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The increasing prevalence of non-tuberculous mycobacterium (NTM) infections alongside tuberculosis (TB) underscores a pressing public health challenge. Yet, the mechanisms governing their infection within the lung remain poorly understood. Here, we integrate metagenomic sequencing, metabolomic sequencing, machine learning classifiers, SparCC, and MetOrigin methods to profile bronchoalveolar lavage fluid (BALF) samples from NTM/TB patients. Our aim is to unravel the intricate interplay between lung microbial communities and NTM/Mycobacterium tuberculosis infections. Our investigation reveals a discernible reduction in the compositional diversity of the lung microbiota and a diminished degree of mutual interaction concomitant with NTM/TB infections. Notably, NTM patients exhibit a distinct microbial community characterized by marked specialization and notable enrichment of Pseudomonas aeruginosa and Staphylococcus aureus, driving pronounced niche specialization for NTM infection. Simultaneously, these microbial shifts significantly disrupt tryptophan metabolism in NTM infection, leading to an elevation of kynurenine. Mycobacterium intracellulare, Mycobacterium paraintracellulare, Mycobacterium abscessus, and Pseudomonas aeruginosa have been implicated in the metabolic pathways associated with the conversion of indole to tryptophan via tryptophan synthase within NTM patients. Additionally, indoleamine-2,3-dioxygenase converts tryptophan into kynurenine, fostering an immunosuppressive milieu during NTM infection. This strategic modulation supports microbial persistence, enabling evasion from immune surveillance and perpetuating a protracted state of NTM infection. The elucidation of these nuanced microbial and metabolic dynamics provides a profound understanding of the intricate processes underlying NTM and TB infections, offering potential avenues for therapeutic intervention and management.

Cotton, a vital textile raw material, is intricately linked to people’s livelihoods. Throughout the cotton cultivation process, various diseases threaten cotton crops, significantly impacting both cotton quality and yield. Deep learning has emerged as a crucial tool for detecting these diseases. However, deep learning models with high accuracy often come with redundant parameters, making them challenging to deploy on resource-constrained devices. Existing detection models struggle to strike the right balance between accuracy and speed, limiting their utility in this context. This study introduces the CDDLite-YOLO model, an innovation based on the YOLOv8 model, designed for detecting cotton diseases in natural field conditions. The C2f-Faster module replaces the Bottleneck structure in the C2f module within the backbone network, using partial convolution. The neck network adopts Slim-neck structure by replacing the C2f module with the GSConv and VoVGSCSP modules, based on GSConv. In the head, we introduce the MPDIoU loss function, addressing limitations in existing loss functions. Additionally, we designed the PCDetect detection head, integrating the PCD module and replacing some CBS modules with PCDetect. Our experimental results demonstrate the effectiveness of the CDDLite-YOLO model, achieving a remarkable mean average precision (mAP) of 90.6%. With a mere 1.8M parameters, 3.6G FLOPS, and a rapid detection speed of 222.22 FPS, it outperforms other models, showcasing its superiority. It successfully strikes a harmonious balance between detection speed, accuracy, and model size, positioning it as a promising candidate for deployment on an embedded GPU chip without sacrificing performance. Our model serves as a pivotal technical advancement, facilitating timely cotton disease detection and providing valuable insights for the design of detection models for agricultural inspection robots and other resource-constrained agricultural devices.

Corona Virus Disease 2019 (COVID-19) is a highly prevalent and potent infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until now, the world is still endeavoring to develop new ways to diagnose and treat COVID-19. At present, the clinical prevention and treatment of COVID-19 mainly targets the spike protein on the surface of SRAS-CoV-2. However, with the continuous emergence of SARS-CoV-2 Variants of concern (VOC), targeting the spike protein therapy shows a high degree of limitation. The Nucleocapsid Protein (N protein) of SARS-CoV-2 is highly conserved in virus evolution and is involved in the key process of viral infection and assembly. It is the most expressed viral structural protein after SARS-CoV-2 infection in humans and has high immunogenicity. Therefore, N protein as the key factor of virus infection and replication in basic research and clinical application has great potential research value. This article reviews the research progress on the structure and biological function of SARS-CoV-2 N protein, the diagnosis and drug research of targeting N protein, in order to promote researchers’ further understanding of SARS-CoV-2 N protein, and lay a theoretical foundation for the possible outbreak of new and sudden coronavirus infectious diseases in the future.

Annually, more than 15 million people worldwide suffer from stroke, a condition linked to high mortality and disability rates. This disease significantly affects daily life, impairing everyday functioning, executive function, and cognition. Moreover, stroke severely restricts patients’ ability to perform daily activities, diminishing their overall quality of life. Recent scientific studies have identified cuproptosis, a newly discovered form of cell death, as a key factor in stroke development. However, the role of cuproptosis in stroke remains unclear to researchers. Therefore, it is crucial to investigate the mechanisms of cuproptosis in stroke’s pathogenesis. This review examines the physiological role of copper, the characteristics and mechanisms of cuproptosis, the differences and similarities between cuproptosis and other cell death types, and the pathophysiology of cuproptosis in stroke, focusing on mitochondrial dysfunction and immune infiltration. Further research is necessary to understand the relationship between previous strokes and cuproptosis and to clarify the mechanisms behind these associations.

Wild rice, a natural gene pool for rice germplasm innovation and variety improvement, holds immense value in rice breeding due to its disease-resistance genes. Traditional disease resistance identification in wild rice heavily relies on labor-intensive and subjective manual methods, posing significant challenges for large-scale identification. The fusion of unmanned aerial vehicles (UAVs) and deep learning is emerging as a novel trend in intelligent disease resistance identification. Detecting diseases in field conditions is critical in intelligent disease resistance identification. In pursuit of detecting bacterial blight in wild rice within natural field conditions, this study presents the Xoo-YOLO model, a modification of the YOLOv8 model tailored for this purpose. The Xoo-YOLO model incorporates the Large Selective Kernel Network (LSKNet) into its backbone network, allowing for more effective disease detection from the perspective of UAVs. This is achieved by dynamically adjusting its large spatial receptive field. Concurrently, the neck network receives enhancements by integrating the GSConv hybrid convolution module. This addition serves to reduce both the amount of calculation and parameters. To tackle the issue of disease appearing elongated and rotated when viewed from a UAV perspective, we incorporated a rotational angle (theta dimension) into the head layer's output. This enhancement enables precise detection of bacterial blight in any direction in wild rice. The experimental results highlight the effectiveness of our proposed Xoo-YOLO model, boasting a remarkable mean average precision (mAP) of 94.95%. This outperforms other models, underscoring its superiority. Our model strikes a harmonious balance between accuracy and speed in disease detection. It is a technical cornerstone, facilitating the intelligent identification of disease resistance in wild rice on a large scale.

Numerous genetic variants associated with Alzheimer’s disease (AD) have been identified through genome-wide association studies (GWAS), but their interpretation is hindered by the strong linkage disequilibrium (LD) among the variants, making it difficult to identify the causal variants directly. To address this issue, the transcriptome-wide association study (TWAS) was employed to infer the association between gene expression and a trait at the genetic level using expression quantitative trait locus (eQTL) cohorts. In this study, we applied the TWAS theory and utilized the improved Joint-Tissue Imputation (JTI) approach and Mendelian Randomization (MR) framework (MR-JTI) to identify potential AD-associated genes. By integrating LD score, GTEx eQTL data, and GWAS summary statistic data from a large cohort using MR-JTI, a total of 415 AD-associated genes were identified. Then, 2873 differentially expressed genes from 11 AD-related datasets were used for the Fisher test of these AD-associated genes. We finally obtained 36 highly reliable AD-associated genes, including APOC1, CR1, ERBB2, and RIN3. Moreover, the GO and KEGG enrichment analysis revealed that these genes are primarily involved in antigen processing and presentation, amyloid-beta formation, tau protein binding, and response to oxidative stress. The identification of these potential AD-associated genes not only provides insights into the pathogenesis of AD but also offers biomarkers for early diagnosis of the disease.

Allogeneic Hematopoietic stem cell transplantation (HSCT) offers a potential cure for patients with hematologic malignancies. Unfortunately, graft-versus-host disease (GVHD) remains a major obstacle to the greater success of this treatment. Despite intensive research efforts over the past several decades, GVHD is still a major cause of morbidity and mortality in patients receiving allogeneic HSCT. The genetic disparity between donor and recipient is the primary factor that dictates the extent of alloimmune response and the severity of acute GVHD (aGVHD). However, some nongenetic factors are also actively involved in GVHD pathogenesis. Thus, identifying host factors that can be readily modified to reduce GVHD risk is of important clinical significance. We are particularly interested in the potential role of nutrition, as a nongenetic factor, in the etiology and management of aGVHD. In this article, we summarize recent findings regarding how different routes of nutritional support and various dietary factors affect aGVHD. Since diet is one of the most important factors that shape gut microbiota, we also provide evidence for a potential link between certain nutrients and gut microbiota in recipients of allogeneic HSCT. We propose a shifting role of nutrition from support to therapy in GVHD by targeting gut microbiota.

BackgroundThis study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma.MethodsA total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What’s more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis.ResultsThe patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable (P

BackgroundThe antiviral activity and underlying mechanism of Patchouli alcohol remain unclear.MethodsThis study evaluated the cytotoxicity, optimal methods for drug administration, anti-influenza A activity of Patchouli alcohol. The antiviral mechanism of Patchouli alcohol was also assessed via qRT-PCR, western blot, hemagglutination inhibiting (HAI) assay, and hemolysis inhibiting assay.ResultsPatchouli alcohol was shown to have low cytotoxicity and its strongest antiviral effect was associated with premixed administration. Patchouli alcohol inhibited virus replication during the early lifecycle stages of influenza A virus infection and specifically prevented expression of the viral proteins, HA and NP. In both the HAI and hemolysis inhibiting assays, Patchouli alcohol was able to block HA2-mediated membrane fusion under low pH conditions. Patchouli alcohol had lower binding energy with HA2 than HA1.ConclusionThese findings suggest that Patchouli alcohol could be a promising membrane fusion inhibitor for the treatment of influenza A infection.

Human enterovirus 71 (EV71) is one of the major agents of the hand, foot, and mouth disease (HFMD), and occasionally causes severe neurological complications. There is clinical evidence that EV71 infection increases the exosomes in the serum of severe HFMD patients, suggesting a role of exosomes in EV71 pathogenesis. However, the relationship between exosomes and EV71 replication remains elusive. In this study, we initially found that EV71 infection elevated exosome biogenesis in the cultured cells. Among EV71 non-structural proteins, we identified EV71 3A, but not 3B, constitutively promoted exosome secretion. In detail, EV71 3A protein interacted with vacuolar protein sorting 25 (VPS25), while knock-down of VPS25 reduced EV71 3A protein- and EV71-induced exosome production. Further studies revealed VPS25 located on exosomes and its expression correlated to the exosome production. During EV71 infection, knock-down of VPS25 decreased exosome biogenesis to attenuate viral replication. Consistently, GW4869, an exosome inhibitor, exerted an obviously antiviral activity against EV71 replication companied with the decrease of exosome secretion or formation. These findings suggest the binding of EV71 3A and VPS25 benefited exosome biogenesis, thereby boosting viral replication. This study uncovers a novel mechanism underlying EV71-mediated exosomes in the regulation of viral replication, which provides potential anti-viral strategies against the EV71 infection and transmission in HFMD.

ObjectiveCancer and its treatments affect patients’ fertility potential. This study examined the prevalence of reproductive concerns and their relationship with metacognitions among Chinese young adult female cancer survivors (YAFCS).MethodsA total of 318 YAFCS (aged 18–39) completed an online survey from March to December 2021. Participants reported sociodemographic characteristics, reproductive concerns and metacognitions. Reproductive concerns were measured using the Reproductive Concerns after Cancer scale (RCAC), and metacognitions were measured by the Short Form of Metacognitions Questionnaire (MCQ-30). We used Pearson correlation analysis to examine associations between metacognitions and reproductive concerns across multiple domains and multivariable linear regression to determine the influencing factors of reproductive concerns.ResultsThe mean score of reproductive concern among YAFCS was 49.97 ± 12.52. A total of 57.9% of participants reported a high level of concern regarding at least one dimension of reproductive concerns, and they were most concerned about their child’s health and least concerned about partner disclosure of fertility status. We also found a moderate association between RCAC and MCQ-30 scores (r = 0.408, p

BackgroundSepsis-induced cardiomyopathy significantly increased the mortality of patients with sepsis. The diagnostic criteria for septic cardiomyopathy has not been unified, which brings serious difficulties to clinical treatment. This study aimed to provide evidence for the early identification and intervention in patients with sepsis by clarifying the relationship between the ultrasound phenotype of septic cardiomyopathy and the prognosis of patients with sepsis.MethodsThis was a multicenter, prospective cohort study. The study population will consist of all eligible consecutive patients with sepsis or septic shock who meet the Sepsis 3.0 diagnostic criteria and were aged ≥18 years. Clinical data and echocardiographic measurements will be recorded within 2 h, at the 24th hour, at the 72nd hour, and on the 7th day after admission. The prevalence of each phenotype will be described as well, and their association with prognosis will be analyzed statistically.DiscussionTo achieve early recognition, prevent reinjury, achieve precise treatment, and reduce mortality in patients with sepsis, it is important to identify septic cardiac alterations and classify the phenotypes at all stages of sepsis. First, there is a lack of studies on the prevalence of each phenotype in Chinese populations. Second, each phenotype and its corresponding prognosis are not clear. In addition, the prognosis of patients with normal cardiac ultrasound phenotypes vs. those with suppressed or hyperdynamic cardiac phenotypes is unclear. Finally, this study was designed to collect data at four specific timing, then the timing of occurrence, duration, changes over time, impact to outcomes of each phenotype will probably be found. This study is expected to establish a standard and objective method to assess the ultrasound phenotype of septic cardiomyopathy due to its advantages of visualization, non-invasiveness and reproducibility, and to provide more precise information for the hemodynamic management of septic patients. In addition, this research will promote the clinical application of critical care ultrasound, which will play an important role in medical education and make ultrasound the best method to assess cardiac changes in sepsis.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05161104, identifier NCT05161104.

BackgroundAbnormalities of functional connectivity (FC) in certain brain regions are closely related to the pathophysiology of major depressive disorder (MDD). Findings are inconsistent with different presuppositions in regions of interest. Our research focused on voxel-wise brain-wide FC changes in patients with MDD in an unbiased manner.MethodWe examined resting-state functional MRI in 23 patients with MDD and 26 healthy controls. Imaging data were analyzed by using global-brain FC (GFC) and used to explore the correlation of abnormal GFC values with clinical variables.ResultsIncreased GFC values in the left medial superior frontal gyrus (SFGmed) and decreased GFC values in the right supplementary motor area (SMA) were observed in the patients with MDD compared with the controls. The decreased GFC values in the right SMA had a positive correlation with vitamin D and Hamilton Anxiety Scale (HAM-A) scores.ConclusionAbnormal GFC in the hate circuit, particularly increased GFC in the left SFGmed and decreased GFC in the right SMA, appears to be a new sight for comprehending the pathological alterations in MDD.

Root exudates play a pivotal role in the behaviors of polycyclic aromatic hydrocarbons (PAHs) in mangrove sediments, but the knowledge of how mangrove root exudates response to PAHs pollutants is limited. This study examined the root exudates of Bruguiera gymnorrhiza (L.) (B. gymnorrhiza) under exposure in phenanthrene, pyrene, and benzo[a]pyrene solution through a 45 days hydroponic cultivation. The results showed that the root exudates of B. gymnorrhiza were mainly hydrocarbon compounds. Tartaric acid was the dominant low molecular weight organic acids (LMWOAs) in root exudates. Under PAHs stress, the proportion of hydrocarbon compounds in root exudates decreased, while the proportion of amide compounds increased. At the first 15 days exposure, the amounts of dissolved organic carbon, soluble total sugars, total organic acids and LWMOAs all increased and reached the maximum values, subsequently, the amounts of root exudates had dropped. The degradation rates of PAHs followed the sequence of phenanthrene > pyrene > benzo [a] pyrene, and the presence of root exudates can significantly enhance the degradation of PAHs. The results illustrated that PAHs stress can significantly change the concentrations and species of root exudates. This study provides the scientific reference for understanding the ability of B. gymnorrhiza response to PAHs stress.

Esophageal squamous cell carcinoma (ESCC) is one of the most common aggressive malignancies worldwide, particularly in northern China. The absence of specific early symptoms and biomarkers leads to late-stage diagnosis, while early diagnosis and risk stratification are crucial for improving overall prognosis. We performed UPLC-MS/MS on 450 ESCC patients and 588 controls consisting of a discovery group and two validation groups to identify biomarkers for early detection and prognosis. Bioinformatics and clinical statistical methods were used for profiling metabolites and evaluating potential biomarkers. A total of 105 differential metabolites were identified as reliable biomarker candidates for ESCC with the same tendency in three cohorts, mainly including amino acids and fatty acyls. A predictive model of 15 metabolites [all-trans-13,14-dihydroretinol, (±)-myristylcarnitine, (2S,3S)-3-methylphenylalanine, 3-(pyrazol-1-yl)-L-alanine, carnitine C10:1, carnitine C10:1 isomer1, carnitine C14-OH, carnitine C16:2-OH, carnitine C9:1, formononetin, hyodeoxycholic acid, indole-3-carboxylic acid, PysoPE 20:3, PysoPE 20:3(2n isomer1), and resolvin E1] was developed by logistic regression after LASSO and random forest analysis. This model held high predictive accuracies on distinguishing ESCC from controls in the discovery and validation groups (accuracies > 89%). In addition, the levels of four downregulated metabolites [hyodeoxycholic acid, (2S,3S)-3-methylphenylalanine, carnitine C9:1, and indole-3-carboxylic acid] were significantly higher in early cancer than advanced cancer. Furthermore, three independent prognostic markers were identified by multivariate Cox regression analyses with and without clinical indicators: a high level of MG(20:4)isomer and low levels of 9,12-octadecadienoic acid and L-isoleucine correlated with an unfavorable prognosis; the risk score based on these three metabolites was able to stratify patients into low or high risk. Moreover, pathway analysis indicated that retinol metabolism and linoleic acid metabolism were prominent perturbed pathways in ESCC. In conclusion, metabolic profiling revealed that perturbed amino acids and lipid metabolism were crucial metabolic signatures of ESCC. Both panels of diagnostic and prognostic markers showed excellent predictive performances. Targeting retinol and linoleic acid metabolism pathways may be new promising mechanism-based therapeutic approaches. Thus, this study would provide novel insights for the early detection and risk stratification for the clinical management of ESCC and potentially improve the outcomes of ESCC.

ASB17, a member of the ankyrin repeat and SOCS box-containing protein (ASB) family, has been supposed to act as an E3 ubiquitin ligase. Actually, little is known about its biological function. In this study, we found that ASB17 knocking-out impaired the expression of the pro-inflammatory cytokines CCL2 and IL-6 in bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS), indicating an inflammation-promoting role of this gene. We reveal that ASB17 promotes LPS-induced nuclear factor kappa B (NF-κB) signal activation through interacting with TNF receptor-associated factor 6 (TRAF6) which is a crucial adaptor protein downstream of toll-like receptors (TLR). ASB17 via its aa177–250 segment interacts with the Zn finger domain of TRAF6. The interaction of ASB17 stabilizes TRAF6 protein through inhibiting K48-linked TRAF6 polyubiquitination. Therefore, we suggest that ASB17 facilitates LPS-induced NF-κB activation by maintaining TRAF6 protein stability. The inflammation enhancer role of ASB17 is recognized here, which provides new understanding of the activation process of inflammation and immune response.

Pulse pressure variation (PPV) is a mandatory index for hemodynamic monitoring during mechanical ventilation. The changes in pleural pressure (Ppl) and transpulmonary pressure (PL) caused by mechanical ventilation are the basis for PPV and lead to the effect of blood flow. If the state of hypovolemia exists, the effect of the increased Ppl during mechanical ventilation on the right ventricular preload will mainly affect the cardiac output, resulting in a positive PPV. However, PL is more influenced by the change in alveolar pressure, which produces an increase in right heart overload, resulting in high PPV. In particular, if spontaneous breathing is strong, the transvascular pressure will be extremely high, which may lead to the promotion of alveolar flooding and increased RV flow. Asynchronous breathing and mediastinal swing may damage the pulmonary circulation and right heart function. Therefore, according to the principle of PPV, a high PPV can be incorporated into the whole respiratory treatment process to monitor the mechanical ventilation cycle damage/protection regardless of the controlled ventilation or spontaneous breathing. Through the monitoring of PPV, the circulation-protective ventilation can be guided at bedside in real time by PPV.

Background: Vascular dementia (VD) is the second most common type of dementia after Alzheimer’s disease, but there is a lack of definitive treatment for VD. Acupuncture treatment is effective in improving the cognitive impairment and behavioral capacity of patients with VD. In recent years, more studies indicated that peripheral inflammation and abnormal peripheral immune function may aggravate neuroinflammation and cognitive dysfunction. However, there are few studies about the acupuncture and the abnormal peripheral immune function of VD. Also, few studies concern the regulating effect of acupuncture on peripheral immunity of patients with VD.Objective: The aim of this study was to explore the effect of the “sanjiao” acupuncture method on peripheral immunity of patients with mild to moderate VD.Methods: A total of 30 patients with VD were involved in the acupuncture group (AG), which was treated with the “sanjiao” acupuncture method once a day for six times a week and lasted for 12 weeks, and 30 healthy elderly people were assigned to the normal group (NG), which had no treatment. The distribution of lymphocyte subsets and the levels of some inflammatory cytokines in the peripheral blood of subjects were evaluated using the flow cytometry (FCM) and the enzyme-linked immunosorbent assay (ELISA).Results: A total of 60 subjects were involved in this study, while 58 subjects completed the entire trial. Before treatment, the levels of CD3+ T, CD4+ T cells, CD4+/CD8+, Tregs, B cells, IFN-γ, and IL-10 in patients with VD were significantly decreased compared with the normal group (all P < 0.05 or P < 0.01). The level of TNF-α in peripheral blood of patients with VD was significantly increased (P < 0.01). After acupuncture treatment, the levels of CD3+ T, CD4+ T cells, and IFN-γ were significantly increased (all P < 0.05 or P < 0.01). The level of TNF-α was significantly decreased (P < 0.01). The proportion of Tregs was increased (P < 0.01), but it was still lower than that of the normal group (P < 0.05).Conclusion: The acupuncture method can increase the proportion of CD3+, CD4+ T cells, and Tregs in peripheral blood of patients with VD. And, it reduces the levels of pro-inflammatory factor TNF-α, which achieves the anti-inflammatory effects and immunostimulation. It suggests that acupuncture can improve the peripheral immune dysfunction of patients with VD by regulating the distribution of lymphocyte subsets and the levels of inflammatory cytokines.Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR-IOR-17012052].

Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). An impaired intestinal epithelial barrier is an important component of GVHD pathogenesis. However, contributing host factors that modulate mucosal barrier integrity during GVHD are poorly defined. We hypothesized that vitamin A and retinoic acid (RA) exert positive impacts on maintaining intestinal barrier function after HSCT, thus preventing or dampening GVHD severity. Unexpectedly, we found that exogenous RA increased intestinal permeability of recipient mice after allogeneic HSCT. Serum bacterial endotoxin levels were significantly higher in GVHD mice fed a vitamin A-high (VAH) diet compared to those fed a vitamin A-normal (VAN) diet, indicating a more compromised intestinal barrier function. Furthermore, VAH mice showed more severe lung GVHD with increased donor T cell infiltration in this tissue and died significantly faster than VAN recipients. 16S rRNA sequencing of fecal samples revealed significant differences in the diversity and composition of gut microbiota between VAN and VAH transplant recipients. Collectively, we show that retinoic acid signaling may negatively impact intestinal barrier function during GVHD. Mild vitamin A supplementation is associated with increased lung GVHD and more profound gut dysbiosis. Micronutrients such as vitamin A could modulate complications of allogeneic HSCT, which may be mediated by shaping gut microbiota.

Objectives: The longitudinal characterization and risk of poor outcomes related to cytokine overproduction in critical coronavirus disease 2019 (COVID-19) patients with hyperinflammation in bronchoalveolar lavage requires further investigation.Methods: We enrolled two critically ill patients with comorbidities diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected by RT-PCR during hospitalization. Clinical characteristics, longitudinal immunological, and biochemical parameters of each critical COVID-19 case were collected.Main Results: The clinical characteristics and laboratory results of each case demonstrated critical symptoms of COVID-19 with poor outcomes. Both nasopharyngeal swabs and bronchoalveolar lavage fluid (BALF) samples tested positive for SARS-CoV-2. Two patients received targeted treatments against pathogen infection and inflammation in addition to interventional therapies, except for Patient 2, who received an additional artificial liver system treatment. Hyperinflammation with a dominantly high level of IL-6 was observed in BALF samples from both critical cases with decreased T cell populations. High levels of cytokines and pathological parameters were successively maintained in Patient 1, but rapidly reduced at the late treatment stage in Patient 2. The outcome of Patient 1 is death, whereas the outcome of Patient 2 is recovery.Conclusions: This case report suggests that a high risk of poor outcomes was related to a heavily hyperinflammatory milieu in both the blood and lungs of critical COVID-19 patients. The artificial liver intervention on cytokines overproduction might be beneficial for the recovery of critical COVID-19 patients as a reliable therapy that can be coordinated with targeted treatments, which ought to be further tested in adequately designed and powered clinical trials.

Default mode network (DMN) plays a key role in the pathophysiology of in bipolar disorder (BD). However, the homogeneity of this network in BD is still poorly understood. This study aimed to investigate abnormalities in the NH of the DMN at rest and the correlation between the NH of DMN and clinical variables in patients with BD. Forty drug-naive patients with BD and thirty-seven healthy control subjects participated in the study. Network homogeneity (NH) and independent component analysis (ICA) methods were used for data analysis. Support vector machines (SVM) method was used to analyze NH in different brain regions. Compared with healthy controls, significantly increased NH in the left superior medial prefrontal cortex (MPFC) and decreased NH in the right posterior cingulate cortex (PCC) and bilateral precuneus were found in patients with BD. NH in the right PCC was positively correlated with the verbal fluency test and verbal function total scores. NH in the left superior MPFC was negatively correlated with triglyceride (TG). NH in the right PCC was positively correlated with TG but negatively correlated with high-density lipoprotein cholesterol (HDL-C). NH in the bilateral precuneus was positively correlated with cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, NH in the left superior MPFC showed high sensitivity (80.00%), specificity (71.43%), and accuracy (75.61%) in the SVM results. These findings contribute new evidence of the participation of the altered NH of the DMN in the pathophysiology of BD.

ObjectiveThe aim of this study is to analyze the effects of acupuncture on peripheral immune function, inflammation, and cognitive impairment in vascular dementia (VD) rats.MethodsIn this study, 2-month-old healthy male Wistar rats (260–280 g) were assigned to the groups as follows: normal group (Gn, n = 10), sham-operated group (Gs, n = 10), and operated group (Go, n = 45). The Go group was established by permanent, bilateral common carotid artery occlusion (BCCAO). Two months after operation, the operated rats were screened by hidden platform trial and the rats with cognitive dysfunction were further randomly divided into impaired group (Gi), acupoint group (Ga), and non-acupoint group (Gna) with 10 rats in each group. The Ga group was given acupuncture treatment for 14 days with a rest for every 7 days. After treatment, the Morris water maze (MWM) test was performed to evaluate the spatial learning and memory abilities of rats. The lymphocyte subsets in peripheral blood and spleen of rats were measured by flow cytometry. The levels of cytokines [i.e., interleukin (IL)-1β, IL-2, IL-4, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ)], chemokines (i.e., macrophage inflammatory protein-2 (MIP-2)), and other inflammatory mediators (i.e., cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS)) in peripheral blood and hippocampus were measured by enzyme linked immunosorbent assay (ELISA).ResultsCompared with the Gn group, the Gi rats presented long escape latencies to find the platform. After acupuncture treatment, the escape latencies of the Ga group were rescued markedly when compared with the Gi group (P < 0.05). The proportion of CD4 + T lymphocytes in both spleen and peripheral blood in the Ga group increased (P < 0.05) in comparison with the Gi group. There is an obvious reduction in IL-1β (P < 0.05), IL-2 (P < 0.05), TNF-α (P < 0.01), INF-γ (P < 0.01), MIP-2 (P < 0.05), and iNOS (P < 0.01), coming along with the increased levels of IL-4 and IL-10 (P < 0.01) in the Ga group when compared with the Gi group. In addition, the hippocampus proinflammatory factors IL-1β (P < 0.01), IL-2 (P < 0.01), TNF-α (P < 0.05), INF-γ (P < 0.05), MIP-2 (P < 0.05), iNOS (P < 0.01), and COX-2 decreased in the Ga group, whereas the anti-inflammatory factors IL-4 and IL-10 (P < 0.01) increased.ConclusionThere are abnormal immune function and peripheral inflammation in VD rats. Acupuncture can regulate the peripheral immune function and inflammation of the VD rats and can improve the cognitive dysfunction of the rats.

Innate immune cells in the tumor microenvironment have been proposed to control the transition from benign to malignant stages. In many cancers, increased infiltration of natural killer (NK) cells associates with good prognosis. Although the mechanisms that enable NK cells to restrain colorectal cancer (CRC) are unclear, the current study suggests the involvement of Smad4. We found suppressed Smad4 expression in circulating NK cells of untreated metastatic CRC patients. Moreover, NK cell-specific Smad4 deletion promoted colon adenomas in DSS-treated ApcMin/+ mice and adenocarcinomas in AOM/DSS-treated mice. Other studies have shown that Smad4 loss or weak expression in colonic epithelium associates with poor survival in CRC patients. Therefore, targeting Smad4 in both colonic epithelium and NK cells could provide an excellent opportunity to manage CRC. Toward this end, we showed that dietary intervention with black raspberries (BRBs) increased Smad4 expression in colonic epithelium in patients with FAP or CRC and in the two CRC mouse models. Also, benzoate metabolites of BRBs, such as hippurate, upregulated Smad4 and Gzmb expression that might enhance the cytotoxicity of primary human NK cells. Of note, increased levels of hippurate is a metabolomic marker of a healthy gut microbiota in humans, and hippurate also has antitumor effects. In conclusion, our study suggests a new mechanism for the action of benzoate metabolites derived from plant-based foods. This mechanism could be exploited clinically to upregulate Smad4 in colonic epithelium and NK cells, thereby delaying CRC progression.

Background: The pathophysiology of patients with dry eye disease (DED) is associated with abnormal functional connectivity (FC). The present study aims to probe alterations of voxel-wise brain-wide FC in patient with DED at rest in an unbiased way.Method: A total of 20 patients with DED and 23 controls matched by age, sex, and years of education underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was adopted to analyze the images. Support vector machine (SVM) was utilized to differentiate the patients from the controls.Results: Compared with the controls, patients with DED exhibited decreased GFC in the right cerebellum lobule VIII/inferior semi-lunar lobule and left thalamus that belonged to the cerebello-thalamo-cortical network. The GFC values in the left thalamus were positively correlated to the illness duration (r = 0.589, p = 0.006) in the patients. Decreased GFC values in the left thalamus could be used to discriminate the patients from the controls with optimal accuracy, sensitivity and specificity (88.37, 85.00, and 91.30%).Conclusions: Our findings indicate that decreased GFC in the brain regions associated with cerebello-thalamo-cortical network may provide a new insight for understanding the pathological changes of FC in DED. GFC values in the left thalamus may be utilized as a potential biomarker to identify the patients from the controls.

ObjectiveStudies on alterations in the regional neural activity in the brain of patients with bipolar disorder (BD) have provided conflicting results because of different medications used and study designs. A low bone mineral density (BMD) is also observed in patients with BD. This study aimed to further explore regional neural activities in unmedicated patients with BD and their association with BMD.MethodsIn this study, 40 patients with BD and 42 healthy controls were scanned through resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with regional homogeneity (ReHo) and pattern classification. Pearson’s correlation analyses were performed to explore the correlations between abnormal ReHo and BMD.ResultsA significant increase in ReHo values in the left inferior frontal gyrus (IFG)/temporal pole, left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem, and right superior temporal gyrus (STG) and a decrease in ReHo in the occipital gyrus (OG; left middle OG/superior OG/bilateral cuneus) were found in the patients with BD (p < 0.05) compared with those in the healthy controls. No significant correlation was observed between the abnormal ReHo values in any of the brain regions of the patients with BMD.Support vector machine (SVM) analyses revealed that the ReHo values in the right STG for distinguishing patients from healthy controls showed an accuracy of 91.89%, a sensitivity of 75.68%, and a specificity of 83.78%. The ReHo values in the left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem indicated an accuracy of 78.38%, a sensitivity of 75.68%, and a specificity of 81.08%.ConclusionThis study further confirms the abnormal brain activities in extensive regions, and these brain regions are primarily located in the fronto–temporal–occipital circuit and the cerebellum vermis of patients with BD. The regional neural activity in the right STG and the left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem may serve as potential imaging markers to distinguish patients with BD from healthy controls.

Objectives: A series of quality control (QC) targets (SpO2≠100%, PaCO2≮40 mmHg, Pmean≯10 cmH2O) was put forward and widely used in a single intensive care unit (ICU) setting. The aim of this study was to assess whether these QC targets could improve the outcomes of critically ill patients.Methods: The real-time clinical data of patients undergoing mechanical ventilation at ICU admission between May 2013 and May 2017 in the Department of Critical Care Medicine of Peking Union Medical College Hospital were collected and analyzed.Results: A total of 7,670 patients [mean age, 58 years; 3,943 (51.5%) male] were divided into the before QC (n = 3,936) and after QC (n = 3,734) groups. QC targets (SpO2, PaCO2, and Pmean) and respiratory parameters (FiO2%, PaO2, PEEP, tidal volume, and respiratory rate) within 72 h of ICU admission, primary outcomes (ICU mortality, 28-, 60-, and 90-day mortality) and secondary outcomes (discharge against medical advice, ICU admission days, mechanical ventilation times, and central venous pressure) were measured and compared between the before and after QC groups. The 72 h average of the Pmean, FiO2%, PaO2, and VT were significantly lower and PaCO2 was higher in the after QC than in the before QC group (P < 0.05). A lower 90-day mortality rate, less discharge against medical advice, fewer ICU admission days, and reduced mechanical ventilation times were found in the after QC group compared with the before QC group (P < 0.05). Interestingly, CVP was significantly lower in the after QC group than in the before QC group (P < 0.05).Conclusions: The QC targets (SpO2≠100%, PaCO2≮40 mmHg, Pmean≯10 cmH2O) contributed to avoiding high oxygen level hazards, protecting against lung injury, and improving circulatory function, which resulted in a better prognosis of critically ill patients.

Background: Altered functional connectivity (FC) is related to pathophysiology of patients with cervical dystonia (CD). However, inconsistent results may be obtained due to different selected regions of interest. We explored voxel-wise brain-wide FC changes in patients with CD at rest in an unbiased manner and analyzed their correlations with symptomatic severity using the Tsui scale.Method: A total of 19 patients with CD and 21 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was applied to analyze the images. Support vector machine was used to distinguish the patients from the controls.Results: Patients with CD exhibited decreased GFC in the right precentral gyrus and right supplementary motor area (SMA) that belonged to the M1-SMA motor network. Significantly negative correlation was observed between GFC values in the right precentral gyrus and symptomatic severity in the patients (r = −0.476, p = 0.039, uncorrected). Decreased GFC values in these two brain regions could be utilized to differentiate the patients from the controls with good accuracies, sensitivities and specificities (83.33, 85.71, and 80.95% in the right precentral gyrus; and 87.59, 89.49, and 85.71% in the right SMA).Conclusions: Our investigation suggests that patients with CD show reduced GFC in brain regions of the M1-SMA motor network and provides further insights into the pathophysiology of CD. GFC values in the right precentral gyrus and right SMA may be used as potential biomarkers to recognize the patients from the controls.

Dengue virus (DENV) infection causes several diseases ranging from dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome characterized by endothelial dysfunction, vascular leakage, and shock. Here, we identify a potential mechanism by which DENV induces tissue injury and vascular leakage by promoting the activation of interleukin (IL)-1β. DENV facilitates IL-1β secretion in infected patients, mice, human peripheral blood mononuclear cells (PBMCs), mouse bone marrow-derived macrophages (BMDMs), and monocyte-differentiated macrophages (THP-1) via activating the NLRP3 inflammasome. The accumulated data suggest that IL-1β probably induces vascular leakage and tissue injury in interferon-alpha/beta receptor 1 deficient C57BL/6 mice (IFNAR–/– C57BL/6), whereas IL-1 receptor antagonist (IL-1RA) alleviates these effects of IL-1β. Finally, administration of recombinant IL-1β protein results in vascular leakage and tissue injury in C57BL/6 mice. Together, the accumulated results demonstrate that IL-1β contributes to DENV-associated pathology and suggest that IL-1RA acts as a potential agent for the treatment of DENV-associated diseases.

Background: The Frank-Starling curve is the basis of hemodynamics. Changes in cardiac output (CO) caused by central venous pressure (CVP) are the most important concerns in the treatment of critically ill patients.Objectives: To explore the use of CVP and its relevant mechanisms with respect to CO in the clinic.Methods: A total of 134 patients with circulatory shock were retrospectively included and analyzed. Hemodynamic data were recorded and analyzed at PICCO initiation and 24 h after PICCO. Data regarding 28-day mortality and renal function were also collected.Results: The patients were divided into a CVP↑+ CO↑ group (n = 23), a CVP↑+ CO↓ group (n = 29), a CVP↓+ CO↑ group (n = 44), and a CVP↓+ CO↓ group (n = 38) based on values at PICCO initiation and 24 h after PICCO. Post- hoc tests showed that the CVP↓+ CO↑ group had a higher 28-day survival than the other groups [log-rank (Mantel-Cox) = 8.758, 95%, CI, 20.112–23.499, P = 0.033]. In terms of hemodynamic characteristics, the CVP↓+ CO↑ group had a lower cardiac function index (CFI) (4.1 ± 1.4/min) and higher extravascular lung water index (EVLWI) (11.0 ± 4.7 ml/kg) at PICCO initiation. This group used more cardiotonic drugs (77.3%, P < 0.001) and had a negative fluid balance (−780.4 ± 1720.6 ml/24 h, P = 0.018) 24 h after PICCO than the other three groups. Cardiotonic drug use and dehydration treatment were associated with increased CFI (from 4.1 ± 1.4 /min to 4.5 ± 1.3/min, P = 0.07) and reduced ELVWI (from 11.0 ± 4.7 ml/kg to 9.0 ± 3.5 ml/kg, P = 0.029). Renal function tests showed that SCr and BUN levels in the CVP↓+ CO↑ group were significantly improved (SCr from 197.1 ± 128.9 mmol/L to 154.4 ± 90.8 mmol/L; BUN from 14.3 μmol/L ± 7.3 to 11.6 ± 7.0 μmol/L, P < 0.05).Conclusions: Lower CVP was associated with increased CO, which may improve the 28-day prognosis in patients with circulatory shock. Notably, higher CO derived from lower CVP may also contribute to renal function improvement.

The notion of dysconnectivity in schizophrenia has been put forward for many years and results in substantial attempts to explore altered functional connectivity (FC) within different networks with inconsistent results. Clinical, demographical, and methodological heterogeneity may contribute to the inconsistency. Forty-four patients with first-episode, drug-naive schizophrenia, 42 unaffected siblings of schizophrenia patients and 44 healthy controls took part in this study. Global-brain FC (GFC) was employed to analyze the imaging data. Compared with healthy controls, patients with schizophrenia and unaffected siblings shared enhanced GFC in the left superior frontal gyrus (SFG). In addition, patients had increased GFC mainly in the thalamo-cortical network, including the bilateral thalamus, bilateral posterior cingulate cortex (PCC)/precuneus, left superior medial prefrontal cortex (MPFC), right angular gyrus, and right SFG/middle frontal gyrus and decreased GFC in the left ITG/cerebellum Crus I. No other altered GFC values were observed in the siblings group relative to the control group. Further ROC analysis showed that increased GFC in the left SFG could separate the patients or the siblings from the controls with acceptable sensitivities. Our findings suggest that increased GFC in the left SFG may serve as a potential endophenotype for schizophrenia.

Natural products and their derivatives have long been used as pharmacological agents in the fight against cancer. Human natural killer (NK) cells are critical in our immune system in that they are capable of destroying tumor cells directly. However, there are few reports that elucidate the role of natural products in activating NK cells. In this study, we discovered that a synthetic disaccharide derivative of diphyllin, 4-O-{[2′′,3′′,4′′-tri-O-acetyl-α-D-arabinopyranosyl-(1′′→4′)]-2′,3′-di-O-acetyl-α-L-rhamnopyranosyl}diphyllin (TAARD), can alone stimulate interferon (IFN)-γ secretion in primary human NK cells and the NKL cell line. Additionally, it had an additive effect with IL-12 or IL-15 on IFN-γ production, but little adverse effects on NK cells. Mechanistically, TAARD induced the phosphorylation of NF-κB and STAT3, resulting in their binding on the IFNG promoter, which was dependent on TLR1 and TLR3 signaling, respectively. STAT3 and NF-κB knockdown with lentivirus shRNA as well as the NF-κB-specific inhibitor, N-tosyl-l-phenylalaninechloromethyl ketone, significantly suppressed TAARD-induced IFN-γ generation in primary NK cells. Blockade of TLR1 and TLR3 with neutralizing antibodies considerably decreased TAARD-induced activation of NF-κB and STAT3, respectively, as well as IFN-γ generation in NK cells. Collectively, our data suggest that TAARD can induce NK cell IFN-γ production through TLR1-NF-κB and TLR3-STAT3 signaling pathways, rendering its potential use as an agent for cancer prevention or treatment.

Natural killer (NK) cells are an essential component of innate immunity against cancer development. Many studies have been conducted to evaluate immune-modulating effects using dietary compounds. Our laboratory has been investigating the chemopreventive potential of black raspberries (BRBs) and previously demonstrated their beneficial modulation of genetic and epigenetic biomarkers in patients with colorectal cancer (CRC). The current study investigated their potential on modulating NK cells. To avoid the excessive inflammation caused by the dextran sulfate sodium (DSS) treatment that leads to colitis, we treated the mice with overnight DSS so that it would slightly irritate the colon but still promote colon carcinogenesis with 100% incidence in both the ApcMin/+ mice and azoxymethane (AOM)-treated mice. A significant decrease of tissue-infiltrating NK cells along the progression of microadenoma-to-adenoma and adenoma-to-adenocarcinoma was observed in the ApcMin/+/DSS and AOM/DSS mice, respectively. Depletion of NK cells significantly promoted the development of CRC, suggesting a critical role of NK cells in combating CRC progression. BRBs significantly suppressed the CRC progression and increased the number of tissue-infiltrating NK cells in both mouse models. Moreover, we further determined BRBs’ effects on NK cells in the human biopsy specimens collected from our previously completed clinical trial, in which CRC patients consumed BRBs for an average of 4 weeks during a presurgical window. We observed an increased number and an enhanced cytotoxicity of NK cells by BRB intervention. The current study provides evidence that BRBs have the potential to enhance the tumor immunesurveillance of NK cells that can be beneficial in the setting of CRC prevention and treatment.

The increasing prevalence of non-tuberculous mycobacterium (NTM) infections alongside tuberculosis (TB) underscores a pressing public health challenge. Yet, the mechanisms governing their infection within the lung remain poorly understood. Here, we integrate metagenomic sequencing, metabolomic sequencing, machine learning classifiers, SparCC, and MetOrigin methods to profile bronchoalveolar lavage fluid (BALF) samples from NTM/TB patients. Our aim is to unravel the intricate interplay between lung microbial communities and NTM/ Mycobacterium tuberculosis infections. Our investigation reveals a discernible reduction in the compositional diversity of the lung microbiota and a diminished degree of mutual interaction concomitant with NTM/TB infections. Notably, NTM patients exhibit a distinct microbial community characterized by marked specialization and notable enrichment of Pseudomonas aeruginosa and Staphylococcus aureus , driving pronounced niche specialization for NTM infection. Simultaneously, these microbial shifts significantly disrupt tryptophan metabolism in NTM infection, leading to an elevation of kynurenine. Mycobacterium intracellulare , Mycobacterium paraintracellulare , Mycobacterium abscessus , and Pseudomonas aeruginosa have been implicated in the metabolic pathways associated with the conversion of indole to tryptophan via tryptophan synthase within NTM patients. Additionally, indoleamine-2,3-dioxygenase converts tryptophan into kynurenine, fostering an immunosuppressive milieu during NTM infection. This strategic modulation supports microbial persistence, enabling evasion from immune surveillance and perpetuating a protracted state of NTM infection. The elucidation of these nuanced microbial and metabolic dynamics provides a profound understanding of the intricate processes underlying NTM and TB infections, offering potential avenues for therapeutic intervention and management. [ABSTRACT FROM AUTHOR]

Understanding the complex influencing factors of soil erosion is critical for maintaining regional ecological security. The revised wind erosion equation (RWEQ) and partial least squares regression (PLSR) model were used to reveal the primary factors affecting soil erosion. Based on the results of the RWEQ model, the wind erosion area was 8,439.3 km2 in 2018, accounting for 54.3% of the total planning area, and mild erosion, moderate erosion, intense erosion, very intense erosion, and fierce erosion accounted for 18.22%, 11.43%, 11.78%, 10.16%, and 2.74% of the total planning area, respectively. Based on the results of the PLSR model, the results indicate that the proportion of mining land, meteorological indicators, and mean square deviation of slope difference were positively correlated with the soil erosion area, intensity, and severity, respectively. The proportion of grassland and forest land was negatively correlated with the soil erosion area, intensity, and severity. The mean square deviation of slope difference, the mean square deviation of difference in elevation, and the proportion of urban land use contributed the most to the soil erosion severity index, with variable importance in projection (VIP) scores of 1.55, 1.44 and 1.43, respectively. The mean square deviation of slope difference, the proportion of urban land, and the mean square deviation of difference in elevation contributed the most to the soil erosion area, with VIP scores of 1.53, 1.26 and 1.24, respectively. The results provide new insights into wind erosion and the influences of weather conditions and human influences, which can guide regional soil and water conservation planning in wind erosion regions. [ABSTRACT FROM AUTHOR]

This document is a corrigendum for an article titled "Plastic biodegradation by in vitro environmental microorganisms and in vivo gut microorganisms of insects." The corrigendum addresses errors in the article, including an error in a section title and incorrect information in Tables 2 and 3. The corrected information is provided, and the authors state that these errors do not change the scientific conclusions of the article. The corrigendum also includes a note from the publisher stating that the claims expressed in the article are solely those of the authors and do not necessarily represent the views of the publisher or affiliated organizations. The provided document is a list of references for various scientific studies on the biodegradation of plastic by different insect larvae. The studies explore the ability of larvae from species such as Tribolium confusum, Zophobas atratus, Tenebrio molitor, Galleria mellonella, and others to degrade different types of plastics, including polystyrene and polyethylene. The research examines the effects of plastic diets on the gut microbiota of the larvae and investigates the potential for complete digestion and biodegradation of plastics. The studies provide valuable insights into the role of insects in plastic waste management and offer potential solutions for plastic pollution. [Extracted from the article]

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD),which is themost prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpiumcitri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD. [ABSTRACT FROM AUTHOR]

Introduction: We here describe a new method for distinguishing authentic Bletilla striata from similar decoctions (namely, Gastrodia elata, Polygonatum odoratum, and Bletilla ochracea schltr). Methods: Preliminary identification and analysis of four types of decoction pieces were conducted following the Chinese Pharmacopoeia and local standards. Intelligent sensory data were then collected using an electronic nose, an electronic tongue, and an electronic eye, and chromatography data were obtained via high-performance liquid chromatography (HPLC). Partial least squares discriminant analysis (PLS-DA), support vector machines (SVM), and back propagation neural network (BP-NN) models were built using each set of single-source data for authenticity identification (binary classification of B. striata vs. other samples) and for species determination (multi-class sample identification). Features were extracted from all datasets using an unsupervised approach [principal component analysis (PCA)] and a supervised approach (PLS-DA). Mid-level data fusion was then used to combine features from the four datasets and the effects of feature extraction methods on model performance were compared. Results and Discussion: Gas chromatography-ion mobility spectrometry (GC- IMS) showed significant differences in the types and abundances of volatile organic compounds between the four sample types. In authenticity determination, the PLS-DA and SVM models based on fused latent variables (LVs) performed the best, with 100% accuracy in both the calibration and validation sets. In species identification, the PLS-DA model built with fused principal components (PCs) or fused LVs had the best performance, with 100% accuracy in the calibration set and just one misclassification in the validation set. In the PLS-DAand SVM authenticity identification models, fused LVs performed better than fused PCs. Model analysis was used to identify PCs that strongly contributed to accurate sample classification, and a PC factor loading matrix was used to assess the correlation between PCs and the original variables. This study serves as a reference for future efforts to accurately evaluate the quality of Chinese medicine decoction pieces, promoting medicinal formulation safety. [ABSTRACT FROM AUTHOR]

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA. Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects. To validate the accuracy of our findings, we also utilized the Multiplex Ligation-dependent Probe Amplification (MLPA) to confirm the reliability of screening results obtained by quantitative real-time PCR. Result: Among the 39,647 participants who were screened, 726 participants were the carriers of SMN1. The overall carrier rate was calculated to be 1.83% (95% confidence interval: 0.86-2.8%). After undergoing screening, a total of 592 pregnancy carriers were provided with genetic counseling and only 503 of their spouses (84.97, 95% confidence interval: 82.09-87.85%) voluntarily underwent SMA screening. Conclusion: This study provides crucial insights into the prevalence and distribution of SMA carriers among the female population. The identification of 726 asymptomatic carriers highlights the necessity of comprehensive screening programs to identify at-risk individuals and ensure appropriate interventions are in place to minimize the impact of SMA-related conditions. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p < 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p < 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. [ABSTRACT FROM AUTHOR]

Allogeneic Hematopoietic stem cell transplantation (HSCT) offers a potential cure for patients with hematologic malignancies. Unfortunately, graft-versus-host disease (GVHD) remains a major obstacle to the greater success of this treatment. Despite intensive research efforts over the past several decades, GVHD is still a major cause of morbidity and mortality in patients receiving allogeneic HSCT. The genetic disparity between donor and recipient is the primary factor that dictates the extent of alloimmune response and the severity of acute GVHD (aGVHD). However, some nongenetic factors are also actively involved in GVHD pathogenesis. Thus, identifying host factors that can be readily modified to reduce GVHD risk is of important clinical significance. We are particularly interested in the potential role of nutrition, as a nongenetic factor, in the etiology and management of aGVHD. In this article, we summarize recent findings regarding how different routes of nutritional support and various dietary factors affect aGVHD. Since diet is one of the most important factors that shape gut microbiota, we also provide evidence for a potential link between certain nutrients and gut microbiota in recipients of allogeneic HSCT. We propose a shifting role of nutrition from support to therapy in GVHD by targeting gut microbiota. [ABSTRACT FROM AUTHOR]

Bacteriophages, the most abundant organisms on earth, have the potential to address the rise of multidrug-resistant bacteria resulting from the overuse of antibiotics. However, their high specificity and limited host range can hinder their effectiveness. Phage engineering, through the use of gene editing techniques, offers a means to enhance the host range of bacteria, improve phage efficacy, and facilitate efficient cell-free production of phage drugs. To engineer phages effectively, it is necessary to understand the interaction between phages and host bacteria. Understanding the interaction between the receptor recognition protein of bacteriophages and host receptors can serve as a valuable guide for modifying or replacing these proteins, thereby altering the receptor range of the bacteriophage. Research and development focused on the CRISPR-Cas bacterial immune system against bacteriophage nucleic acids can provide the necessary tools to promote recombination and counter-selection in engineered bacteriophage programs. Additionally, studying the transcription and assembly functions of bacteriophages in host bacteria can facilitate the engineered assembly of bacteriophage genomes in non-host environments. This review highlights a comprehensive summary of phage engineering methods, including in-host and out-of-host engineering, and the use of high-throughput methods to understand their role. The main aim of these techniques is to harness the intricate interactions between bacteriophages and hosts to inform and guide the engineering of bacteriophages, particularly in the context of studying and manipulating the host range of bacteriophages. By employing advanced highthroughput methods to identify specific bacteriophage receptor recognition genes, and subsequently introducing modifications or performing gene swapping through in-host recombination or out-of-host synthesis, it becomes possible to strategically alter the host range of bacteriophages. This capability holds immense significance for leveraging bacteriophages as a promising therapeutic approach against antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Traditional plastics, such as polyethylene (PE), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyurethane (PUR), and other plastic polymers, are difficult to degrade and are gradually accumulated in the environment to cause a serious environmental problem, which is urgently needed to develop novel treatments or control technology. The biodegradation of plastics has gained great attention due to the advantages of green and safe characteristics. Microorganisms play a vital role in the biodegradation of plastics, including environmental microbes (in vitro) and gut microbes of insects (in vivo). Microbial degradation in environmental conditions in vitro is extremely slow for major plastics at degradation rates on the basis of a month or even a year time, but recent discoveries show that the fast biodegradation of specific plastics, such as PS, PE, and PUR, in some invertebrates, especially insects, could be enhanced at rates on basis of hours; the biodegradation in insects is likely to be gut microbial- dependent or synergetic bioreactions in animal digestive systems. This review comprehensively summarizes the latest 7-year (2016-2022) publications on plastic biodegradation by insects and microorganisms, elucidates the mechanism of plastic degradation in insects and environmental microbes, and highlights the cutting-edge perspectives for the potential applications of plastic biodegradation. [ABSTRACT FROM AUTHOR]

Functional constipation (FC) is a high morbidity gastrointestinal disease for which dysfunction in the enteric nervous system is a major pathogenesis mechanism. To enhance our understanding of the involvement of intestinal microbiota and its metabolites in the pathogenesis of FC, we conducted a shotgun metagenomic sequencing analysis of gut microbiota and serum short-chain fatty acids (SCFAs) analysis in 460 Chinese women with different defecation frequencies. We observed that the abundance of Fusobacterium_varium, a butyric acidproducing bacterium, was positively correlated (P = 0.0096) with the frequency of defecation; however, the concentrations of serum butyric acid was negatively correlated (P = 3.51E-05) with defecation frequency. These results were verified in an independent cohort (6 patients with FC and 6 controls). To further study the effects of butyric acid on intestinal nerve cells, we treated mouse intestinal neurons in vitro with various concentrations of butyrate (0.1, 0.5, 1, and 2.5 mM). We found that intestinal neurons treated with 0.5 mM butyrate proliferated better than those in the other treatment groups, with significant differences in cell cycle and oxidative phosphorylation signal pathways. We suggest that the decreased butyrate production resulting from the reduced abundance of Fusobacterium in gut microbiota affects the proliferation of intestinal neurons and the energy supply of intestinal cells. However, with FC disease advancing, the consumption and excretion of butyric acid reduce, leading to its accumulation in the intestine. Moreover, the accumulation of an excessively high amount of butyric acid inhibits the proliferation of nerve cells and subsequently exacerbates the disease. [ABSTRACT FROM AUTHOR]

As the canonical model organism to dissect bacterial morphological development, Streptomyces species has attracted much attention from the microbiological society. However, the evolution of development-related genes in Streptomyces remains elusive. Here, we evaluated the distribution of development-related genes, thus indicating that the majority of these genes were ubiquitous in Streptomyces genomes. Furthermore, the phylogenetic topologies of related strict orthologous genes were compared to the species tree of Streptomyces from both concatenation and single-gene tree analyses. Meanwhile, the reconciled gene tree and normalization based on the number of parsimony-informative sites were also employed to reduce the impact of phylogenetic conflicts, which was induced by uncertainty in single-gene tree inference based merely on the sequence and the bias in the amount of phylogenetic information caused by variable numbers of parsimony-informative sites. We found that the development-related genes had higher congruence to the species tree than other strict orthologous genes. Considering that the development-related genes could also be tracked back to the common ancestor of Streptomyces, these results suggest that morphological development follows the same pattern as species divergence. [ABSTRACT FROM AUTHOR]