Advances in the chemical constituents, pharmacological activity, and clinical application of Smilacis Glabrae Rhizoma: A review and predictive analysis of quality markers (Q-markers).

Smilacis Glabrae Rhizoma (SGR) is recognized in traditional Chinese medicine for its distinctive therapeutic properties and abundant supply. Its phytochemical profile is diverse, encompassing flavonoids, steroids, saccharides, phenolic glycosides, volatile constituents, organic acids, phenylpropanoids, stilbenoids, among others. Recent pharmacological investigations reveal that SGR possesses a broad spectrum of pharmacological effects with multifaceted clinical applications. This review collates the current knowledge on SGR's chemical composition, pharmacological activities, and its clinical utility. Utilizing network pharmacology and molecular docking approaches, this study provides a preliminary identification of potential quality markers (Q-Markers) within SGR. The findings suggest that compounds such as astilbin, isoengelitin, neoisoastilbin, neoastilbin, astragaloside, diosgenin, resveratrol, stigmasterol, ß-sitosterol, and quercetin in SGR are promising candidates for Q-Markers. While flavonoids are the most extensively studied, there is a pressing need to further explore the active monomeric compounds within SGR. The introduction of Q-Markers is instrumental in developing standardized quality metrics. Specifically, astilbin has been noted for its antitumor, antidiabetic, antihypertensive, anti-hyperuricemic, and hepatoprotective potential, warranting further research for therapeutic applications.

Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis.

Objective: This study aimed to explore the mechanism of the Danggui Jixueteng decoction (DJD) in treating Myelosuppression after chemotherapy (MAC) through network pharmacology and metabolomics. Methods: We obtained the chemical structures of DJD compounds from TCMSP and PubMed. SwissTargetPrediction, STITCH, CTD, GeneCards, and OMIM were utilized to acquire component targets and MAC-related targets. We identified the key compounds, core targets, main biological processes, and signaling pathways related to DJD by constructing and analyzing related networks. The main active compounds and key proteins of DJD in treating AA were confirmed by molecular docking. A MAC rat model was established through intraperitoneal injection of cyclophosphamide to confirm DJD's effect on the bone marrow hematopoietic system. Untargeted metabolomics analyzed serum metabolite differences between MAC rats and the control group, and before and after DJD treatment, to explore DJD's mechanism in treating MAC. Results: Of the 93 active compounds identified under screening conditions, 275 compound targets and 3113 MAC-related targets were obtained, including 95 intersecting targets; AKT1, STAT3, CASP3, and JUN were key proteins in MAC treatment. The phosphatidylinositol-3-kinase/RAC-alpha serine/threonine-protein kinase (PI3K/AKT) signaling pathway may play a crucial role in MAC treatment with DJD. Molecular docking results showed good docking effects of key protein AKT1 with luteolin, ß-sitosterol, kaempferol, and glycyrrhizal chalcone A. In vivo experiments indicated that, compared to the model group, in the DJD group, levels of WBCs, RBCs, HGB, and PLTs in peripheral blood cells, thymus index increased, spleen index decreased, serum IL-3, GM-CSF levels increased, and IL-6, TNF-α, and VEGF levels decreased (p < 0.01); the pathological morphology of femoral bone marrow improved. Eleven differential metabolites were identified as differential serum metabolites, mainly concentrated in phenylalanine, tyrosine, and tryptophan biosynthesis pathways, phenylalanine metabolism, and arachidonic acid metabolism. Conclusion: This study revealed that DJD's therapeutic effects are due to multiple ingredients, targets, and pathways. DJD may activate the PI3K/AKT signaling pathway, promote hematopoietic-related cytokine production, regulate related metabolic pathways, and effectively alleviate cyclophosphamide-induced myelosuppression after chemotherapy in rats.

Intestinal toxicity alleviation and efficacy potentiation through therapeutic administration of Lactobacillus paracasei GY-1 in the treatment of gout flares with colchicine.

Gout flares have emerged as a significant public health concern. Colchicine (COL) is a first-line and standard drug for treating gout flares. However, its clinical use is limited due to various adverse effects. Besides, COL fails to adequately meet the needs of patients, particularly young patients. In this study, we investigate the therapeutic administration of Lactobacillus paracasei GY-1 (GY-1) to overcome the limitations of COL. Our results demonstrate that GY-1 attenuates COL toxicity in terms of body weight loss, decreased feed intake, mortality, reduced locomotor activity, colon shortening, increased oxidative stress, histological damage, and impaired gut permeability. Meanwhile, we demonstrate that GY-1 enhances the therapeutic effect for gout flares when combined with COL, as evidenced by the reduction in paw swelling, decreased levels of proinflammatory cytokines including IL-1ß and TNF-α, and an increase in the anti-inflammatory cytokine IL-10. Additionally, the absolute quantification of the gut microbiota shows that GY-1 restores the gut microbiota imbalance caused by COL. Furthermore, GY-1 reduces the abundance of 4 Alistipes species and 6 Porphyromonadaceae species, which may be responsible for toxicity alleviation. At the same time, GY-1 increases the abundance of Bacteroides sartorii and Enterococcus sp., which may contribute to its therapeutic efficacy. This study demonstrates the feasibility of developing probiotic-based adjuvant therapy or bacteriotherapy for treating gout flares. To our knowledge, GY-1 is the first probiotic that could be used as an alternative synergetic agent with COL for the therapeutic treatment of gout flares.

Comparison Between a Modified Fast 3-Dimensional Turbo Spin-Echo and Diffusion-Weighted Imaging With Background Suppression in Evaluation of Lumbosacral Plexus and Its Branches.

OBJECTIVES: To compare the fast 3-dimensional NerveVIEW (3D NerveVIEW) with diffusion-weighted imaging with background suppression (DWIBS) in imaging of lumbosacral plexus and its branches. METHODS: A prospective study was performed on 30 healthy volunteers and patients who had undergone compressed sensing 3D NerveVIEW and DWIBS scans. There were 11 healthy subjects, 15 patients with lumbar disc herniation, and 4 patients with chronic inflammatory demyelinating polyradiculoneuropathy. Image quality was rated using a 4-point subjective scale. Quantitative evaluation of the nerves was done by measuring signal-to-noise ratio, contrast-to-noise ratio, and signal-to-background ratio, and the consistency in the measurements of nerve root cross-sectional areas was also assessed. The differences of signal-to-noise ratio, contrast-to-noise ratio, signal-to-background ratio, and the scores of image quality between 2 sequences were compared. RESULTS: The overall average image quality score of 3D NerveVIEW was significantly higher than that of DWIBS (2.72 ± 0.45 and 2.45 ± 0.81, respectively; P < 0.01). In terms of individual nerves, there was no significant difference between the 2 sequences in the display of the nerves from L2 to S1; however, 3D NerveVIEW was significantly better than DWIBS in demonstration of the S2-S3 nerves, as well as the nerve details. Regarding quantitative measurements, these sequences achieved comparable results with excellent interobserver agreements. CONCLUSION: Fast 3D NerveVIEW was superior to DWIBS with improved conspicuity of small distal nerves of S2-S3 and nerve details.

Bone marrow mesenchymal stem cell-derived exosomal microRNA regulates microglial polarization.

Objective: This study aimed to explore the effects of bone marrow mesenchymal stem cell (BMSC)-derived exosomal miR-146a-5p on microglial polarization and the potential underlying mechanisms in oxygen-glucose deprivation (OGD)-exposed microglial cells. Methods: Exosomes were isolated from BMSCs, and their characteristics were examined. The effects of BMSC-derived exosomes on microglial polarization were investigated in OGD-exposed BV-2 cells. Differentially expressed miRNAs were identified and their biological function was explored using enrichment analyses. The regulatory role of miR-146a-5p in microglial polarization was studied via flow cytometry. Finally, the downstream target gene Traf6 was validated, and the role of the miR-146a-5p/Traf6 axis in modulating microglial polarization was investigated in OGD-exposed BV-2 cells. Results: BMSC-derived exosomes were successfully isolated and characterized. A total of 10 upregulated and 33 downregulated miRNAs were identified. Exosomal treatment resulted in significant changes in microglial polarization markers. miR-146a-5p was found to be significantly downregulated in OGD-exposed microglial cells treated with exosomes. Manipulation of miR-146a-5p expression modulated microglial polarization. Moreover, the miR-146a-5p/Traf6 axis regulated microglial polarization. Conclusion: Our findings demonstrate that BMSC-derived exosomal via miR-146a-5p modulates microglial polarization by targeting Traf6, providing a potential thermal target for the treatment of neurological diseases involving microglial activation.

Mitochondrial transplantation reduces lower limb ischemia-reperfusion injury by increasing skeletal muscle energy and adipocyte browning.

Recent studies have shown that mitochondrial transplantation can repair lower limb IRI, but the underlying mechanism of the repair effect remains unclear. In this study, we found that in addition to being taken up by skeletal muscle cells, human umbilical cord mesenchymal stem cells (hMSCs)-derived mitochondria were also taken up by adipocytes, which was accompanied by an increase in optic atrophy 1 (OPA1) and uncoupling protein 1. Transplantation of hMSCs-derived mitochondria could not only supplement the original damaged mitochondrial function of skeletal muscle, but also promote adipocyte browning by increasing the expression of OPA1. In this process, mitochondrial transplantation can reduce cell apoptosis and repair muscle tissue, which promotes the recovery of motor function in vivo. To the best of our knowledge, there is no study on the therapeutic mechanism of mitochondrial transplantation from this perspective, which could provide a theoretical basis.

A multidimensional feature fusion network based on MGSE and TAAC for video-based human action recognition.

With the maturity of intelligent technology such as human-computer interaction, human action recognition (HAR) technology has been widely used in virtual reality, video surveillance, and other fields. However, the current video-based HAR methods still cannot fully extract abstract action features, and there is still a lack of action collection and recognition for special personnel such as prisoners and elderly people living alone. To solve the above problems, this paper proposes a multidimensional feature fusion network, called P-MTSC3D, a parallel network based on context modeling and temporal adaptive attention module. It consists of three branches. The first branch serves as the basic network branch, which extracts basic feature information. The second branch consists of a feature pre-extraction layer and two multiscale-convolution-based global context modeling combined squeeze and excitation (MGSE) modules, which can extract spatial and channel features. The third branch consists of two temporal adaptive attention units based on convolution (TAAC) to extract temporal dimension features. In order to verify the validity of the proposed network, this paper conducts experiments on the University of Central Florida (UCF) 101 dataset and the human motion database (HMDB) 51 dataset. The recognition accuracy of the proposed P-MTSC3D network is 97.92% on the UCF101 dataset and 75.59% on the HMDB51 dataset, respectively. The FLOPs of the P-MTSC3D network is 30.85G, and the test time is 2.83 s/16 samples on the UCF101 dataset. The experimental results demonstrate that the P-MTSC3D network has better overall performance than the state-of-the-art networks. In addition, a prison action (PA) dataset is constructed in this paper to verify the application effect of the proposed network in actual scenarios.

Prognostic models based on lymph node density for primary gastrointestinal melanoma: a SEER population-based analysis.

OBJECTIVE: This study aimed to construct prognostic models to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with primary gastrointestinal melanoma (PGIM). DESIGN: An observational and retrospective study. SETTING: Data were obtained from the Surveillance, Epidemiology and End Results (SEER) programme database, encompassing a broad geographical and demographic spectrum of patients across the USA. PARTICIPANTS: A total of 991 patients diagnosed with PGIM were included in this study. METHODS: A total of 991 patients with PGIM were selected from the SEER database. They were further divided into a training cohort and a validation cohort. Independent prognostic factors were identified by Cox regression analysis. Two prognostic models were constructed based on the results of multivariable Cox regression analysis. The concordance index (C-index) and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the discriminative ability. Calibration curves were plotted to evaluate the agreement between the probability as predicted by the models and the actual probability. Risk stratification was developed given the model. RESULTS: By the multivariable Cox regression analysis, we identified four independent risk factors (age, stage, lymph node density and surgery) for OS, and three independent risk factors (stage, lymph node density and surgery) for CSS, which were used to construct prognostic models. C-index, time-dependent AUC, calibration curves and Kaplan-Meier curves of risk stratification indicated that these two models had good discriminative ability, predictive ability as well as clinical value. CONCLUSIONS: The prognostic models of OS and CSS had satisfactory accuracy and were of clinical value in evaluating the prognosis of patients with PGIM.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level: A single-center, retrospective cohort study.

BACKGROUND: Autoimmune pancreatitis (AIP) has been linked with elevated immunoglobulin (Ig) G4 levels. The characteristics and outcomes of AIP based on serum markers have not been fully evaluated. AIM: To compare clinical features, treatment efficacy, and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse. METHODS: A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021. According to the serum IgG4 level, all patients were divided into two groups, the abnormal group (n = 148) with a high level of IgG4 [> 2 × upper limit of normal (ULN)] and the normal group (n = 65). The t-test or Mann-Whitney U test was used to compare continuous variables. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were established to assess the cumulative relapse rates. Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse. RESULTS: Compared with the normal group, the abnormal group had a higher average male age (60.3 ± 10.4 vs 56.5 ± 12.9 years, P = 0.047); higher level of serum total protein (72.5 ± 7.9 g/L vs 67.2 ± 7.5 g/L, P < 0.001), IgG4 (1420.5 ± 1110.9 mg/dL vs 252.7 ± 106.6 mg/dL, P < 0.001), and IgE (635.6 ± 958.1 IU/mL vs 231.7 ± 352.5 IU/mL, P = 0.002); and a lower level of serum complement C3 (100.6 ± 36.2 mg/dL vs 119.0 ± 45.7 mg/dL, P = 0.050). In addition, a lower number of cases with abnormal pancreatic duct and pancreatic atrophy (23.6% vs 37.9%, P = 0.045; 1.6% vs 8.6%, P = 0.020, respectively) and a higher rate of relapse (17.6% vs 6.2%, P = 0.030) were seen in the abnormal group. Multivariate analyses revealed that serum IgG4 [(> 2 × ULN), hazard ratio (HR): 3.583; 95% confidence interval (CI): 1.218-10.545; P = 0.020] and IgA (> 1 × ULN; HR: 5.908; 95%CI: 1.199-29.120; P = 0.029) and age > 55 years (HR: 2.383; 95%CI: 1.056-5.378; P = 0.036) were independent risk factors of relapse. CONCLUSION: AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate. Several factors, such as IgG4 and IgA, are associated with relapse.

Birds of a feather flocking together on Instagram: How racially similar followers and followings on Instagram are linked to young women's body image.

In light of recent studies demonstrating the detrimental effects of social media use on young women's body image, we examined the racial composition of young women's Instagram followers, as well as the racial composition of the individuals in young women's followed Instagram accounts, in relation to their appearance ideals and body image. Based on social identity theory (Tajfel & Turner, 1979), we tested two main propositions. First, women who have racially similar followers and followed accounts will be more likely to internalize body ideal preferences that are relevant to their in-group (i.e., thinness for Asian-American and White women; curviness for Black and Latina women). Second, following and being followed by people of one's racial identity in-group will have ameliorative effects on young women's body image (i.e., more body appreciation; less body dissatisfaction). Our sample included 533 U.S. women who identified as Asian-American (n = 97), Black (n = 101), Latina (n = 98), or White (n = 237). The results provided more support for the notion that racially similar followers and accounts followed are related to better body image outcomes rather than to the internalization of body ideals. Specifically, following a higher percentage of racially similar accounts was positively associated with body appreciation among Asian-American and White participants and negatively associated with body dissatisfaction among Asian-American participants. Likewise, being followed by a higher percentage of racially similar others was positively associated with body appreciation among Asian-American, Black, and White participants, and negatively associated with body dissatisfaction among Latina participants. The findings are discussed in light of social identity theory.

Development and validation of a nomogram model for central venous access device-related thrombosis in hospitalized children.

This study aimed to develop and validate a nomogram model of central venous access device-related thrombosis (CRT) for hospitalized children. A total of 503 consecutive cases from a hospital in Changsha City, Hunan Province were stochastically classified into the training set and internal validation set at a ratio of 7:3, and 85 consecutive cases in two hospitals in Urumqi City, Xinjiang Uygur Autonomous Region were collected as an external validation set. Univariate analysis and multivariate analysis on CRT-related risk factors of hospitalized children were conducted, a logistic regression model was employed to establish the nomogram, and the discrimination, calibration, and decision curve analysis was performed to assess the proposed nomogram model. The nomogram model involved seven independent risk factors, including blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h. The discrimination results showed that the area under the receiver operating characteristic curve of the training set, internal validation set, and external validation set was 0.74, 0.71, and 0.76 respectively, and the accuracy rates of the proposed nomogram model were 79%, 72%, and 71% in the training set, internal validation set, and external validation set. The calibration results also showed that the calibration curve had great fitness for each dataset. More importantly, the decision curve suggested that the proposed nomogram model had a prominent clinical significance. CONCLUSION: The nomogram model can be used as a risk assessment tool to reduce the missed diagnosis rate and the incidence of CRT in hospitalized children. WHAT IS KNOWN: • Central venous access device-related thrombosis is generally asymptomatic for hospitalized children, causing the missed diagnosis of central venous access device-related thrombosis easily. • No risk prediction nomogram model for central venous access device-related thrombosis in hospitalized children has been established. WHAT IS NEW: • A visual and personalized nomogram model was built by seven accessible variables (blind catheterization, abnormal liver function, central line-associated bloodstream infection, infection, number of catheter lines, leukemia, and bed rest > 72 h). • The model can effectively predict the risk of central venous access device-related thrombosis for hospitalized children.

Fostering mask-wearing with virality metrics and social media literacy: evidence from the U.S. and Korea.

Although social media can pose threats to the public health by spreading misinformation and causing confusion, they can also provide wider access to health information and opportunities for health surveillance. The current study investigates the ways in which preventive health behaviors and norms can be promoted on social media by analyzing data from surveys and experiments conducted in the U.S. and South Korea. Survey results suggest that the pathway from social media use for COVID-19 information to mask-wearing behavior through mask-wearing norms emerges only among individuals with strong perceived social media literacy in the U.S. Experimental findings show that wear-a-mask campaign posts on social media foster mask-wearing norms and behavioral intention when they come with large (vs. small) virality metrics (e.g., Likes, shares) in both the U.S. and South Korea. Additionally, American users are more willing to engage with posts that come with supportive (vs. mixed) comments by Liking, sharing and commenting. The results highlight the need to cultivate social media literacy and opportunities for exploiting social media virality metrics for promoting public health norms and behaviors.

Clinical Analysis of Intestinal Tuberculosis: A Retrospective Study.

PURPOSE: This study aimed to summarize and analyze the clinical data of intestinal tuberculosis (ITB) in order to provide guidance for accurate diagnosis and treatment of ITB. METHODS: This study consecutively included patients with ITB who were admitted to our hospital from 2008 to 2021 and retrospectively analyzed their clinical features. RESULTS: Forty-six patients were included. The most common clinical symptom was weight loss (67.4%). Seventy percent of 20 patients were positive for tuberculin skin test; 57.1% of 14 patients were positive for mycobacterium tuberculosis specific cellular immune response test, while 84.6% of 26 patients were positive for tuberculosis infection T cell spot test. By chest computed tomography (CT) examination, 25% and 5.6% of 36 patients were diagnosed with active pulmonary tuberculosis and with inactive pulmonary tuberculosis, respectively. By abdominal CT examination, the most common sign was abdominal lymph node enlargement (43.2%). Forty-two patients underwent colonoscopy, and the most common endoscopic manifestation was ileocecal ulcer (59.5%), followed by colonic ulcer (35.7%) and ileocecal valve deformity (26.2%). ITB most frequently involved the terminal ileum/ileocecal region (76.1%). Granulomatous inflammation with multinucleated giant cells and caseous necrosis was found via endoscopic biopsies, the ultrasound-guided percutaneous biopsy of enlarged mesentery lymph nodes, and surgical interventions. The acid-fast bacilli were discovered in 53.1% of 32 samples. Twenty-one cases highly suspected of ITB were confirmed after responding to empiric anti-tuberculosis therapy. CONCLUSIONS: It was necessary to comprehensively analyze clinical features to make an accurate diagnosis of ITB and aid in distinguishing ITB from diseases such as Crohn's disease and malignant tumors.

Lipophilic NO-Driven Nanomotors as Drug Balloon Coating for the Treatment of Atherosclerosis.

Drug-coated balloons (DCB) intervention is an important approach for the treatment of atherosclerosis (AS). However, this therapeutic approach has the drawbacks of poor drug retention and penetration at the lesion site. Here, a lipophilic drug-loaded nanomotor as a modified balloon coating for the treatment of AS is reported. First, a lipophilic nanomotor PMA-TPP/PTX loaded with drug PTX and lipophilic triphenylphosphine (TPP) compounds is synthesized. The PMA-TPP/PTX nanomotors use nitric oxide (NO) as the driving force, which is produced from the reaction between arginine on the motor substrate and excess reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in the AS microenvironment. The final in vitro and in vivo experimental results confirm that the introduction of the lipophilic drug-loaded nanomotor technology can greatly enhance the drug retention and permeability in atherosclerotic lesions. In particular, NO can also play an anti-AS role in improving endothelial cell function and reducing oxidative stress. The chemotherapeutic drug PTX loaded onto the nanomotors can inhibit cell division and proliferation, thereby exerting the effect of inhibiting vascular intimal hyperplasia, which is helpful for the multiple therapies of AS. Using nanomotor technology to solve cardiovascular diseases may be a promising research direction.

Revealing the Potential Markers of N(4)-Acetylcytidine through acRIP-seq in Triple-Negative Breast Cancer.

Understanding the causes of tumorigenesis and progression in triple-receptor negative breast cancer (TNBC) can help the design of novel and personalized therapies and prognostic assessments. Abnormal RNA modification is a recently discovered process in TNBC development. TNBC samples from The Cancer Genome Atlas database were categorized according to the expression level of NAT10, which drives acetylation of cytidine in RNA to N(4)-acetylcytidine (ac4C) and affects mRNA stability. A total of 703 differentially expressed long non-coding RNAs (lncRNAs) were found between high- and low-expressed NAT10 groups in TNBC. Twenty of these lncRNAs were significantly associated with prognosis. Two breast cancer tissues and their paired normal tissues were sequenced at the whole genome level using acetylated RNA immunoprecipitation sequencing (acRIP-seq) technology to identify acetylation features in TNBC, and 180 genes were significantly differentially ac4c acetylated in patients. We also analyzed the genome-wide lncRNA expression profile and constructed a co-expression network, containing 116 ac4C genes and 1080 lncRNAs. Three of these lncRNAs were prognostic risk lncRNAs affected by NAT10 and contained in the network. The corresponding reciprocal pairs were "LINC01614-COL3A1", "OIP5-AS1-USP8", and "RP5-908M14.9-TRIR". These results indicate that RNA ac4c acetylation involves lncRNAs and affects the tumor process and prognosis of TNBC. This will aid the prediction of drug targets and drug sensitivity.

Excavation of Molecular Subtypes of Endometrial Cancer Based on DNA Methylation.

Tumor heterogeneity makes the diagnosis and treatment of endometrial cancer difficult. As an important modulator of gene expression, DNA methylation can affect tumor heterogeneity and, therefore, provide effective information for clinical treatment. In this study, we explored specific prognostic clusters based on 482 examples of endometrial cancer methylation data in the TCGA database. By analyzing 4870 CpG clusters, we distinguished three clusters with different prognostics. Differences in DNA methylation levels are associated with differences in age, grade, clinical pathological staging, and prognosis. Subsequently, we screened out 264 specific hypermethylation and hypomethylation sites and constructed a prognostic model for Bayesian network classification, which corresponded to the classification of the test set to the classification results of the train set. Since the tumor microenvironment plays a key role in determining immunotherapy responses, we conducted relevant analyses based on clusters separated from DNA methylation data to determine the immune function of each cluster. We also predicted their sensitivity to chemotherapy drugs. Specific classifications of DNA methylation may help to address the heterogeneity of previously existing molecular clusters of endometrial cancer, as well as to develop more effective, individualized treatments.

Constructing metagenome-assembled genomes for almost all components in a real bacterial consortium for binning benchmarking.

BACKGROUND: So far, a lot of binning approaches have been intensively developed for untangling metagenome-assembled genomes (MAGs) and evaluated by two main strategies. The strategy by comparison to known genomes prevails over the other strategy by using single-copy genes. However, there is still no dataset with all known genomes for a real (not simulated) bacterial consortium yet. RESULTS: Here, we continue investigating the real bacterial consortium F1RT enriched and sequenced by us previously, considering the high possibility to unearth all MAGs, due to its low complexity. The improved F1RT metagenome reassembled by metaSPAdes here utilizes about 98.62% of reads, and a series of analyses for the remaining reads suggests that the possibility of containing other low-abundance organisms in F1RT is greatly low, demonstrating that almost all MAGs are successfully assembled. Then, 4 isolates are obtained and individually sequenced. Based on the 4 isolate genomes and the entire metagenome, an elaborate pipeline is then in-house developed to construct all F1RT MAGs. A series of assessments extensively prove the high reliability of the herein reconstruction. Next, our findings further show that this dataset harbors several properties challenging for binning and thus is suitable to compare advanced binning tools available now or benchmark novel binners. Using this dataset, 8 advanced binning algorithms are assessed, giving useful insights for developing novel approaches. In addition, compared with our previous study, two novel MAGs termed FC8 and FC9 are discovered here, and 7 MAGs are solidly unearthed for species without any available genomes. CONCLUSION: To our knowledge, it is the first time to construct a dataset with almost all known MAGs for a not simulated consortium. We hope that this dataset will be used as a routine toolkit to complement mock datasets for evaluating binning methods to further facilitate binning and metagenomic studies in the future.

Rational construction of a fluorescent sensor for simultaneous detection and imaging of hypochlorous acid and peroxynitrite in living cells, tissues and inflammatory rat models.

Modern medical research indicates that hypochlorous acid (HClO) and peroxynitrite (ONOO-) are important biomarkers of oxidative stress. However, the up- or down-regulation of HClO or ONOO- has been closely associated with the occurrence and development of various diseases. In order to investigate the intrinsic entanglement relationship between HClO and ONOO- and their relationship with the occurrence and development of inflammation, it is very valuable to develop fluorescent sensors that are capable of displaying different signals towards HClO, ONOO- and HClO/ONOO-. In this work, we rationally design and construct a novel robust small organic molecule fluorescent sensor (RhNp-ClO-ONOO) towards ONOO-, HClO and HClO/ONOO- with green, red, and green-red three different fluorescent signal outputs, respectively. RhNp-ClO-ONOO has fast responsive time for HClO (∼60 s) and ONOO- (∼20 s). Also it has markedly low detection limits for HClO (∼25.3 nM) and ONOO- (12.4 nM) respectively. In addition, RhNp-ClO-ONOO could be further shown to detect endogenous HClO/ONOO- in living cells, inflammatory tissues and rat model successfully. Therefore, this novel fluorescent sensor with double responsive moiety can offer a powerful tool for studying the role of HClO and ONOO- and the occurrence and development of inflammatory diseases.

The relationship between Parkinson's disease and gastrointestinal diseases.

An increasing number of studies have provided evidence for the hypothesis that the pathogenesis of Parkinson's disease (PD) may derive from the gut. Firstly, Lewy pathology can be induced in the enteric nervous system (ENS) and be transported to the central nervous system (CNS) via the vagal nerve. Secondly, the altered composition of gut microbiota causes an imbalance between beneficial and deleterious microbial metabolites which interacts with the increased gut permeability and the gut inflammation as well as the systemic inflammation. The activated inflammatory status then affects the CNS and promotes the pathology of PD. Given the above-mentioned findings, researchers start to pay attention to the connection between PD and gastrointestinal diseases including irritable bowel syndrome, inflammatory bowel disease (IBD), microscopic colitis (MC), gastrointestinal infections, gastrointestinal neoplasms, and colonic diverticular disease (CDD). This review focuses on the association between PD and gastrointestinal diseases as well as the pathogenesis of PD from the gut.

FRAGTE2: An Enhanced Algorithm to Pre-Select Closely Related Genomes for Bacterial Species Demarcation.

We previously reported on FRAGTE (hereafter termed FRAGTE1), a promising algorithm for sieving (pre-selecting genome pairs for whole-genome species demarcation). However, the overall amount of pairs sieved by FRAGTE1 is still large, requiring seriously unaffordable computing cost, especially for large datasets. Here, we present FRAGTE2. Tests on simulated genomes, real genomes, and metagenome-assembled genomes revealed that (i) FRAGTE2 outstandingly reduces ~50-60.10% of the overall amount of pairs sieved by FRAGTE1, dramatically decreasing the computing cost required for whole-genome species demarcation afterward; (ii) FRAGTE2 shows superior sensitivity than FRAGTE1; (iii) FRAGTE2 shows higher specificity than FRAGTE1; and (iv) FRAGTE2 is faster than or comparable with FRAGTE1. Besides, FRAGTE2 is independent of genome completeness, the same as FRAGTE1. We therefore recommend FRAGTE2 tailored for sieving to facilitate species demarcation in prokaryotes.