Light Induced Proton Coupled Charge Transfer Triggers Counterion Directional Translocation.

We demonstrate directed translocation of ClO4- anions from cationic to neutral binding site along the synthetized BPym-OH dye molecule that exhibits coupled excited-state intramolecular proton-transfer (ESIPT) and charge-transfer (CT) reaction (PCCT). The results of steady-state and time-resolved spectroscopy together with computer simulation and modeling show that in low polar toluene the excited-state redistribution of electronic charge enhanced by ESIPT generates the driving force, which is much stronger than by CT reaction itself and provides more informative gigantic shifts of fluorescence spectra signaling on ultrafast ion motion. The associated with ion translocation red-shifted fluorescence band (at 750 nm, extending to near-IR region) appears at the time ~ 83 ps as a result of electrochromic modulation of PCCT reaction. It occurs at substantial delay to PCCT that displayed fluorescence band at 640 nm and risetime of < 200 fs. Thus, it becomes possible to visualize the manifestations of light-triggered ion translocation and of its driving force by fluorescence techniques and to separate them in time and energy domains.

Palmatine improves cognitive dysfunction in Alzheimer's disease model rats through autophagy pathway and regulation of gut microbiota.

Alzheimer's disease (AD) is a primary degenerative encephalopathy that first appeared as a decline in memory and learning skills. Over time, the condition's severity grew. Palmatine (Pal) alleviates Alzheimer's disease symptoms, which has neuroprotective benefits. Numerous investigations have demonstrated a close relationship among AD and gut structure changes. The aim of the research was investigating whether the improvement of Pal on AD is linked to regulating gut flora and autophagy. First, we used Aß1-40 to induce apoptosis in HT22 cells. After Pal treatment, apoptosis can be improved. Then, We used bilateral intracranial hippocampal injection of Aß1-40 for establishing the AD model, after treatment with Pal, the morris water maze experiment and eight-arm maze test demonstrated that Pal enhanced the AD rats' capacity for learning and memory, HE staining illustrated that Pal improved the morphological abnormalities of brain cells and gut tissue damage. Pal reduced the death of hippocampus neurons, as shown by Nissl staining. Pal substantially reduced Tau hyperphosphorylation and Aß accumulation in the brain, according to immunohistochemical labelling. Pal improved the expression of LC3, Beclin 1, AMPK, and suppressed the expression of mTOR and P62, as validated by RT-qPCR and immunofluorescence labelling. This suggests that Pal's treatment of AD may be associated with the control of the AMPK/mTOR autophagy signalling system. 16S rRNA sequencing and short-chain fatty acids (SCFAs) content detection analysis illustrated that Pal has the potential to enhance the content of SCFAs, reverse the alterations in gut microorganisms. It has been showed by the study that Pal could improve AD by activating autophagy signaling pathway and improving gut barrier changes.

Total paeony glycoside relieves neuroinflammation to exert antidepressant effect via the interplay between NLRP3 inflammasome, pyroptosis and autophagy.

BACKGROUND: Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied. PURPOSE: To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy. STUDY DESIGN: A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG. METHODS: The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated. RESULTS: TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1ß, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG. CONCLUSION: These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.

Prevalence of Mycobacterium bovis in deer in mainland China: a systematic review and meta-analysis.

Background: Deer tuberculosis is a chronic zoonotic infectious disease, despite the existence of socio-economic and zoonotic risk factors, but at present, there has been no systematic review of deer tuberculosis prevalence in mainland China. The aim of this meta-analysis was to estimate the overall prevalence of deer TB in mainland China and to assess possible associations between potential risk factors and the prevalence of deer tuberculosis. Methodology: This study was searched in six databases in Chinese and English, respectively (1981 to December 2023). Four authors independently reviewed the titles and abstracts of all retrieved articles to establish the inclusion exclusion criteria. Using the meta-analysis package estimated the combined effects. Cochran's Q-statistic was used to analyze heterogeneity. Funnel plots (symmetry) and used the Egger's test identifying publication bias. Trim-and-fill analysis methods were used for validation and sensitivity analysis. we also performed subgroup and meta-regression analyses. Results: In this study, we obtained 4,400 studies, 20 cross-sectional studies were screened and conducted a systematic review and meta-analysis. Results show: The overall prevalence of tuberculosis in deer in mainland China was 16.1% (95% confidence interval (CI):10.5 24.6; (Deer tuberculosis infected 5,367 out of 22,215 deer in mainland China) 5,367/22215; 1981 to 2023). The prevalence in Central China was the highest 17.5% (95% CI:14.0-21.9; 63/362), and among provinces, the prevalence in Heilongjiang was the highest at 26.5% (95% CI:13.2-53.0; 1557/4291). Elaphurus davidianus was the most commonly infected species, with a prevalence of 35.3% (95% CI:18.5-67.2; 6/17). We also assessed the association between geographic risk factors and the incidence of deer tuberculosis. Conclusion: Deer tuberculosis is still present in some areas of China. Assessing the association between risk factors and the prevalence of deer tuberculosis showed that reasonable and scientific-based breeding methods, a suitable breeding environment, and rapid and accurate detection methods could effectively reduce the prevalence of deer tuberculosis. In addition, in the management and operation of the breeding base, improving the scientific feed nutrition standards and establishing comprehensive standards for disease prevention, immunization, quarantine, treatment, and disinfection according to the breeding varieties and scale, are suggested as ways to reduce the prevalence of deer tuberculosis.

Enhancing regeneration and repair of long-distance peripheral nerve defect injuries with continuous microcurrent electrical nerve stimulation.

Introduction: Peripheral nerve injuries, especially those involving long-distance deficits, pose significant challenges in clinical repair. This study explores the potential of continuous microcurrent electrical nerve stimulation (cMENS) as an adjunctive strategy to promote regeneration and repair in such cases. Methods: The study initially optimized cMENS parameters and assessed its impact on Schwann cell activity, neurotrophic factor secretion, and the nerve regeneration microenvironment. Subsequently, a rat sciatic nerve defect-bridge repair model was employed to evaluate the reparative effects of cMENS as an adjuvant treatment. Functional recovery was assessed through gait analysis, motor function tests, and nerve conduction assessments. Additionally, nerve regeneration and denervated muscle atrophy were observed through histological examination. Results: The study identified a 10-day regimen of 100uA microcurrent stimulation as optimal. Evaluation focused on Schwann cell activity and the microenvironment, revealing the positive impact of cMENS on maintaining denervated Schwann cell proliferation and enhancing neurotrophic factor secretion. In the rat model of sciatic nerve defect-bridge repair, cMENS demonstrated superior effects compared to control groups, promoting motor function recovery, nerve conduction, and sensory and motor neuron regeneration. Histological examinations revealed enhanced maturation of regenerated nerve fibers and reduced denervated muscle atrophy. Discussion: While cMENS shows promise as an adjuvant treatment for long-distance nerve defects, future research should explore extended stimulation durations and potential synergies with tissue engineering grafts to improve outcomes. This study contributes comprehensive evidence supporting the efficacy of cMENS in enhancing peripheral nerve regeneration.

Structural characterisation of deer sinew peptides as calcium carriers, their promotion of MC3T3-E1 cell proliferation and their effect on bone deposition in mice.

Deer sinew as a by-product has high collagen and nutritional value. This study focuses on its hydrolysate being used as a calcium carrier to develop functional foods. The chelation mechanism was analyzed by SEM, EDS, UV-vis, FTIR, and fluorescence spectroscopy and zeta potential analysis after using peptide-sequenced deer sinew peptides for chelation with calcium ions. The results showed that the chelation of deer sinew peptides with calcium ions occurs mainly at the O and N atoms of carboxyl, amino and amide bonds. In vitro and in vivo studies revealed that deer sinew peptide-calcium chelate (DSPs-Ca) promoted the proliferation of MC3T3-E1 cells without toxic side effects and increased the alkaline phosphatase activity. The DSPs-Ca group improved the bone microstructure induced by low calcium, as well as up-regulated the expression of genes responsible for calcium uptake in the kidneys, as evidenced by serum markers, bone sections, bone parameters, and gene expression analyses in low-calcium-fed mice. From the above, it can be concluded that DSPs-Ca is expected to be a calcium supplement food for promoting bone health.

Mechanism of action of vinegared Cornu Cervi Degelatinatum in suppressing spleen kidney yang deficient ulcerative colitis through NCK2-JNK pathway.

As a traditional Chinese herbal medicine, Cornu Cervi Degelatinatum (CCD) has the effect of warming the kidney to support yang, astringing, and stopping bleeding, and is used for spleen kidney yang deficient (SKYD). This experiment was to investigate the therapeutic effects of different processes of CCD on SKYD type ulcerative colitis (UC) rats and to explore its impact on the intestinal flora of rats. METHODS: ELISA was used to study the anti-inflammatory activity of Cornu Cervi Degelatinatum processed with water (WCCD) and Cornu Cervi Degelatinatum processed with vinegar (VCCD). 16SrRNA and transcriptome sequencing were used to detect the composition of rat intestinal flora and gene expression; RT-PCR and Western blot were used to verify the role of WCCD and VCCD in treating UC. RESULTS: WCCD and VCCD have therapeutic effects on UC, could reduce tissue damage. VCCD performed better in improving Bacteroidetes/Firmicutes ratios and species evenness and abundance; performed better in increasing the quantity of lactobacillus. VCCD simultaneously inhibit the intestinal inflammatory response through NCK2, PAK4, and JNK signaling pathways. CONCLUSIONS: WCCD and VCCD play a therapeutic role in UC by regulating the proportion of different flora in the intestinal flora. VCCD regulates the intestinal flora and inflammatory response by interfering with the NCK2, PAK4 and JNK signaling pathways.

Enhancing Electrochemical Non-Enzymatic Dopamine Sensing Based on Bimetallic Nickel/Cobalt Phosphide Nanosheets.

In this study, the successful synthesis of bimetallic nickel/cobalt phosphide nanosheets (Ni-Co-P NSs) via the hydrothermal method and the subsequent high-temperature phosphorization process were both confirmed. Ni-Co-P NSs exhibited excellent electrocatalytic activity for the electrochemical non-enzymatic DA sensing. The surface morphologies and physicochemical properties of Ni-Co-P NSs were characterized by atomic force microscopy (AFM), field-emission scanning (FESEM), field-emission transmission electron microscopy (FETEM), and X-ray diffraction (XRD). Further, the electrochemical performance was evaluated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The metallic nature of phosphide and the synergistic effect of Ni/Co atoms in Ni-Co-P NSs provided abundant catalytic active sites for the electrochemical redox reaction of DA, which exhibited a remarkable consequence with a wide linear range from 0.3~50 µM, a high sensitivity of 2.033 µA µM-1 cm-2, a low limit of detection of 0.016 µM, and anti-interference ability. As a result, the proposed Ni-Co-P NSs can be considered an ideal electrode material for the electrochemical non-enzymatic DA sensing.

Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue.

ETHNOPHARMACOLOGICAL RELEVANCE: Antler glue is a classic medicinal to enhance sexual function in traditional Chinese medicine (TCM), which was first recorded in Shen Nong Ben Cao Jing (Shennong's Classic of the Materia Medica). Vinegar-processing is a classic method of processing traditional Chinese medicine. The method of preparing antler glue by boiling antlers in vinegar and then concentrating them is recorded in Lei Gong Pao Zhi Lun (Master Lei's Discourse on Medicinal Processing). In modern times, the typical processing method of antler glue is water extraction and concentration. However, it is not clear whether there is a difference in the effect of these two processing methods on the chemical composition and pharmacological activity of antler glue. AIM OF THE STUDY: The Chinese Pharmacopoeia (2020) records that the processing method of antler glue is water extraction and concentration. But Lei Gong Pao Zhi Lun differs in Chinese Pharmacopoeia (2020), which records the processing method of vinegar extraction and concentration. The effect of the two processing methods on antler glue's chemical composition and pharmacological activity is unknown. So this study aimed to elucidate the difference between different processing methods on the chemical composition and the treatment effect on oligoasthenospermia of antler glue. MATERIALS AND METHODS: So the automatic amino acid analyzer is used to determine the amino acid content of two different processing methods of antler glue. Proteomics was performed to detect the protein components of two different processing methods of antler glue and analyze them. Cyclophosphamide-induced mice models of oligoasthenospermia were used to study the different pharmacological effects of antler glue in two different processing methods. An automatic sperm analyzer observed the quantity and quality of sperm in mice epididymis. Serum sex hormone testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in mice were tested using the enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin-eosin (H&E) staining was used to analyze pathological alterations in mouse testicular tissue. The transcriptome has been used to reveal the potential mechanism of antler glue in treating oligoasthenospermia. Mitochondrial complex activity assay kits were used to assay the activity of mitochondrial respiratory chain complex I-V in mouse testicular tissue. Western blot was used to determine the expression of related proteins in mouse testicular tissue. RESULTS: Vinegar-processing can increase the alanine, proline, and glycine content in antler glue, reduce the length of protein peptides in antler glue, and produce a variety of unique proteins. Vinegar-processed antler glue (VAG) increased sperm density, sperm survival, sperm viability, and serum sex hormone levels in oligozoospermic mice. It reversed testicular damage caused by cyclophosphamide, and the effects were differently superior to those of water-processed antler glue (WAG). In addition, transcriptomics and related experiments have shown that VAG can increase the expression of Ndufa2, Uqcr11, Cox6b1, and Atp5i genes and proteins in mouse testis, thus promoting adenosine diphosphate (ATP) synthesis by increasing the activity of mitochondrial respiratory chain complexes I, III, IV and V. By promoting the oxidative phosphorylation process to produce more ATP, VAG can achieve the therapeutic effect of oligoasthenospermia. CONCLUSION: Vinegar-processing method can increase the content of active ingredients in antler glue. VAG increases ATP levels in the testes by promoting the process of oxidative phosphorylation to treat oligozoospermia.

Assessment of cytotoxicity, acute, subacute toxicities and antioxidant activities (in vitro) of Sanghuangporus vaninii crude polysaccharide.

ETHNOPHARMACOLOGY RELEVANCE: Sanghuangporus vaninii (S. vaninii), as a traditional large medicinal fungus, has a history of more than 2000 years in Chinese history and has been widely used to treat female diseases such as vaginal discharge, amenorrhea, and uterine bleeding, and recent pharmacological studies have also found that it has antioxidant, anti-inflammatory, and anti-tumor physiological activity, which has received more and more attention. AIM OF THE STUDY: The objective was to evaluate cytotoxicity and the acute, subacute toxicity, and in vitro antioxidant activity of S. vaninii crude polysaccharide (SVP). MATERIALS AND METHODS: The monosaccharide composition of SVP was determined by HPLC (high-performance liquid chromatography). The cytotoxicity of different concentrations of SVP on three types of cells (HT-22, Kupffer macrophages, HEK293) was assessed using CCk-8. The acute toxicity in vivo was evaluated for 14 days after the administration of SVP (2500,5000, or 10,000 mg/mL). For the evaluation of subacute toxicity, mice were daily treated for 28 days with SVP (2500,5000, or 10,000 mg/mL). In addition, DPPH, hydroxyl radical, and superoxide anion radical were used to evaluate the in vitro antioxidant activity of SVP. RESULTS: SVP was not toxic in all three cell lines tested. In vitro antioxidant tests on the extracts showed that SVP possessed a strong antioxidant capacity in vitro. In the acute study, the no-observed-adverse-effect level (NOAEL) in male and female rats was 10，000 mg/kg body weight. There were also no deaths or severe toxicity associated with SVP in subacute studies. However, SVP treatment had a decreasing effect on body weight in mice of both sexes (2500, 5000, and 10000 mg/kg). At doses (5000 and 10,000 mg/kg), SVP had a reduced effect on food intake in both male and female mice. In addition, there were significant effects on organ coefficients of the liver, lung, and kidney. Hematological analysis showed significantly lower LYM (%) values in mice of both sexes, with significantly lower MCH (pg) values obtained in males (5000 mg/kg and 10000 mg/kg) and higher GRAN (%) values in females. In addition, the RDW-SD (fL) values were significantly lower in the male mice given the highest dose. Biochemical tests showed that there were no significant changes in ALT, AST, TP, and Cr levels after SVP treatment. In histopathological analysis, mild liver toxicity was observed in both female mice treated with 10,000 mg/kg SVP. CONCLUSION: The extract of SVP showed a predominance of polysaccharide compounds, with non-toxic action in vivo. Our approach revealed SVP on the chemical composition and suggests a high margin of safety in the popular use of medicinal fungi. In conclusion, our results suggest that SVP is safe, and can be used as health care products and food.

Protective Effect of Baicalin on Chlorpyrifos-Induced Liver Injury and Its Mechanism.

Chlorpyrifos (CPF) plays a vital role in the control of various pests in agriculture and household life, even though some studies have indicated that CPF residues pose a significant risk to human health. Baicalin (BA) is a flavonoid drug with an obvious effect on the prevention and treatment of liver diseases. In this study, the protective effect of BA in vitro and in vivo was investigated by establishing a CPF-induced AML12 cell damage model and a CPF-induced Kunming female mouse liver injury model. The AML12 cell damage model indicated that BA had a good positive regulatory effect on various inflammatory factors, redox indexes, and abnormal apoptosis factors induced by CPF. The liver injury model of female mice in Kunming showed that BA significantly improved the liver function indexes, inflammatory response, and fibrosis of mice. In addition, BA alleviated CPF-induced AML12 cell damage and Kunming female mouse liver injury by enhancing autophagy and regulating apoptosis pathways through Western blotting. Collectively, these data suggest that the potential mechanism of BA is a multi-target and multi-channel treatment for chlorpyrifos-induced liver injury.

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms.

Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.

Ginseng Stem-and-Leaf Saponins Mitigate Chlorpyrifos-Evoked Intestinal Toxicity In Vivo and In Vitro: Oxidative Stress, Inflammatory Response and Apoptosis.

In recent years, the phenomenon of acute poisoning and organ damage caused by organophosphorus pesticides (OPs) has been a frequent occurrence. Chlorpyrifos (CPF) is one of the most widely used organophosphorus pesticides. The main active components of ginseng stems and leaves are total ginseng stem-and-leaf saponins (GSLSs), which have various biological effects, including anti-inflammatory, antioxidant and anti-tumor activities. We speculate that these could have great potential in the treatment of severe diseases and the relief of organophosphorus-pesticide-induced side effects; however, their mechanism of action is still unknown. At present, our work aims to evaluate the effects of GSLSs on the antioxidation of CPF in vivo and in vitro and their potential pharmacological mechanisms. Mice treated with CPF (5 mg/kg) showed severe intestinal mucosal injury, an elevated diamine oxidase (DAO) index, the decreased expression of occlusive protein-1 (ZO-1) and occlusive protein, an impaired intestinal mucosal oxidation system and intestinal villi relaxation. In addition, chlorpyrifos exposure significantly increased the contents of the inflammatory factor TNF-α and the oxidative-stress-related indicators superoxide dismutase (SOD), catalase (CAT), glutathione SH (GSH), glutathione peroxidase (GSH-PX), reactive oxygen species (ROS) and total antioxidant capacity (T-AOC); elevated the level of lipid peroxide malondialdehyde (MDA); reversed the expression of Bax and caspase; and activated NF-κB-related proteins. Interestingly, GSLS supplementation at doses of 100 and 200 mg/kg significantly reversed these changes after treatment. Similar results were observed in cultured RAW264.7 cells. Using flow cytometry, Hoechst staining showed that GSLSs (30 µg/mL, 60 µg/mL) could improve the cell injury and apoptosis caused by CPF and reduce the accumulation of ROS in cells. In conclusion, GSLSs play a protective role against CPF-induced enterotoxicity by inhibiting NF-κB-mediated apoptosis and alleviating oxidative stress and inflammation.

Six-year analysis of key monitoring for bacterial strain distribution and antibiotic sensitivity in a hospital.

BACKGROUND: With the widespread use of antimicrobial drugs, bacterial resistance has become a significant problem, posing a serious threat to public health. The prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical practice. AIM: To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting, thereby guiding effective antibiotic usage by clinicians. METHODS: Specimens from across the institution were collected by the microbiology laboratory. The VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing, and the WHONET5.6 software was utilized for statistical analysis. RESULTS: A total of 12062 bacterial strains of key monitoring significance were detected. Staphylococcus aureus demonstrated widespread resistance to penicillin, but none of the strains were resistant to vancomycin or linezolid. Moreover, 219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were detected. Enterococcus faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin, but its resistance to nitrofurantoin and tetracycline was low. Enterococcus faecium displayed significantly lower resistance to third- and fourth-generation quinolones than Enterococcus faecalis. The resistance of two key monitoring strains, Escherichia coli and Klebsiella pneumoniae, to piperacillin/tazobactam was 5%-8%. However, none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to meropenem. The resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%. Nonetheless, the resistance to tigecycline was low, and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test, maintaining a resistance of < 10% to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 years. The resistance to amikacin remained at 0.2% over the past 3 years. CONCLUSION: Our hospital's overall antibiotic resistance rate was relatively stable from 2017 to 2022. The detection rates of key monitoring strains are reported quarterly and their resistance dynamics are monitored and communicated to the entire hospital, which can guide clinical antibiotic selection.

[Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1ß signaling pathway].

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1ß(IL-1ß). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1ß signaling pathway-mediated microglia p38/IL-1ß inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.

Study on Dihydromyricetin Improving Aflatoxin Induced Liver Injury Based on Network Pharmacology and Molecular Docking.

Aflatoxin B1 (AFB1) is a toxic food/feed contaminant and the liver is its main target organ, thus it poses a great danger to organisms. Dihydromyricetin (DHM), a natural flavonoid compound, can be used as a food additive with high safety and has been shown to have strong hepatoprotective effects. In this experiment, PPI network and KEGG pathway analysis were constructed by network pharmacological analysis technique using software and platforms such as Swiss, String, and David and Cytoscape. We screened AFB1 and DHM cross-targets and pathways of action, followed by molecular docking based on the strength of binding affinity of genes to DHM. In addition, we exposed AFB1 (200 µg/kg) to mice to establish a liver injury model. Histological observation, biochemical assay, oxidative stress indicator assay, TUNEL staining and Western blot were used to evaluate the liver injury. Network pharmacological results were screened to obtain 25 cross-targets of action and 20 pathways of action. It was found that DHM may exert anti-hepatic injury effects by inhibiting the overexpression of Caspase-3 protein and increasing the expression of Bcl-2 protein. DHM (200 mg/kg) was found to reduce AFB1-induced liver indices such as alanine aminotransferase (ALT) and aspartate acyltransferase (AST), and attenuate hepatic histopathological damage through animal models. Importantly, DHM inhibited malondialdehyde (MDA) formation in liver tissue and attenuated AFB1-induced oxidative stress injury by increasing glutathione-S-transferase (GST) glutathione (GPX) catalase (CAT) and superoxide dismutase (SOD). Meanwhile, DHM also restored the expression of anti-apoptotic protein Bcl-2 and antioxidant proteins, Nrf2, Keap1 and its downstream HO-1, and down-regulated the expression of pro-apoptotic proteins Bax and Caspase-3 in AFB1-induced liver tissues. The results confirmed that liver injury caused by AFB1 exposure could be alleviated by DHM, providing valuable guidance for in-depth study of DHM in the treatment of liver-related diseases, and laying the foundation for in-depth development and utilization of DHM.

The P1 protein of wheat yellow mosaic virus exerts RNA silencing suppression activity to facilitate virus infection in wheat plants.

Wheat yellow mosaic virus (WYMV) causes severe wheat viral disease in Asia. However, the viral suppressor of RNA silencing (VSR) encoded by WYMV has not been identified. Here, the P1 protein encoded by WYMV RNA2 was shown to suppress RNA silencing in Nicotiana benthamiana. Mutagenesis assays revealed that the alanine substitution mutant G175A of P1 abolished VSR activity and mutant Y10A VSR activity remained only in younger leaves. P1, but not G175A, interacted with gene silencing-related protein, N. benthamiana calmodulin-like protein (NbCaM), and calmodulin-binding transcription activator 3 (NbCAMTA3), and Y10A interacted with NbCAMTA3 only. Competitive Bimolecular fluorescence complementation and co-immunoprecipitation assays showed that the ability of P1 disturbing the interaction between NbCaM and NbCAMTA3 was stronger than Y10A, Y10A was stronger than G175A. In vitro transcript inoculation of infectious WYMV clones further demonstrated that VSR-defective mutants G175A and Y10A reduced WYMV infection in wheat (Triticum aestivum L.), G175A had a more significant effect on virus accumulation in upper leaves of wheat than Y10A. Moreover, RNA silencing, temperature, and autophagy have significant effects on the accumulation of P1 in N. benthamiana. Taken together, WYMV P1 acts as VSR by interfering with calmodulin-associated antiviral RNAi defense to facilitate virus infection in wheat, which has provided clear insights into the function of P1 in the process of WYMV infection.

Diagnostic performance of GenBody COVID-19 rapid antigen test for laboratory and non-laboratory medical professionals in real practice: A retrospective study.

Point-of-care tests for coronavirus disease 2019 (COVID-19) antigen detection have been widely used for rapid diagnosis in various settings. However, research on the diagnostic performance of the COVID-19 antigen test performed by non-laboratory personnel is limited. In this study, we aimed to elucidate the diagnostic performance of GenBody COVID-19 rapid antigen between laboratory professionals and non-laboratory staff. We retrospectively analyzed the data of patients who underwent both GenBody COVID-19 rapid antigen testing and reverse transcription polymerase chain reaction (RT-PCR) between November 01, 2021, and June 30, 2022. The diagnostic performance of the antigen test was compared between laboratory and non-laboratory operators, using RT-PCR as the gold standard. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy were calculated and sensitivity analysis was performed based on the PCR cycle threshold (Ct) value. Of the 11,963 patients, 1273 (10.6%) tested positive using real-time RT-PCR. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy of the GenBody COVID-19 rapid antigen test with 95% confidence interval were 79.92% (77.26%-82.39%), 99.23% (98.73%-99.57%), 103.25 (62.31-171.11), 0.2 (0.18-0.23), 510.18 (299.81-868.18), 98.11% (96.91%-98.85%), 90.75% (89.64%-91.75%) and 92.76% (91.76%-93.67%), respectively, for non-laboratory staff and 79.80% (74.78%-84.22%), 99.99% (99.94%-100.00%), 6983.92 (983.03-49617.00), 0.2 (0.16-0.25), 34566.45 (4770.30-250474.46) 99.58% (97.09%-99.94%), 99.32% (99.15%-99.46%), and 99.33% (99.13%-99.48%), respectively, for laboratory staff. Notably, when the PCR Ct value exceeded 25, the sensitivity of both the groups decreased to < 40%. The diagnostic performance of GenBody COVID-19 rapid antigen performed by non-laboratory staff was comparable to that of laboratory professionals. However, it should be noted that the sensitivity of the antigen tests decreased when the PCR Ct value exceeded 25. Overall, the GenBody COVID-19 antigen test is a viable option for non-laboratory staff during an epidemic.

Extraction, Purification, and Structural Characterization of Polysaccharides from Sanghuangporus vaninii with Anti-Inflammatory Activity.

In order to obtain homogeneous Sanghuangporus vaninii polysaccharides with antioxidant and anti-inflammatory activities, a response surface method (RSM) was used to compare the polysaccharide extraction rate of hot water extraction and ultrasonic-assisted extraction from Sanghuangporus vaninii. The optimal conditions for ultrasonic-assisted extraction were determined as follows: an extraction temperature of 60 °C, an extraction time of 60 min, a solid-liquid ratio of 40 g/mL, and an ultrasonic power of 70 W. An SVP (Sanghuangporus vaninii polysaccharides) extraction rate of 1.41% was achieved. Five homogeneous monosaccharides were obtained by gradient ethanol precipitation with diethylaminoethyl-cellulose (DEAE) and SephadexG-100 separation and purification. The five polysaccharides were characterized by high performance liquid chromatography, the ultraviolet spectrum, the Fourier transform infrared spectrum, TG (thermogravimetric analysis), the Zeta potential, and SEM (scanning electron microscopy). The five polysaccharides had certain levels of antioxidant activity in vitro. In addition, we the investigated the anti-inflammatory effects of polysaccharides derived from Sanghuangporus vaninii on lipopolysaccharide (LPS)-induced RAW 264.7 cells and Kupffer cells. Further, we found that SVP-60 significantly inhibited the levels of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-induced RAW 264.7 cells and promoted the level of the anti-inflammatory cytokine IL-10 in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our study provides theoretical support for the potential application of Sanghuangporus vaninii in the field of antioxidant and anti-inflammatory activities in vitro.

lncRNA ASBEL and lncRNA Erbb4-IR reduce chemoresistance against gemcitabine and cisplatin in stage IV lung squamous cell carcinoma via the microRNA-21/LZTFL1 axis.

Drug resistance is a major cause of treatment failure and post-treatment disease progression in patients with cancer. This study aimed to investigate the mechanisms of chemoresistance to gemcitabine (GEM) plus cisplatin (cis-diamminedichloroplatinum, DDP) combination therapy in stage IV lung squamous cell carcinoma (LSCC). It also examined the functional role of lncRNA ASBEL and lncRNA Erbb4-IR in the malignant progression of LSCC. The expression of lncRNA ASBEL, lncRNA Erbb4-IR, miR-21, and LZTFL1 mRNA was examined in human stage IV LSCC tissues and adjacent normal tissues, human LSCC cells and normal human bronchial epithelial cells using qRT-PCR. Furthermore, LZTFL1 protein levels were also examined using western blots. Cell proliferation, cell migration and invasion, and cell cycle progression and apoptosis were evaluated in vitro using the CCK-8, transwell, and flow cytometry assays, respectively. Based on the treatment response, LSCC tissues were classified as GEM-, DDP-, and GEM+DDP-sensitive/resistant. The MTT assay was performed to assess the chemoresistance of human LSCC cells to GEM, DDP, and GEM+DDP following transfection experiments. The results showed that lncRNA ASBEL, lncRNA Erbb4-IR, and LZTFL1 were down-regulated in human LSCC tissues and cells, whereas miR-21 was up-regulated. In stage IV human LSCC tissues, miR-21 levels were negatively correlated with those of lncRNA ASBEL, lncRNA Erbb4-IR, and LZTFL1 mRNA. The overexpression of lncRNA ASBEL and lncRNA Erbb4-IR inhibited cell proliferation, migration, and invasion. It also blocked cell cycle entry and accelerated apoptosis. These effects were mediated by the miR-21/LZTFL1 axis and reduced chemoresistance to GEM+DDP combination therapy in stage IV human LSCC. These findings indicate that lncRNA ASBEL and lncRNA Erbb4-IR function as tumor suppressors in stage IV LSCC and attenuate chemoresistance to GEM+DDP combination therapy via the miR-21/LZTFL1 axis. Hence, lncRNA ASBEL, lncRNA Erbb4-IR, and LZTFL1 may be targeted to enhance the efficacy of GEM+DDP combination chemotherapy against LSCC.