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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.

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.

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.