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Abstract Regular physical activity is widely recognized for reducing the risk of various disorders, with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues. However, many individuals, particularly the elderly and those with clinical conditions, are unable to engage in physical exercise, necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules. Histone acetylation and deacetylation significantly influence exercise-induced gene expression, suggesting that targeting histone deacetylases (HDACs) could mimic some exercise responses. In this study, we explored the effects of the HDAC inhibitor Trichostatin A (TSA) on human skeletal muscle myoblasts (HSMMs). Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles (EVs) enriched with miR-873-3p. These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs) by targeting H2 calponin (CNN2). In vivo, systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass. Moreover, TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs, suggesting that HDAC inhibition can replicate exercise-induced bone health benefits. These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis, particularly for individuals unable to exercise. Given the FDA-approved status of various HDAC inhibitors, this approach holds significant promise for rapid clinical translation in osteoporosis treatment.

Abstract Remote sensing technology has the potential to enhance the lake’s large-scale and long-term dynamic monitoring capabilities significantly. High-quality in-situ datasets are essential for improving the accuracy and reliability of remote sensing retrieval of lake ecosystems. This dataset provides satellite-ground synchronized in-situ data on water multi-parameters for typical lakes in China spanning the period between 2020 and 2023. It includes quality-checked water optical parameters (remote sensing reflectance (Rrs), chlorophyll-a (Chl-a), total suspended matter (TSM) and Secchi disk depth (SDD)), and water surface temperature (WST) data. It encompasses 586 sampling points across 18 lakes. The dataset exhibits two significant highlights: Firstly, synchronous observations from multiple satellites are coordinated during the data collection effectively supporting the retrieval and validation of water remote sensing products. Secondly, it encompasses diverse data types, collecting synchronous measurements of Rrs and various parameters. This dataset will continuously update, substantially enhancing regional and global lake monitoring capabilities through satellite remote sensing data.

Abstract Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.

Abstract Phytoalexin sakuranetin functions in resistance against rice blast. However, the mechanisms underlying the effects of sakuranetin remains elusive. Here, we report that rice lines expressing resistance (R) genes were found to contain high levels of sakuranetin, which correlates with attenuated endocytic trafficking of plasma membrane (PM) proteins. Exogenous and endogenous sakuranetin attenuates the endocytosis of various PM proteins and the fungal effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, resulting from uptake into rice cells by Magnaporthe oryzae, was reduced following treatment with sakuranetin. Pharmacological manipulation of clathrin-mediated endocytic (CME) suggests that this pathway is targeted by sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey resistance against rice blast. Our data reveals a mechanism of rice against M. oryzae by increasing sakuranetin levels and repressing the CME of pathogen effectors, which is distinct from the action of many R genes that mainly function by modulating transcription.

Abstract Background Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. Methods The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. Results Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. Conclusions Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

In recent years, the residues of nitrofurans (NFs) and their metabolites in animal-derived food and environmental samples have gained widespread attention. The parent drugs and their metabolites have displayed significant toxicity to human health including carcinogenic, mutagenic and teratogenic effects, leading to banned in animal husbandry in many countries. Hence, monitoring the residues of NFs is necessary to guarantee public health and ecological security. This review aims to summarize and assess the structural properties, residue status, sample pretreatment methods (liquid-liquid extraction, solid-phase extraction, Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS), and field-assisted extraction), and detection methods (chromatographic analysis, immunoassay, and some innovative detection methods) for NFs and their metabolites in animal-derived food and environmental samples. This paper provides a detailed reference and discussion for the analysis of NFs and their metabolites, which can effectively promote the establishment of innovative detection methods for NFs and their metabolites residues.

The combination therapy of Tislelizumab plus Lenvatinib has recently emerged as the new standard of care for unresectable hepatocellular carcinoma (HCC). This treatment has demonstrated a significant reduction in tumor burden, raising the possibility of conversion therapy. However, the full safety and efficacy of this combination in real-world settings are not yet fully understood. We recently reported the case of a 36-year-old man with initially unresectable massive HCC, for whom radical surgery (RS) was contraindicated. After receiving Tislelizumab/Lenvatinib plus transarterial chemoembolization (TACE), the patient achieved complete pathological remission and subsequently underwent RS. The patient did not experience postoperative severe complications, and there was no recurrence during the follow-up period. Tislelizumab/Lenvatinib plus TACE therapy may lead to a complete pathological response in advanced HCC. Nevertheless, the safety of prolonged treatment needs to be assessed.

Two‐dimensional (2D) intrinsic vacancy semiconductors possess great application prospects in optoelectronics fields, originating from abundant intrinsic vacancy structures and exceptional physical properties. Understanding the structure‐activity relationship between vacancies and physical/photoelectric properties is significant for building advanced photoelectric devices. However, limited by the increasing instability of 2D structure induced by intrinsic vacancies, the precise synthesis of 2D intrinsic vacancy semiconductors faces great challenges. Here, high‐quality 2D intrinsic vacancy semiconductor α‐Ga2Se3 is synthesized via low‐pressure and space‐confined physical vapor deposition. The vacancy structures induce an intermediate energy level and a super‐bandgap photoluminescence (PL) peak, which are verified by temperature‐dependent PL spectra. Furthermore, the vacancy energy level favorably endows 2D α‐Ga2Se3‐based photodetector with a UV‐vis‐NIR super‐bandgap photoresponse, excellent ultraviolet detection ability (photoresponsivity (41.86 A W−1), epitaxial quantum efficiency (1.42 × 104%), and detectivity (6.69 × 1011 Jones) @365 nm), fast photoresponse (20 ms), and superior photocurrent‐light power‐fitting factors. In addition, 2D α‐Ga2Se3‐based phototransistor displays p‐type transport behavior with a responsivity of 105 A W−1@365 nm at a gate voltage of −40 V. This work suggests a bright future of 2D intrinsic vacancy semiconductors in tailoring physical properties and enabling sophisticated device functionality.

Background: The COVID-19 pandemic had a substantial impact on cancer services. The aim of our study was to evaluate the recovery of endoscopic activity and cancer detection after the COVID-19 pandemic. Methods: Endoscopic data from January 2019 to December 2020 were retrospectively collected to assess the endoscopic activity and cancer detection during the COVID-19 peak period (February 2020) and the post-COVID-19 peak period (March to July 2020). Results: The COVID-19 pandemic almost brought endoscopic activity and cancer detection to a standstill. Diagnostic procedure and endoscopic resection showed the greatest reduction. With the decline in COVID-19 infections, endoscopic activity gradually returned to previous level in July. However, the detection rate of gastric cancer resumed in September, whereas colorectal cancer resumed in August. The monthly detection rates of gastric and colorectal cancers decreased from their initial peaks of 2.98 % and 6.45 %, respectively, and finally were even lower than the average in 2019. Similarly, the mean age of patients who received endoscopy also declined as the detection rates resumed. The increasing colonoscopies allowed the missing colorectal cancer patients to be caught up. In contrast, it was expected that 6.69 % of gastric cancer patients were missed and did not receive needed endoscopy. Conclusions: The recovery of cancer detection occurred later than that of endoscopic activity, especially for gastric cancer. Older people were vulnerable to the continuous impact of COVID-19 pandemic than young people for seeking medical services. Urgent efforts are required to recover and maintain cancer services before subsequent waves of the COVID-19 pandemic.

Abstract Background Immunogenic cell death (ICD) has been identified as regulated cell death, which is sufficient to activate the adaptive immune response. This study aimed to research ICD-related genes and create a gene model to predict pancreatic ductal adenocarcinoma (PAAD) patients’ prognosis. Methods The RNA sequencing and clinical data were downloaded from the TGCA and GEO databases. The PAAD samples were classified into two subtypes based on the expression levels of ICD-related genes using consensus clustering. Based on the differentially expressed genes (DEGs), a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the prognosis of PAAD patients. Moreover, colony formation assay was performed to confirm the prognostic value of those genes. Results We identified two ICD cluster by consensus clustering, and found that the the ICD-high group was closely associated with immune-hot phenotype, favorable clinical outcomes. We established an ICD-related prognostic model which can predict the prognosis of pancreatic ductal adenocarcinoma. Moreover, depletion of NT5E, ATG5, FOXP3, and IFNG inhibited the colony formation ability of pancreatic cancer cell. Conclusion We identified a novel classification for PAAD based on the expression of ICD-related genes, which may provide a potential strategy for therapeutics against PAAD.

Abstract Background Vascular endothelial cells are pivotal in the pathophysiological progression following spinal cord injury (SCI). The UTX (Ubiquitously Transcribed Tetratripeptide Repeat on Chromosome X) serves as a significant regulator of endothelial cell phenotype. The manipulation of endogenous neural stem cells (NSCs) offers a compelling strategy for the amelioration of SCI. Methods Two mouse models were used to investigate SCI: NSCs lineage-traced mice and mice with conditional UTX knockout (UTX KO) in endothelial cells. To study the effects of UTX KO on neural differentiation, we harvested extracellular vesicles (EVs) from both UTX KO spinal cord microvascular endothelial cells (SCMECs) and negative control SCMECs. These EVs were then employed to modulate the differentiation trajectory of endogenous NSCs in the SCI model. Results In our NSCs lineage-traced mice model of SCI, a marked decrease in neurogenesis was observed post-injury. Notably, NSCs in UTX KO SCMECs mice showed enhanced neuronal differentiation compared to controls. RNA sequencing and western blot analyses revealed an upregulation of L1 cell adhesion molecule (L1CAM), a gene associated with neurogenesis, in UTX KO SCMECs and their secreted EVs. This aligns with the observed promotion of neurogenesis in UTX KO conditions. In vivo administration of L1CAM-rich EVs from UTX KO SCMECs (KO EVs) to the mice significantly enhanced neural differentiation. Similarly, in vitro exposure of NSCs to KO EVs resulted in increased activation of the Akt signaling pathway, further promoting neural differentiation. Conversely, inhibiting Akt phosphorylation or knocking down L1CAM negated the beneficial effects of KO EVs on NSC neuronal differentiation. Conclusions In conclusion, our findings substantiate that EVs derived from UTX KO SCMECs can act as facilitators of neural differentiation following SCI. This study not only elucidates a novel mechanism but also opens new horizons for therapeutic interventions in the treatment of SCI. Video Abstract Graphical Abstract

Mitochondria are crucial in sustaining and orchestrating cellular functions. Capitalizing on this, we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury (SCI). In our study, we developed an engineered mitochondrial compound tailored to target macrophages within the SCI region. Sourced from IL-10-induced Mertkhi bone marrow-derived macrophages, we conjugated a peptide sequence, cations-cysteine-alanine-glutamine-lysine (CAQK), with the mitochondria, optimizing its targeting affinity for the injury site. Our data demonstrated that these compounds significantly enhanced macrophage phagocytosis of myelin debris, curtailed lipid buildup, ameliorated mitochondrial dysfunction, and attenuated pro-inflammatory profiles in macrophages, both in vitro and in vivo. The intravenously delivered mitochondrial compounds targeted the SCI epicenter, with macrophages being the primary recipients. Critically, they promoted tissue regeneration and bolstered functional recovery in SCI mice. This study heralds a transformative approach to mitochondrial transplantation in SCI, spotlighting the modulation of macrophage activity, phagocytosis, and phenotype.

Abstract Objective There is no scientific consensus about the treatment of perforated gastric cancer (PGC). Therefore, the aim of this study was to investigate which is the better treatment option for PGC between the single-stage and two-stage strategies. Methods All 81 PGC patients from 13 medical institutions were retrospectively enrolled in this study. The PGC patients who underwent R0 gastrectomy were divided into one-stage surgery and two-stage surgery groups. The clinicopathological characteristics of the two groups were compared, and 415 regular gastric cancer patients without perforation were randomly selected as a control. The propensity score matching (PSM) method was used to find matched regular GC patients with similar clinicopathological parameters. The OS (overall survival) and the number harvested lymph nodes from PGC patients and regular GC patients were compared. Results Compared with PGC patients who underwent one-stage surgery, those who underwent two-stage surgery harvested significantly more lymph nodes [31(27, 38) vs 17 (12, 24), P

An in-depth exploration of fractional vegetation coverage (FVC) changes and driving mechanisms in the Yangtze River Delta (YRD) is crucial for maintaining regional ecological health and achieving sustainable development. We therefore calculate FVC in the YRD from 2012 to 2021 based on MODIS NDVI data, and analyze its spatiotemporal evolution. Multiple regression residual analysis and geographic detector model were used along with various auxiliary data to further explore its driving mechanisms in a hierarchical manner. Finally, the Hurst index was used to forecast future trends in FVC. The results show that: 1) Significant changes in FVC occurred around 2016, rapidly declining at a rate of 8.9×10-3a-1 from 2012 to 2016, followed by fluctuating growth at a rate of 5.2×10-3a-1 thereafter. 2) Although the overall development of FVC in the YRD tends toward stability, the fluctuation was pronounced in the Taihu Lake Basin. Improvement areas were mainly concentrated on both sides of the Yangtze River in the central part of the YRD and in the southern mountainous region. Degraded areas were concentrated in cities north of the Huai River. 3) Dynamic changes in FVC were primarily driven by a combination of climate and human activities, whereas spatial heterogeneity was mainly driven by factors such as elevation, slope, and landform type. The improvement in the explanatory power of anthropogenic factors for spatial heterogeneity when combined with natural factors was significant.

Herein, in situ water reflectance and TSM data obtained from several experiments on the Nanyi Lake from 2018 to 2022 and the Sentinel-3 Ocean and Land Colour Instrument (OLCI) satellite synchronization data were used to compare four atmospheric correction methods (FLAASH, 6S, ACOLITE, and C2RCC) and construct an empirical model for TSM inversion in the Nanyi Lake to analyze the spatial and temporal changes in the water quality in the Nanyi Lake from 2018 to 2023. On the Sentinel-3 OLCI data, the C2RCC algorithm showed the highest accuracy and overall performance stability (RMSE: 0.0014–0.0051 Sr−1, MAPE: 18.44%–68.47%, and BIAS: from −3.68% to 23.63%). The highest correlation was observed between the three-band ratio (B9 + B18)/B10 and the in situ TSM; the TSM inversion model constructed based on this inversion factor showed the best accuracy for the Nanyi Lake (R2: 0.76, RMSE: 5.01 mg/L, and MAPE: 28.46%). The spatial and temporal changes in TSM in the Nanyi Lake exhibited significant regularity. Specifically, the TSM was higher in 2018–2019, significantly decreased in 2020, and stabilized in 2021–2023. Owing to the effects of human activities, precipitation, and illumination, seasonal variation in the TSM in the Nanyi Lake was detected, with TSM decreasing in the following order: summer > autumn > spring > winter. Concerning spatial variations, high TSM was observed in the northwest, northeast, and southeast of the Nanyi Lake reclamation area and its surrounding lake area. River confluence and human activities affected the area, leading to significant fluctuations in TSM in 2018–2023.

The on-orbit radiometric calibration of spaceborne sensors is the foundation of quantitative remote sensing, and the calibration accuracy directly affects the quality of quantitative remote sensing products. The wide swath of the Chinese Ocean Color and Temperature Scanner (COCTS) onboard the HY-1C satellite makes it difficult to ignore errors caused by viewing angles during calibration. Thus, this article proposes a cross-calibration method based on the bottom-of-atmosphere (BOA) and top-of-atmosphere (TOA) spectral band adjustment factors (SBAFs). This method cross calibrates the COCTS sensor after correcting viewing geometry and radiometric differences. It is based on the Sentinel-3/ocean and land color instrument (OLCI) sensor. First, time-series data from the OLCI sensor were used to select calibration points in the Dunhuang area. Subsequently, the bidirectional reflectance distribution function (BRDF) for each corresponding spectral band of the OLCI sensor was constructed point by point. Next, the BOA and TOA SBAFs were calculated using the interpolated continuous spectra obtained from MOD09GA products. After correcting for the BRDF and SBAF, cross calibration between COCTS and OLCI was achieved. The results showed that the BOA SBAF model achieved higher precision calibration coefficients than the TOA SBAF model, with errors in each band below 5.76%. The proposed method can provide technical support for the cross calibration of wide-swath sensors.

Numerous spatiotemporal fusion (STF) methods have been developed to generate surface reflectance data with high spatial and temporal resolutions for dynamic monitoring. Although comparative studies have been conducted to assess various fusion methods, selecting the most suitable fusion method for acquiring long-term time series data remains a challenge. This article compared four representative STF methods based on the effect of 8 × n-day (n = 1, 2, …, 7) time scales between base and predicted data. These methods included the spatial and temporal adaptive reflectance fusion model (STARFM), flexible spatiotemporal data fusion (FSDAF), enhanced STARFM (ESTARFM), and sensor-bias driven spatio-temporal fusion model (BiaSTF). Accuracy was assessed using metrics such as the root-mean-square error, correlation coefficients, erreur relative globale adimensionnelle de synthèse, and spectral angle mapper. The results indicate that as the time scale increases, fusion accuracy decreases, with a significant drop observed at the 40-day mark. Compared with the 8-day scale, at the 40-day scale, the ERGAS of STARFM decreased by 20.66%, that of FSDAF by 17.00%, that of ESTARFM by 14.37%, and that of BiaSTF by 11.48%. Furthermore, STF methods based on two pairs of images demonstrate a notable advantage in capturing data from distant temporal phases. In regions with pronounced phenological changes and longer time scales, BiaSTF consistently exhibits the best fusion performance (ERGAS = 1.67), followed by ESTARFM (ERGAS = 1.85). These findings can aid in determining the most suitable STF methods and provide guidelines for the development of new methods.

Blood smear analysis is often used to diagnose diseases like malaria, Anemia, Leukemia, etc. Morphological changes, such as size, shapes, and color, are receiving much attention in pathological analysis. Existing methods for detecting, diagnosing and analyzing blood smears cannot quantify overlapped, irregular boundaries and complex structures. This work proposes and evaluates a framework that utilizes Generative adversarial networks (GANs) for the segmentation and classification of blood elements, that is, white blood cells (WBCs), red blood cells (RBCs), and platelets (PLTs) simultaneously. The Generator of the network determines the mapping from microscopic images of blood cells to a confidence map. This mapping stipulates the probabilities of the pixel of the microscopic blood cell images with respect to ground truth. The Discriminator of the network is essential to castigate the mismatch between the microscopic blood cells images and confidence map. Additionally, adversarial learning enables the Generator to generate a qualitative confidence map that is converted into segmented images. We have calculated minimum, maximum, and average losses to judge the performance of the proposed model. We measure structural similarity, peak signal-to-noise ratio, pixel classification error, and finally, classified cells. The proposed framework can analyze all the blood cell elements simultaneously. The proposed framework shows a significant improvement in the segmentation and classification of blood cell elements compared to state-of-the-art techniques. During the training process, generator total loss reduces by 12.18%, 5.39%, and 3.62% for RBCs, WBCs, and PLTs, respectively. Our results demonstrate that the proposed framework outperforms existing state-of-the-art techniques, achieving the highest pixel correctly classified (PCC) ratio for the segmentation of blood cells as 99.8%, 93.4%, and 99.9% for WBCs, RBCs, and PLTs, respectively. Our framework attains 95.45% and 88.89% classification accuracy for WBCs on ALL-IDB-I and ALL-IDB-II datasets. The dataset used for this study can be found at https://drive.google.com/drive/folders/1F7kZ1SRWUD9R6aHLMkj3wsjcHnvlGuwP?usp=sharing

The leaf area index (LAI) is one of the most important biophysical parameters of vegetation canopy, which is of great significance for estimating the growth and yield of tea trees. In the present era, tea plantations are becoming increasingly densely packed. However, there is a lack of accurate methods for measuring the LAI of densely planted tea trees. To explore LAI measurement and inversion methods applicable to densely planted tea trees, this study used tea trees in Langxi County as a case study. Using two commonly used measurement methods for densely and sparsely grown row crops and a measurement method for densely grown tea trees proposed based on practice, three sets of tea tree LAI were measured and compared with the true LAI value obtained using direct measurements. Using the set with the best performance to construct a regression model with vegetation indices, the LAI during the new shoot period of tea leaves is inverted. The results are summarized as follows. 1) According to the analysis of the direct measurements, the proposed measurement method for densely grown tea trees is the closest LAI values to the true values for densely planted tea trees in Langxi. 2) According to the fitting analysis, the common vegetation indices were significantly correlated with the LAI. The vegetation indices constructed with green, red edge, and shortwave infrared bands exhibited a higher correlation with the LAI than those constructed without these bands. Among them, EVIre exhibited the highest fitting accuracy.

Abstract Background and objectives Helicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis. Methods A prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected. Results A total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P

ABSTRACTWhite tea (Camillia sinensis L.) is the least processed tea, and due to simpler processing steps involved, its flavor and nutritive compound composition is least disturbed. However, only a limited number of research has explored the key metabolomic changes during white tea processing (especially drying). The freshly harvested leaves of C. sinensis var. Tieguanyin were initially withered at room temperature for 72 h, and first-dried on fire at 70°C for 3 h. Then, they were spread at room temperature for 7 days and fully dried at 80°C for 4 h, followed by cooled at room temperature. The metabolome of the tea leaves before (CK) and after full drying (RO) were compared using UPLC-MS/MS. The LC-MS/MS analysis identified 1,253 compounds belonging to 11 classes. The highest number of accumulated compounds belonged to flavonoids, phenolic acids, and lipids. Of the 57 differentially accumulated metabolites (DAMs), 49 were up-accumulated in RO. These were classified as amino acids derivatives, lipids, organic acids, vitamins, alkaloids, nucleotides and derivatives, flavonoids, tannins, terpenoids, lignans and coumarins. We found that several health beneficial compounds showed up-accumulation in RO compared to CK. We concluded that Hot-air full drying alters white team metabolome composition.

AimTo identify the associations of 19 single nucleotide polymorphisms (SNPs) in genes involved in inflammation and endothelial function and carotid atherosclerosis with subsequent ischemic stroke and other vascular events in the high-risk stroke population.MethodsThis was a multicenter community-based sectional survey and prospective cohort study in Sichuan, southwestern China. Eight communities were randomly selected, and the residents in each community were surveyed using a structured face-to-face questionnaire. Carotid ultrasonography and DNA information were obtained from 2,377 out of 2,893 individuals belonging to a high-risk stroke population. Genotypes of the 19 SNPs in genes involved in inflammation and endothelial function were measured. All the 2,377 subjects were followed up for 4.7 years after the face-to-face survey. The primary outcome was ischemic stroke, and the secondary outcome was a composite of vascular events.ResultsAmong the 2,377 subjects, 2,205 (92.8%) completed a 4.7-year follow-up, 947 (42.9%) had carotid atherosclerosis [372 (16.9%) carotid vulnerable plaque, 405 (18.4%) mean IMT > 0.9 mm, 285 (12.0%) carotid stenosis ≥15%]. Outcomes occurred in 158 (7.2%) subjects [92 (4.2%) ischemic stroke, 17 (0.8%) hemorrhagic stroke, 48 (2.2%) myocardial infarction, and 26 (1.2%) death] during follow-up. There was a significant gene–gene interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 in the 19 SNPs. The multivariate logistic regression model revealed that carotid atherosclerosis and the high-risk interactive genotypes among the three SNPs were independent with a higher risk for ischemic stroke (OR = 2.67, 95% CI: 1.52–6.78, p = 0.004; and OR = 3.11, 95% CI: 2.12–9.27, p

Background/objectiveThe aim of this study was to evaluate tumor progression and recurrence patterns of radiofrequency ablation (RFA) with or without transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) that meets Milan criteria.MethodsThis retrospective study included consecutive HCC patients meeting Milan criteria who underwent percutaneous RFA with or without TACE as initial treatment at a tertiary academic center between December 2017 and 2022. Technical success rate, local recurrence-free survival (LRFS), progression-free survival (PFS) and recurrence patterns were recorded.ResultsA total of 135 HCC patients (109 male [80.7%]) with a mean age of 62 years and 147 target lesions were retrospectively enrolled. The technical success rate was 99.3%. The median LRFS was 60 months, and the cumulative 1-, 3-, and 5-year LRFS were 88.9%, 70.1%, and 30.0%, respectively. Additionally, the median PFS was 23 months, with cumulative 1-, 3-, and 5-year PFS of 74%, 30%, and 0%, respectively. Multivariate analysis confirmed that age > 60, alpha-fetoprotein (AFP) (> 10), and albumin were associated with PFS (2.34, p = 0.004; 1.96, p = 0.021; 0.94, p = 0.007, respectively). Six recurrence patterns were identified: local tumor progression (LTP) alone (n = 15, 25.0%), intrahepatic distant recurrence (IDR) alone (n = 34, 56.7%), extrahepatic recurrence (ER) alone (n = 2, 3.3%), IDR + ER (n = 2, 3.3%), LTP + IDR (n = 5, 8.8%), and LTP + IDR + ER (n = 2, 3.3%). IDR occurred most frequently as a sign of good local treatment.ConclusionsRFA in combination with TACE does not appear to provide an advantage over RFA alone in improving tumor progression in patients with HCC meeting the Milan criteria. However, further prospective studies are needed to confirm these findings and to determine the optimal treatment approach for this patient population.

Background/ObjectiveTreatment of hepatocellular carcinoma (HCC) with ablation alone often results in high rates of recurrence and metastasis, reaching up to 25.9% within two years. Therefore, this study aimed to examine the efficacy and safety of transarterial chemoembolization (TACE)-assisted multi-image guided radiofrequency ablation (RFA) for the treatment of stage Ia HCC according to the China liver cancer staging (CNLC).MethodsThis study enrolled and analyzed a total of 118 patients diagnosed with HCC, each with a single nodular lesion no larger than 5 cm, who received TACE-RFA as first-line therapy between February 1, 2014, and December 31, 2021. The median/mean follow-up period was 29.0 months [95% confidence interval (CI): 21.8-36.2 months] and 31.8 months (95% CI: 27.5-36.0 months), respectively. We assessed the treatment’s effectiveness, potential complications, and survival rate.ResultsThe technical success rate was 100% (118/118) after the initial treatment. Out of the total, 3 out of 118 patients (2.5%) developed local tumor progression (LTP) during the follow-up period. The median time for LTP was 29.0 months (95%CI: 21.9-36.1 months; mean: 31.5 months; range 1-92 months). At 1, 3, 5, and 7 years after treatment, the cumulative LTP rates were 0%, 4.6%, 4.6%, and 4.6%, respectively. The overall survival rates at 1, 3, 5, and 7 years were 100%, 95.2%, 95.2%, and 95.2%, respectively. In total, 28 patients experienced minor Grade B complications, and no major complications or treatment-related mortality occurred.ConclusionThe treatment of CNLC stage Ia HCC using TACE-assisted multi-image-guided RFA was found to be both safe and feasible.

T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M−KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M−KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M−KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.

Background: Helicobacter pylori (H. pylori) biofilm formation is a key factor in refractory H. pylori infection. The aim of this study was to understand research trends in H. pylori biofilms. Methods: The Web of Science Core Collection database was used to retrieve publications published from 1998 to 2023. Different kinds of software, EXCEL, an online bibliometric analysis platform, and the VOS viewer were used to evaluate and visualize the bibliometric data. Results: In total, 184 publications were identified, and the number of publications increased annually. The USA made the greatest contributions to this research field, while Helicobacter was the most productive journal. Grande rossella published the most papers, and the most productive institution was Gabriele D'Annunzio university. Co-occurrence network maps revealed that the keyword “Helicobacter pylori” ranked first in research field, and the keyword of “biofilm formation” and “in vitro” began to appear in the past three to five years. The majority of the five most-cited articles (60%) were published in USA and focused on the mechanism of H. pylori biofilm formation. Conclusion: The annual number of publications on H. pylori biofilms has increased steadily over the past two decades and will continue to increase. Future studies should focus on evaluate the pharmacological effects, efficacy and safety of these anti-biofilm treatments in animal models and clinical trials.

Abstract This work demonstrates the fabrication and characterization of single-layer MoS2 field-effect transistors using biodegradable albumen (chicken eggwhite) as gate dielectric. By introducing albumen as an insulator for MoS2 transistors high carrier mobilities (up to ~90 cm2 V−1 s−1) are observed, which is remarkably superior to that obtained with commonly used SiO2 dielectric which we attribute to ionic gating due to the formation of an electric double layer in the albumen MoS2 interface. In addition, the investigated devices are characterized upon illumination, observing responsivities of 4.5 AW−1 (operated in photogating regime) and rise times as low as 52 ms (operated in photoconductivity regime). The presented study reveals the combination of albumen with van der Waals materials for prospective biodegradable and biocompatible optoelectronic device applications. Furthermore, the demonstrated universal fabrication process can be easily adopted to fabricate albumen-based devices with any other van der Waals material.

Abstract Spinal cord injury (SCI) can prompt an immediate disruption to the blood–spinal cord barrier (BSCB). Restoring the integrity of this barrier is vital for the recovery of neurological function post-SCI. The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. However, it is unclear whether UTX knockout could facilitate the recovery of the BSCB by reducing its permeability. In this study, we systematically studied BSCB disruption and permeability at different time points after SCI and found that conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI. Subsequently, we used RNA sequencing and ChIP-qPCR to confirm that conditional UTX knockout in ECs can down-regulate expression of myosin light chain kinase (MLCK), which specifically mediates myosin light chain (MLC) phosphorylation and is involved in actin contraction, cell retraction, and tight junctions (TJs) protein integrity. Moreover, we found that MLCK overexpression can increase the ratio of p-MLC/MLC, further break TJs, and exacerbate BSCB deterioration. Overall, our findings indicate that UTX knockout could inhibit the MLCK/p-MLC pathway, resulting in decreased BSCB permeability, and ultimately promoting neurological recovery in mice. These results suggest that UTX is a promising new target for treating SCI. Graphical Abstract

Abstract Background Lumbar facet joint osteoarthritis (LFJ OA) is a common disease, and there is still a lack of effective disease-modifying therapies. Our aim was to determine the therapeutic effect of hypoxia-treated adipose mesenchymal stem cell (ADSC)-derived exosomes (Hypo-ADSC-Exos) on the protective effect against LFJ OA. Methods The protective effect of Hypo-ADSC-Exos against LFJ OA was examined in lumbar spinal instability (LSI)-induced LFJ OA models. Spinal pain behavioural assessments and CGRP (Calcitonin Gene-Related Peptide positive) immunofluorescence were evaluated. Cartilage degradation and subchondral bone remodelling were assessed by histological methods, immunohistochemistry, synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR), and 3D X-ray microscope scanning. Results Hypoxia enhanced the protective effect of ADSC-Exos on LFJ OA. Specifically, tail vein injection of Hypo-ADSC-Exos protected articular cartilage from degradation, as demonstrated by lower FJ OA scores of articular cartilage and less proteoglycan loss in lumbar facet joint (LFJ) cartilage than in the ADSC-Exo group, and these parameters were significantly improved compared to those in the PBS group. In addition, the levels and distribution of collagen and proteoglycan in LFJ cartilage were increased in the Hypo-ADSC-Exo group compared to the ADSC-Exo or PBS group by SR-FTIR. Furthermore, Hypo-ADSC-Exos normalized uncoupled bone remodelling and aberrant H-type vessel formation in subchondral bone and effectively reduced symptomatic spinal pain caused by LFJ OA in mice compared with those in the ADSC-Exo or PBS group. Conclusions Our results show that hypoxia is an effective method to improve the therapeutic effect of ADSC-Exos on ameliorating spinal pain and LFJ OA progression.

Owing to their high volumetric capacity, low cost and high safety, rechargeable aluminum batteries have become promising candidates for energy applications. However, the high charge density of Al3+ leads to strong coulombic interactions between anions and the cathode, resulting in sluggish diffusion kinetics and irreversible collapse of the cathode structure. Furthermore, AlCl3-based ionic liquids, which are commonly used as electrolytes in such batteries, corrode battery components and are prone to side reactions. The above problems lead to low capacity and poor cycling stability. Herein, we propose a reduced graphene oxide (rGO) cathode with a three-dimensional porous structure prepared using a simple and scalable method. The lamellar edges and oxygen-containing group defects of rGO synergistically provide abundant ion storage sites and enhance ion transfer kinetics. We matched the prepared rGO cathode with noncorrosive electrolyte 0.5 mol·L−1 Al(OTF)3/[BMIM]OTF and Al metal to construct a high-performance battery, Al||rGO-150, with good cycling stability for 2700 cycles. Quasi-in-situ physicochemical characterization results show that the ion storage mechanism is codominated by diffusion and capacitance. The capacity consists of the insertion of Al-based species cations as well as synergistic adsorption of Al(OTF)x(3−x)+ (x < 3) and [BMIM]+. The present study promotes the fundamental and applied research on rechargeable aluminum batteries.

Abstract Macrophages polarized to the M2 subtype after spinal cord injury (SCI) are beneficial for promoting neurological recovery. The crosstalk between endothelial cells (ECs) and macrophages is crucial for the imbalance between proinflammatory and pro-resolving responses caused by macrophage heterogeneity; however, this crosstalk is strengthened post-SCI, leading to inflammatory cascades and second damage. As a powerful means to regulate gene expression, epigenetic regulation of the interaction between immune cells and ECs in SCI is still largely unknown. Our previous research demonstrated that the histone demethylase UTX deletion in ECs (UTX−/− ECs) promotes neurological recovery, while the precise mechanism is unrevealed. Here, we discovered that UTX−/− ECs polarize macrophages toward the M2 subtype post-SCI. Macrophage deficiency could block the neurological recovery caused by the knockdown of UTX. The exosomes from UTX−/− ECs mediate this crosstalk. In addition, we found UTX, H3K27, and miR-467b-3p/Sfmbt2 promoters forming a regulatory complex that upregulates the miR-467b-3p in UTX−/− ECs. And then, miR-467b-3p transfers to macrophages by exosomes and activates the PI3K/AKT/mTOR signaling by decreasing PTEN expression, finally polarizing macrophage to the M2 subtype. This study reveals a mechanism by epigenetic regulation of ECs-macrophages crosstalk and identifies potential targets, which may provide opportunities for treating SCI. Graphical Abstract

Abstract Background Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism. Methods We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement. Results We found that EPC-EXOs decreased the macrophages’ pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P’s effects on macrophage polarization and mouse motor behavior. Conclusion Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs’ role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.

ABSTRACTCompelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g., hyperlipidemia). However, the regulatory profile of individual bacterial species and strain on lipid homeostasis remains largely unknown. Herein, we performed a large-scale screening of 2250 human gut bacterial strains (186 species) for the lipid-decreasing activity. Different strains in the same species usually displayed distinct lipid-modulatory actions, showing evident strain-specificity. Among the tested strains, Blautia producta exhibited the most potency to suppress cellular lipid accumulation and effectively ameliorated hyperlipidemia in high fat diet (HFD)-feeding mice. Taking a joint comparative approach of pharmacology, genomics and metabolomics, we identified an anteiso-fatty acid, 12-methylmyristic acid (12-MMA), as the key active metabolite of Bl. Producta. In vivo experiment confirmed that 12-MMA could exert potent hyperlipidemia-ameliorating efficacy and improve glucose metabolism via activating G protein-coupled receptor 120 (GPR120). Altogether, our work reveals a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, emphasizes the strain-specific function of gut bacteria, and provides a possibility to develop microbial therapeutics against hyperlipidemia based on Bl. producta and its metabolite.

Abstract Bone metastasis is the main cause of death in patients with prostate cancer (PCa), but there lacks effective treatment method. Immunotherapy shows new hopes for bone metastatic PCa patients, while the efficacy is still unsatisfactory and limited by the unique immunosuppressive microenvironment in metastatic bone site. Here, we developed a bone-targeted nano-delivery system as a nano-regulator to enhance the immunotherapy of bone metastatic PCa. The nanosystem was assembled via coordination between phytic acid (PA) and Fe3+ to form nano-sized metal–organic framework (MOF), through which mitoxantrone (MTO) was encapsulated. At cellular level, the nanosystem showed selective cytotoxicity towards RM-1 PCa cells over immune cells, and could induce tumor cells immunogenic cell death (ICD) to improve the immunogenicity of the tumor. Moreover, the nanosystem was able to induce ubiquitination of TGFβ receptor (TβR) on immune cells to promote its degradation, thus serving as a nano-regulator to block the functions of TGF-β, an abundant cytokine that has a systematically immunosuppressive effect in the tumor microenvironment. Upon intravenous injection, the nanoparticle showed pro-longed blood circulation and targeting accumulation into bone metastatic site, and imposed robust anti-tumor effect in combination with αCTLA-4. In addition, bone destruction was significantly alleviated after treatment to reduce the skeletal-related events. Overall, this work provides a biocompatible nanomedicine to restore immune sensitivity of bone metastatic tumor for enhanced immunotherapy by blocking TGF-β signaling pathway.

Abstract A physical unclonable function (PUF) is a foundation of anti-counterfeiting processes due to its inherent uniqueness. However, the self-limitation of conventional graphical/spectral PUFs in materials often makes it difficult to have both high code flexibility and high environmental stability in practice. In this study, we propose a universal, fractal-guided film annealing strategy to realize the random Au network-based PUFs that can be designed on demand in complexity, enabling the tags’ intrinsic uniqueness and stability. A dynamic deep learning-based authentication system with an expandable database is built to identify and trace the PUFs, achieving an efficient and reliable authentication with 0% “false positives”. Based on the roughening-enabled plasmonic network platform, Raman-based chemical encoding is conceptionally demonstrated, showing the potential for improvements in security. The configurable tags in mass production can serve as competitive PUF carriers for high-level anti-counterfeiting and data encryption.

Paper-based devices have attracted extensive attention due to the growing demand for disposable flexible electronics. Herein, we integrate semiconducting devices on cellulose paper substrate through a simple abrasion technique that yields high-performance photodetectors. A solvent-free WS2 film deposited on paper favors an effective electron-hole separation and hampers recombination. The as-prepared paper-based WS2 photodetectors exhibit a sensitive photoresponse over a wide spectral range spanning from ultraviolet (365 nm) to near-infrared (940 nm). Their responsivity value reaches up to ~270 mA W−1 at 35 V under a power density of 35 mW cm−2. A high performance photodetector was achieved by controlling the environmental exposure as the ambient oxygen molecules were found to decrease the photoresponse and stability of the WS2 photodetector. Furthermore, we have built a spectrometer using such a paper-based WS2 device as the photodetecting component to illustrate its potential application. The present work could promote the development of cost-effective disposable photodetection devices.

Abstract Introduction Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high‐risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. Methods The multivariate Cox proportional hazards regression was used to select recurrence‐related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT‐PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. Results In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence‐free survival (RFS). Then, the recurrence‐related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012–1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231–0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819–7.194; p

The largefin longbarbel catfish, Hemibagrus macropterus, is an economically important fish species in southwestern China, with males growing faster than females. This study presents a high-quality chromosome-level genome assembly of the largefin longbarbel catfish, generated by integrating Illumina short reads, PacBio HiFi long reads, and Hi-C data. The assembled genome size was 858.5 Mb, with a contig and scaffold N50 of 5.8 Mb and 28.4 Mb, respectively. A total of 656 contigs were successfully anchored to 30 pseudochromosomes with a BUSCO score of 97.7%, consistent with the number of chromosomes analyzed by karyotype. The genome contained 29.5% repeat sequences, and a predicted total of 26,613 protein-coding genes, of which 25,769 (96.8%) were functionally annotated in different databases. Evolutionary analysis showed that H. macropterus was most closely related to H. wyckioides, with a divergence time of approximately 16.3 million years. Chromosomal syntenic relationships among H. macropterus, H. wyckioides, and Pelteobagrus fulvidraco revealed a one-to-one relationship for most chromosomes, except for break, fission, and inversion of some chromosomes. The first high-quality reference genome will not only provide a valuable genetic resource for the study of sex determination mechanisms and genetic breeding of largefin longbarbel catfish, but also contribute to comparative analyses of genome and chromosome evolution within Siluriformes.

This study aimed to investigate the effects of mesenchymal stem cell exosomes loaded with Fe3O4 magnetic particles (Fe3O4@ MSC-exo) on the survival and neural differentiation of PC12 cells. Exosomes were separated from Fe3O4 magnetic nanoparticles-primed umbilical cord mesenchymal stem cells condition medium by ultracentrifugation and characterized by transmission electron microscopy, flow nano analysis, and western blotting. PC12 cells were treated with culture medium containing exosomes. The effects of Fe3O4@ MSC-exo on PC12 cell proliferation, migration, and neural differentiation were analyzed using CCK-8 assay, transwell migration assay, RT-qPCR, and immunofluorescence, respectively. Additionally, miRNA sequencing was performed on Fe3O4@ MSC-exo, followed by bioinformatic analysis of the results. We found that Fe3O4@ MSC-exo can promote PC12 cell proliferation, migration, and neural differentiation. According to the sequencing results, there were a total of 43 differentially expressed miRNAs. The present study indicated that Fe3O4@ MSC-exo might enhance nerve cell function, laying the foundation for targeted therapy of nerve injury.

Background: To develop the preoperative prediction of ovarian lesions using regression-based statistics analyses and machine learning methods based on multiple serological biomarkers in China. Methods: 1137 patients with ovarian lesions in Zhujiang Hospital and 518 patients in others hospital in China were randomly assigned to training, test and external validation cohorts. Five machine learning classifiers, including Random Forest (RF), Extreme Gradient Boosting (XGB), Support Vector Classifier (SVC), K-nearest Neighbor (KN), Multi-Layer Perceptron (MLP) and the Lasso-Logistics prediction model (LLRM) were used to derive diagnostic information from 23 predictors. Results: The RF model had a high diagnostic value (AUC = 0.968) in predicting benign and malignant ovarian disease. Age and MLR were also potential diagnostic indicators for predicting ovarian disease except tumor indicators. The RF model well distinguished borderline ovarian tumors (AUC = 0.742). The RFM had a high predictive power to identify ovarian serous adenocarcinoma (AUC = 0.943) and ovarian endometriosis cysts (AUC = 0.914). Conclusions: The RF models can effectively predict adnexal lesions, promising to be adjuncts to the preoperative prediction of ovarian cancer.

Abstract As a typical two‐dimensional (2D) transition metal dichalcogenides (TMDCs) material with nonzero band gap, MoS2 has a wide range of potential applications as building blocks in the field of nanoelectronics. The stability and reliability of the corresponding nanoelectronic devices depend critically on the mechanical performance and cyclic reliability of 2D MoS2. Although an in situ technique has been used to analyze the mechanical properties of 2D materials, the cyclic mechanical behavior, that is, fatigue, remains a major challenge in the practical application of the devices. This study was aimed at analyzing the planar cyclic performance and deformation behavior of three‐layer MoS2 nanosheets (NSs) using an in situ transmission electron microscopy (TEM) variable‐amplitude uniaxial low‐frequency and cyclic loading–unloading tensile acceleration test. We also elucidated the strengthening effect of the natural overlaying affix fragments (other external NSs) or wrinkle folds (internal folds from the NS itself) on cycling performances and service life of MoS2 NSs by delaying the whole process of fatigue crack initiation, propagation, and fracture. The results have been confirmed by molecular dynamics (MDs) simulations. The overlaying enhancement effect effectively ensures the long‐term reliability and stability of nanoelectronic devices made of few‐layer 2D materials.

BackgroundThis review summarizes the factors influencing the efficacy and safety of the COVID-19 vaccine in LTR through meta-analysis, hoping to provide strategies for vaccine use.MethodsElectronic databases were screened for studies on mRNA vaccines in LTR. The primary outcome was the pooled seroconversion rate, and the secondary outcome was the incidence of adverse events+breakthrough infections. Subgroup analyses were made based on BMI, associated comorbidities, presence of baseline leukopenia, time since transplant, and drugs used.ResultIn total, 31 articles got included. The pooled seroconversion rate after at least two doses of SARS-CoV-2 vaccination was 72% (95% CI [0.52-0.91). With significant heterogeneity among studies I2 = 99.9%, the seroconversion rate was about 72% (95%CI [0.66-0.75]), from the studies reporting two doses of vaccine slightly higher around 75%(95%CI [0.29-1.22]) from studies reporting three doses. The pooled seroconversion rate within the lower to normal BMI group was 74% (95% CI [0.22-1.27], Pi=0.005) against 67% (95% CI [0.52-0.81], Pi=0.000) in the high BMI group. The pooled seroconversion rate in the ‘‘positive leukopenia’’ group was the lowest, 59%. Leukopenia could influence the vaccine seroconversion rate in LTR. From the time since transplant analysis after setting seven years as cut off point, the pooled seroconversion rate after at least two doses of COVID-19 vaccination was 53% (95% CI [0.18-0.83], P=0.003, I2 = 99.6%) in 7years group. The only time since transplantation had reached statistical significance to be considered a risk factor predictor of poor serological response (OR=1.27 95%CI [1.03-1.55], P=0.024). The breakthrough infection rate after vaccination was very low2% (95% CI 0.01-0.03, I2 = 63.0%), and the overall incidence of adverse events, which included mainly pain at the injection site and fatigue, was 18% (95%CI [0.11-0.25], I2 = 98.6%, Pi=0.000).ConclusionThe seroconversion rate in LTR vaccinated with at least two doses of mRNA COVID-19 vaccine could be significantly affected by the vaccine type, immunosuppressant used, BMI, leukopenia, associated comorbidities, and time since transplantation. Nevertheless, booster doses are still recommended for LTR.

Emerging Internet of Things (IoT) technologies and applications have enabled the Smart Grid Utility control center to connect, monitor, control, and exchange data between the smart appliances, smart meters (SMs), data concentrators (DCs) and control center server (CCS) over the Internet. In particular, DC receives different Advanced Metering Infrastructure (AMI) applications data from multiple SMs for processing, queuing, aggregation, and forwarding onward towards the CCS over the things networking. However, DCs are expensive component of the AMI network. Recently, SMs are used as relay-devices to accomplish a cost-effective AMI network infrastructure to avoid the DC placement and bottleneck problem. However, SMs are recourse constrained (limited CPU, RAM, storage, and network capacity) intelligent devices which faces numerous communication challenges during outage conditions and summer peak hours where bulk amount of data with different traffic rates and latency are exchanged with the Utility control center. Therefore, an efficient data aggregation is required at relay-devices to deal with high volume of data exchange rates in order to optimize the constrained-resources of the AMI network. In this article, we propose a hybrid data aggregation strategy implemented on an aggregator-head (AH) in the clustering topology which performs data aggregation on the Interval Meter Reading (IMR) application data. AH induction greatly reduces the workload of the cluster-heads (CHs), and efficiently utilizes the constrained-resource of AMI devices in a cost effective-manner. The proposed strategy is evaluated for different existing approaches using the CloudSim simulation tool. Experimental and simulation results are obtained and compared which show the effectiveness of the proposed strategy such that limited resources are optimized, CH workload is minimized, and QoS of AMI applications are maintained.

Abstract Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.

Abstract Background Traumatic aortic pseudoaneurysms (PSAs) classified as grade III aortic injuries are conventionally repaired as procedural emergencies, generally within 24 h of arrival. These patients typically require adequate resuscitation and treatment of multiple traumatic injuries, which complicate optimal management strategies of aortic PSAs. This study reviews the experience of an Asian single center to evaluate the efficacy and safety of delayed (> 24 h) endovascular repair for PSAs. Methods Twenty-seven patients with blunt aortic injury (BTAI) were brought to our institution between February 2014 and May 2020. Patients with other grades of aortic injuries (grade I, II, or IV) were excluded from the study, and the remaining patients with grade III aortic injuries were placed into the early ( 24 h) groups according to the timing of repair. Medical records and follow-up computed tomography (CT) scans were reviewed to document the outcomes of the procedures. Primary outcomes included mortality and complications. Results During this period, there were 14 patients (13 males and 1 females) with aortic PSAs, and each patient received thoracic endovascular aortic repair (TEVAR). Of these 14 patients, 1 underwent emergent TEVAR, and 13 underwent delayed repair (median 7 days, range, 3–14 days). Over a period of 8 years, the overall survival of our series was 100%. No paraplegia, stroke, ischemia of limb or other serious procedural complications were observed during the duration of follow-up. Conclusion The experience of our center indicates that delayed repair for selected PSAs could be permissible, which enables a repair in more controlled circumstances.

Abstract The purpose was to investigate effect of edible bird's nest (EBN) on the immunological properties of mice with lung injury induced by sulfur dioxide (SO2). In mice, SO2 exposure caused symptoms that included a cough, tiredness, and weight loss. Administering EBN improved the immunological function of mice with lung injury in a dose‐dependent manner, leading to recovery of the lung tissue and increasing thymus and spleen indices. IL‐2 and IFN‐γ in the serum by Th1 cells in response to EBN played a leading role in cellular immune regulation. Moreover, a medium dose of EBN regulated the immune stress response, inhibited apoptosis of splenic lymphocytes, and promoted cellular immunity. EBN inhibited production of IL‐8 and MDA and upregulated mRNA expression of atrophin‐1 and cyclooxygenase‐2 in lung tissue. EBN attenuates the lung injury induced by SO2 in mice through a mechanism that involves the inhibition of inflammation and regulation of immunological balance.

AbstractTo evaluate the effect of hysteroscopy and suture on uterine scar diverticulum (CSD) after caesarean section and its influence on blood loss, operation time and antibiotic time. Eighty-nine patients with CSD were divided into observation group (n = 41 cases) and control group (n = 48 cases). Control group received laparoscopic scar diverticulum resection and suture, while the observation group received hysteroscopic resection of scar diverticulum. The operation time of the observation group was longer, while the bleeding volume and antibiotic administration time were significantly lower. The surgical treatment efficiency of the observation group (97.56%) was significantly higher. After treatment, the observation group’s diverticulum repair indexes (width, depth and lower uterine muscular layer thickness) were better than those of the control group (p

BackgroundCurrently, the available evidence regarding the relationship between the lipid profile and Helicobacter pylori (H. pylori) infection is limited and conflicting. There is also a dearth of studies that have explored the possibility of sex-specific differences in the association between H. pylori infection and triglyceride levels.MethodsWe conducted a cross-sectional study involving 1,146 participants utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 conducted in the United States. A logistic regression model was employed to evaluate the association between H. pylori seropositivity and triglyceride levels. Subgroup analyses stratified by sex were conducted to explore sex-specific differences in this association.ResultsSerum triglyceride levels were significantly higher in H. pylori-seropositive participants than in H. pylori-seronegative participants. In the logistic regression analysis, there was a positive correlation between H. pylori seropositivity and triglyceride levels (OR=1.231; 95% CI, 1.016-1.491; P=0.033). In the subgroup analysis, the adjusted association between serum triglycerides and H. pylori seropositivity was significant in females (OR=1.732; 95% CI, 1.113-2.696; P=0.015) but not in males (OR=1.091; 95% CI, 0.698-1.705; P=0.704).ConclusionThe association between high triglyceride levels and H. pylori infection is specific to the female population.

ObjectiveGhrelin is a protein that regulate appetite and energy balance in the human body, which is encoded by the ghrelin prepropeptide gene (GHRL). GHRL is linked with carcinogenesis and immune regulation. However, the correlation of GHRL to prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains unclear.MethodsIn this study, we assessed the transcriptional expression, prognosis, and different clinicopathological features about GHRL and the correlation between GHRL and tumor infiltration immune cells in GC patients based on the data published in the following databases: TIMER, GEPIA, GEO, STRING, UALCAN, TISIDB, and Kaplan–Meier Plotter. Furthermore, R software analysis for GC Correa’ cascade was also provided. Finally, GHRL expression in GC tissues was assayed using quantitative real-time polymerase chain reaction and immunohistochemistry.ResultsWe found that GHRL expression in GC samples was lower than in normal samples and verified by quantitative PCR (qPCR) and immunohistochemistry. However, sample type, cancer stage, and worse survival were correlated to high GHRL expression. We also found that the expression of GHRL in dysplasia was significantly lower than that in CNAG and in GC. High GHRL expression was connected with immunomodulators, chemokines, and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC.ConclusionsGHRL is a prognostic biomarker for GC patients, and it is correlated with progression of precancerous lesions in GC. It might lead to poor prognosis by regulating tumor immune microenvironment. Studies are important to explore therapeutic targeting GHRL in the future.