Cyclic Peroxides and Analogs: Antibacterial, Antimalarial, and Cytotoxic Marine Products from Xisha Sponge Diacarnus sp.

A chemical investigation of the dichloromethane extract from the Xisha sponge Diacarnus sp. revealed seven undescribed norterpene cyclic peroxides, named diacarperoxides T-Z, and five unreported related norterpenes, named diacarnoids E-I, and eleven previously reported compounds. The structures of these isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, Snatzke's method, [Rh2(OCOCF3)4]-induced ECD spectra, and modified Mosher's method. Bioassays were performed to assess the antibacterial activity against six pathogenic bacteria, cytotoxicities toward three cancer cell lines, and antimalarial activity against Plasmodium parasites. Most of the cyclic peroxides exhibited substantial antibacterial activity (MIC 1-8 µg/mL). Diacarperoxide W and nuapapuin A showed substantial antimalarial activity with IC50 values of 0.98 and 2.83 µM. Moreover, many compounds exhibited <50% cell survival rates, and IC50 values of 0.22-6.33 µM. The apoptosis assay showed that nuapapuin A induced cancer cell apoptosis in a dose-dependent manner.

The potential molecular mechanism underlying gypenoside amelioration of atherosclerosis in ApoE-/- mice: A multi-omics investigation.

Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE-/- mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that "Fatty acid metabolism", "Fatty acid elongation", "Cytokine-cytokine receptor interaction", and "PI3K-Akt signaling pathway", amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.

Overexpressing PagGS1;2 maintains carbon and nitrogen balance under high-ammonium conditions and shows increased tolerance to ammonium toxicity in 84K Poplar.

In plants, the glutamine synthetase - glutamic acid synthetase (GS/GOGAT) cycle plays important roles in nitrogen metabolism, growth, development, and stress resistance. Excess ammonium (NH4+) restricts plant growth, but GS can help to alleviate NH4+ toxicity. In this study, 84K poplar (Populus alba × P. glandulosa) showed reduced biomass accumulation and leaf chlorosis under high-NH4+ stress. These symptoms were less severe in lines overexpressing the gene encoding glutamine synthetase (PagGS1;2-OE), and more severe in lines with inhibition of PagGS1;2 expression (PagGS1;2-RNAi). Compared with the wild type（WT）, the PagGS1;2-OE lines showed significantly increased GS and GOGAT activities and higher contents of free amino acids, soluble protein, total nitrogen, and chlorophyll under high-NH4+ stress. In contrast, the antioxidant capacity and NH4+ assimilation capacity of PagGS1;2-RNAi lines were decreased under high-NH4+ stress. The total carbon (C) content and C/N ratio (C/N) of roots and leaves of PagGS1;2-OE lines were significantly higher than those of WT under high-NH4+ stress. Overexpression of PagGS1;2 led to increased accumulation of various amino acids (3-methylaspartic acid, glutamic acid, proline, serine, and histidine); reduced contents of carbohydrates (fructose, starch, galactose, glucose 1-phosphate, fructose 6-phosphate); and increased contents of sugar alcohols (sedum heptanose, maltose, mannitol, galactose, sorbitol) in the roots under high-NH4+ stress. Under high-NH4+ stress, genes related to amino acid biosynthesis, sucrose and starch degradation, galactose metabolism, and the antioxidant system were significantly up-regulated in the roots of PagGS1;2-OE lines, compared with those of wild type. Thus, PagGS1;2 overexpression affected C metabolism and amino acid metabolism pathways under high-NH4+ stress, which helped to maintain the balance of C and N metabolism and alleviate the symptoms of NH4+ toxicity. Modification of the GS/GOGAT cycle by genetic engineering is a promising strategy to improve NH4+ tolerance of forest trees.

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.

Characterization and mitigation of artifacts derived from NGS library preparation due to structure-specific sequences in the human genome.

BACKGROUND: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. RESULTS: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses. CONCLUSIONS: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Unraveling the Promise of RET Inhibitors in Precision Cancer Therapy by Targeting RET Mutations.

Over the past decades, the role of rearranged during transfection (RET) alterations in tumorigenesis has been firmly established. RET kinase inhibition is an essential therapeutic target in patients with RET-altered cancers. In clinical practice, initial efficacy can be achieved in patients through the utilization of multikinase inhibitors (MKIs) with RET inhibitory activity. However, the effectiveness of these MKIs is impeded by the adverse events associated with off-target effects. Recently, many RET-selective inhibitors, characterized by heightened specificity and potency, have been developed, representing a substantial breakthrough in the field of RET precision oncology. This Perspective focuses on the contemporary understanding of RET mutations, recent advancements in next-generation RET inhibitors, and the challenges associated with resistance to RET inhibitors. It provides valuable insights for the development of next-generation MKIs and selective RET inhibitors.

A comprehensive performance evaluation, comparison, and integration of computational methods for detecting and estimating cross-contamination of human samples in cancer next-generation sequencing analysis.

Cross-sample contamination is one of the major issues in next-generation sequencing (NGS)-based molecular assays. This type of contamination, even at very low levels, can significantly impact the results of an analysis, especially in the detection of somatic alterations in tumor samples. Several contamination identification tools have been developed and implemented as a crucial quality-control step in the routine NGS bioinformatic pipeline. However, no study has been published to comprehensively and systematically investigate, evaluate, and compare these computational methods in the cancer NGS analysis. In this study, we comprehensively investigated nine state-of-the-art computational methods for detecting cross-sample contamination. To explore their application in cancer NGS analysis, we further compared the performance of five representative tools by qualitative and quantitative analyses using in silico and simulated experimental NGS data. The results showed that Conpair achieved the best performance for identifying contamination and predicting the level of contamination in solid tumors NGS analysis. Moreover, based on Conpair, we developed a Python script, Contamination Source Predictor (ConSPr), to identify the source of contamination. We anticipate that this comprehensive survey and the proposed tool for predicting the source of contamination will assist researchers in selecting appropriate cross-contamination detection tools in cancer NGS analysis and inspire the development of computational methods for detecting sample cross-contamination and identifying its source in the future.

Comparison of minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF) with bilateral decompression via unilateral approach and open-TLIF with bilateral decompression for degenerative lumbar diseases: a retrospective cohort study.

OBJECTIVE: Presently, no study has compared the clinical outcomes of minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF) with bilateral decompression via the unilateral approach (BDUA) and Open-TLIF with bilateral decompression for degenerative lumbar diseases (DLD). We aimed to compare the clinical outcomes of through Mis-TLIF combined with BDUA and Open-TLIF with bilateral decompression for the treatment of DLD, and reported the learning curve of the procedure of MIS-TLIF with BDUA. METHODS: We retrospectively analyzed the prospectively collected data of consecutive DLD patients in the two groups from January 2016 to January 2020. RESULTS: The operative time (OT) was significantly longer in the Mis-TLIF group (n = 113) than in the Open-TLIF group (n = 135). The postoperative drainage volume (PDV) and length of stay (LOS) were significantly higher in the Open-TLIF group than in the Mis-TLIF group. Additionally, the complication rate was significantly higher in the Open-TLIF group than in the Mis-TLIF group (14.8% vs. 6.2%, P = 0.030), while there was no significant difference in the reoperation and adjacent segment disease rates between the two groups. There were no significant differences in back pain and leg pain Numerical Rating Scale (NRS) scores and Oswestry Disability Index (ODI) between the two groups preoperatively, at discharge, and 2 years postoperatively. Patients in both groups showed significant improvements in NRS scores and ODI scores after surgery. OT was negatively correlated with the number of surgeries performed (P < 0.001, r = -0.43). The learning curve of Mis-TLIF with BDUA was steep, with OT tapered to steady state in 43 cases. CONCLUSION: Compared with Open-TLIF with bilateral decompression, Mis-TLIF with BDUA can achieve equivalent clinical outcomes, lower PDV and LOS, and lower complication rates. Although this procedure took longer, it could be a viable alternative for the treatment of DLD after a steep learning curve.

Design and synthesis 1H-Pyrrolo[2,3-b]pyridine derivatives as FLT3 inhibitors for the treatment of Acute myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.

The Potential Association of TFR1/SLC11A2/GPX4 with Ferroptosis in Mediating Lipid Metabolism Disorders in Atherosclerosis.

PURPOSE: Atherosclerosis is the most common and significant form of arterial disease, characterized primarily by lipid accumulation and inflammatory cell infiltration as its main pathological basis. This study aims to investigate the molecular mechanisms and associated pathways by which iron accumulation may be involved in lipid metabolism abnormalities in atherosclerotic mice. METHODS: Relying on ApoE-/- mouse body position observation, blood biochemical analysis, oxidative stress test and aortic tissue sectioning techniques, the effects of ferroptosis on lipid metabolism in atherosclerotic mice were analyzed. Use RT-PCR analysis and transcriptomics tests to understand the specific molecular mechanism. RESULTS: Our analysis reveals a correlation between Ferroptosis and elevated levels of TC, TG, ALT, AST, IL-1ß, and TNF-α in the blood of atherosclerotic model mice. At the same time, it exacerbates the pathological changes of mouse aorta tissue. Our results suggest a potential link between ferroptosis and the dysregulation of TFR1/SLC11A2/GPX4 expression, along with the presence of oxidative stress, in the progression of AS. Transcriptomics results indicate that ferroptosis- mediated deterioration of atherosclerosis in ApoE-/- mice is potentially associated with cell phagocytosis, apoptosis involving TNF-α, and the expression of atherosclerotic and other process-related genes. CONCLUSION: Ferroptosis exacerbated the lipid metabolism disorder in atherosclerotic mice. The core mechanism of its effect is that ferroptosis activates the TFR1/SLC11A2/GPX4 signaling pathway, which leads to the up-regulation of oxidative stress in ApoE-/- mice, and ultimately aggravates the abnormal lipid metabolism in ApoE-/- mice.

The sonic hedgehog pathway suppresses oxidative stress and senescence in nucleus pulposus cells to alleviate intervertebral disc degeneration via GPX4.

Disruption of intervertebral disc (IVD) homeostasis caused by oxidative stress and nucleus pulposus cell (NPC) senescence is a main cause of intervertebral disc degeneration (IDD). The sonic hedgehog (Shh) pathway plays an important role in IVD development, but its roles in IDD are unknown. This study aimed to investigate the effects of the Shh pathway on the alleviation of IDD and the related mechanisms. In vivo, the effect of the Shh pathway on IVD homeostasis was studied by intraperitoneal injection of recombinant Shh (rShh) and GANT61 based on puncture-induced IDD. GANT61, lentivirus-coated sh-Gli1 and rShh were used to investigate the role and mechanism of the Shh pathway in NPCs based on senescence induced by Braco19 and oxidative stress induced by TBHP. Shh pathway expression decreased, and senescence and oxidative stress increased with age. Intraperitoneal injection of rShh activated the Shh pathway to suppress oxidative stress and NPC senescence and consequently alleviated needle puncture-induced IDD. In vitro, the Shh pathway upregulated glutathione peroxidase 4 (GPX4) expression to suppress oxidative stress and senescence in NPCs. Moreover, GPX4 suppression in NPCs by si-GPX4 significantly reduced the protective effect of the Shh pathway on oxidative stress and senescence in NPCs. Our results demonstrate for the first time that the Shh pathway plays a key role in the alleviation of IDD by suppressing oxidative stress and cell senescence in NP tissues. This study provides a new potential target for the prevention and reversal of IDD.

Validation of a real-time PCR panel for detection and quantification of nine pathogens commonly associated with canine infectious respiratory disease.

Canine infectious respiratory disease (CIRD) is a complicated respiratory syndrome in dogs [1], [2], [3]. A panel PCR was developed [4] to detect nine pathogens commonly associated with CIRD: Mycoplasma cynos, Mycoplasma canis, Bordetella bronchiseptica; canine adenovirus type 2, canine herpesvirus 1, canine parainfluenza virus, canine distemper virus, canine influenza virus and canine respiratory coronavirus [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. To evaluate diagnostic performance of the assay, 740 nasal swab and lung tissue samples were collected and tested with the new assay, and compared to an older version of the assay detecting the same pathogens except that it does not differentiate the two Mycoplasma species. Results indicated that the new assay had the same level of specificity, but with higher diagnostic sensitivity and had identified additional samples with potential co-infections. To confirm the new assay is detecting the correct pathogens, samples with discrepant results between the two assays were sequence-confirmed. Spiking a high concertation target to samples carrying lower concentrations of other targets was carried out and the results demonstrated that there was no apparent interference among targets in the same PCR reaction. Another spike-in experiment was used to determine detection sensitivity between nasal swab and lung tissue samples, and similar results were obtained.•A nine-pathogen CIRD PCR panel assay had identified 139 positives from 740 clinical samples with 60 co-infections;•High-concentration target does not have apparent effect on detecting low-concentration targets;•Detection sensitivity were similar between nasal swab and lung tissue samples.

Preclinical characterization of danatinib as a novel FLT3 inhibitor with excellent efficacy against resistant acute myeloid leukemia.

The therapeutic benefits of available FLT3 inhibitors for AML are limited by drug resistance, which is related to mutations, as well toxicity caused by off-target effects. In this study, we introduce a new small molecule FLT3 inhibitor called danatinib, which was designed to overcome the limitations of currently approved agents. Danatinib demonstrated greater potency and selectivity, resulting in cytotoxic activity specific to FLT3-ITD and/or FLT3-TKD mutated models. It also showed a superior kinome inhibition profile compared to several currently approved FLT3 inhibitors. In diverse FLT3-TKD models, danatinib exhibited substantially improved activity at clinically relevant doses, outperforming approved FLT3 inhibitors. In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates.

Utility of G protein-coupled oestrogen receptor 1 as a biomarker for pan-cancer diagnosis, prognosis and immune infiltration: a comprehensive bioinformatics analysis.

BACKGROUND: The G protein-coupled oestrogen receptor (GPER) 1 mediates non-genomic oestrogen-related signalling and plays an important role in the regulation of cell growth and programmed cell death through multiple downstream pathways. Despite the increasing interest in the role of GPER1 in cancer development, no pan-cancer analysis has been available for GPER1. METHODS: In this study we performed a comprehensive analysis of the role of GPER1 in pan-cancer via Human Protein Atlas (HPA), The Cancer Genome Atlas (TCGA), University of California, Santa Cruz Xena (UCSC XENA), Genotype-Tissue Expression (GTEx), MethSurv, The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), cBioPortal, STRING and TISIDB detabases, followed by enrichment analysis using R software. RESULTS: GPER1 was widely expressed in tissues and organs and differed in expression from normal tissue in a variety of cancers. In diagnostic assessment, it's Area Under the Curve (AUC) surpassed 0.9 in nine cancer types. Survival analysis showed that GPER1 was correlated with the prognosis of 11 cancer types. Moreover, GPER1 expression was associated with immune infiltration in multiple cancers. CONCLUSIONS: In summary, GPER1 has good diagnostic or prognostic value across various malignancies. Together with its extensive correlation with immune components, the aforementioned results suggests that GPER1 shows promise in tumour diagnosis and prognosis, providing new ideas for precise and personalised anti-tumour strategies.

Metal-Phenolic Networks for Chronic Wounds Therapy.

Chronic wounds are recalcitrant complications of a variety of diseases, with pathologic features including bacterial infection, persistent inflammation, and proliferation of reactive oxygen species (ROS) levels in the wound microenvironment. Currently, the use of antimicrobial drugs, debridement, hyperbaric oxygen therapy, and other methods in clinical for chronic wound treatment is prone to problems such as bacterial resistance, wound expansion, and even exacerbation. In recent years, researchers have proposed many novel materials for the treatment of chronic wounds targeting the disease characteristics, among which metal-phenolic networks (MPNs) are supramolecular network structures that utilize multivalent metal ions and natural polyphenols complexed through ligand bonds. They have a flexible and versatile combination of structural forms and a variety of formations (nanoparticles, coatings, hydrogels, etc.) that can be constructed. Functionally, MPNs combine the chemocatalytic and bactericidal properties of metal ions as well as the anti-inflammatory and antioxidant properties of polyphenol compounds. Together with the excellent properties of rapid synthesis and negligible cytotoxicity, MPNs have attracted researchers' great attention in biomedical fields such as anti-tumor, anti-bacterial, and anti-inflammatory. This paper will focus on the composition of MPNs, the mechanisms of MPNs for the treatment of chronic wounds, and the application of MPNs in novel chronic wound therapies.

Application of quantitative real-time PCR to detect Mink Circovirus in minks, foxes and raccoon dogs in northern China.

Mink circovirus disease caused by Mink Circovirus (MiCV) is a serious infectious disease of mink that has become prevalent in recent years in China, severely affecting the reproductive performance of mink and causing significant economic losses to farms. To date, there have been few studies on MiCV, its pathogenic mechanism is not clear, and there is no effective vaccine or drug to prevent and control the disease. Therefore, it is necessary to establish a rapid and reliable molecular diagnostic method, which would aid future studies of this novel virus. In our study, we developed a sensitive and specific TaqMan-based quantitative real-time PCR assay targeting the MiCV Cap gene. The assay showed no cross-reaction with other tested animal viruses. The assay is highly sensitive, with a detection limit of as low as 10 plasmid DNA copies and 2.38 × 10-2 pg of viral DNA. The intra and inter--assay coefficients of variation were both low. The positive detection rate of MiCV in clinical samples from minks, foxes, and raccoon dogs were 58.8% (133/226), 50.7% (72/142), and 42.2% (54/128), respectively, giving a total positive detection rate of 52.2% (259/496). Higher contamination levels were observed in samples from the environment in direct or indirect contact with animals, with a total positive detection rate of 75.1% (220/293). These epidemiological results showed that minks, foxes, and raccoon dogs had high infection rates of MiCV. This was also the first study to detect MiCV on the ground and equipment of fur-bearing animal farms. Our assay is highly sensitive and specific for the diagnosis and quantification of MiCV, and should provide a reliable real-time tool for epidemiological and pathogenetic study of MiCV infection.

Enhanced recovery after microdiscectomy: reductions in opioid use, length of stay and cost.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are widely used worldwide. Recently, studies of the ERAS program in spinal surgery subspecialties have been reported. The aim of this study was to evaluate the impacts of ERAS in minimally invasive microdiscectomy (MD) surgery. METHODS: This was a retrospective cohort study of patients undergoing MD at a single center. From March 2018 to March 2021, 286 patients were in the ERAS group. A total of 140 patients from March 2017 to February 2018 were in the conventional group. The outcomes included length of stay (LOS), the postoperative numeric rating scale (NRS), complications, 30-day readmission rate, 30-day reoperation rate and cost. Moreover, perioperative factors were also evaluated. RESULTS: Compared with the conventional group, the LOS and cost were reduced in the ERAS group. There were no significant differences in the NRS, complication rate, 30-day readmission or reoperation rates between the groups. Furthermore, postoperative drainage volume, and postoperative opioid use were lower in the ERAS group. CONCLUSIONS: The ERAS protocol for MD surgery reduces LOS, cost and opioid use and accelerates patient recovery.

Natural products as potential lead compounds to develop new antiviral drugs over the past decade.

Virus infection has been one of the main causes of human death since the ancient times. Even though more and more antiviral drugs have been approved in clinic, long-term use can easily lead to the emergence of drug resistance and side effects. Fortunately, there are many kinds of metabolites which were produced by plants, marine organisms and microorganisms in nature with rich structural skeletons, and they are natural treasure house for people to find antiviral active substances. Aiming at many types of viruses that had caused serious harm to human health in recent years, this review summarizes the natural products with antiviral activity that had been reported for the first time in the past ten years, we also sort out the source, chemical structure and safety indicators in order to provide potential lead compounds for the research and development of new antiviral drugs.