Removal of arsenic from water by silver nanoparticles and Fe-Ce mixed oxide supported on polymeric anion exchanger.

By encapsulating nanoscale particles of goethite (α-FeO(OH)), hydrous ceric oxide (CeO2·H2O, HCO) and silver nanoparticles (AgNPs) in the pores of polystyrene anion exchanger D201, a novel nanocomposite FeO(OH)-HCO-Ag-D201 was prepared for the effective removal of arsenic from water. The isotherm study shows that FeO(OH)-HCO-Ag-D201 has excellent adsorption performance for As(III) and As(V), with an increased adsorption capacity of As(III) to 40.12 mg/g compared to that of 22.03 mg/g by the composite adsorbent without AgNPs (FeO(OH)-HCO-D201). The adsorption kinetics data showed that the sorption rate of FeO(OH)-HCO-Ag-D201 for As(III) is less than that for As(V), and the adsorption of As(III) and As(V) were consistent with the pseudo-second-order model and the pseudo-first-order model, respectively. Neutral or basic conditions are favored for the adsorption of As(III/V) by FeO(OH)-HCO-Ag-D201. Compared with nitrate/chloride/bicarbonate, sulfate/silicate/phosphate showed more remarkable inhibition of arsenic removal by FeO(OH)-HCO-Ag-D201, whereas natural organic matter showed no interference to the arsenic removal. The As(V) adsorption involved different interactions such as electrostatic attraction and surface complexation, while the adsorption of As(III) involved the part oxidization of As(III) to As(V) and the simultaneous adsorption of As(III) and As(V). In addition to the Ce(IV) in CeO2·H2O acted as an oxidant, the synergistic effect of α-FeO(OH) and AgNPs also contributed to the oxidization of As(III) to As(V). Moreover, the reusable property suggested that this FeO(OH)-HCO-Ag-D201 nanocomposite has great potential for arsenic-contaminated water purification.

Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway.

As a highly contagious acute respiratory disease, influenza A virus (A/WSN/1933) poses a huge threat to human health and public health. influenza A virus proliferation relies on glucose metabolism in host cells, yet the effects of influenza A virus on glucose metabolism and the underlying molecular mechanisms remain unclear. Here, we created models of WSN virus-infected mice and A549 cells, along with analyzing metabolomics and transcriptomics data, to investigate how WSN virus infection affects host cell glucose metabolism and specific mechanisms. Analysis of metabolites and gene expression showed that WSN virus infection triggers glycolysis in A549 cells, with notable upregulation of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), hypoxia-inducible factor-1 alpha (HIF-1α), and elevated lactate levels. Additionally, it leads to mitochondrial impairment and heightened reactive oxygen species (ROS) generation. Elevated levels of glucose may enhance the replication of WSN virus, whereas inhibitors of glycolysis can reduce it. Enhancement of HIF-1α activation facilitated replication of WSN virus through stimulation of lactate synthesis, with the primary influence of glycolysis on WSN virus replication being mediated by ROS/HIF-1α signaling. Mice given HIF-1α inhibitor PTX-478 or glycolysis inhibitor 2-Deoxyglucose (2-DG) exhibited reduced lactate levels and decreased WSN virus replication, along with mitigated weight loss and lung damage. In summary, WSN virus-induced glycolysis has been demonstrated to enhance virus replication through the activation of the ROS/HIF-1α pathway, suggesting potential new targets for combating the virus.

Single-cell RNA sequencing highlights the role of proinflammatory fibroblasts, vascular endothelial cells, and immune cells in the keloid immune microenvironment.

BACKGROUND: Keloids, characterized by an aberrant wound-healing process and a highly complex immune microenvironment, pose significant challenges for clinical management. Fibroblasts and vascular endothelial cells (VEC) were identified as the leading cells of keloid development. However, their roles in the keloid immune landscape have yet to be thoroughly elucidated. METHODS: To explore the functional state of cells in the immune landscape of keloids, we conducted a single-cell RNA sequencing analysis on the tissue from three keloid lesions and two specimens of healthy skin. We simultaneously utilized available keloid data from the public database for external validation. RESULTS: Specific subsets, such as proinflammatory fibroblasts (piF) and VEC, were markedly elevated in lesional skin compared to normal skin. Subsequent differential gene expression and Gene Ontology analyses indicated that these subsets may be involved in shaping the microenvironment. In keloids, there is an increased expression of immune-associated genes (P < 0.05), including TNFRSF6B, HGF, and TGFB3, alongside a decreased expression of inflammatory chemokines in the piF. Moreover, the significant upregulation of immune suppressive genes (P < 0.05), including CD39, CD73, and HIF1A, suggested the potential involvement of VEC as a conditional immune subpopulation in the keloid microenvironment. Immune cell communication analysis revealed preferential enrichment of macrophages and Tregs, highlighting intensified macrophage-centered interactions within the keloid microenvironment. CONCLUSION: Our study highlighted the role of piF and VEC in the immune microenvironment of keloids for the first time, providing potential targets for therapeutic development.

Expert Consensus on Big Data Collection of Skin and Appendage Disease Phenotypes in Chinese.

The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.

First report of basal stem rot on sugarcane (var. Badila) caused by Sclerotium rolfsii in China.

Badila (Saccharum officinarum) is one of the important chewing cane in south China. During the year 2019-2020, as much as 60.2%-87.5% of sugarcane plants stem showed red rot developments were observed in the fields of Yongning District, Nanning city, Guangxi province. Symptomatic plants showed red rot at basal stem nodes and sheath, when the disease serious, the epidermis and aerial roots decomposed and exfoliated, then formed sclerotiums, the upper stem also occurred the symptom. Infected plant tissues were dissected into small pieces with 0.1 × 0.1cm in size and surface sterilized in 0.1% HCl2 for 2 min, followed by 75% ethanol for 30 s, rinsed three times with sterile distilled water. Then the tissues were placed onto potato dextrose agar (PDA) plates and incubated at 25 °C for 3 days. Numerous white globoid sclerotia were formed on PDA after 5 days of growth. The sclerotia (2 to 3 mm in diameter) were white at first and then gradually turned dark brown. Aerial mycelia usually formed many narrow hyphal strands 4 to 9 µm wide. Five uniform isolates were obtained from diseased sugarcane plants. Pathogenicity of representative strain W1 was confirmed by inoculating 120-day-old Badila plants grown in field. Five plants were inoculated with colonized agar discs (6mm in diameter) by applying toothpick tips to the lower part of the stem. Five non-inoculated plants served as control. The inoculated and non-inoculated plants were sprayed sterile water then incubated with plastic film for maintained high moisture. All the plants were placed inside of a growth chamber at 26 ± 2°C with a 14-h photoperiod and 80% relative humidity. All inoculated plants showed red rot at stem and sheath after 2 weeks, whereas the control plants were symptomless. By the third week, mycelium and sclerotia developed on the crown on the inoculated plants. The fungus was re-isolated from the artificially inoculated plants. To confirm the species-level identification, partial of the ribosomal DNA internal transcribed spacer (ITS), mitocondrial small subunit (SSU), and nuclear ribosomal large subunit (LSU) regions of representative strain W1 were amplified and sequenced using the primers pairs ITS1/ITS4 (White et al. 1990), ITS-Fu-F /ITS-Fu-R and SRLSU1//SRLSU2 (Kumar et al., 2016), respectively. The resulting ITS, SSU and LSU sequences were deposited in GenBank (GenBank accession no. MW620994, MW617878, and MW617872) and shared 99.42%, 100% and 100% sequence identity with Athelia rolfsii isolate (JN017199, OM319631, and MT225781). Phylogenetic analysis conducted with neighbor-joining (NJ) method using MEGA6.0 revealed that the isolate share a common clade with reference sequence of A. rolfsii in GenBank Data Library. Based on morphological and molecular characteristics, the fungus was identified as A. rolfsii (anamorph: Sclerotium rolfsii) (Paul et al. 2017; Paparu et al. 2020). Although S. rolfsii has been reported causing sugarcane sett rot in Australia (Bhuiyan et al., 2019) and seedlings of sugarcane in Indian (Gopi et al., 2023), as we know, this is the first report of sugarcane basal stem rot disease caused by this fungus in China. This study will be helpful for the prevention and control sugarcane basal stem rot in the future.

Utilization of Tea Polyphenols as Color Developers in Reversible Thermochromic Dyes for Thermosensitive Color Change and Enhanced Functionality of Polyester Fabrics.

Thermochromic textiles possess the capability to indicate ambient temperature through color changes, enabling real-time temperature monitoring and providing temperature warnings for body heat management. In this study, three thermochromic dyes-blue, red, and yellow-were synthesized using crystalline violet lactone (CVL), 6'-(diethylamino)-1',3'-dimethyl-fluoran (DDF), and 3',6'-dimethoxyfluoran (DOF) as leuco dyes, respectively, with biomass tea polyphenol serving as the color developer and tetradecanol as the phase change material. The chemical structures of these dyes were characterized using UV spectroscopy, infrared spectroscopy, Raman spectroscopy and 1H NMR. The thermochromic mechanisms were investigated, revealing that the binding bonds between the leuco dyes and the color developer broke and reorganized with temperature changes, imparting reversible thermochromic property. Polyester fabrics were dyed using an impregnation method to produce three reversible thermochromic fabrics in blue, red, and yellow. The structure and properties of these fabrics were analyzed, showing a significant increase in the UPF value from 26.3 to approximately 100, indicating enhanced UV resistance. Water contact angle measurements revealed that the contact angle of undyed polyester fabrics was 139°, while that of dyed polyester fabrics decreased by about 40°, indicating improved hydrophilicity. Additionally, the fabric inductive static tester showed that the static voltage half-life of dyed polyester fabric was less than 1 s, demonstrating a significant antistatic effect. Infrared thermal imaging results indicated that during the warming and cooling process, the thermochromic polyester fabric exhibited specific energy storage and insulation effects at 38 °C, close to the human body temperature. This study presented a novel approach to developing smart color-changing textiles using biomass-derived thermochromic dyes, offering diverse materials for personal thermal management, and intelligent insulation applications.

An Automated Clubbed Fingers Detection System Based on YOLOv8 and U-Net: A Tool for Early Prediction of Lung and Cardiovascular Diseases.

Background/Objectives: Lung and cardiovascular diseases are leading causes of mortality worldwide, yet early detection remains challenging due to the subtle symptoms. Digital clubbing, characterized by the bulbous enlargement of the fingertips, serves as an early indicator of these diseases. This study aims to develop an automated system for detecting digital clubbing using deep-learning models for real-time monitoring and early intervention. Methods: The proposed system utilizes the YOLOv8 model for object detection and U-Net for image segmentation, integrated with the ESP32-CAM development board to capture and analyze finger images. The severity of digital clubbing is determined using a custom algorithm based on the Lovibond angle theory, categorizing the condition into normal, mild, moderate, and severe. The system was evaluated using 1768 images and achieved cloud-based and real-time processing capabilities. Results: The system demonstrated high accuracy (98.34%) in real-time detection with precision (98.22%), sensitivity (99.48%), and specificity (98.22%). Cloud-based processing achieved slightly lower but robust results, with an accuracy of 96.38%. The average processing time was 0.15 s per image, showcasing its real-time potential. Conclusions: This automated system provides a scalable and cost-effective solution for the early detection of digital clubbing, enabling timely intervention for lung and cardiovascular diseases. Its high accuracy and real-time capabilities make it suitable for both clinical and home-based health monitoring.

Endoplasmic reticulum stress induces renal fibrosis in high­fat diet mice via the TGF­ß/SMAD pathway.

The aim of the present study was to investigate the role and mechanism of endoplasmic reticulum stress (ERS) in kidney injury caused by high­fat diet (HFD). An obese mouse model was established via HFD feeding and intervention was performed by intraperitoneal injection of the ERS inhibitor salubrinal (Sal). Changes in the body and kidney weight and serum biochemical indices of the mice were determined. Hematoxylin and eosin and Masson staining were used to observe the pathological changes of renal tissues. Reverse transcription­quantitative PCR and western blotting were used to observe the expression of ERS­related proteins and TGF­ß/SMAD pathway­related proteins. Immunohistochemistry was employed to explore the distribution of these proteins. Compared with those in the control group, the weight gain, lipid metabolism disorders and deterioration of renal function in the model group were greater. Malondialdehyde was elevated and superoxide dismutase was decreased in renal tissues. The mRNA and protein levels of TGF­ß1, SMAD2/3, α­smooth muscle actin, collagen I, glucose­regulated protein 78 and C/EBP­homologous protein were markedly elevated, whereas SMAD7 was markedly decreased. Sal markedly inhibited the aforementioned effects. This investigation revealed a link between ERS and renal injury caused by HFD. ERS in HFD­fed mice triggers renal fibrosis through the TGF­ß/SMAD pathway.

DaxibotulinumtoxinA for injection to treat moderate or severe glabellar lines: A randomized, multicenter, Phase III, double-blind, placebo-controlled trial in China.

BACKGROUND: DaxibotulinumtoxinA for injection (DAXI), a novel botulinum toxin type A formulation, is FDA-approved for glabellar lines treatment. Its clinical efficacy has been demonstrated in two Phase III trials (SAKURA 1 and SAKURA 2). OBJECTIVE: To evaluate DAXI efficacy and safety in Chinese adults with moderate/severe glabellar lines. METHODS: In this Phase III, randomized (2:1), double-blind trial, Chinese adults with moderate/severe glabellar lines received 40 U DAXI or placebo into the corrugator muscles bilaterally and the procerus. Glabellar line severity was evaluated by investigators (Investigator Global Assessment-Frown Wrinkle Severity [IGA-FWS] scale) and participants (Patient Frown Wrinkle Severity [PFWS] scale) for ≥24 to 36 weeks. The primary endpoint was the proportion of 2-point composite responders achieving ≥2-point reduction in IGA-FWS and PFWS scores at week 4 post-treatment. RESULTS: Overall, 307 participants received treatment (DAXI, 205; placebo, 102). A significantly greater proportion of participants in the DAXI arm vs the placebo arm achieved a 2-point composite response at week 4: 125 (61.0%) vs 1 (1.0%); difference, 60.0% [95% CI 49.40-66.46]; 2-sided p < 0.0001). At week 4, 94.1% of the DAXI-treated participants achieved an IGA-FWS score 0/1 (none/mild) and 86.3% achieved PFWS 0/1; median time to loss of none/mild on IGA-FWS and PFWS was 23.9 weeks. The benefits of DAXI over placebo through week 24 occurred regardless of the baseline IGA-FWS score, prior botulinum toxin type A (BoNTA) exposure, sex or age. DAXI was well tolerated with no new safety signals. CONCLUSION: DAXI provided durable efficacy and acceptable safety for treating moderate/severe glabellar lines in Chinese participants.

Fatigue strength analysis of a new left atrial appendage occluder at different release scales.

Owing to its low incidence, small trauma, fast recovery, and high efficiency, left atrial appendage occlusion has become a new strategy for preventing stroke caused by atrial fibrillation. Due to a lack of relevant research information on this emerging technology, the effectiveness, stability, or related complications of occluders are mostly observed from a clinical perspective. However, there are fewer studies on the mechanical properties and safety of these occluders. In this study, a new left atrial appendage occluder is proposed, and a complete numerical simulation analysis framework is established through the finite element method to simulate the actual implantation and service process of the left atrial appendage occluder. Besides, the influence of the structural size and release scale of the occluder on its support performance, occluding effect, and safety is also explored. The results demonstrate that the structural size and release scale exert a significant impact on the support performance, occluding effect, and safety of the occluder. The structural optimization of the occluder contributes to enhancing its mechanical performance, thus ensuring its stability and effectiveness after implantation. Overall, these efforts may lay a scientific foundation for the structural optimization, safety evaluation, and effectiveness prediction of the occluder. Furthermore, these findings also provide effective reference for the application of numerical simulation technology in the research on the left atrial appendage occlusion.

Lycium barbarum polysaccharide increases thermogenesis and energy metabolism through modulation of the gut microbiota to confer resistance to cold temperatures.

Traditional Chinese medical literature contains numerous records of many traditional Chinese herbal medicines that exhibit efficacy in enhancing resistance to cold, yet there is a lack of scientific explanation. Lycium barbarum is among the herbal medicines that are explicitly documented to enhance resistance to cold in the "Ben Cao Gang Mu (Compendium of Materia Medica)". Herein, we investigated L. barbarum polysaccharide (LBP)-induced browning of inguinal white adipose tissue (iWAT), energy expenditure and thermogenic function in a long-term (4 months) treatment mouse model. LBP supplementation resulted in a significant reduction in weight and adipocyte size in iWAT, along with increased gut microbiota diversity. Specifically, the levels of Lachnospiraceae, Ruminococcaceae and Bacteroidaceae (short-chain fatty acid-producing bacteria) were elevated, leading to a higher level of short-chain fatty acids (SCFAs) in the caecal content. These effects subsequently triggered the release of glucagon-like peptide-1 (GLP-1) and activated the CREB/PGC1α signaling pathway in iWAT, thereby increasing energy expenditure and enhancing thermogenic function. The antibiotic treatment experiments confirmed that the LBP-mediated gut microbiota participated in the process of iWAT browning. In summary, our findings provide the first scientific explanation and mechanistic insights into the cold resistance of L. barbarum and identify potentially safe natural product supplements for individuals in alpine areas.

Transcranial magnetic stimulation of the right inferior frontal gyrus impairs bilinguals' performance in language-switching tasks.

It is widely accepted that bilinguals activate both languages simultaneously, even when intending to speak only one. A prevailing theory proposes that bilinguals inhibit the nontarget language to produce the target language, thought to be supported by evidence that the right inferior frontal gyrus (rIFG), a region typically associated with inhibition, is activated during language-switching tasks. However, it remains unclear whether the rIFG plays a causal or epiphenomenal role in this process. To explore the role of the rIFG, the present study employed transcranial magnetic stimulation (TMS) to modulate its neural activity and evaluate subsequent behavior in bilinguals. Specifically, twenty-nine Chinese-English bilinguals participated in the study and performed picture-naming tasks in single- and dual-language contexts after receiving sham stimulation (Sham), continuous theta burst stimulation (cTBS), or intermittent theta burst stimulation (iTBS) over the rIFG in three separate visits. Sham served as a control, with cTBS and iTBS intended to decrease and increase cortical excitability, respectively. We found that, compared to Sham, cTBS led to larger asymmetric switching costs and smaller asymmetric mixing costs, whereas iTBS resulted only in smaller asymmetric mixing costs. These findings suggest that cTBS targeting the rIFG likely impairs both local and global control. However, iTBS applied to the rIFG alone may not necessarily enhance language control mechanisms and could even hinder global control. Moreover, exploratory analyses found pronounced TMS-induced impairments in less balanced bilinguals, implying their potentially greater reliance on bilingual language control. Overall, this study is the first to suggest a causal role of the rIFG in language switching.

Word concreteness modulates bilingual language control during reading comprehension.

Controversies persist in the literature regarding the existence of bilingual language control during comprehension, which may be attributed to overlooking the modulating effect of word concreteness. To test this hypothesis, we conducted an experiment using abstract and concrete words, thereby manipulating the activation level of the nontarget language. Sixty Chinese-English bilinguals were instructed to switch between two languages in word reading tasks. We found that abstract words (e.g., [correct], wrong) did not show switching costs, indicating no additional time for switching between languages compared to repeating the same language. In contrast, concrete words (e.g., [sunny], rainy) elicited significant larger switching costs. These findings might suggest greater language control demands on the nontarget language when reading more concrete words. This study offers insights into the modulating effect of word concreteness in language processing on bilingual language control during reading comprehension. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

AerialIRGAN: unpaired aerial visible-to-infrared image translation with dual-encoder structure.

Due to the high cost of equipment and the constraints of shooting conditions, obtaining aerial infrared images of specific targets is very challenging. Most methods using Generative Adversarial Networks for translating visible images to infrared greatly depend on registered data and struggle to handle the diversity and complexity of scenes in aerial infrared targets. This paper proposes a one side end-to-end unpaired aerial visible-to-infrared image translation algorithm, termed AerialIRGAN. AerialIRGAN introduces a dual-encoder structure, where one encoder is designed based on the Segment Anything Model to extract deep semantic features from visible images, and the other encoder is designed based on UniRepLKNet to capture small-scale patterns and sparse patterns from visible images. Subsequently, AerialIRGAN constructs a bridging module to deeply integrate the features of both encoders and their corresponding decoders. Finally, AerialIRGAN proposes a structural appearance consistency loss to guide the synthetic infrared images to maintain the structure of the source image while possessing distinct infrared characteristics. The experimental results show that compared to the existing typical infrared image generation algorithms, the proposed method can generate higher-quality infrared images and achieve better performance in both subjective visual description and objective metric evaluation.

Global Incidence of Diarrheal Diseases-An Update Using an Interpretable Predictive Model Based on XGBoost and SHAP: A Systematic Analysis.

BACKGROUND: Diarrheal disease remains a significant public health issue, particularly affecting young children and older adults. Despite efforts to control and prevent these diseases, their incidence continues to be a global concern. Understanding the trends in diarrhea incidence and the factors influencing these trends is crucial for developing effective public health strategies. OBJECTIVE: This study aimed to explore the temporal trends in diarrhea incidence and associated factors from 1990 to 2019 and to project the incidence for the period 2020-2040 at global, regional, and national levels. We aimed to identify key factors influencing these trends to inform future prevention and control strategies. METHODS: The eXtreme Gradient Boosting (XGBoost) model was used to predict the incidence from 2020 to 2040 based on demographic, meteorological, water sanitation, and sanitation and hygiene indicators. SHapley Additive exPlanations (SHAP) value was performed to explain the impact of variables in the model on the incidence. Estimated annual percentage change (EAPC) was calculated to assess the temporal trends of age-standardized incidence rates (ASIRs) from 1990 to 2019 and from 2020 to 2040. RESULTS: Globally, both incident cases and ASIRs of diarrhea increased between 2010 and 2019. The incident cases are expected to rise from 2020 to 2040, while the ASIRs and incidence rates are predicted to slightly decrease. During the observed (1990-2019) and predicted (2020-2040) periods, adults aged 60 years and above exhibited an upward trend in incidence rate as age increased, while children aged < 5 years consistently had the highest incident cases. The SHAP framework was applied to explain the model predictions. We identified several risk factors associated with an increased incidence of diarrhea, including age over 60 years, yearly precipitation exceeding 3000 mm, temperature above 20 °C for both maximum and minimum values, and vapor pressure deficit over 1500 Pa. A decreased incidence rate was associated with relative humidity over 60%, wind speed over 4 m/s, and populations with above 80% using safely managed drinking water services and over 40% using safely managed sanitation services. CONCLUSIONS: Diarrheal diseases are still serious public health concerns, with predicted increases in the incident cases despite decreasing ASIRs globally. Children aged < 5 years remain highly susceptible to diarrheal diseases, yet the incidence rate in the older adults aged 60 plus years still warrants additional attention. Additionally, more targeted efforts to improve access to safe drinking water and sanitation services are crucial for reducing the incidence of diarrheal diseases globally.

Rifaximin ameliorates influenza A virus infection-induced lung barrier damage by regulating gut microbiota.

Prior research has indicated that the gut-lung-axis can be influenced by the intestinal microbiota, thereby impacting lung immunity. Rifaximin is a broad-spectrum antibacterial drug that can maintain the homeostasis of intestinal microflora. In this study, we established an influenza A virus (IAV)-infected mice model with or without rifaximin supplementation to investigate whether rifaximin could ameliorate lung injury induced by IAV and explore the molecular mechanism involved. Our results showed that IAV caused significant weight loss and disrupted the structure of the lung and intestine. The analysis results of 16S rRNA and metabolomics indicated a notable reduction in the levels of probiotics Lachnoclostridium, Ruminococcaceae_UCG-013, and tryptophan metabolites in the fecal samples of mice infected with IAV. In contrast, supplementation with 50 mg/kg rifaximin reversed these changes, including promoting the repair of the lung barrier and increasing the abundance of Muribaculum, Papillibacter and tryptophan-related metabolites content in the feces. Additionally, rifaximin treatment increased ILC3 cell numbers, IL-22 level, and the expression of RORγ and STAT-3 protein in the lung. Furthermore, our findings demonstrated that the administration of rifaximin can mitigate damage to the intestinal barrier while enhancing the expression of AHR, IDO-1, and tight junction proteins in the small intestine. Overall, our results provided that rifaximin alleviated the imbalance in gut microbiota homeostasis induced by IAV infection and promoted the production of tryptophan-related metabolites. Tryptophan functions as a signal to facilitate the activation and movement of ILC3 cells from the intestine to the lung through the AHR/STAT3/IL-22 pathway, thereby aiding in the restoration of the barrier. KEY POINTS: • Rifaximin ameliorated IAV infection-caused lung barrier injury and induced ILC3 cell activation. • Rifaximin alleviated IAV-induced gut dysbiosis and recovered tryptophan metabolism. • Tryptophan mediates rifaximin-induced ILC3 cell activation via the AHR/STAT3/IL-22 pathway.

Identification of two molecularly and prognostically distinct subtypes in acral melanoma using network prediction method.

BACKGROUND: Acral melanoma, characterized by its aggressiveness and poor prognosis compared to other melanoma subtypes, poses significant challenges in clinical management. However, the molecular underpinnings driving the biological and clinical features of this disease remain poorly understood. OBJECTIVES: In this study, our aim was to elucidate the molecular landscape and the correlation between subtypes and clinical features of acral melanoma. METHODS: We conducted comprehensive analyses to dissect the molecular characteristics of acral melanoma, employing a combination of multi-omics data analysis and network-based disease gene prediction algorithms. Single-cell RNA-Seq data were utilized to investigate the contribution of immunocytes to the molecular classification of acral melanoma. Additionally, we used clinical samples to validate the correlation between new subtypes and the prognosis of acral melanoma and the expression of subtype markers and verified the interaction between macrophages and acral melanoma cells at cellular level. RESULTS: Our study reveals the existence of two distinct subtypes of acral melanoma exhibiting marked differences in clinical behaviour, cellular and molecular mechanisms. We identified a robust biomarker panel (EREG, VSIG4, FCGR3A and RAB20) that accurately distinguishes these two subtypes with an impressive AUC of 0.946, validated using clinical samples. Subtype I, characterized by thinner Breslow thickness, demonstrates a favourable prognosis, whereas Subtype II represents a high-risk subtype with a propensity for dermal invasion. Notably, the signature gene EREG of Subtype I is enriched in FCN1+ macrophages, known for promoting inflammatory and immune responses. Conversely, signature genes VSIG4 and FCGR3A of Subtype II are enriched in SPP1+ macrophages, which exhibit significant crosstalk with tumour cells. CONCLUSIONS: Our findings significantly enhance the understanding of the molecular landscape of acral melanoma and offer novel insights into its clinical management by identifying distinct subtypes and potential therapeutic targets. The findings have to be confirmed in different cohorts in the future for full validation.

Predictors of survival in immunotherapy-based treatments in advanced melanoma: a meta-analysis.

The introduction of immunotherapy-based strategies has significantly improved the prognosis for melanoma patients. Nevertheless, some patients still have dismal outcomes, emphasizing the significance of survival predictive indicators in immunotherapy-based approaches. We systematically searched randomized controlled clinical trials investigating dual immunotherapy or chemoimmunotherapy versus placebo or mono-immunotherapy or chemotherapy alone in advanced melanoma patients. R version 4.3.0. was employed to perform all analyses. A comprehensive analysis was conducted on a total of 13,809 patients with advanced melanoma from 19 randomized clinical trials. Immunotherapy-based strategies (alone or in combination) could significantly lengthen the overall survival(OS) and recurrence-free survival (RFS) compared with corresponding controls. Mono-immunotherapy improved RFS and OS in PD-L1 positive patients, in stage AJCC IIIC, and with 4 or more positive lymph nodes, compared with chemotherapy. Combined immunotherapy statistically improved RFS and OS in those aged < 65, with an Eastern Cooperative Oncology Group (ECOG) status of 0, and LDH ≤ ULN at baseline compared with single treatment alone. Our findings indicated that certain clinicopathological and molecular features could assist in choosing appropriate melanoma patients for immune-based treatments.

Signals from intestinal microbiota mediate the crosstalk between the lung-gut axis in an influenza infection mouse model.

Introduction: Introduction: The influenza virus primarily targets the respiratory tract, yet both the respiratory and intestinal systems suffer damage during infection. The connection between lung and intestinal damage remains unclear. Methods: Our experiment employs 16S rRNA technology and Liquid Chromatography-Mass Spectrometry (LC-MS) to detect the impact of influenza virus infection on the fecal content and metabolites in mice. Additionally, it investigates the effect of influenza virus infection on intestinal damage and its underlying mechanisms through HE staining, Western blot, Q-PCR, and flow cytometry. Results: Our study found that influenza virus infection caused significant damage to both the lungs and intestines, with the virus detected exclusively in the lungs. Antibiotic treatment worsened the severity of lung and intestinal damage. Moreover, mRNA levels of Toll-like receptor 7 (TLR7) and Interferon-b (IFN-b) significantly increased in the lungs post-infection. Analysis of intestinal microbiota revealed notable shifts in composition after influenza infection, including increased Enterobacteriaceae and decreased Lactobacillaceae. Conversely, antibiotic treatment reduced microbial diversity, notably affecting Firmicutes, Proteobacteria, and Bacteroidetes. Metabolomics showed altered amino acid metabolism pathways due to influenza infection and antibiotics. Abnormal expression of indoleamine 2,3-dioxygenase 1 (IDO1) in the colon disrupted the balance between helper T17 cells (Th17) and regulatory T cells (Treg cells) in the intestine. Mice infected with the influenza virus and supplemented with tryptophan and Lactobacillus showed reduced lung and intestinal damage, decreased Enterobacteriaceae levels in the intestine, and decreased IDO1 activity. Discussion: Overall, influenza infection caused damage to lung and intestinal tissues, disrupted intestinal microbiota and metabolites, and affected Th17/Treg balance. Antibiotic treatment exacerbated these effects. Supplementation with tryptophan and Lactobacillus improved lung and intestinal health, highlighting a new understanding of the lung-intestine connection in influenza-induced intestinal disease.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.