Salidroside Reduced Ca2+-CaM-CAMKII-Dependent eNOS/NO Activation to Decrease Endothelial Cell Injury Induced by Cold Combined with Hypoxia.

To investigate vascular endothelium damage in rats exposed to hypoxic and cold and the effect of salidroside in protecting against this damage. A rat isolated aortic ring hypoxia/cold model was established to simulate exposure to hypoxic and cold. The levels of endothelial cell injury markers were measured by ELISA. TEM was performed to observe the ultrastructure of vascular ring endothelial cells. In vitro assays were performed to verify the effect of salidroside on endothelial cells. CCK-8 and flow cytometry were performed to analyze endothelial cell survival and apoptosis, respectively. Ca2+ concentrations were measured by Flow cytometry, and the expressions of NOS/NO pathway-related proteins were measured by WB. Endothelial cell damage, mitochondrial swelling, autophagy, and apoptosis were increased in the hypoxia group and hypoxia/hypothermia group. All of these effects were inhibited by salidroside. Moreover, exposure to cold combined with hypoxia reduced the NO levels, Ca2+ concentrations and NOS/NO pathway-related protein expression in the hypoxia group and hypoxia/hypothermia group. Salidroside treatment reversed these changes. Salidroside protected against endothelial cell injury induced by cold and hypoxia through reduction of Ca2+-CaM-CAMKII-dependent eNOS/NO activation, thereby preventing mitochondrial damage, reducing ROS levels, and inhibiting apoptosis.

Integrated metabolomics and network pharmacology approach to exploring the anti-inflammatory mechanisms of Chuanwang xiaoyan capsules.

Chuanwang xiaoyan capsules (CWXYC) have anti-inflammatory and detoxification effect, are used in the treatment of acute and chronic tonsillitis, pharyngitis and other inflammation-related diseases clinically. However, the anti-inflammatory mechanisms have not been elucidated. This study aimed to investigate the anti-inflammatory mechanisms of CWXYC using cell metabolomics and network pharmacology strategy. Specifically, CWXYC could efficiently reduce the content of nitric oxide (NO), the cytokines Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in LPS-induced RAW264.7 cells. Furthermore, metabolomics was performed to achieve 23 differential metabolites and 9 metabolic pathways containing glutamate metabolism, glutathione metabolism, arginine and proline metabolism, urea cycle, malate-aspartate shuttle, phosphatidylcholine biosynthesis, transfer of acetyl groups into mitochondria, cysteine metabolism and ammonia recycling. The results of network pharmacology showed that CWXYC could treat inflammation through 10 active components, 10 key targets and 55 pathways. Then the results of molecular docking also approved that there existed strong binding energy between the active components and the key targets. Finally, metabolomics and network pharmacology were integrated to get core targets AKT1, SRC and EGFR. Western blot experiments verified that CWXYC could exert anti-inflammatory effect by down-regulating the activated Akt1 and Src proteins. This study demonstrated that CWXYC exerted effects against inflammation, and the potential mechanisms were elucidated. These novel findings will provide an important basis for further mechanism investigations.

A comprehensive study of Chuanwang Xiaoyan capsule based on characterization of chemical constituents in vitro and in vivo using ultra-high-performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry and pharmacokinetic study of multiple components in rats using ultra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry.

Chuanwang Xiaoyan (CWXY) capsule is primarily used to treat a variety of acute and chronic inflammations, including acute and chronic pharyngitis and tonsillitis. However, a systematic study of its chemical constituents is still not available. This study evaluated the chemical constituents in vitro and metabolite profiles in vivo of CWXY using ultra-high-performance liquid chromatography (UHPLC) coupled with Q-Exactive Orbitrap mass spectrometry, and the pharmacokinetic behaviors of the nine main components in rats were detected using ultra-high-performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-QQQ-MS/MS). A total of 92 chemical constituents in CWXY were preliminarily identified in vitro. After oral administration to rats, 56 prototype components and 128 metabolites of CWXY were detected in the biological samples of rat plasma, urine, bile, and feces. Of these prototype components and metabolites, seven new compounds, namely M15, M16, M25, M30, M31, M71, and M128, were detected for the first time. The quantitation method of nine components in rat plasma was developed using a pharmacokinetic study. To the best of our knowledge, this study was the first to investigate the pharmacokinetic behavior of triumbelletin.

Yak meat content in feed and its impact on the growth of rats.

To evaluate the effects of varying proportions of yak meat in feed on the growth of rats and provide a theoretical basis for selecting the optimal feed proportion suitable for rats. This study was designed as a one-variable experiment. Fifty male rats were divided into five groups. The ratios of yak meat to basal feed of rats in four dietary treatment groups were 2:8, 4:6, 6:4, and 8:2, respectively, while those in the control group were only provided a basal diet. In the feeding experiment, the body weights of the rats were recorded on Day 0 and subsequently in the first, second, third, and fourth weeks, along with quantities of feed intake. The body and tail lengths, as well as the waist circumference of the rats, were measured, and blood samples were collected in the fourth week for routine blood and biochemistry investigations. The rats in the 4:6 feed group had the best body condition. They had normal body and tail lengths, smaller waist circumferences, good posture, and were in better overall health than rats in the other groups. The results indicate that the 4:6 diet was optimal for enhancing rats' growth performance compared to the other diets.

Exploring the gut microbiota mediated biotransformation of Senecio scandens Buch.-Ham.: Insights from metabolite spectrum with UHPLC-Q-Orbitrap HRMS and bioinformatics analysis of gut microbiota metabolites.

Senecio scandens Buch.-Ham., a traditional Chinese medicine commonly used clinically, exhibits various pharmacological properties, including anti-inflammatory, anti-tumor, antiviral, and antibacterial activities. However, its water extracts' chemical components and metabolites are inadequately understood, limiting further research. In this study, the chemical components and metabolism processes of Senecio scandens, both in vivo (plasma, feces, urine, and bile) and in vitro (gut microbiota and liver microsomes), were characterized based on ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry. Additionally, metabolites detectable in fecal samples and intestinal microbiota incubated but absent in liver microsomes were identified as characteristic metabolites of intestinal microbiota. The targets of the characteristic metabolites of intestinal microbiota were collected, followed by exploration of potential pathways through KEGG enrichment analysis. As a result, a total of 133 chemical components were preliminarily identified, including 35 organic acids, 21 alkaloids, 19 flavonoids and their glycosides, 17 phenylpropanoids, 10 jacaranda ketones, and 31 other compounds. Notably, 12 of these were potentially novel compounds. In addition, 39 prototype components in rats and 109 metabolites were identified and characterized, including 102 in vivo and 52 metabolites in vitro (51 in rat gut microbiota and 24 in rat liver microsomes). The main metabolic pathways include oxidation, reduction, hydrolysis, methylation, glucuronidation, sulfonation, and acetylation reactions. Furthermore, KEGG enrichment analysis revealed that the characteristic metabolites of intestinal microbiota may be related to the ErbB, FoxO, mTOR, and MAPK signaling pathways, exhibiting anti-inflammatory and anti-tumor effects. In summary, the chemical components and metabolites of Senecio scandens were comprehensively identified using a rapid and accurate method, providing a scientific basis for the in-depth study of the material basis and its clinical application of Senecio scandens.

Integrated serum pharmacochemistry, network pharmacology, and pharmacokinetics to clarify the effective components and pharmacological mechanisms of the proprietary Chinese medicine Jinkui Shenqi Pill in treating kidney yang deficiency syndrome.

The proprietary Chinese medicine Jinkui Shenqi Pill (PCM-JKSQP) is a classic compound used for the effective clinical treatment of kidney yang deficiency syndrome (KYDS), a metabolic disease accompanied by kidney injury. However, its active ingredients and therapeutic mechanisms are not clear. This study employed serum pharmacochemistry, network pharmacology, and pharmacokinetics (PK) to identify the bioactive components of PCM-JKSQP and preliminarily clarify its mechanism in treating KYDS. One hundred and forty chemical components of PCM-JKSQP, 47 (20 parent compouds and 27 metabolites) of which were absorbed into the blood, were identified by ultra-high-performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). The topological parameters of network pharmacology and high concentrations in blood found six parent components as PK markers (cinnamic acid, paeonol, loganin, morroniside, apigenin, and poricoic acid A). PK analysis further identified these six compounds as active ingredients. Protein-protein interaction (PPI) analysis and molecular docking simulation predicted and verified eight core targets (TP53, ESR1, CTNNB1, EP300, EGFR, AKT1, ERBB2, and TNF). Most were concentrated in the MAPK, HIF-1, and PI3K-AKT signaling pathways, indicating that these six active ingredients may mainly exert therapeutic effects through these three pathways via their core targets. The PK results also showed these six components were absorbed quickly, although cinnamic acid and paeonol were rapidly metabolized, with a short half-life and retention time. Loganin and morroniside did not have high peak concentrations, and apigenin and poricoic acid A had long retention times. This study provides a new overall perspective for exploring the bioactive components and mechanisms underlying the effects of PCM-JKSQP in treating KYDS.

Identification of Scutebarbatine B metabolites in rats using UHPLC-Q-Orbitrap-MS/MS and exploration of its mechanism of reversal multidrug resistance in breast cancer by network pharmacology and molecular docking studies.

Scutebarbatine B (SBT-B) is a neo-clerodane diterpenic compound isolated from Scutellaria barbata D. Don (S. barbata), which has been reported to exhibit inhibitory P-glycoprotein (P-gp) property in MCF-7/ADR cells. However, its metabolism and molecular mechanism of reversal multidrug resistance (MDR) in breast cancer remains unclear. This study investigated the metabolite profile of SBT-B in rats by UHPLC-Q-Orbitrap-MS/MS, and explored its mechanism of reversal MDR through network pharmacology and molecular docking studies. A total of 16 Phase I metabolites and 2 Phase II metabolites were identified, and 18 metabolites were all newly discovered metabolites as novel compounds. The metabolic pathway of SBT-B mainly includes oxidization, reduction, hydrolysis, acetylation and glycination. Meanwhile, network pharmacology analyses showed that SBT-B mainly regulated p27 phosphorylation during cell cycle progression, p53 signaling pathway, influence of Ras and Rho proteins on G1 to S Transition. Molecular docking studies revealed that SBT-B exhibits the potential to inhibit P-gp expression by selectively binding to GLN721 and ALA981 residue sites at the interface of P-gp. In addition, SBT-B exhibits moderate binding affinity with CDK2 and E2F1. This study illustrated the major metabolic pathways of SBT-B in vivo, clarified detailed information on SBT-B metabolites in rats, and uncovered the potential mechanism of SBT-B reversal MDR in breast cancer, providing new insights for the development of P-gp inhibitors.

Clinical study reveals the efficacy of sirolimus in treating primary immune thrombocytopenia: findings from a single-center study.

Immune thrombocytopenia (ITP) is an autoimmune disease that arises because of self-destruction of circulating platelets. The mechanism remains complicated and lacks a standard clinical treatment. Current first-line and second-line medications for ITP have shown limited effectiveness, necessitating the exploration of new therapeutic options. Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in the treatment of ITP. This study aimed to evaluate the clinical efficacy of sirolimus as a second-line drug in patients with ITP. The starting dose of sirolimus for adults ranged from 2 to 4 mg/day, with a maintenance dose of 1 to 2 mg/day. For children, the starting dose was 1-2 mg/day, with a maintenance dose of 0.5-1 mg/day. The dosage could be adjusted if needed to maintain a specific blood concentration of sirolimus, typically between 5 and 15 ng/ml, throughout the treatment period. After 3 months, the overall response rate was 60% (12/20), with 30% of patients (6/20) achieving a complete response (CR) and 30% (6/20) achieving a partial response (PR). The CR rate at 6 months remained consistent with the 3-month assessment. No major adverse events were reported, indicating that sirolimus was well tolerated and safe. Analysis of peripheral blood Treg cell percentages in both the control and ITP showed no significant difference before treatment. The percentage of Treg cells increased after treatment with sirolimus, suggesting that sirolimus increases Treg cells. These findings suggest that sirolimus serves as an effective second-line treatment option for ITP, demonstrating favorable clinical efficacy.

Cholesterol-regulated cellular stiffness may enhance evasion of NK cell-mediated cytotoxicity in gastric cancer stem cells.

Gastric cancer has a high rate of recurrence, and as such, immunotherapy strategies are being investigated as a potential therapeutic strategy. Although the involvement of immune checkpoints in immunotherapy is well studied, biomechanical cues, such as target cell stiffness, have not yet been subject to the same level of investigation. Changes in the cholesterol content of the cell membrane directly influence tumor cell stiffness. Here, we investigated the effect of cholesterol on NK cell-mediated killing of gastric cancer stem-like cells. We report that surviving tumor cells with stem-like properties elevated cholesterol metabolism to evade NK cell cytotoxicity. Inhibition of cholesterol metabolism enhances NK cell-mediated killing of gastric cancer stem-like cells, highlighting a potential avenue for improving immunotherapy efficacy. This study suggests a possible effect of cancer cell stiffness on immune evasion and offers insights into enhancing immunotherapeutic strategies against tumors.

Comparative efficacy of acupuncture-related therapy for postmenopausal osteoporosis: protocol for Bayesian network meta-analysis.

INTRODUCTION: The review aims to conduct the first network meta-analysis to comprehensively evaluate the application of multiple acupuncture techniques in patients with postmenopausal osteoporosis, ranking the best acupuncture treatment and providing a reference for clinical treatment extensively. METHODS AND ANALYSIS: Randomised controlled trials of different acupuncture-related therapies for postmenopausal osteoporosis will be searched in the following databases from 1 January 2002 to 31 December 2022, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, VIP Database, Wanfang Database and China Biomedical Literature Database. Overall, clinical efficacy rate, bone mineral density and a Visual Analogue Scale score are used as the primary outcome indicators. In addition, the secondary outcome indicator is adverse reactions. The entire screening process will be conducted by two independent investigators; meanwhile, Stata (V.14.0) and RevMan (V.5.4) will be used to conduct the network meta-analysis. If the data are permissible and feasible, we will also perform meta-regression and subgroup analyses to address the underlying causes of data inconsistency and heterogeneity in the statistical analyses. Besides, to improve the credibility of this network meta-analysis, we will evaluate the quality of evidence in this research according to the GRADE assessment. ETHICS AND DISSEMINATION: Ethics approval is not required for network meta-analyses, which do not involve animals' or people's welfare. The results of this network meta-analysis will be submitted to a recognised journal for publication. PROSPERO REGISTRATION NUMBER: CRD42023401003.

A HER2-targeted Antibody-Drug Conjugate, RC48-ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer.

More than half of non-muscle-invasive bladder cancer (NMIBC) patients eventually relapse even if treated with surgery and BCG without optional bladder-preserving therapy. This study aims to investigate the antitumor activity and safety of a HER2-targeted antibody-drug conjugate, RC48-ADC, intravesical instillation for NMIBC treatment. In this preclinical study, it is revealed that human epidermal growth factor receptor 2 (HER2) expression scores of 1+, 2+, and 3+ are recorded for 16.7%, 56.2%, and 14.6% of NMIBC cases. The antitumor effect of RC48-ADC is positively correlated with HER2 expression in bladder cancer (BCa) cell lines and organoid models. Furthermore, RC48-ADC is revealed to exert its antitumor effect by inducing G2/M arrest and caspase-dependent apoptosis. In an orthotopic BCa model, tumor growth is significantly inhibited by intravesical instillation of RC48-ADC versus disitamab, monomethyl auristatin E, epirubicin, or phosphate-buffered saline control. The potential toxicity of intravesical RC48-ADC is also assessed by dose escalation in normal nude mice and revealed that administration of RC48-ADC by intravesical instillation is safe within the range of effective therapeutic doses. Taken together, RC48-ADC demonstrates promising antitumor effects and safety with intravesical administration in multiple preclinical models. These findings provide a rational for clinical trials of intravesical RC48-ADC in NMIBC patients.

Early transthoracic echocardiography and long-term mortality in moderate- to-severe acute respiratory distress syndrome: An analysis of the Medical Information Mart for Intensive Care database.

BACKGROUND: The clinical use of transthoracic echocardiography (TTE) in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) has dramatically increased, its impact on long-term prognosis in these patients has not been studied. This study aimed to explore the effect of early-TTE on long-term mortality in patients with moderate-to-severe ARDS in ICU. METHODS: A total of 2833 patients with moderate-to-severe ARDS who had or had not received early-TTE were obtained from the Medical Information Mart for Intensive Care (MIMIC-III) database after imputing missing values by a random forest model, patients were divided into early-TTE group and non-early-TTE group according to whether they received TTE examination in ICU. A variety of statistical methods were used to balance 41 covariates and increase the reliability of this study, including propensity score matching, inverse probability of treatment weight, covariate balancing propensity score, multivariable regression, and doubly robust estimation. Chi-Square test and t-tests were used to examine the differences between groups for categorical and continuous data, respectively. RESULTS: There was a significant improvement in 90-day mortality in the early-TTE group compared to non-early-TTE group (odds ratio = 0.79, 95% CI: 0.64-0.98, p-value = 0.036), revealing a beneficial effect of early-TTE. Net-input was significantly decreased in the early-TTE group on the third day of ICU admission and throughout the ICU stay, compared with non-early-TTE group (838.57 vs. 1181.89 mL, p-value = 0.014; 4542.54 vs. 8025.25 mL, p-value = 0.05). There was a significant difference in the reduction of serum lactate between the two groups, revealing the beneficial effect of early-TTE (0.59 vs. 0.83, p-value = 0.009). Furthermore, the reduction in the proportion of acute kidney injury demonstrated a correlation between early-TTE and kidney protection (33% vs. 40%, p-value < 0.001). CONCLUSIONS: Early application of TTE is beneficial to improve the long-term mortality of patients with moderate-to-severe ARDS.

Prediction of pulmonary metastasis in esophageal carcinoma patients with indeterminate pulmonary nodules.

BACKGROUND: Indeterminate pulmonary nodules (IPNs) are common after surgery for esophageal cancer. The paucity of data on postoperative IPNs for esophageal cancer causes a clinical dilemma. OBJECTIVE: The aim of this study was to identify the characteristics and clinical significance of IPNs after radical esophagectomy for metastatic esophageal cancer, determine the risk factors for pulmonary metastasis, and construct a risk score model to standardize the appropriate time to either follow up or treat the patient. METHODS: All consecutive patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between 2013 and 2016 were included in this retrospective study. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop risk score models. RESULTS: A total of 816 patients were enrolled in the study. During a median follow-up period of 45 months, IPNs were detected in 221 (27.1%) patients, of whom 66 (29.9%) were diagnosed with pulmonary metastases. The following five variables maintained prognostic significance after multivariate analyses: the pathologic N category, number of IPNs, shape of IPNs, time of detection of IPNs, and size of IPNs. The Pulmonary Metastasis Prediction Model (PMPM) scale ranges from 0 to 15 points, and patients with higher scores have a higher probability of pulmonary metastases. The Hosmer-Lemeshow test showed a good calibration performance of the clinical prediction model (χ2 = 8.573, P = 0.380). After validation, the PMPM scale showed good discrimination with an AUC of 0.939. CONCLUSION: A PMPM scale for IPNs in patients who underwent esophagectomy for ESCC may be clinically useful for diagnostic and therapeutic decision-making.

Bottom-up strategy of multi-level structured boron-doped diamond for the durable electrode in water purification.

Long-term exposition of electrodes to aqueous media inevitably results in biofouling and adhesion of bacteria, reducing the electrolysis efficiency of electrodes for water treatment. To ensure technically efficient antifouling of materials for durable electrodes, hierarchical micro-/nano structured boron-doped diamond (BDD) electrodes were designed and synthesized. Multi-level structured BDD was coated on titanium mesh by a bottom-up strategy, based on a combination of self-assembly seeding and hot filament chemical vapor deposition (HFCVD) growth. The morphology of the BDD coating can be controlled by manipulating the seeding density and boron doping concentration. The designed micro/nano hierarchical structure of the BDD electrode suppressed bacterial adhesion greatly and exhibited excellent anti-biofouling efficiency with an antibacterial rate of âˆ¼ 93 %, which entails simplified self-cleaning and durable BDD-coated electrodes. The BDD-coated electrodes were employed to electrochemically treat Escherichia coli-contaminated water, killing virtually all bacteria (≥99.9 %) in 1 min. Finally, real river water was electrochemically treated, reducing the chemical oxygen demand (COD) down to 5 mg/L in 4 h. The excellent performance shows the great potential of the structured BDD electrodes for long-term water purification.

Characterization of chemical ingredients and in rats metabolic profiling of Lingyang Qingfei pills via ultra-high-performance liquid chromatography combined with Quadrupole-Exactive Orbitrap high-resolution mass spectrometry.

Lingyang Qingfei pills (LQP), the renowned traditional Chinese medicine recipe, have been extensively utilized for the therapy of xerostomia, sore throat, bronchiolitis, and pneumonia in clinics. However, its phytochemicals remain equivocal, which severely limits the development of quality control and activity mechanisms. In the current research, a trusted method founded on ultra-high performance liquid chromatography with Quadrupole-Exactive Orbitrap mass spectrometry technique was proposed for the comprehensive screening of in vitro and in vivo chemical compositions of LQP. As a consequence, 239 constituents were preliminarily characterized, 37 of which were accurately confirmed by reference standards. In addition, a total of 208 xenobiotics, containing 71 absorbed prototypes and 137 metabolites, were revealed in rat plasma, bile, urine, and feces, respectively. The metabolic reaction of hydrolysis, hydroxylation, methylation, glycosylation, sulfation, and mixed-mode was detected in the biotransformations of flavonoids, terpenoids, alkaloids, anthraquinones, organic acids, phenylpropanoids, and so forth. And 12 of the metabolites were new compounds. This experiment acted as the first reference for chemical substances and metabolites of LQP, which could provide valuable chemical information for further clarifying pharmacodynamic substances and pharmacokinetic studies.

An 8-gene predicting survival model of hepatocellular carcinoma (HCC) related to pyroptosis and cuproptosis.

BACKGROUND: The study aimed to establish a prognostic survival model with 8 pyroptosis-and-cuproptosis-related genes to examine the prognostic effect in patients of hepatocellular carcinoma (HCC). METHODS: We downloaded gene expression data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The clustering analysis and cox regression with LASSO were used for constructing an 8 PCmRNAs survival model. Using TCGA, ICGC and GEO cohort, the overall survival (OS) between high- and low- risk group was determined. We also evaluated independent prognostic indicators using univariate and multivariate analyses. The relatively bioinformatics analysis, including immune cell infiltration, function enrichment and drug sensitivity analyses, was performed as well. The gene expression of 8 PCmRNAs in vitro were validated in several HCC cell lines by qRT-PCR and Western blot. The relationship between GZMA and Fludarabine were further checked by CCK-8 assay. RESULTS: The survival prognostic model was constructed with ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA using data from TCGA cohort. The ICGC and GEO cohort were used for model validation. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Risk scores had the highest predictable value for survival among Stage, Age, Gender and Grade. Most Immune cells and immune functions were decreased in high-risk group. Besides, function enrichment analyses showed that steroid metabolic process, hormone metabolic process, collagen - containing extracellular matrix, oxidoreductase activity and pyruvate metabolism were enriched. Potential drugs targeted different PCDEGs like Nelarabine, Dexamethasone and Fludarabine were found as well. ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NOD1 were upregulated while NLRP6 and GZMA were downregulated in most HCC cell lines. The potential therapy of Fludarabine was demonstrated when GZMA was low expressed in Huh7 cell line. CONCLUSION: We constructed a novel 8-gene (ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA) prognostic model and explored potential functional information and microenvironment of HCC, which might be worthy of clinical application. In addition, several potential chemotherapy drugs were screened and Fludarabine might be effective for HCC patients whose GZMA was low expressed.

Benzophenoxazine-based colorimetric and fluorescent probe for highly sensitive detection of amines and food freshness.

In this work, we reported a chromogenic and near infrared (NIR) region fluorogenic dual-channel probe NRB, which could visually detect gaseous amines with high sensitivity (eg. 50 and 17 ppt for methylamine (MeNH2) via naked eyes and fluorescence spectrometer respectively). It exhibited a wide fluorescent emission band extending to the NIR region with a peak at 615 nm when stimulated by the MeNH2 solution. The plausible sensing mechanism was proved by mass spectrometry, where the reaction process was based on a nucleophilic substitution between the probe and amines rather than the ester group hydrolysis. Furthermore, NRB was successfully applied to monitor the food freshness (seafood and meat food), because of its low cytotoxicity and excellent photophysical properties. It was worth mentioning that real time monitoring for food quality can be realized visually by using a 365 nm UV lamp. In addition, the probe was stable during the quality guarantee period for perishable packaged food. It was believed that the applied experiments have demonstrated the value of this probe in the practical applications for food safety.

Altered gut microbiota profile in patients with perimenopausal panic disorder.

Introduction: Females in the perimenopausal period are susceptible to mood disorders. Perimenopausal panic disorder (PPD) is characterized by repeated and unpredictable panic attacks during perimenopause, and it impacts the patient's physical and mental health and social function. Pharmacotherapy is limited in the clinic, and its pathological mechanism is unclear. Recent studies have demonstrated that gut microbiota is strongly linked to emotion; however, the relation between PPD and microbiota is limitedly known. Methods: This study aimed to discover specific microbiota in PPD patients and the intrinsic connection between them. Gut microbiota was analyzed in PPD patients (n = 40) and healthy controls (n = 40) by 16S rRNA sequencing. Results: The results showed reduced α-diversity (richness) in the gut microbiota of PPD patients. ß-diversity indicated that PPD and healthy controls had different intestinal microbiota compositions. At the genus level, 30 species of microbiota abundance had significantly different between the PPD and healthy controls. In addition, HAMA, PDSS, and PASS scales were collected in two groups. It was found that Bacteroides and Alistipes were positively correlated with PASS, PDSS, and HAMA. Discussion: Bacteroides and Alistipes dysbiosis dominate imbalanced microbiota in PPD patients. This microbial alteration may be a potential pathogenesis and physio-pathological feature of PPD. The distinct gut microbiota can be a potential diagnostic marker and a new therapeutic target for PPD.