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Abstract Background The causal relationships between sexually transmitted infections, depression, and self-harm remain unclear. Methods We executed various Mendelian Randomization (MR) analyses. At the same time, a cross-sectional analysis from NHANES was used for verification and an enrichment analysis was also utilized to explore the potential common gene functions. Results We found that STIs may have a potential causal effect on depression (P = 0.002) and self-harm (P = 0.003). Conversely, self-harm has been identified as a risk factor for the acquisition of STIs (P = 0.006), while there is no evidence to support an effect of depression on STIs. Furthermore, mediation MR indicated that monocyte absolute count played a mediating role in the association between STIs and depression, accounting for 7.7%. And then, the weighted regression analysis of the cross-sectional analysis demonstrated a significant association between one of the common STIs, HPV, and depression. Gene enrichment analysis suggested that the PI3K-Akt signalling pathway and the infectious virus signalling pathway may represent a common underlying pathogenesis. Conclusion STIs may increase the risk of depression and self-harm, while self-harm might also represent a risk factor for STIs, which could provide insights and a foundation for the control of STIs and mental health monitoring in clinical practice.

This study aimed to analyze the effect of Issatchenkia orientalis on the microbial community structure and volatile flavor substance synthesis in Nongxiangxing Baijiu Jiupei in order to explore its effect on the microbial interaction and metabolism in the Jiupei. Under laboratory conditions, the microbial system for Nongxiangxing Baijiu brewing consisting of the Jiupei and Huangshui, a by-product of Baijiu brewing, was fermented directly (control group) or after inoculation with a strain of I. orientalis isolated from the Jiupei (experimental group). The composition of microbial communities, microbial interactions, and volatile flavor substances in the 2 groups were analyzed. The results showed that the microbial abundance of Jiupei changed after inoculation with I. orientalis; the relative abundance of Lactobacillus and Issatchenkia increased, and the relative abundance of Paenibacillus and Aspergillus decreased. Moreover, the microbial interaction was strengthened, making the microbial network structure more complex and compact. Compared with the control group, the volatile flavor substances in the experimental group increased significantly, 20 significantly differential volatile flavor substances were identified, and the contents of isopropanol, isoamylol and isobutanol increased significantly. The results of this study disclose the influences of inoculating I. orientalis on the microbial community structure and volatile flavor substances in Nongxiangxing Baijiu Jiupei and help to understand the impact of functional microorganisms on the microbial perturbation and metabolite synthesis in Jiupei.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. Methods We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. Results A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. Conclusions These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Abstract Post‐stroke depression is a common complication that imposes significant burdens and challenges on patients. The occurrence of depression is often associated with frontal lobe hemorrhage, however, current understanding of the underlying mechanisms remains limited. Here, the pathogenic mechanisms associated with the circuitry connectivity, electrophysiological alterations, and molecular characteristics are investigated related to the frontal lobe in adult male mice following unilateral injection of blood in the medial prefrontal cortex (mPFC). It is demonstrated that depression is a specific neurological complication in the unilateral hematoma model of the mPFC, and the ventral tegmental area (VTA) shows a higher percentage of connectivity disruption compared to the lateral habenula (LHb) and striatum (STR). Additionally, long‐range projections originating from the frontal lobe demonstrate higher damage percentages within the connections between each region and the mPFC. mPFC neurons reveal reduced neuronal excitability and altered synaptic communication. Furthermore, transcriptomic analysis identifies the involvement of the Janus Kinase‐Signal Transducer and Activator of Transcription (JAK‐STAT) signaling pathway, and targeting the JAK‐STAT pathway significantly alleviates the severity of depressive symptoms. These findings improve the understanding of post‐hemorrhagic depression and may guide the development of efficient treatments.

Due to significant anatomical variations in medical images across different cases, medical image segmentation is a highly challenging task. Convolutional neural networks have shown faster and more accurate performance in medical image segmentation. However, existing networks for medical image segmentation mostly rely on independent training of the model using data samples and loss functions, lacking interactive training and feedback mechanisms. This leads to a relatively singular training approach for the models, and furthermore, some networks can only perform segmentation for specific diseases. In this paper, we propose a causal relationship-based generative medical image segmentation model named GU-Net. We integrate a counterfactual attention mechanism combined with CBAM into the decoder of U-Net as a generative network, and then combine it with a GAN network where the discriminator is used for backpropagation. This enables alternate optimization and training between the generative network and discriminator, enhancing the expressive and learning capabilities of the network model to output prediction segmentation results closer to the ground truth. Additionally, the interaction and transmission of information help the network model capture richer feature representations, extract more accurate features, reduce overfitting, and improve model stability and robustness through feedback mechanisms. Experimental results demonstrate that our proposed GU-Net network achieves better segmentation performance not only in cases with abundant data samples and relatively simple segmentation targets or high contrast between the target and background regions but also in scenarios with limited data samples and challenging segmentation tasks. Comparing with existing U-Net networks with attention mechanisms, GU-Net consistently improves Dice scores by 1.19%, 2.93%, 5.01%, and 5.50% on ISIC 2016, ISIC 2017, ISIC 2018, and Gland Segmentation datasets, respectively.

BackgroundBotrytis cinerea a blueberry gray mold, is one of the main diseases affecting postharvest storage, causing significant losses. Several studies have shown that Bacillus tequilensis can prevent the growth of plant pathogens by producing various antibacterial substances, and can induce plant resistance. However, research on the biological management of post-harvest gray mold in blueberries using B. tequilensis remains unclear.MethodsTo better control the postharvest gray mold of blueberry, the effects of B. tequilensis KXF6501 fermentation solution (YY) and KXF6501 cell-free supernatant (SQ) on the induction of disease resistance in blueberry fruits were studied using biochemical and transcriptomic analyses.ResultsWe found that YY controlled the conidial germination and mycelial growth of B. cinerea in vitro, followed by SQ. After 3 d of culture, the lesion diameter and incidence of gray mold in blueberry fruits inoculated with YY and SQ were smaller than those in the control group. Therefore, gray mold in blueberries was effectively controlled during the prevention period, and the control effect of YY was better than that of SQ. Transcription spectrum analysis of blueberry peel tissue showed that the YY- and SQ-induced phenylpropane metabolic pathways had more differentially expressed genes (DEGs) than other biological pathways. In addition, biochemical analyses showed that YY treatment effectively enhanced the activity of enzymes related to the phenylpropane pathway (phenylalanine ammonialyase [PAL], cinnamate 4-hydroxylase [C4H], 4-coumarate CoA ligase [4CL], and polyphenol oxidase [PPO]) and stimulated the synthesis of lignin, total phenols, and flavonoids, followed by SQ. Compared with the control, the YY and SQ treatments reduced the weight loss rate and better maintained the appearance and nutritional quality of the blueberry fruits.ConclusionOur findings suggest that B. tequilensis KXF6501 is potentially useful as a suitable bio-control agent in harvested blueberries.

Oxidative stress and its impact on aging are critical areas of research. Natural anti-oxidants, such as saponins found in Polygonatum sibiricum, hold promise as potential clinical interventions against aging. In this study, we utilized the nematode model organism, Caenorhabditis elegans, to investigate the pharmacological effects of Polygonatum sibiricum saponins (PKS) on antioxidation and anti-aging. The results demonstrated a significant anti-aging biological activity associated with PKS. Through experiments involving lifespan and stress, lipofuscin, q-PCR, and ROS measurement, we found that PKS effectively mitigated aging-related processes. Furthermore, the mechanism underlying these anti-aging effects was linked to the SKN-1 signaling pathway. PKS increased the nuclear localization of the SKN-1 transcription factor, leading to the up-regulation of downstream anti-oxidant genes, such as gst-4 and sod-3, and a substantial reduction in intracellular ROS levels within the nematode. In conclusion, our study sheds light on the anti-oxidant and anti-aging properties of PKS in C. elegans. This research not only contributes to understanding the biological mechanisms involved but also highlights the potential therapeutic applications of these natural compounds in combating aging-related processes.

Convolutional neural network-based methods have significantly enhanced the segmentation performance of biomedical images in recent years. Nevertheless, medical image segmentation presents a challenge marked by layout specificity, with limited variation between samples in medical datasets but significant variation within each individual sample. This aspect has been often overlooked by many models. Consequently, we propose a novel architecture called Attention based multi-scale nested network (AMNNet), specifically designed for efficient biomedical image segmentation. AMNNet comprises four components: early ReSidual U-CBAM (RSUC) modules and convolutional stages, a MLP stage in latent stage, and Convolutional Block Attention Modules (CBAM) integrated into the decoder stage. We introduce a lightweight CBAM to concentrate on regions proximate to the target and suppress extraneous features without substantial parameter increments. The RSUC module is proposed to combine receptive fields of different sizes, capturing comprehensive contextual information across various scales in medical samples. Extensive experiments conducted on the AMNNet reveal its outperformance compared to prevailing medical image segmentation methods across the ISIC2018, CVC-ClinicDB, CVC-ColonDB, BUSI, and GlaS datasets. Notably, AMNNet achieves Dice Similarity Coefficients (DSC) of 91.35%, 90.01%, 90.80%, 81.61%, and 94.31%, respectively.

In recent years, with the rapid development of live-streaming commerce, the social dynamics and psychological impact of such online activities merit further discussion. In this study, we investigate the sensory experiences of viewers watching live streaming and examine how these online experiences influence consumer well-being. We developed a conceptual model to understand this mechanism based on the relationship between social presence, shopping enjoyment, familiarity, and consumer well-being. The results of 410 samples indicate that (1) social presence in live-streaming commerce has a significant positive effect on consumer well-being; (2) shopping enjoyment plays a mediating role in the process of social presence predicting consumer well-being; and (3) familiarity plays a moderating role in the second half of the indirect effect of social presence on well-being. This study examines the relationship between social presence and consumer well-being in the context of live-streaming marketing, expanding the research scenario of consumer well-being and clarifying the psychological mechanisms and boundary conditions of the effect of social presence on consumers well-being, which has important implications for online interactive marketing enterprises to enhance social presence and promote consumers long-term well-being.

BackgroundThis study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS.MethodsA total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied.ResultsThe male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8–13.1 years), the disease duration was 1.0 month (IQR, 0.5–2.0 months), and follow-up was 36.5 months (IQR, 25.7–50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)—these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001).ConclusionEndothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.

Abstract Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications. Herein, we report the rational design and synthesis of water‐soluble keratins using a simple methodology named the QTY code. In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200‐fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins. Homotypic self‐assembly was observed for the first time in recombinant keratins in an aqueous environment, without urea and after QTY modification. Cell and animal experiments showed the in situ gel‐forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins. Our work not only presented a simple and feasible pathway to produce large amounts of water‐soluble keratins using QTY modification but also validated the enhanced self‐assembly, hemostasis, and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.

Biochar application has received much attention because biochar can be used as an organic amendment. The nutrient release patterns and interactions in straw biochar produced at different temperatures are not well understood. In this study, we observed the release patterns of carbon (C), nitrogen (N), phosphorus (P), and potassium (K) and the interaction between released C, N, P, and K from straw biochar prepared from 225 to 600 °C through a 180-day degradation experiment. The results showed that the degradation rate of the two kinds of straw biochar was faster in the first 30 days at different temperatures, and that of the straw biochar prepared before 300 °C was more rapid, indicating that 300 °C is an important turning point. The rule of nutrient release in the straw biochar showed that the K release rate was the highest and most rapid and was more than 60% in the first 30 days. The nutrient release rates for the two kinds of straw biochar were in the order K > N > P > C. The release of nutrients accompanied the decomposition of the straw biochar, and there was an exponential relationship between the amount of nutrients released from straw biochar and its degradation mass. There were collaborative or similar release processes indicated by significant positive correlations between the released C and N (R2 = 0.96) and P and K (R2 = 0.94) in the tobacco straw biochar and an obvious correlation between the released C and N (R2 = 0.76) in the rice straw biochar. These results indicated that the released C and N, P, and K in tobacco straw biochar, as well as C and N in rice straw biochar, have synergistic effects and the same degradation path. The application of straw biochar can provide a source of P and N in the short term and a source of P and C in the long term. This study suggests that returning straw biochar to the soil could appropriately reduce the input of K fertilizer in the early stage.

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Abstract Background Researches and practice of traditional Chinese medicine indicated that Agrimonia pilosa Ledeb could improve insulin resistance (IR) and treat type 2 diabetes (T2DM). To reveal its underling mechanisms, we isolated Flavonoid component (FC) from Agrimonia pilosa Ledeb and elucidated its effects on glucose metabolism to improve IR by suppressing oxidative stress and inflammation. Methods Adipocytes or mice IR model was established with overdosed glucose and insulin or high-fat diet. The uptake of 2-NBDG and glucose consumption were measured to verify insulin sensitivity in vitro and vivo. Reactive oxidative species (ROS) were detected by flow cytometry, and superoxide dismutase (SOD) activity as well as the malondialdehyde (MDA) content were also measured. Meanwhile, factors associated with insulin signal pathway including PPARγ, insulin receptor substrate-1 (IRS-1), GLUT4, and oxidative stress including NF-E2-related factor 2 (Nrf2), as well as the related inflammatory cytokines such as NF-κB, IL-1β, IL-6 and TNF-α were tested. Furthermore, the JNK/PI3K/Akt signal pathway was also explored. Results FC extracted from Agrimonia pilosa Ledeb ameliorated the impaired glucose metabolism significantly. Further study indicated that FC could regulate the insulin signal pathway to improve insulin resistance. Moreover, it could upregulate PPARγ with the similar efficacy as pioglitazone (Piog) straightway. FC also decreased the endogenous ROS and MDA content, increased SOD activity and Nrf2 expression to facilitate oxidative homeostasis. It attenuated expression and secretion of inflammatory cytokines obviously. At last, our results indicated JNK/PI3K/Akt pathway was regulated by FC in adipocytes and adipose tissue. Conclusion FC could ameliorate glucose metabolism and improve IR. It exerted these effects by suppressing oxidative stress and inflammation. FC from Agrimonia pilosa Ledeb has a good prospect to be drugs or functional foods for IR and T2DM.

Abstract In this paper, using the notion of w-distance in metric spaces, we introduce two types of nonlinear contractions, ( ι , ψ , φ , ϕ , p ) $(\iota ,\psi ,\varphi ,\phi ,p)$ and rational- ( ι , ψ , φ , ϕ , p ) $(\iota ,\psi , \varphi ,\phi ,p)$ contractions. Based on these contractions, we prove the existence and uniqueness of a φ-fixed point for the corresponding contraction. We also provide some examples to demonstrate the correctness and practicability of our results, along with a numerical experiment. Finally, we apply the obtained results to linear matrix equations and nonlinear Fredholm integral equations.

PurposeWe aimed to compare the relative diagnostic efficacy of 68Ga-Labeled DOTA-ibandronic acid (68Ga-DOTA-IBA) to that of18F-NaF PET/CT as a mean of detecting bone metastases in patients with a range of cancer typesMethodsThis study retrospectively enrolled patients with bone metastases associated with various underlying malignancies. All patients underwent both 68Ga-DOTA-IBA and 18F-NaF PET/CT scans. Histopathology and follow-up CT or MRI imaging results were used as reference criteria, with a minimum follow-up period of 3 months. The maximum Standardized Uptake Value (SUVmax) and number of bone metastases were recorded. The Target-Background Ratio (TBR) was calculated along with the detection rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 68Ga-DOTA-IBA and 18F-NaF PET/CT imaging for overall and partial primary solid tumor bone metastases. Pearson chi-square test, McNemar test, and Kappa test was conducted to assess the correlation and consistency of diagnostic efficiency between the two imaging agents. Receiver Operating Characteristic curve (ROC curve) was performed to compare diagnostic performance and the area under the curve of the two imaging agents, determining optimal critical values for SUVmax and TBR in diagnosing bone metastasis. Differences in SUVmax and TBR values between the two imaging agents for detecting bone metastases were analyzed using the Wilcoxon signed rank test. The difference was statistically significant when P < 0.05ResultsA total of 24 patients (13 women and 11 men) were included in this study, with a mean age of 52 (interquartile range, 49-64 years). The detection rate, sensitivity, specificity, PPV, NPV, accuracy, and AUC of 68Ga-DOTA-IBA and 18F-NaF PET/CT for bone metastases were 81%, 90%, 62%, 95%, 43%, 88%, 0.763, and 89%, 99%, 59%, 95%, 89%, 95%, 0.789, respectively. There was no significant difference between the two imaging methods (P < 0.01), and there was a significant correlation (X2=168.43, P < 0.001) and a strong consistency (Kappa=0.774,P < 0.001) between the diagnostic results of the two imaging agents. The SUVmax values of lesions measured by 68Ga-DOTA-IBA and 18F-NaF imaging in 22 patients with bone metastasis were 5.1 ± 5.4 and 19.6 ± 15.1, respectively, with statistically significant differences (P

Abstract Background Bone defects remain a challenge today. In addition to osteogenic activation, the crucial role of angiogenesis has also gained attention. In particular, vascular endothelial growth factor (VEGF) is likely to play a significant role in bone regeneration, not only to restore blood supply but also to be directly involved in the osteogenic differentiation of mesenchymal stem cells. In this study, to produce additive angiogenic-osteogenic effects in the process of bone regeneration, VEGF and Runt-related transcription factor 2 (Runx2), an essential transcription factor for osteogenic differentiation, were coadministered with messenger RNAs (mRNAs) to bone defects in the rat mandible. Methods The mRNAs encoding VEGF or Runx2 were prepared via in vitro transcription (IVT). Osteogenic differentiation after mRNA transfection was evaluated using primary osteoblast-like cells, followed by an evaluation of the gene expression levels of osteogenic markers. The mRNAs were then administered to a bone defect prepared in the rat mandible using our original cationic polymer-based carrier, the polyplex nanomicelle. The bone regeneration was evaluated by micro-computerized tomography (μCT) imaging, and histologic analyses. Results Osteogenic markers such as osteocalcin (Ocn) and osteopontin (Opn) were significantly upregulated after mRNA transfection. VEGF mRNA was revealed to have a distinct osteoblastic function similar to that of Runx2 mRNA, and the combined use of the two mRNAs resulted in further upregulation of the markers. After in vivo administration into the bone defect, the two mRNAs induced significant enhancement of bone regeneration with increased bone mineralization. Histological analyses using antibodies against the Cluster of Differentiation 31 protein (CD31), alkaline phosphatase (ALP), or OCN revealed that the mRNAs induced the upregulation of osteogenic markers in the defect, together with increased vessel formation, leading to rapid bone formation. Conclusions These results demonstrate the feasibility of using mRNA medicines to introduce various therapeutic factors, including transcription factors, into target sites. This study provides valuable information for the development of mRNA therapeutics for tissue engineering.

Background Maintaining brain health is an advanced goal of healthy ageing. Eating a diet with appropriate nutrients has been identified as a promising approach to reducing the risk of dementia, but community-dwelling residents have inadequate or no health guidance from medical workers since there is no detailed and comprehensive clinical dietary nutrients management program for brain health promotion for community-dwelling people . Objective To search, evaluate and summarize the evidence on dietary nutrients management for brain health promotion in community-dwelling people, providing an evidence-based basis for clinical implementation of such management for this group of population. Methods In March 2022, we searched UpToDate, BMJ Best Practice, JBI Model of Evidence-based Healthcare, National Institute on Aging, Registered Nurses' Association of Ontario, the Cochrane Library, PubMed, CNKI, Medlive and other databases to collect literature (involving clinical decisions, recommended practices, guidelines, evidence summaries, expert consensuses and systematic reviews) regarding dietary nutrients management for brain health promotion in community-dwelling people. The retrieval period was from January 1, 2017 to March 29, 2022. Two researchers systematically trained in evidence-based medicine independently screened literature, extracted data, and evaluated the quality of the included literature. Then evidence was extracted from the included literature, and its quality was graded, then the best evidence was summarized. Results A total of 28 studies with an overall high methodological quality were included, including three clinical guidelines, five expert consensuses, one clinical decision and 19 systematic reviews. Finally, 23 pieces of best evidence were summarized, involving seven aspects of intervention timing, dietary nutrients assessment and screening, dietary patterns and components, specific nutrients, coffee intake, body weight management, health education and guidance. Conclusion Eating a diet with appropriate nutrients can promote brain health of residents. Community medical workers should develop an individualized dietary nutrients management program for brain health for them in accordance with the practical clinical situation, residents' current dietary nutrients status and preferences, and insights from the best evidence.

Abstract Background Syphilis is a sexually transmitted disease caused by Treponema pallidum, and the infection source is syphilis patients. This study aimed to estimate the incidence, mortality rate, and disability-adjusted life years (DALYs) of syphilis to improve the understanding of the current global situation of syphilis. Methods This study collected data on syphilis incidence, mortality, and DALYs from the 2019 Global Burden of Disease database. Results The global number of incident cases and age-standardized incidence rate (ASIR) increased from 8,845,220 (95% UI: 6,562,510–11,588,860) in 1990 to 14,114,110 (95% UI: 10,648,490–18,415,970) in 2019 and 160.03/100,000 persons (95% UI: 120.66–208.1) to 178.48/100,000 persons (95% UI: 134.94–232.34), respectively. The estimated annual percentage change (EAPC) in the ASIR was 0.16 (95% CI: 0.07–0.26). The EAPC in the ASIR associated with high and high-middle sociodemographic indices increased. The ASIR increased among males but decreased among females, and the incidence peaked among males and females between the ages of 20 and 30 years. The EAPCs in the age-standardized death rate and age-standardized DALY rate decreased. Conclusions The incidence and ASIR of syphilis increased worldwide from 1990 to 2019. Only the regions with high and high-middle sociodemographic indices showed an increase in the ASIR. Moreover, the ASIR increased among males but decreased among females. The age-standardized death rate and DALY rate both declined worldwide. The increase in the global ASIR of syphilis is a challenge.

Accurate segmentation of skin lesions is a challenging task because the task is highly influenced by factors such as location, shape and scale. In recent years, Convolutional Neural Networks (CNNs) have achieved advanced performance in automated medical image segmentation. However, existing CNNs have problems such as inability to highlight relevant features and preserve local features, which limit their application in clinical decision-making. This paper proposes a CNN with an added attention mechanism (EA-Net) for more accurate medical image segmentation.EA-Net is based on the U-Net network model framework. Specifically, we added a pixel-level attention module (PA) to the encoder section to preserve the local features of the image during downsampling, making the feature maps input to the decoder more relevant to the ground-truth. At the same time, we added a spatial multi-scale attention module (SA) after the decoding process to increase the spatial weight of the feature maps that are more relevant to the ground-truth, thereby reducing the gap between the output results and the ground-truth. We conducted extensive segmentation experiments on skin lesion images from the ISIC 2017 and ISIC 2018 datasets. The results demonstrate that, when compared to U-Net, our proposed EA-Net achieves an average Dice score improvement of 1.94% and 5.38% for skin lesion tissue segmentation on the ISIC 2017 and ISIC 2018 datasets, respectively. The IoU also increases by 2.69% and 8.31%, and the ASSD decreases by 0.3783 pix and 0.5432 pix, indicating superior segmentation performance. EA-Net can achieve better segmentation results when the original image of skin lesions has an obscure boundary and the segmentation area contains interference factors, which proves that the addition of attention mechanism in the encoder and the application of comprehensive attention mechanism can improve the performance of neural network in the field of skin lesions image segmentation.

Infectious wounds have become serious challenges for both treatment and management in clinical practice, so development of new antibiotics has been considered an increasingly difficult task. Here, we report the design and synthesis of keratin 31 (K31)-peptide glycine-leucine-amide (PGLa) photopolymerized hydrogels to rescue the antibiotic activity of antibiotics for infectious wound healing promotion. K31-PGLa displayed an outstanding synergistic effect with commercial antibiotics against drug-resistant bacteria by down-regulating the synthesis genes of efflux pump. Furthermore, the photopolymerized K31-PGLa/PEGDA hydrogels effectively suppressed drug-resistant bacteria growth and enhanced skin wound closure in murine. This study provided a promising alternative strategy for infectious wound treatment.

AbstractBackground Cardiopulmonary bypass (CPB) is frequently employed for cardiac surgery, and selecting a suitable priming fluid is a prerequisite for CPB. Currently, the commonly used priming fluids in clinics are classified as crystalloids and colloids, including balanced crystalloids, albumin, dextran, gelatin and hydroxyethyl starch (HES). This network meta-analysis compared the effects of eight fluids used during CPB in adults to determine optimal priming fluid during CPB surgery.Methods Randomised controlled trials assessing priming fluids for CPB in adult cardiac surgery published before 13 April 2023 were searched across Ovid MEDLINE(R) ALL, OVID EMbase, and Cochrane Central Register of Controlled Trials. Various priming fluids were classified into eight categories, including balanced crystalloids, 0.9% NaCl, iso-oncotic human albumin, hyperoncotic human albumin, HES with molecular weight 130k, HES with molecular weight 200k, gelatin and dextran.Results The NMA of platelet counts revealed no significant differences in any result. In direct comparison results, only the comparison of HES with molecular weight 130k vs. gelatin (standard mean difference = −0.40, 95% confidence interval [95%CI: −0.63, −0.16) revealed a significant difference. According to the SUCRA, balanced crystalloids had the highest platelet count, followed by gelatin, and HES with a molecular weight of 130k had the lowest platelet, followed by HES with a molecular weight of 200k.Conclusion Patients using dextran have a low mortality rate and a short mean CPB time, the use of balanced crystalloids is beneficial in terms of platelet count, and HES with molecular weight 130k is beneficial for postoperative urine volume at 24h. However, all priming fluids have pros and cons quite, and the optimal choice of priming fluids remains unsupported by current evidences. When performing CPB surgery, the type of priming fluid should be selected according to the actual situation in CPB for adult cardiac surgery.

Objective Intervertebral disc degeneration (IDD) is the main cause of back pain, and its treatment is a serious socio‐economic burden. The safety and treatment of fecal microbiota transplantation (FMT) has been established. However, the relationship between FMT and IDD still unclear. We aimed to explore whether FMT plays a role in IDD to provide a reference for the treatment of IDD. Methods An experimental model of IDD was established using 2‐month‐old male Sprague–Dawley rats. FMT was performed by intragastric gavage of IDD rats with a fecal bacterial solution. Rat serum, feces, and vertebral disc tissue were collected after surgery for 2 months. The levels of TNF‐α, IL‐1β, IL‐6, matrix metalloproteinase (MMP)‐3, MMP‐13, Collagen II, and aggrecan in the serum or vertebral disc tissue were measured by an enzyme‐linked immunosorbent assay, immunohistochemistry, quantitative real‐time polymerase chain reaction, or western blotting. We also examined the pathology of the vertebral disc tissue using hematoxylin and eosin (HE) and safranin O‐fast green staining. Finally, we examined the gut microbiota in rat feces using 16 S rRNA gene sequencing. Results We found that the expression of TNF‐α, IL‐1β, IL‐6, MMP‐3, MMP‐13, NLRP3 and Caspase‐1 increased in the IDD group rats. In contrast, Collagen II and aggrecan levels were downregulated. Additionally, vertebral disc tissue was severely damaged in the IDD group, with disordered cell arrangement and uneven safranin coloration. FMT reversed the effects of IDD modeling on these factors and alleviated cartilage tissue damage. In addition, FMT increased the gut microbiota diversity and microbial abundance in rats treated with IDD. Conclusion Our findings suggest that FMT has a positive effect in maintaining cellular stability in the vertebral disc and alleviating histopathological damage. It affects the diversity and abundance of gut microbiota in rats with IDD. Therefore, FMT may serve as a promising target for amelioration of IDD.

Background: Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) may enhance the efficacy of treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT); however, it remains unclear. We aim to evaluate the efficacy of TACE combined with TKIs. Methods: A thorough literature search was performed on major databases since their inception until October 2022. Based on the eligibility criteria, eight studies (2103 patients) were included. Results: Meta-analysis showed that TACE+sorafenib/apatinib had a better tumor response (objective response rate (ORR): RR = 4.85, 95% CI 2.68–8.75, disease control rate (DCR): RR = 3.23, 95% CI 1.88–5.56), and prolonged OS (HR = 0.50, 95%CI 0.42–0.60, p < 0.00001) than TACE alone. TACE+lenvatinib was stronger than TACE+sorafenib in ORR (60.7% vs. 38.9%) and TTP (HR = 0.61, 95% CI 0.43–0.86), whereas it was similar in DCR (96.4% vs. 96.3%) and OS (HR = 0.70 95% CI 0.46–1.05). Conclusions: TACE plus sorafenib or apatinib was superior to TACE alone for hepatocellular carcinoma with PVTT; no significant advantage was found between TACE+lenvatinib and TACE+sorafenib, although TACE+lenvatinib performed better in terms of ORR and TTP.

Abstract Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates, resistance to combined therapy, and dismal prognosis. Glioma stem cells (GSCs) are likely responsible for tumor progression, resistance to therapy, recurrence, and poor prognosis owing to their high self-renewal and tumorigenic potential. As a family member of BMP signaling, bone morphogenetic protein4 (BMP4) has been reported to induce the differentiation of GSCs and neural stem cells (NSCs). However, the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear. In this study, we treated hGSCs and hNSCs with BMP4 and compared the phenotypic and transcriptional changes between these two cell types. Phenotypically, we found that the growth of hGSCs was greatly inhibited by BMP4, but the same treatment only increased the cell size of hNSCs. While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs, the profiles of differentially expressed genes were distinct between the two groups. A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture. Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation. Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

Abstract In this paper, we first introduce several new contractions by some auxiliary functions. Then we establish some φ-fixed point results for ( γ , ψ , φ , ϕ ) $(\gamma ,\psi ,\varphi ,\phi )$ contractions, rational- ( γ , ψ , φ , ϕ ) $(\gamma , \psi ,\varphi ,\phi )$ contractions and almost- ( γ , ψ , φ , ϕ ) $(\gamma ,\psi , \varphi ,\phi )$ contractions and φ-fixed disc results for ( ψ , φ , ϕ ) x 0 $(\psi ,\varphi ,\phi )_{x_{0}}$ type 1 contractions, ( ψ , φ , ϕ ) x 0 $(\psi ,\varphi ,\phi )_{x_{0}}$ type 2 contractions, and ( ψ , φ , ϕ ) x 0 $(\psi ,\varphi ,\phi )_{x_{0}}$ type 3 contractions in metric spaces. We generalize some existing φ-fixed point and φ-fixed circle results in the literature. Further, we give some examples to demonstrate the usefulness of our results and investigate the existence and uniqueness of solutions of nonlinear integral equations.

Abstract Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-β) is well known for its anti-proliferative efficacy in diverse cancers. IFN-β also displayed potent antitumor effects in malignant glioma. IFN-β affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-β on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-β between human GSCs and normal NSCs. We found that IFN-β preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-β treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-β stimulation. We also found that continuous IFN-β stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-β treatment. These results may contribute to improve the applications of IFN-β in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.

Abstract Introduction To explore the role of IL‐6/JAK/STAT signaling in tubal infertility. Methods The fimbriae tissues of 14 patients with a history of infertility and hydrosalpinx and 14 patients with no history of infertility and no fallopian tube disease were collected. The tissues were then divided into hydrosalpinx group and control group followed by analysis of the protein expression of key factors in the IL‐6/JAK/STAT signaling by immunohistochemistry and Western blot. Results Immunohistochemical staining showed significantly higher level of IL‐6, JAK1, p‐JAK1, JAK2, p‐JAK2, STAT1, p‐STAT1, STAT3, and p‐STAT3 in hydrosalpinx group than those in control group with IL‐6 being mainly located in the cytoplasm and p‐JAK2, STAT1, p‐STAT1, STAT3, and p‐STAT3 in the cytoplasm and nucleus. JAK1 and p‐JAK1 was mainly located in the cytoplasm and JAK2 is in the cytoplasm and nucleus without difference of their expression between two groups. Consistently, hydrosalpinx group presented significantly higher protein levels of IL‐6, JAK1, p‐JAK1, JAK2, p‐JAK2, STAT1, p‐STAT1, STAT3, and p‐STAT3 than control group without difference of JAK1, p‐JAK1, JAK2 level. Conclusion The activation of IL‐6/JAK2/STAT1 and STAT3 signaling pathways are found in the hydrosalpinx in infertile patients, indicating that they might be involved in the pathogenesis of hydrosalpinx.

In this paper, we introduce α-admissible extended Z-contraction in the extended rectangular b-metric spaces, then we provide some other conditions in Theorem 3.1, which are different from that in Chifu et al. [1], and obtain the existence and uniqueness of fixed point in such spaces. Moreover, some examples are given to show the validity of our main theorems, and we give some corollaries related to our main results. As an application, we apply our main results to solve the existence of solutions for a class of boundary value problems of second order ordinary differential equations.

Polysaccharides including water-soluble fraction (W), 1,2-Cyclohexanediaminetetraacetic acid (CDTA)-soluble fraction (CA), sodium carbonate (Na2CO3)-soluble fraction (SC), 1 M potassium hydroxide (KOH)-soluble fractions (PH1), and 4 M KOH-soluble fraction (PH4) were successively extracted from Dendrocalamus brandisii bamboo shoot shells using water, CDTA, Na2CO3, and KOH solution. The analytical methods were employed to initially identify the structural characteristics of the five polysaccharide fractions, and their antioxidant capacities in vitro were determined. According to the data, the average molecular weight of the five polysaccharide fractions was between 4 816 and 993 935 Da. In all four types (CA, SC, PH1, and PH4), xylose was the most abundant monosaccharide, especially in PH1 and PH4. Both PH1 and PH4 were found to contain 1,4-β-d-Xylp as their main chain, as determined by nuclear magnetic resonance (NMR) spectroscopy. Additional research into CA and SC's antioxidant potential is required since they both showed potent in vitro antioxidant activities.

Aim: This study focusses on the anti-inflammatory and immune-modulatory roles of berberine (BBR) in ulcerative colitis (UC) treatment. Additionally, the underlying mechanisms of BBR were systematically explored. Methods: A 3% (w/v) dextran sodium sulphate (DSS) solution was used for establishing the mice UC model. M2 macrophage polarisation was induced in RAW 264.7 cells using interleukin 4 (IL-4), whereas M1 macrophage polarisation was induced using lipopolysaccharide. Colon length, colon mucosa damage index (CMDI), and haematoxylin–eosin (HE) staining were used to evaluate colon damage induced by DSS. M1/M2 macrophages in the colon tissue were identified using immunofluorescence (IF) staining with CD86+ or CD163+. M1/M2 macrophages in the abdomen were examined using flow cytometry. An enzyme-linked immunosorbent assay was conducted to identify M1/M2 macrophage supernatant biomarkers in RAW 264.7 cells. Western blotting, immunohistochemical staining, and real-time PCR were performed to investigate the potential mechanisms of BBR for treating UC in vivo and in vitro. Results: BBR was found to prolong colon length, ameliorate CMDI and alleviate the colon's pathological changes in UC mice. In DSS-induced UC mice, M1 macrophages predominated. BBR promoted M2 macrophages and suppressed M1 macrophages in the colon and abdomen of DSS-induced UC mice. Additionally, BBR significantly decreased M1-specific markers (IFN-γ and IL-1β) while increasing M2-specific markers (IL-10 and TGF-β) in the supernatants of RAW 264.7 cells. BBR upregulated the mRNA expression of IL-4, STAT6, and Chil3 while downregulating TNF-α, IFN-γ, and NOS2 expression in vivo. Moreover, BBR activated the downstream targets of the IL-4-STAT6 signalling pathway and enhanced the phosphorylation of STAT6 in vivo and in vitro to polarise M2 macrophage. Conclusion: In UC mice, BBR suppressed M1 macrophages while promoting M2 macrophages. M1 macrophage suppression and M2 macrophage activation were strongly correlated with the anti-inflammatory and immune-modulating activities of BBR. BBR induced the polarisation of M2 macrophages by activating the IL-4-STAT6 signalling pathway, which contributed to its therapeutic efficacy against UC.

Objective Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cystatin C (sCysC) are available clinically and beneficial in diagnosing acute kidney injury (AKI). Our purpose is to identify the performance of their combined diagnosis for AKI in critically ill patients.Design A prospectively recruited, observational study was performed.Setting Adults admitted to the intensive care unit of a tertiary hospital in China.Participants A total of 1222 critically ill patients were enrolled in the study.Main outcome measures To identify the performance of the combined diagnosis of serum NT-proBNP and sCysC for AKI in critically ill patients. The area under the receiver operating characteristic curve (AUC-ROC), category-free net reclassification index (NRI) and incremental discrimination improvement (IDI) were utilised for comparing the discriminative powers of a combined and single biomarker adjusted model of clinical variables enriched with NT-proBNP and sCysC for AKI.Results AKI was detected in 256 out of 1222 included patients (20.9%). AUC-ROC for NT-proBNP and sCysC to detect AKI had a significantly higher accuracy than any individual biomarker (p

Aims: To evaluate the efficacy of different pharmacologic treatment for severe hypertension during pregnancy.Methods: Two reviewers searched Ovid MEDLINE, Ovid EMbase, and the Cochrane Library for randomized clinical trials from the establishment of the database to 15 July 2021 that were eligible for inclusion and analyzed the pharmaceuticals used for severe hypertension in pregnancy.Results: 29 relevant trials with 2,521 participants were involved. Compared with diazoxide in rate of achieving target blood pressure, other pharmaceuticals, including epoprostenol (RR:1.58, 95%CI:1.01–2.47), hydralazine\dihydralazine (RR:1.57, 95%CI:1.07–2.31), ketanserin (RR:1.67, 95%CI:1.09–2.55), labetalol (RR:1.54, 95%CI:1.04–2.28), nifedipine (RR:1.54, 95%CI:1.04–2.29), and urapidil (RR:1.57, 95%CI:1.00–2.47), were statistically significant in the rate of achieving target blood pressure. According to the SUCRA, diazoxide showed the best therapeutic effect, followed by nicardipine, nifedipine, labetalol, and nitroglycerine. The three pharmaceuticals with the worst therapeutic effect were ketanserin, hydralazine, and urapidil. It is worth noting that the high ranking of the top two pharmaceuticals, including diazoxide and nicardipine, comes from extremely low sample sizes. Other outcomes were reported in the main text.Conclusion: This comprehensive network meta-analysis demonstrated that the nifedipine should be recommended as a strategy for blood pressure management in pregnant women with severe hypertension. Moreover, the conventional pharmaceuticals, including labetalol and hydralazine, showed limited efficacy. However, it was important to note that the instability of hydralazine reducing blood pressure and the high benefit of labetalol with high dosages intakes should also be of concern to clinicians.

Background and aimsPrevious studies showed that inflammation affects depressive symptoms. Dietary fiber may be associated with inflammation and depressive symptoms. We aimed to investigate the relationship between inflammation and depressive symptoms at different levels of dietary fiber intake and to explore whether dietary fiber affects depression through inflammation.MethodsA total of 8,430 National Health and Nutrition Examination Survey (NHANES) samples were collected between 2015 and 2018. Factor analysis was used to determine dietary patterns. Linear regression and logistic regression analysis were used to explore the relationship between nutrients, inflammation, and depressive symptoms, and the mediation analysis was conducted using the bootstrap method.ResultsFactor 3 (dietary fiber and vitamins) was inversely associated with depressive symptoms and inflammation. The upper quartile scores of the dietary inflammatory index (DII) and C-reactive protein (CRP) were associated with depressive symptoms compared with controls (DII: OR = 1.851, 95% CI: 1.267–2.705; CRP: OR = 1.737, 95% CI: 1.136–2.656). The DII score and CRP were associated with depressive symptoms in the group with low dietary fiber intake (DII: OR = 2.736, 95% CI: 1.628–4.598; CRP: OR = 2.092, 95% CI: 1.196–3.658) but not in the high dietary fiber intake group. Mediating analysis showed that CRP partially mediated the effect of dietary fiber intake on depressive symptoms (βindirect = −0.0025, 95% CI: −0.0038 to −0.0013), and the mediated proportion was 10.5%.ConclusionIn this study, we found that DII scores and CRP were not associated with depressive symptoms in participants with high dietary fiber intake, and inflammation partially mediates the effect of dietary fiber on depressive symptoms.

This meta-analysis assessed the clinical significance of omega-3 polyunsaturated fatty acids (PUFAs) in the management of patients with colorectal cancer (CRC) after radical resection. We comprehensively searched electronic databases, such as EMBASE, PubMed, MEDLINE and Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Database (CBM), Wanfang Electronic Database, and VIP Medical Information System (VIP) from inception to 10 April 2022. Randomized controlled trials (RCTs) of omega-3 PUFAs and conventional nutrition or blank treatments were selected. The following were evaluated in the pooled analysis: immune function-related indices (IgA, IgG, IgM, CD3+, CD4+, CD8+, and ratio of CD4+/CD8+), nutritional status-related indices [total protein (TP), albumin (ALB), and prealbumin (PA)], and their corresponding 95% confidence intervals (CIs). Next, we conducted heterogeneity detection, sensitivity analysis, contour-enhanced funnel plot to detect possible publication bias, and meta-regression analysis. In all, 20 studies, including 1,613 patients (809 in the omega-3 PUFAs group and 804 in the control group), were selected in the final analysis. The results of the pooled analysis showed that omega-3 PUFAs significantly increased the humoral immune function indices, including IgA [standardized mean difference (SMD) = 0.54, 95% CI 0.10–0.99], IgM (SMD = 0.52, 95% CI 0.05–0.99), IgG (SMD = 0.65, 95% CI 0.47–0.84); T cell immune function indices, including CD3+ (SMD = 0.73, 95% CI 0.54–0.92), CD4+ (SMD = 0.76, 95% CI 0.53–0.98), and ratio of CD4+/CD8+ (SMD = 0.66, 95% CI 0.39–0.92). However, CD8+ was markedly reduced after intervention of omega-3 PUFAs (SMD = –0.28, 95% CI –0.66–0.09). In addition, pooled analysis indicated that omega-3 PUFAs markedly improved the nutritional status indicators, including TP (SMD = 0.53, 95% CI 0.17–0.88), ALB (SMD = 0.43, 95% CI 0.15–0.70), and PA (SMD = 0.46, 95% CI 0.01–0.90). The meta-regression analysis revealed that the covariates of the small sample affected the robustness and credibility of the CD4+ results. Conclusively, this study suggested that omega-3 PUFAs have the potential to be used as a valid immunonutritional therapy/support for treating patients with CRC postoperatively. This meta-analysis protocol was registered in PROSPERO (no. CRD42021288487).Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288487], identifier [CRD42021288487].

This meta-analysis intended to systematically evaluate the clinical implications of indocyanine green fluorescence (ICG) in patients undergoing laparoscopic colorectal surgery. PubMed, MEDLINE, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Medical Information System and China Biomedical Database were synthetically searched for studies published from inception to April 14, 2022. The randomized controlled trials comparing ICG-use with controls were selected. The incidence of anastomotic leakage (AL), lymph node detection, operation duration, intraoperative bleeding, postoperative morbidity, and hospitalization time were evaluated in summary analysis, and calculated the corresponding 95% confidence intervals (CI). Subsequently, in addition to subgroup analyses, studies for heterogeneity, sensitivity, and publication bias were carried out. Consequently, 3453 patients in the enrolled 15 studies were included; 1616 patients were allocated to the experimental group, and 1837 patients were assigned to the control group. The ICG group had a significantly decreased risk of AL (RR: 0.50, 95% CI: 0.37–0.67) and shorter hospitalization time (SMD: -0.31, 95% CI: -0.54–0.08) compared to the control group. Meanwhile, the ICG showed clearly better lymph node detection (SMD: 0.19, 95% CI: 0.02–0.36). However, when the content of operation duration (SMD: -0.07, 95% CI: -0.30–0.15) and intraoperative bleeding (SMD: -0.16, 95% CI: -0.35–0.04) were compared, no statistical significance was found. Furthermore, the pooled analysis of postoperative morbidity was not statistically significant (RR:0.79, 95% CI: 0.58–1.08). The results of the subgroup analysis of AL indicated that there may be regional variations in AL (RR: 0.50, 95% CI: 0.37–0.67) but not in postoperative morbidity (RR: 0.79, 95% CI: 0.58–1.08). In conclusion, the application of ICG in laparoscopic colorectal surgery can effectively reduce the AL, lymph node detection, and hospitalization time. However, more multicenter large-sample randomized controlled trials are required to further confirm its advantages. The meta-analysis was registered in PROSPERO (no. CRD42022288054).

BackgroundCutaneous verrucous carcinoma (CVC) is a rare variant of squamous cell carcinoma and sometimes shares similar clinical and histopathological features with other verrucous lesions.MethodsWe performed a retrospective study of 21 patients diagnosed with CVC between 2012 and 2022 by reviewing clinical and histopathological data. We also compared the clinicopathological features of patients with CVC, giant condyloma acuminatum (GCA), and pseudoepitheliomatous hyperplasia (PEH). We obtained follow-up data by reviewing medical records and telephone interviews.ResultsThe average age of patients with CVC was 63.6 years, with a male predominance. The location of disease is mostly found in the foot, followed by the lower legs. Histologically, CVC is characterized by an exo-endophytic growth pattern with severe keratinization and a blunted rete ridge with pushing margins. Clinical features including exudation and crusting, induration, irregular borders, and warty surface, as well as pathological features including growth pattern, koilocytotic cells, depth and morphologic features of acanthosis, severe keratinization, and degree of dermal inflammation, were significant in distinguishing cutaneous CVC, GCA, and PEH.ConclusionIdentification of the clinicopathological features is essential to distinguish CVC from its mimics and to make an early diagnosis. Because of the potential for recurrence and metastasis, CVC requires aggressive treatment.

Camellia fascicularis is a unique plant rich in bioactive components. However, the isolation of the active substances in C. fascicularis leaves via sequential extraction with solvents of different polarity and the determination of their antioxidant and antitumor activities have not been reported. In this study, the total methanol extract of C. fascicularis leaves was sequentially extracted with different polar solvents, and the corresponding petroleum ether extract (PEE), ethyl acetate extract (EAE), and water extract (WE) were analyzed for their contents in active substances such as flavonoids, polyphenols, polysaccharides, and saponins. The antioxidant ability of the polar extracts was investigated by determining their reducing power and the radical scavenging rate on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radicals, and CCK-8 and Annexin-FITC/propidium iodide staining assays were conducted to investigate their inhibitory effects on HCCLM6 and HGC27 tumor cells. The results showed that PEE had a high saponin content of 197.35 ± 16.21 mg OAE/g, while EAE and WE exhibited a relatively higher polysaccharide content of 254.37 ± 1.99 and 373.27 ± 8.67 mg GE/g, respectively. The EAE demonstrated the greatest reducing power and the strongest clearing abilities on ABTS and DPPH radicals with respective EC50 values of 343.45 ± 20.12 and 14.07 ± 0.06 μg/ml. Moreover, the antitumor ability of the different polar extracts was dose-dependent, with WE showing the most potent inhibitory ability against HCCLM6 and HGC27 cells.

Melanoma is a highly aggressive skin cancer and accounts for most of the skin cancer-related deaths. The efficacy of current therapies for melanoma remains to be improved. The isopropanolamine derivative of β-elemene LXX-8250 was reported to present better water solubility and stronger toxicity to tumor cells than β-elemene. Herein, LXX-8250 treatment showed 4-5-fold more toxicity to melanoma cells than the well-known anti-melanoma drug, Dacarbazine. LXX-8250 treatment induced apoptosis remarkably, which was caused by the impairment of autophagic flux. To clarify the molecular mechanism, microarray analyses were conducted, and PFKFB4 expression was found to be suppressed by LXX-8250 treatment. The cells overexpressed with PFKFB4 exhibited resistance to apoptosis induction and autophagic flux inhibition by LXX-8250 treatment. Moreover, LXX-8250 treatment suppressed glycolysis, to which the cells overexpressed with PFKFB4 were tolerant. LXX-8250 treatment inhibited the growth of melanoma xenografts and suppressed PFKFB4 expression and glycolysis in vivo. Taken together, LXX-8250 treatment induced apoptosis through inhibiting autophagic flux and glycolysis in melanoma cells, which was mediated by suppression of PFKFB4 expression. The study provides a novel strategy to melanoma treatment.

Although grazing is the most common use of grassland, the ecological function of grassland far exceeds its productivity. Therefore, the protection of plant diversity is of the utmost importance and cannot be ignored. Existing research on the effect of grazing on grassland mainly focuses on grazing intensity and the type of livestock, but the consequences of the timing of the grazing on the vegetation community remains unclear. We investigated plant community characteristics of winter pastures in alpine meadow with different grazing termination times (grazing before and during the grassland greenup periods) in Maqu County, eastern QTP. The results showed that vegetation height, coverage, aboveground biomass and Graminoid biomass were lower in grassland when grazing happened during the greenup period compared to grassland where grazing was terminated before the greenup period. However, the total plant species richness and forbs richness were higher in grassland with grazing during the greenup period compared to grassland without grazing during the greenup period. Our structural equation modeling reveals a potential indirect implication for the total plant species richness and forbs richness of winter pastures mainly through a decrease in the vegetation coverage and grass biomass abundance. Our findings imply that grazing during the grassland greenup period may facilitate the maintenance of plant diversity in winter pastures. These findings have important implications for grassland ecosystem functioning and for the conservation of plant diversity.

Anthracnose disease caused by Colletotrichum fructicola is a serious disease that can afflict Camellia oleifera. Biological control is a rapidly growing approach for the management of plant diseases. In this study, we investigated the bio-control efficiency and the defense responses of an endophytic Bacillus tequilensis strain YYC 155, which was isolated from the root nodules of the Crotalaria pallida against anthracnose disease, caused by C. fructicola in C. oleifera. B. tequilensis YYC 155 exhibited significant inhibitory activity against anthracnose disease, caused by C. fructicola in C. oleifera. YYC 155 can secrete extracellular hydrolases, such as chitinase and β-1, 3-glucanase, which produce lipopeptides that are antimicrobial and forms strong biofilms. In addition, in treatment with YYC 155, the cell membranes of C. fructicola were injured and the leakage of cell contents from the mycelia of the pathogen was increased. Spraying 1 × 107 cells mL–1 bacterial suspension of YYC 155 on C. oleifera leaves enhanced the activity of key enzymes in C. oleifera associated with the phenylpropanoid pathway and increased the content of phenolic compounds and flavonoids. Results of our study indicate that B. tequilensis YYC 155 may potentially represent an effective biocontrol agent against anthracnose disease in C. oleifera.

ABSTRACT Sepsis-associated encephalopathy (SAE) is common in septic patients and is associated with adverse outcomes. The gut microbiota has been recognized as a key mediator of neurological disease development. However, the exact role of the gut microbiota in regulating SAE remains elusive. Here, we investigated the role of the gut microbiota in SAE and its underlying mechanisms. Cecal ligation and puncture (CLP) was conducted to induce sepsis in mice. Neurological scores were recorded to distinguish SAE-resistant (SER) (score of >6 at 36 h postoperatively) from SAE-susceptible (SES) (score of ≤6 at 36 h postoperatively) mice. 16S rRNA gene sequencing and metabolomics analyses were used to characterize the gut microbiota in the two groups. Fecal microbiota transplantation was performed to validate the role of the gut microbiota in SAE progression. The gut microbiota was more severely disrupted in SES mice than in SER mice after sepsis modeling. Interestingly, mice receiving postoperative feces from SES mice exhibited more severe cortical inflammation than mice receiving feces from SER mice. Indole-3-propionic acid (IPA), a neuroprotective molecule, was more enriched in feces from SER mice than in feces from SES mice. IPA alleviated CLP-induced anxiety and spatial memory impairment in septic mice. Moreover, IPA markedly inhibited NLRP3 inflammasome activation and interleukin-1β (IL-1β) secretion in lipopolysaccharide-stimulated microglia. These responses were attenuated after antagonizing the aryl hydrocarbon receptor. Our study indicates that the variability in sepsis-induced gut dysbiosis mediates the differential susceptibility to SAE in CLP-induced experimental sepsis mice, and microbially derived IPA is possibly involved in SAE development as a neuroprotective compound. IMPORTANCE The bidirectional interactions between the gut microbiota and sepsis-associated encephalopathy (SAE) are not well characterized. We found that the gut microbiota was more severely disturbed in SAE-susceptible (SES) mice than in SAE-resistant (SER) mice after sepsis modeling. Mice gavaged with postoperative feces from SES mice exhibited more severe neuroinflammation than mice gavaged with feces from SER mice. The gut microbiota from SER mice enriched a neuroprotective metabolite, IPA, which appeared to protect mice from SAE. The potential underlying mechanism of the protective effect of IPA may be mediated via the inhibition of NLRP3 inflammasome activation and IL-1β secretion in microglia. These anti-inflammatory effects of IPA may be regulated by aryl hydrocarbon receptors. These results enhance our understanding of the role of the intestinal microbiota in sepsis. In particular, gut microbiota-derived IPA may serve as a potential therapeutic agent to prevent neuroinflammation in SAE.

ABSTRACT The effects of using gut microbiota metabolites instead of live microorganisms to modulate sepsis-induced gut dysbiosis remain largely unknown. We assessed the effects of microbiota metabolite indole-3-propionic acid (IPA) on gut microbiota in mice during sepsis. Sepsis models were constructed by cecal ligation and puncture (CLP) methods. Fecal microbiota composition analysis was performed to characterize the gut microbiota composition. Fecal microbiota transplantation was performed to validate the roles of gut microbiota on sepsis progression. IPA-treated mice exhibited lower serum inflammatory mediator levels and a higher survival rate than those of saline-treated mice after modeling of sepsis, which were negated in the presence of antibiotics. Compared with saline-treated mice after modeling, IPA-treated mice showed a markedly different intestinal microbiota composition, with an enrichment of Bifidobacteriaceae family and a depletion of Enterobacteriaceae family. Mice gavaged with postoperative feces from IPA-treated animals displayed better survival than mice gavaged with feces from saline-treated animals. Overall, these data suggest that IPA offers a microbe-modulated survival advantage in septic mice, indicating that some microbiota metabolites could replace live microorganisms as potential options for regulation of sepsis-induced gut dysbiosis. IMPORTANCE The role of gut microbiota in the pathophysiology of sepsis is gaining increasing attention and developing effective and safe sepsis therapies targeting intestinal microorganisms is promising. Given the safety of probiotic supplementation or fecal microbiota transplantation in critically ill patients, identifying an abiotic agent to regulate the intestinal microbiota of septic patients is of clinical significance. This study revealed that IPA, a microbiota-generated tryptophan metabolite, ameliorated sepsis-induced mortality and decreased the serum levels of proinflammatory cytokines by modulating intestinal microbiota. Although IPA did not increase the abundance and diversity of the microbiota of septic mice, it significantly decreased the number of Enterobacteriaceae family. These findings indicate that a specific microbiota metabolite (e.g., IPA) can mediate the intestinal microbiota apart from FMT or probiotics.