established an efficient protocol for the regeneration of S. portulacastrum but also developed a novel method for improving the rooting of microshoots and plantlet growth. The established propagation system could be used for producing a large number of S. portulacastrum plantlets for commercial use and also for genetic transformation.

Intrahepatic cholestasis of pregnancy (ICP) is one of the common pregnancy complications that may threaten the health of both pregnant women and their fetuses. Hence, it is of vital importance to identify key moleculars and the associated functional pathways of ICP, which will help us to better understand the pathological mechanisms as well as to develop precise clinical biomarkers. The emerging and developing of multiple omics approaches enable comprehensive studies of the genome, transcriptome, proteome and metabolome of clinical samples. The present review collected and summarized the omics based studies of ICP, aiming to provide an overview of the current progress, limitations and future directions. Briefly, these studies covered a broad range of research contents by the comparing of different experimental groups including ICP patients, ICP subtypes, ICP fetuses, ICP models and other complications. Correspondingly, the studied samples contain various types of clinical samples, in vitro cultured tissues, cell lines and the samples from animal models. According to the main research objectives, we further categorized these studies into two groups: pathogenesis and diagnosis analyses. The pathogenesis studies identified tens of functional pathways that may represent the key regulatory events for the occurrence, progression, treatment and fetal effects of ICP. On the other hand, the diagnosis studies tested more than 40 potential models for the early-prediction, diagnosis, grading, prognosis or differential diagnosis of ICP. Apart from these achievements, we also evaluated the limitations of current studies, and emphasized that many aspects of clinical characteristics, sample processing, and analytical method can greatly affect the reliability and repeatability of omics results. Finally, we also pointed out several new directions for the omics based analyses of ICP and other perinatal associated conditions in the future.

Moso bamboo (Phyllostachys pubescens) stands as a pivotal economic bamboo species globally, holding substantial potential for carbon sequestration. Accurate estimation of aboveground biomass (AGB) in Moso bamboo forests is crucial due to its close ties with the ecosystem's carbon cycle. Despite the maturation of monitoring techniques for Pantana phyllostachysae Chao, a significant pest of Moso bamboo, its interplay with AGB in these forests remains enigmatic. This study addressed this gap by categorizing P. phyllostachysae's impact on Moso bamboo forests into four levels: healthy, mild damage, moderate damage, and severe damage. By scrutinizing field data, we delved into the shifts in Moso bamboo leaf biomass under P. phyllostachysae stress. Leveraging Sentinel-2A/B imagery, we extracted diverse correlation factors, including original wave bands, vegetation indices, texture attributes, and vegetation's physical and chemical parameters. Subsequently, machine learning algorithms-namely, random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB) were employed to achieve remote sensing inversion of AGB in Moso bamboo forests, accounting for the presence of insect pests. We analyzed the response of Moso bamboo biomass sensitive factors and to further clarify the changes of AGB of Moso bamboo forests under insect pest stress at the remote sensing level ultimately. The results showed that (1) the degree of Moso bamboo leaf biomass damage was positively related to the damage level, which gradually increased from 15.15 % to 59.42 %; (2) the RF algorithm excelled in estimating Moso bamboo forest AGB, particularly in May, and inclusion of insect pest considerations enhanced AGB estimation accuracy; (3) among the four factor types, Band information and vegetation indices emerged as most impactful, and Band5, Band11, Band12, NDVI68a and MSAVI were selected the most often; (4) at the remote sensing level, AGB in Moso bamboo forests significantly varies under P. phyllostachysae stress. Healthy areas demonstrate an AGB of 66.9037 Mg ha−1, while heavily affected regions drop to 52.6591 Mg ha−1. It can be seen that combining pest factors for Moso bamboo biomass estimation solves the problem of rough biomass estimation, and this study provides a more promising method for forest growth monitoring.

Variegated temple bamboo (Sinobambusa tootsik f. luteoloalbostriata) is one of the native variegated bamboo species has some whole green (WG) and whole white (WW) leaves in addition to striped green and white ones. The life span of WW leaves is short, but the life span of striped leaves (SLs) is unaffected by the area of white mesophyll, and the SL phenotype is well maintained. To explore the mechanism of phenotypic stability of SL, we took five leaf phenotypes as study materials: WG, WW, SL, the green part of SL (SG), and the white part of SL (SW). Through the measurement of photosynthetic pigments, leaf nutrient elements, chloroplast synthesis–related hormones and their precursors in the leaves, and antioxidant system parameters, we examined the antioxidant adaptation mechanism of the white mesophyll cells of S. tootsik f. luteoloalbostriata. The results indicated that abscisic acid (ABA) levels were substantially higher in WW leaves than in SW leaves, and salicylic acid (SA) levels were significantly higher in SW leaves compared with WW leaves. Levels of 12-oxo-phytodienoic acid (OPDA), and SA were substantially higher in WW and SW than in the leaves of the other three phenotypes. Glutathione (GSH) levels were substantially higher in SW than in SG and reactive oxygen species (ROS) levels were significantly lower. Overall, the white mesophyll cells of S. tootsik f. luteoloalbostriata had strong antioxidant properties. SA and OPDA jointly act on the antioxidant pathway to reduce the content of ROS in leaves, thus ensuring the stability of SL.

Bamboo groves predominantly thrive in tropical or subtropical regions. Assessing the efficacy of remote sensing data of various types in extracting bamboo forest information from bright and shadow areas is a critical issue for achieving precise identification of bamboo forests in complex terrain. In this study, 34 features were obtained from Sentinel-1 SAR and Sentinel-2 optical images using the Google Earth Engine platform. The normalized shaded vegetation index (NSVI) was then employed to segment the bright and shadow woodlands. Different features from diverse data sources were evaluated to extract bamboo forest information in the bright and shadow areas, then use the random forest (RF) classification algorithm to extract bamboo forest. The results showed that (1) the red-edge and short-wave infrared bands of Sentinel-2 optical images and their corresponding vegetation indices are significant in bamboo forest information extraction. (2) The dissimilarity and homogeneity of Sentinel-2 texture features in the bright area and dissimilarity in the shadow area, the Sentinel-1 backscatter features in the bright area and the VV and VH in the bright area and VV-VH in the shadow area have some variability between bamboo and nonbamboo forests, which can be used as effective features for bamboo forest extraction. (3) The combination of spectral, texture and backscatter features yields the highest overall classification accuracy and Kappa coefficient, at 87.96% and 0.7435, respectively. This study has the potential for remote sensing refinement of bamboo forest identification in complex terrain areas by utilizing subregion classification methods combined with optical and radar image features.

Exploring the combined effects of multisensory interactions in open spaces can help improve the comfort of campus environments. Nine typical spaces on a university campus in Fuzhou were selected for this study. Subjects perceived the environment and then completed an on-site subjective questionnaire. At the same time, meteorological data (global radiation, air temperature, globe temperature, wind speed, relative humidity, and illumination intensity) were measured to determine the interactions between visual and acoustic and thermal perceptions. Differences in the meteorological parameters between the measuring points were described using a one-way ANOVA and Tukey’s post hoc test, and a chi-square test of independence was used to determine significant associations between thermal, acoustic, and visual comfort, which in turn led to the study of interactions between visual, acoustic, and thermal comfort using a two-way ANOVA. The following conclusions were drawn: (1) the Thermal Comfort Vote (TCV) increased with the increasing Acoustic Comfort Vote (ACV) at all levels of thermal stress. (2) The highest and lowest Acoustic Sensation Vote (ASV) values for each sound type were derived from either “slightly cold” or “warm” conditions. Both the Thermal Comfort Vote (TCV) and the Acoustic Comfort Vote (ACV) were positively correlated. (3) When “neutral”, the Thermal Sensation Vote (TSV) increased with increasing illumination intensity (LUX). (4) The Sunlight Sensation Vote (SSV) increased with the increasing Universal Thermal Climate Index (UTCI) when illumination intensity (LUX) was moderate and bright. (5) The highest and lowest Acoustic Sensation Vote (ASV) values for each sound type came from either “slightly cold” or “warm” conditions.

The objective of this study was to deeply understand the adaptation mechanism of the functional traits of Moso bamboo Phyllostachys pubescens syn. edulis (Poales: Poaceae) leaves to the environment under different Pantana phyllostachysae Chao damage levels, analyzing the changes in the relationship between specific leaf area (SLA) and leaf dry matter content (LDMC). We combined different machine learning models (decision tree, RF, XGBoost, and CatBoost regression models), and used different canopy heights and different levels of infestation, to analyze the changes in the relationship between the two under different levels of infestation based on the results of the best estimation model. The results showed the following: (1) The SLA of Ph. pubescens showed a decreasing trend with the increase om insect pest degree, and LDMC showed an inverse trend. (2) The SLA of bamboo leaves was negatively correlated with the LDMC under different insect pest degrees; the correlation of the data under the healthy class was higher than that of other insect pest levels, and at the same time better than that of the full sample, which laterally confirmed the effect of insect pest stress on the functional traits of Ph. pubescens leaves. (3) When modeling under different infestation levels, the CatBoost model was used for heavy damage and the RF model was used for the rest of the cases; the decision tree regression model was used when modeling different canopy heights. The findings contribute certain insights into the nuanced responses and adaptive mechanisms of Ph. pubescens forests to environmental fluctuations. Moreover, these results furnish a robust scientific foundation, essential for ensuring the enduring sustainability of Ph. pubescens forest ecosystems.

Background: Intrahepatic cholestasis of pregnancy (ICP) is likely to lead to unfavorable consequences. Total bile acid (TBA) is thought to be the sole ICP indicator available as of now, but it comes with some kind of restrictions in terms of sensitivity and specificity. We were endeavoring to find potential diagnostic biomarkers for ICP in this investigation. Methods: This case-control study with a prospective nature included 40 females in the stage of pregnancy who were diagnosed with ICP. It also included another 20 females who were also pregnant but with sound physical condition(control). Placental and plasma samples were collected from all females that were in the stage of pregnancy, except for 20 ICP patients, in which only plasma was collected. We used four-dimensional data-independent acquisition followed by enzyme-linked immunosorbent assay and immunohistochemistry to identify and validate plasma and placental profiles in ICP patients and controls. Bioinformatics was adopted in an effort to demonstrate the relevant biological processes and signalling pathways. Correlation analysis was used to analyse the consistency of tissue and plasma protein expression and the correlation between sequencing and experimental results. Results: The expression levels of nectin-1 (NECTIN1), Kunitz-type protease inhibitor 1 (SPINT1), and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) were remarkably higher in ICP patients than in controls. However, heparin cofactor 2 (SERPIND1) expression levels in female participants in the stage of pregnancy who were diagnosed with ICP were remarkably lower than those pregnant females with good physical fitness. In addition to the negative correlation between SERPIND1 and TBA, NECTIN1, SPINT1, and ITIH3 expression positively correlated with TBA. Area under the receiver operating characteristic curve (AUC) values of 0.7925, 0.8313, 0.8163, and 0.9025, respectively, were used to assess the diagnostic accuracies of NECTIN1, SPINT1, ITIH3, and SERPIND1. AUC (0.9438) was considerably greater when NECTIN1, SPINT1, and SERPIND1 were integrated, according to binary logistic regression. The AUC of the ROC curve for various combinations of SERPIND1 and other indicators was higher than itself, thus providing a more reliable ICP diagnosis. Furthermore, according to the bioinformatics analysis, the NECTIN1, SPINT1, ITIH3, and SERPIND1 were identified as secreted proteins because they were localized in the extracellular region. Conclusions: This research discovered new non-invasive ICP indicators. On top of this, it sheds new light on the crucial diagnostic function of secreted proteins in ICP.

IntroductionThis study explored the associations of intrinsic capacity (IC), fall risk, and frailty in geriatric inpatients.MethodsA total of 703 hospitalized patients aged 75 years or older were recruited for this retrospective observational study from Zhejiang Hospital using a comprehensive geriatric assessment. The IC composite score was constructed from the scores of the Chinese version of the Mini-Mental State Examination, Short Physical Performance Battery, Short Form Mini Nutritional Assessment, 15-item Geriatric Depression Scale, and self-reported hearing and vision impairment. Adverse outcomes were recorded as the fall risk and frailty using the Morse Fall Scale and the Clinical Frailty Scale. Spearman’s correlation coefficient analyses and multivariate logistic regression models were used to explore the associations between IC, high fall risk, and frailty.ResultsDeclined IC composite scores were associated with increased risks of falls [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.57–0.72] and frailty (OR = 0.45, 95%CI: 0.37–0.54) among older hospitalized patients after adjusting for the related potential confounders. In addition, decreased cognitive, vitality, locomotion, and psychological scores were associated with increased adverse health conditions, with ORs ranging from 0.26 to 0.70. Vision impairment was observed to increase the risk of frailty (OR = 0.42, 95%CI: 0.23–0.76) after adjusting for the related potential confounders.DiscussionThis study indicated that declined IC was associated with fall risk and frailty in older inpatients. Further prospective studies are needed to explore the longitudinal associations between baseline IC and subsequent risk of falls and frailty.

Analyzing the coupling coordination interactions of higher education (HE) and digital economy (DE) to achieve sustainable growth is crucial. Thus, we constructed the coupling coordination interaction mechanism and the comprehensive evaluation system of the two subsystems to measure their coordination interactions; then, we processed the temporal-spatial analysis of the development status and the coupling coordination degree (CCD) in the case of China. Furthermore, we used the gray correlation model to determine the primary influencing factors and proposed differentiated policymaking suggestions. We found that: (1) the development status of higher education (HE-D) was more stable than that of the digital economy (DE-D), which showed a slight upward trend; besides, there were noticeable spatial differences for HE-D and DE-D. (2) The temporal changes of CCD were not noticeable. (3) Expenditure on research activities in HE and the number of patents were the significant factors affecting DE; the popularity rate of mobile phones and the number of employees in the DE industry were the significant factors affecting HE; besides, HE's output benefits and DE's input was more influential in the coordination relations. Furthermore, we also put forward targeted, specific, and differentiated policymaking suggestions, which can guide policymakers to formulate regional sustainable development policies.

Abstract Ciclopirox (CPX), an antifungal drug, has recently been identified as a promising agent for cancer treatment. However, the effects and underlying mechanism of CPX as an antitumor agent of gastric cancer (GC) remain largely unknown. Here, we found that CPX dramatically suppresses GC xenograft growth in vitro via inhibiting proliferation and stimulating autophagic cell death rather than apoptosis. Moreover, CPX (20 mg/kg, intraperitoneally) substantially inhibits GC xenograft tumor growth in vivo. Mechanistically, CPX promotes growth arrest and autophagic cell death through suppressing the phosphorylation of signal transducers and activators of transcription 3 (STAT3) at tyrosine 705 (Tyr705) and serine 727 (Ser727) sites, respectively. Additionally, CPX induces STAT3 ubiquitination, which subsequently leads to a decrease in the p-STAT3 (Ser727) level. On the other hand, CPX represses the p-STAT3 (Tyr705) level via p-Src (Tyr416) inhibition. Collectively, our findings unmask a novel mechanism by which CPX regulates growth and autophagic cell death in GC cells via regulating the phosphorylation of STAT3 both at Tyr705 and Ser727 residues, and suggest that CPX may be a potential treatment for GC.

Abstract Background Sleep disturbance, chronic pain and depressive symptoms later in life are modifiable risk factors and may contribute to frailty. However, much less is known about sex differences in the association between these concurrent symptoms and frailty in older patients. Therefore, we conducted this study to explore the associations of poor sleep quality, chronic pain, and depressive symptoms with frailty in older patients, and the sex-specific associations. Methods In an observational population-based study, 540 older hospitalized patients from Zhejiang Hospital in China were enrolled. We collected data on poor sleep quality, pain, depressive symptoms and frailty using the Pittsburgh Sleep Quality Index, the Numerical Rating Scale, the 15-item Geriatric Depression Scale, and the Clinical Frailty Scale. Multivariate logistic regression models were used to explore the total sample and sex-specific associations among symptom burdens, symptom combination patterns and symptom counts, and frailty. Results After adjusting for the potential covariates, concurrent poor sleep quality and depressive symptoms (OR = 4.02, 95% CI 1.57–10.26), concurrent poor sleep quality and chronic pain (OR = 2.05, 95% CI 1.04–4.05), and having three symptoms (OR = 3.52, 95% CI 1.19–10.44) were associated with a higher likelihood of frailty in older inpatients. In addition, older patients with 2 or 3 symptoms (2 and 3 vs. 0 symptoms) had a higher risk of frailty, and the odds ratios were 2.40 and 3.51, respectively. Interaction analysis and sex-stratified associations exhibited conflicting results. The nonsignificant effect of the interaction of sex and symptoms on frailty, but not the sex-stratified associations, showed that individual symptoms, symptom combination patterns, and symptom counts were associated with elevated risks of frailty in older male patients, but not in older female patients. Conclusions Increased symptom burdens were associated with a higher risk of frailty in older inpatients, especially in those with poor sleep quality concurrent with at least one of the other two symptoms. Thus, a multidisciplinary program addressing these common symptoms is required to reduce adverse outcomes.

Mendelian randomization can be used to mimic the effects of protein-targeting drugs in a population of individuals. Here, the authors have identified potential causal proteins for stroke in a two-sample Mendelian randomization framework, providing potential stroke therapeutic targets.

Abstract Background Angiotensin-converting enzyme 2 (ACE2) is known as a tumor suppressor and lowly expressed in most cancers. The expression pattern and role of ACE2 in breast cancer (BC) have not been deeply elucidated. Methods A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). The correlation of ACE2 expression and immunological characteristics in the BC tumor microenvironment (TME) was evaluated. The role of ACE2 in predicting the response to therapeutic options was estimated. Moreover, the pharmacodynamic effect of angiotensin-(1–7) (Ang-1–7), the product of ACE2, on chemotherapy and immunotherapy was evaluated on the BALB/c mouse BC model. In addition, the plasma samples from BC patients receiving neoadjuvant chemotherapy were collected and subjected to the correlation analysis of the expression level of Ang-1–7 and the response to neoadjuvant chemotherapy. Results ACE2 was lowly expressed in BC tissues compared with that in adjacent tissues. Interestingly, ACE2 was shown the highest correlation with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB) in BC. In addition, a high level of ACE2 indicated a low response to endocrine therapy and a high response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. In the mouse model, Ang-1–7 sensitized mouse BC to the chemotherapy and anti-PD-1 immunotherapy, which revealed its significant anti-tumor effect. Moreover, a high plasma level of Ang-1–7 was associated with a better response to neoadjuvant chemotherapy. Conclusions ACE2 identifies immuno-hot tumors in BC, and its enzymatic product Ang-1–7 sensitizes BC to the chemotherapy and immunotherapy by remodeling the TME.

This study aims to explore the influence of spatial functional differences on the overall relationship between soundscape and visual landscape in the context of historical blocks and then propose design guidelines for audiovisual elements. Audiovisual stimulus materials were collected from 11 representative locations in typical urban historical blocks along the southeast coast of China and classified into residential, cultural leisure, and commercial spaces based on their primary function, activity, and visual environment characteristics. An evaluation environment was created in the laboratory using virtual reality technology, and a subjective evaluation questionnaire was administered to 71 volunteers regarding the perception of audiovisual elements and the evaluation of the overall environment. Structural equation modeling was used to elucidate the relationships between sound source perception, soundscape perception, visual landscape satisfaction, and overall harmony of the environment and to compare the effects of functional differences at different locations on the overall relationships. The results show significant differences in the types of perceived sound sources at different functional locations, which makes the sound sources affecting soundscape perception and visual landscape satisfaction different. Residential space is mainly affected by artificial sound and mechanical noise; in cultural and leisure spaces, all three types of sound sources have a significant impact, and only natural sound has enhanced subjective perception; the impact of artificial sound in commercial space is crucial. In addition, visual landscape satisfaction should be prioritized over soundscape pleasure to enhance the overall harmony of the environment. In residential and commercial spaces, reducing artificial and mechanical noise can effectively enhance the harmony of the environment; in cultural and leisure areas, reducing artificial sounds and increasing natural sounds or historical landscape elements can enhance the overall harmony of the environment. The results of this paper provide empirical evidence for understanding the overall relationship between soundscape factors in urban contexts and suggest that place function should be considered an important context when designing soundscapes.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has a prevalence of ∼25% worldwide, with significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants in mitochondrial amidoxime-reducing component 1 (MTARC1) have been associated with NAFLD and liver-related mortality; however, its pathophysiological role and the cell type(s) mediating these effects remain unclear. We aimed to investigate how MTARC1 exerts its effects on NAFLD by integrating human genetics with in vitro and in vivo studies of mARC1 knockdown. Methods: Analyses including multi-trait colocalisation and Mendelian randomisation were used to assess the genetic associations of MTARC1. In addition, we established an in vitro long-term primary human hepatocyte model with metabolic readouts and used the Gubra Amylin NASH (GAN)-diet non-alcoholic steatohepatitis mouse model treated with hepatocyte-specific N-acetylgalactosamine (GalNAc)–siRNA to understand the in vivo impacts of MTARC1. Results: We showed that genetic variants within the MTARC1 locus are associated with liver enzymes, liver fat, plasma lipids, and body composition, and these associations are attributable to the same causal variant (p.A165T, rs2642438 G>A), suggesting a shared mechanism. We demonstrated that increased MTARC1 mRNA had an adverse effect on these traits using Mendelian randomisation, implying therapeutic inhibition of mARC1 could be beneficial. In vitro mARC1 knockdown decreased lipid accumulation and increased triglyceride secretion, and in vivo GalNAc–siRNA-mediated knockdown of mARC1 lowered hepatic but increased plasma triglycerides. We found alterations in pathways regulating lipid metabolism and decreased secretion of 3-hydroxybutyrate upon mARC1 knockdown in vitro and in vivo. Conclusions: Collectively, our findings from human genetics, and in vitro and in vivo hepatocyte-specific mARC1 knockdown support the potential efficacy of hepatocyte-specific targeting of mARC1 for treatment of NAFLD. Impact and implications: We report that genetically predicted increases in MTARC1 mRNA associate with poor liver health. Furthermore, knockdown of mARC1 reduces hepatic steatosis in primary human hepatocytes and a murine NASH model. Together, these findings further underscore the therapeutic potential of targeting hepatocyte MTARC1 for NAFLD.

Breast cancer has been confirmed to have lipid disorders in the tumour microenvironment. Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcriptional factor that belongs to the family of nuclear receptors. PPARα regulates the expression of genes involved in fatty acid homeostasis and is a major regulator of lipid metabolism. Because of its effects on lipid metabolism, an increasing number of studies have investigated the relationship of PPARα with breast cancer. PPARα has been shown to impact the cell cycle and apoptosis in normal cells and tumoral cells through regulating genes of the lipogenic pathway, fatty acid oxidation, fatty acid activation, and uptake of exogenous fatty acids. Besides, PPARα is involved in the regulation of the tumour microenvironment (anti-inflammation and inhibition of angiogenesis) by modulating different signal pathways such as NF-κB and PI3K/AKT/mTOR. Some synthetic PPARα ligands are used in adjuvant therapy for breast cancer. PPARα agonists are reported to reduce the side effects of chemotherapy and endocrine therapy. In addition, PPARα agonists enhance the curative effects of targeted therapy and radiation therapy. Interestingly, with the emerging role of immunotherapy, attention has been focused on the tumour microenvironment. The dual functions of PPARα agonists in immunotherapy need further research. This review aims to consolidate the operations of PPARα in lipid-related and other ways, as well as discuss the current and potential applications of PPARα agonists in tackling breast cancer.

Many individual genetic risk loci associate with multiple diseases, but the molecular basis of these loci often remains unclear. Here, the authors provide a framework to reveal the genetic cross-disease associations at the PROCR vascular disease locus.

The acoustic environment can influence people’s perceptions and experiences and shape the soundscape. The soundscape has a unique role in shaping the cultural identity of a regional culture. Artificial sounds are an essential source of sounds in historical blocks; research has shown the influence of the ratio of perceived artificial sounds to the perceived extent of natural sounds on environmental perception in historical blocks. In order to explore this impact, this study uses the red soundscape index (RSIn), which represents the ratio of perceived artificial sounds to natural sounds, and constructs a structural equation model to elucidate the relationship between RSIn, soundscape perception, and sense of place. The results show that: (1) The evaluation of the sense of place is inversely related to the perception of artificial sounds and positively related to the perception of natural sounds. (2) Different artificial sounds have different effects on soundscape perception and the sense of place; the traditional culture soundscape index (TRSIn) has a significant impact on soundscape pleasantness (β = −0.13, p < 0.001) and soundscape quality (β = −0.09, p < 0.01). (3) The human soundscape index (ARSIn) has a significant impact on the sense of place (β = −0.14, p < 0.001). (4) The music soundscape index (MRSIn) has a significant negative impact on soundscape quality (β = −0.13, p < 0.05) and the sense of place (β = −0.12, p < 0.05). Therefore, the different dominant artificial sound sources should be considered and emphasized when designing and optimizing the soundscape of historic districts. The results of this study can serve as design guidelines and supporting data, providing a reference for the optimization and enhancement of the soundscape of historical blocks.

Abstract Background It has been revealed that B7H4 is negatively correlated with PDL1 and identifies immuno-cold tumors in glioma. However, the application of the B7H4-PDL1 classifier in cancers has not been well testified. Methods A pan-cancer analysis was conducted to evaluate the immunological role of B7H4 using the RNA-sequencing data downloaded from the Cancer Genome Atlas (TCGA). Immunohistochemistry (IHC) and multiplexed quantitative immunofluorescence (QIF) were performed to validate the primary results revealed by bioinformatics analysis. Results The pan-cancer analysis revealed that B7H4 was negatively correlated with PDL1 expression and immune cell infiltration in CeCa. In addition, patients with high B7H4 exhibited the shortest overall survival (OS) and relapse-free survival (RFS) while those with high PDL1 exhibited a better prognosis. Multiplexed QIF showed that B7H4 was mutually exclusive with PDL1 expression and the B7H4-high group exhibited the lowest CD8 + T cell infiltration. Besides, B7H4-high predicted highly proliferative subtypes, which expressed the highest Ki67 antigen. Moreover, B7H4-high also indicated a lower response to multiple therapies. Conclusions Totally, the B7H4-PDL1 classifier identifies the immunogenicity and predicts proliferative subtypes and limited therapeutic options in CeCa, which may be a convenient and feasible biomarker in clinical practice.

Biochemical components of Moso bamboo (Phyllostachys pubescens) are critical to physiological and ecological processes and play an important role in the material and energy cycles of the ecosystem. The coupled PROSPECT with SAIL (PROSAIL) radiative transfer model is widely used for vegetation biochemical component content inversion. However, the presence of leaf-eating pests, such as Pantana phyllostachysae Chao (PPC), weakens the performance of the model for estimating biochemical components of Moso bamboo and thus must be considered. Therefore, this study considered pest-induced stress signals associated with Sentinel-2A/B images and field data and established multiple sets of biochemical canopy reflectance look-up tables (LUTs) based on the PROSAIL framework by setting different parameter ranges according to infestation levels. Quantitative inversions of leaf area index (LAI), leaf chlorophyll content (LCC), and leaf equivalent water thickness (LEWT) were derived. The scale conversions from LCC to canopy chlorophyll content (CCC) and LEWT to canopy equivalent water thickness (CEWT) were calculated. The results showed that LAI, CCC, and CEWT were inversely related with PPC-induced stress. When applying multiple LUTs, the p-values were

ObjectiveTo evaluate the efficacy of Paxlovid in treating Chinese elder patients infected with SARS-CoV-2 omicron variants.Materials and methodsWe performed a non-randomized, controlled trial in Shanghai, China. Participants infected with SARS-CoV-2 omicron variants were enrolled. All patients were divided into the Paxlovid group or the control group according to the Chinese guideline (version 9). The nucleic acid shedding time was the primary endpoint.ResultsAccording to the inclusion criteria, 142 patients infected with omicron variants were enrolled, 36 patients who did not receive paxlovid were assigned to the control group, and 106 were in the Paxlovid group. The baseline characteristics were similar in either group. No significant difference in BMI, age, time from onset to patient enrollment, the severity on first admission, vaccination status, comorbidity, first symptoms, and laboratory results were recorded. Compared to the control group, participants in the Paxlovid group had a shorter viral shedding time [11.11 (2.67) vs. 9.32 (2.78), P = 0.001].ConclusionIn Chinese elder patients infected with the variant of SARS-CoV-2 omicron, our data suggest that Paxlovid can significantly reduce the nucleic acid shedding time.

Abstract Ciclopirox (CPX) is an antifungal drug that has recently been reported to act as a potential anticancer drug. However, the effects and underlying molecular mechanisms of CPX on glioblastoma multiforme (GBM) remain unknown. Bortezomib (BTZ) is the first proteasome inhibitor-based anticancer drug approved to treat multiple myeloma and mantle cell lymphoma, as BTZ exhibits toxic effects on diverse tumor cells. Herein, we show that CPX displays strong anti-tumorigenic activity on GBM. Mechanistically, CPX inhibits GBM cellular migration and invasion by reducing N-Cadherin, MMP9 and Snail expression. Further analysis revealed that CPX suppresses the expression of several key subunits of mitochondrial enzyme complex, thus leading to the disruption of mitochondrial oxidative phosphorylation (OXPHOS) in GBM cells. In combination with BTZ, CPX promotes apoptosis in GBM cells through the induction of reactive oxygen species (ROS)-mediated c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling. Moreover, CPX and BTZ synergistically activates nuclear factor kappa B (NF-κB) signaling and induces cellular senescence. Our findings suggest that a combination of CPX and BTZ may serve as a novel therapeutic strategy to enhance the anticancer activity of CPX against GBM.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).

Abstract Background Sarcandra glabra is an evergreen and traditional Chinese herb with anti-oxidant, anti-bacterial, anti-inflammatory, and anti-tumor effects. Light is one of the most influential factor affecting the growth and quality of herbs. In recent times, the introduction of Light Emission Diode (LED) technology has been widely used for plants in greenhouse. However, the impact of such lights on plant growth and the regulatory mechanism of phenylpropanoid-derived compounds in S. glabra remain unclear. Results The red LED light (RL) substantially increased the plant height and decreased the stem diameter and leaf area relative to the white LED light (WL), while the blue LED light (BL) significantly reduced the height and leaf area of S. glabra. According to transcriptomic profiling, 861, 378, 47, 10,033, 7917, and 6379 differentially expressed genes (DEGs) were identified among the groups of leaf tissue under BL (BY) vs. leaf tissue under RL (RY), BY vs. leaf tissue under WL (WY), RY vs. WY, root tissue under WL (WG) vs. WY, stem tissue under WL (WJ) vs. WG, and WJ vs. WY, respectively. We identified 46 genes encoding for almost all known enzymes involved in phenylpropanoid biosynthesis, e.g., phenylalanine ammonia lyase (PAL), chalcone synthase (CHS), and flavonol synthase (FLS). We found 53 genes encoding R2R3-MYB proteins and bHLH proteins, respectively, where several were related to flavonoids biosynthesis. A total of 454 metabolites were identified based on metabolomic profiling, of which 44, 87, and 296 compounds were differentially produced in WY vs. RY, WY vs. BY, and WY vs. WG. In BY there was a substantial reduction in the production of esculetin, caffeic acid, isofraxidin, and fraxidin, while the yields of quercitrin and kaempferol were significantly up-regulated. In RY, the contents of cryptochlorogenic acid, cinnamic acid, and kaempferol decreased significantly. Besides, in WG, the production of metabolites (e.g. chlorogenic acid, cryptochlorogenic acid, and scopolin) declined, while their yields increased significantly (e.g. esculetin, fraxetin, isofraxidin, and fraxidin). Conclusion These results provide further insight into the regulatory mechanism of accumulation patterns of phenylpropanoid-derived compounds in S. glabra under various light conditions, allowing optimum breeding conditions to be developed for this plant.

Abstract Background Motoric cognitive risk syndrome (MCR) is a newly proposed predementia syndrome incorporating subjective cognitive complaints and slow gait. Previous studies have reported that subjective cognitive complaints and slow gait are associated with frailty in cognitively unimpaired older adults, but little is known about the link between MCR and frailty in older adults. Therefore, the aim of the study was to explore the associations of MCR and its components with frailty in older Chinese adults. Methods In an observational cross-sectional study, a total of 429 older adults aged 60 years and older were admitted to the geriatric department. According to MCR criteria, all participants were classified into 4 groups: 1) the MCR group; 2) the subjective cognitive complaints only group; 3) the slow gait only group; and 4) the healthy control group. Physical frailty was assessed by the Clinical Frailty Scale (CFS). Multivariate logistic regression analysis was used to examine the association between MCR and frailty in older adults. Results The prevalence rates of subjective cognitive complaints, slow gait and MCR were 15.9, 10.0 and 4.0%, respectively. After adjusting for confounding variables, the logistic regression analysis showed that slow gait (odds ratio [OR]: 3.40, 95% confidence interval [CI]: 1.40–8.23, P = 0.007) and MCR (OR: 5.53, 95% CI: 1.46–20.89, P = 0.012) were independently associated with frailty, but subjective cognitive complaints were not. Conclusions MCR and slow gait were significantly associated with frailty in older Chinese adults. Further studies should prospectively determine the causal relationship between MCR and frailty.

Context The relationship between resveratrol and histone acetylation in renal cell carcinoma (RCC) has not yet been reported. Objective To explore the functional role of resveratrol in RCC. Materials and methods Functional experiments were performed to determine proliferatio n of ACHN cells with treatment of resveratrol (0, 7.8125, 15.625, 31.25 and 62.5 μg/mL, for 12, 24 and 48 h of culture) or 0.1 μM SAHA. The enzyme activities of MMP-2/-9 were measured by gelatine zymography and histone acetylation by Western blot. Results When the cells were treated with 15.625, 31.25 and 62.5 μg/mL resveratrol, ACHN cells viability was 73.2 ± 3.5%, 61.4 ± 3.1%, 50.2 ± 4.7% for 12 h, 62.7 ± 4.5%, 52.4 ± 5.5%, 40.2 ± 3.8% for 24 h, and 60.8 ± 3.7%, 39.4 ± 5.1%, 37.6 ± 2.7% for 48 h, and the wound closure (%) of migration was increased from 0.6 to 0.7, 0.85, 0.9 for 12 h and from 0.23 to 0.3, 0.48, 0.59 for 24 h. The invasion rate was 8.5 ± 0.9%, 7.4 ± 0.3% and 5.8 ± 0.6%, and cell cycle was arrested at G1 from 42.5 ± 2.9% to 55.3 ± 5.7%, 59.8 ± 3.4%, 68.7 ± 4.6%. MMP-2/-9 expression (p

Systemic lupus erythematosus (SLE) shows a striking bias towards higher prevalence in females. Here, the authors perform fine-mapping of an SLE-associated locus at Xp21.2 and characterise a candidate gene, CXorf21, as IFN-responsive in immune cells that shows sexually dimorphic expression.

Abstract Zinc finger 644 (Zfp644 in mouse, ZNF644 in human) gene is a transcription factor whose mutation S672G is considered a potential genetic factor of inherited high myopia. ZNF644 interacts with G9a/GLP complex, which functions as a H3K9 methyltransferase to silence transcription. In this study, we generated mouse models to unravel the mechanisms leading to symptoms associated with high myopia. Employing TALEN technology, two mice mutants were generated, either with the disease-carrying mutation (Zfp644 S673G ) or with a truncated form of Zfp644 (Zfp644 Δ8 ). Eye morphology and visual functions were analysed in both mutants, revealing a significant difference in a vitreous chamber depth and lens diameter, however the physiological function of retina was preserved as found under the high-myopia conditions. Our findings prove that ZNF644/Zfp644 is involved in the development of high-myopia, indicating that mutations such as, Zfp644 S673G and Zfp644 Δ8 are causative for changes connected with the disease. The developed models represent a valuable tool to investigate the molecular basis of myopia pathogenesis and its potential treatment.

Adolescence is a developmental epoch characterized by massive neural circuit remodeling; thus, the brain is particularly vulnerable to environmental influences during this period. Excessive high-fat diet (HFD) consumption, which is very common among adolescents, has long been recognized as a potent risk factor for multiple mood disorders, including depression and anxiety. However, the precise mechanisms underlying the influences of HFD consumption in adolescence on emotional health are far from clear. In the present study, C57BL/6 mice were fed a control diet (CD) or HFD for about 4 weeks from postnatal day (P) 28 to P60, spanning most of the adolescence period, and then subjected to behavioral assessments and histological examinations. HFD mice exhibited elevated levels of depression and anxiety, decreased hippocampal neurogenesis, and excessive microglial activation in the ventral hippocampus. Furthermore, in HFD-fed mice, microglia showed increased DCX+ inclusions, suggesting aberrant microglial engulfment of newborn neurons in HFD-fed adolescents. To our knowledge, this is the first observation suggesting that the negative effects of HFD consumption in adolescence on emotion and neuroplasticity may be attributed at least in part to aberrant microglial engulfment of nascent neurons, extending our understanding of the mechanism underlying HFD-related affective disorders in young people.

Branch patterns play a key role in assessing plant architecture and are adapted to forest ecosystems. The study aimed to reveal the pattern of branch traits at various distances and orientations from the seashore. For that reason, four sites with various distances from the seashore (SP1: 50–60 m, SP2: 60–100 m, SP3: 100–200 m, and SP4: 200–800 m) were selected and branch traits of Dendrocalamus minor var. amoenus were determined in Dongshan Island, China. The results showed that there were differences in the branch traits between both the 1st-order and 2nd-order branches, and distance from seashore had a significant impact on branch angle, length, diameter, and the number of leaves of 1st-order branches, whereas branch diameter, length, and the number of leaves of 2nd-order branches. In different orientations, the branch angle, length, number, and diameters of the 1st-order and 2nd-order branches showed no significant differences. Nonetheless, the number of leaves of the 1st-order branches were significantly influenced by different orientations. D. minor var. amoenus exhibited strong phenotypic plasticity with longer branches and formed a sparse crown shape. It adjusted the fractal dimension of the crown and branches by modulating the allometric growth relationships among branching traits to adapt to harsh coastal pressure. This study would provide valuable recommendations for D. minor var. amoenus as windbreaks in the coastal climate.

Bambusa albolineata (local name: Hua Zhu) is found in Zhejiang, Jiangxi, Fujian, Taiwan, and Guangdong provinces of China, and is often cultivated on low hills, flatlands, and along streams and rivers. Due to its long internodes and flexible material, it is used as timber wood in China. In the current research, the complete chloroplast (CP) genome of B. albolineata was sequenced and reported for the first time. The complete CP genome sequence was 139,326 bp, including a large single-copy (LSC) region of 82,862 bp, a small single-copy (SSC) region of 12,870 bp, and a pair of invert repeats (IR) regions of 21,798 bp. Besides, the plastid genome consisted of 129 genes; having 82 protein-coding genes, 39 tRNA genes, and eight rRNA genes. The overall GC content of the genome was 44.2%. The phylogenetic analysis based on the complete chloroplast genome indicates that B. albolineata is strongly related to B. flexuosa and B. boniopsis.