Relevance and regulation of alternative splicing in plant secondary metabolism: current understanding and future directions.

The secondary metabolism of plants is an essential life process enabling organisms to navigate various stages of plant development and cope with ever-changing environmental stresses. Secondary metabolites, abundantly found in nature, possess significant medicinal value. Among the regulatory mechanisms governing these metabolic processes, alternative splicing stands out as a widely observed post-transcriptional mechanism present in multicellular organisms. It facilitates the generation of multiple mRNA transcripts from a single gene by selecting different splicing sites. Selective splicing events in plants are widely induced by various signals, including external environmental stress and hormone signals. These events ultimately regulate the secondary metabolic processes and the accumulation of essential secondary metabolites in plants by influencing the synthesis of primary metabolites, hormone metabolism, biomass accumulation, and capillary density. Simultaneously, alternative splicing plays a crucial role in enhancing protein diversity and the abundance of the transcriptome. This paper provides a summary of the factors inducing alternative splicing events in plants and systematically describes the progress in regulating alternative splicing with respect to different secondary metabolites, including terpenoid, phenolic compounds, and nitrogen-containing compounds. Such elucidation offers critical foundational insights for understanding the role of alternative splicing in regulating plant metabolism and presents novel avenues and perspectives for bioengineering.

Identification of novel biomarkers for lupus nephritis.

Lupus nephritis (LN) is an autoimmune disease that rapidly progresses as a secondary consequence of systemic lupus erythematosus (SLE) and has a very poor prognosis. Therefore, this study aimed to identify characteristics of immune cell infiltration and investigate potential therapeutic targets using bioinformatics methods and the Murphy Roths Large/lymphoproliferation (MRL/lpr) mouse model. In this study, a total of 2,810 differentially expressed genes (DEGs) were identified, which were primarily enriched in inflammatory and immune regulation pathways. From these DEGs, 226 immune-related genes (IRGs) were also identified. The single-sample gene set enrichment analysis (ssGSEA) revealed that patients with LN had increased infiltration of effector memory CD4+ T cells, effector memory CD8+ T cells, gamma delta T cells, myeloid-derived suppressor cells (MDSC), follicular helper T cells, Th1 cells, and Th2 cells, and this was closely correlated with the DEG-IRGs. Furthermore, the potential therapeutic biomarkers, CD244, S100 calcium binding protein P (S100P), and vascular endothelial growth factor C (VEGFC), were identified by Random Forest Approach (RFA), which were validated in LN mice. These findings provide new evidence and insights for further research on diagnosis and treatment of LN by identifying critical genes and their associations with immune infiltration.

Cordyceps protein alleviates renal injury by inhibiting T cell infiltration and Th1 cell differentiation in lupus nephritis mice.

BACKGROUND: T cell infiltration and differentiation play a central part in the development of lupus nephritis (LN). Our prior research has indicated that protein, the primary active component of cordyceps (WCP), a traditional Chinese medicine, possesses properties that can enhance renal fibrosis and provide kidney protection. Nonetheless, the connection between WCP and T cell infiltration and differentiation in LN remains poorly understood. OBJECTIVE: The objective of this research was to assess the immunomodulatory impacts of WCP in LN mice and elucidate the underlying mechanism through in vivo and in vitro investigations. METHODS: To investigate the impact and mechanism of WCP in MRL/lpr lupus-prone mice, WCP (1.5 g/kg/d), Bailing capsules (BC, 0.75 g/kg/d), and saline in equivalent quantities were administered to the mice over a period of 8 weeks. The therapeutic effects, T cell infiltration and differentiation of WCP on MRL/lpr mice were verified through ELISA, Hematoxylin-eosin (H&E), Periodic Acid Schiff (PAS) staining, immunofluorescence, Luminex analysis and flow cytometry. The mechanism by which WCP alleviates LN was investigated using tissues of mice, T cells and Mouse Podocyte Clone-5 (MPC-5) cells by transcriptomics, Western blot (WB), and Real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: We found that WCP improved LN in MRL/lpr mice by reducing urinary protein, creatinine, and serum auto antibodies, increasing complement 3 (C3) level, improving renal immunopathology and downregulating serum cytokines, including IFN-γ, IL-12, and RANTES. Notably, the infiltration of CD4+ and CD8+ T cells in the kidney was reduced by WCP. Similarly, the cell transwell co-culturation study showed that the WCP treated MPC-5 cells were weaker in inducing T cell migration. Consistent with this finding, our observations revealed that WCP could inhibit T cell-related chemokine expression in kidney and MPC-5 cells, as well as reduce the levels of TLR4, MYD88, phosphorylated-p38, phosphorylated-ERK, and phosphorylated-JNK. On the other hand, WCP was found to greatly inhibit the Th1 cells differentiation in vivo and in vitro. Cytokine-receptor induced Th1 cell differentiation pathway and PI3K-AKT pathway were the most enriched pathways based on differentially expressed genes (DEGs) enrichment analysis among different cell groups. Results from RT-qPCR and WB showed that WCP notably reduced the levels of IL-12, p-STAT4, IFN-γ, p-STAT1, p-PI3K, and p-AKT in T cells. CONCLUSION: WCP demonstrated positive immunomodulatory effects on LN disease, by decreasing the T cells infiltration through TLR4/MYD88/MAPK signaling pathway and inhibiting Th1 cells differentiation via IL-12-STAT4 and IFN-γ-STAT1 pathways, in addition to the PI3K-AKT pathway.

Advances in biosynthesis and metabolic engineering strategies of cordycepin.

Cordyceps militaris, also called as bei-chong-cao, is an insect-pathogenic fungus from the Ascomycota phylum and the Clavicipitaceae family. It is a valuable filamentous fungus with medicinal and edible properties that has been utilized in traditional Chinese medicine (TCM) and as a nutritious food. Cordycepin is the bioactive compound firstly isolated from C. militaris and has a variety of nutraceutical and health-promoting properties, making it widely employed in nutraceutical and pharmaceutical fields. Due to the low composition and paucity of wild resources, its availability from natural sources is limited. With the elucidation of the cordycepin biosynthetic pathway and the advent of synthetic biology, a green cordycepin biosynthesis in Saccharomyces cerevisiae and Metarhizium robertsii has been developed, indicating a potential sustainable production method of cordycepin. Given that, this review primarily focused on the metabolic engineering and heterologous biosynthesis strategies of cordycepin.

The Cd resistant mechanism of Proteus mirabilis Ch8 through immobilizing and detoxifying.

Cadmium (Cd) pollution is a serious global environmental problem, which requires a global concern and practical solutions. Microbial remediation has received widespread attention owing to advantages, such as environmental friendliness and soil amelioration. However, Cd toxicity also severely deteriorates the remediation performance of functional microorganisms. Analyzing the mechanism of bacterial resistance to Cd stress will be beneficial for the application of Cd remediation. In this study, the bacteria strain, up to 1400 mg/L Cd resistance, was employed and identified as Proteus mirabilis Ch8 (Ch8) through whole genome sequence analyses. The results indicated that the multiple pathways of immobilizing and detoxifying Cd maintained the growth of Ch8 under Cd stress, which also possessed high Cd extracellular adsorption. Firstly, the changes in surface morphology and functional groups of Ch8 cells were observed under different Cd conditions through SEM-EDS and FTIR analyses. Under 100 mg/L Cd, Ch8 cells exhibited aggregation and less flagella; the Cd biosorption of Ch8 was predominately by secreting exopolysaccharides (EPS) and no significant change of functional groups. Under 500 mg/L Cd, Ch8 were present irregular polymers on the cell surface, some cells with wrapping around; the Cd biosorption capacity exhibited outstanding effects (38.80 mg/g), which was mainly immobilizing Cd by secreting and interacting with EPS. Then, Ch8 also significantly enhanced the antioxidant enzyme activity and the antioxidant substance content under different Cd conditions. The activities of SOD and CAT, GSH content of Ch8 under 500 mg/L Cd were significantly increased by 245.47%, 179.52%, and 241.81%, compared to normal condition. Additionally, Ch8 significantly induced the expression of Acr A and Tol C (the resistance-nodulation-division (RND) efflux pump), and some antioxidant genes (SodB, SodC, and Tpx) to reduce Cd damage. In particular, the markedly higher expression levels of SodB under Cd stress. The mechanism of Ch8 lays a foundation for its application in solving soil remediation.

Cordyceps: Alleviating ischemic cardiovascular and cerebrovascular injury - A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps has a long medicinal history as a nourishing herb in traditional Chinese medicine (TCM). Ischemic cardio-cerebrovascular diseases (CCVDs), including cerebral ischemic/reperfusion injury (CI/RI) and myocardial ischemic/reperfusion injury (MI/RI), are major contributors to mortality and disability in humans. Numerous studies have indicated that Cordyceps or its artificial substitutes have significant bioactivity on ischemic CCVDs, however, there is a lack of relevant reviews. AIM OF THE STUDY: This review was conducted to investigate the chemical elements, pharmacological effects, clinical application and drug safety of Cordycepson ischemic CCVDs. MATERIALS AND METHODS: A comprehensive search was conducted on the Web of Science, PubMed, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases using the keywords "Cordyceps", "Cerebral ischemic/reperfusion injury", and "Myocardial ischemic/reperfusion injury" or their synonyms. The retrieved literature was then categorized and summarized. RESULTS: The study findings indicated that Cordyceps and its bioactive components, including adenosine, cordycepin, mannitol, polysaccharide, and protein, have the potential to protect against CI/RI and MI/RI by improving blood perfusion, mitigating damage from reactive oxygen species, suppressing inflammation, preventing cellular apoptosis, and promoting tissue regeneration. Individually, Cordyceps could reduce neuronal excitatory toxicity and blood-brain barrier damage caused by cerebral ischemia. It can also significantly improve cardiac energy metabolism disorders and inhibit calcium overload caused by myocardial ischemia. Additionally, Cordyceps exerts a significant preventive or curative influence on the factors responsible for heart/brain ischemia, including hypertension, thrombosis, atherosclerosis, and arrhythmia. CONCLUSION: This study demonstrates Cordyceps' prospective efficacy and safety in the prevention or treatment of CI/RI and MI/RI, providing novel insights for managing ischemic CCVDs.

Soft interface confined DNA walker for sensitive and specific detection of SARS-CoV-2 variants.

Nucleic acid detection is conducive to preventing the spread of COVID-19 pandemic. In this work, we successfully designed a soft interface confined DNA walker by anchoring hairpin reporter probes on cell membranes for the detection of SARS-CoV-2 variants. In the presence of target RNA, the cyclic self-assembly reaction occurred between hairpin probes H1 and H2, and the continuous walking of target RNA on cell membranes led to the gradual amplification of fluorescence signal. The enrichment of H1 on membranes and the unique fluidity of membranes promoted the collision efficiency between DNA strands in the reaction process, endowing this method with high sensitivity. In addition, the double-blind test of synthetic RNA in 5% normal human serum demonstrated the good stability and anti-interference in complex environment of this method, which exhibited great potential in clinical diagnostics.

Wild Cordyceps proteins reinforce intestinal epithelial barrier through MAPK/NF-κB pathway in MRL/lpr mice.

OBJECTIVES: The effects of wild Cordyceps proteins (WCPs) on the gut microbiota and the immune system of MRL/lpr mice were studied. METHODS: The effects of WCP on serum metabolic indexes (total triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) content was measured by a biochemical analyzer. CD4+, CD8+ cells, intestinal inflammation, and intestinal barrier function in MRL/lpr mice were measured by flow cytometry, 16S ribosomal RNA, western blot, and quantitative real-time polymerase chain reaction RT-PCR. KEY FINDINGS: The results showed that after the intervention of WCP, the content of CD4+ cells in lupus mice increased, and the levels of proinflammatory cytokines were down-regulated, such as tumor necrosis factor-α and interleukin-6. Secondly, WCP up-regulated the proteins and mRNA levels of ZO-1, Claudin-1, and Occludin. Thirdly, it also increased the Firmicutes/Bacteroidetes ratio and the abundance of Oscillospirales, Lachnospirales, Lachnospiraceae, and Clostridia, as well as negatively regulated the MAPK/NF-кB signaling pathway in lupus nephritis (LN) mice. CONCLUSIONS: These findings suggested that WCP may improve the symptoms of LN by altering immune factors and the intestinal barrier.

The Complete Mitochondrial Genome of Paeonia lactiflora Pall. (Saxifragales: Paeoniaceae): Evidence of Gene Transfer from Chloroplast to Mitochondrial Genome.

Paeonia lactiflora (P. lactiflora), a perennial plant renowned for its medicinal roots, provides a unique case for studying the phylogenetic relationships of species based on organelle genomes, as well as the transference of DNA across organelle genomes. In order to investigate this matter, we sequenced and characterized the mitochondrial genome (mitogenome) of P. lactiflora. Similar to the chloroplast genome (cpgenome), the mitogenome of P. lactiflora extends across 181,688 base pairs (bp). Its unique quadripartite structure results from a pair of extensive inverted repeats, each measuring 25,680 bp in length. The annotated mitogenome includes 27 protein-coding genes, 37 tRNAs, 8 rRNAs, and two pseudogenes (rpl5, rpl16). Phylogenetic analysis was performed to identify phylogenetic trees consistent with Paeonia species phylogeny in the APG Ⅳ system. Moreover, a total of 12 MTPT events were identified and 32 RNA editing sites were detected during mitogenome analysis of P. lactiflora. Our research successfully compiled and annotated the mitogenome of P. lactiflora. The study provides valuable insights regarding the taxonomic classification and molecular evolution within the Paeoniaceae family.

Armeniacae semen amarum: a review on its botany, phytochemistry, pharmacology, clinical application, toxicology and pharmacokinetics.

Armeniacae semen amarum-seeds of Prunus armeniaca L. (Rosaceae) (ASA), also known as Kuxingren in Chinese, is a traditional Chinese herbal drug commonly used for lung disease and intestinal disorders. It has long been used to treat coughs and asthma, as well as to lubricate the colon and reduce constipation. ASA refers to the dried ripe seed of diverse species of Rosaceae and contains a variety of phytochemical components, including glycosides, organic acids, amino acids, flavonoids, terpenes, phytosterols, phenylpropanoids, and other components. Extensive data shows that ASA exhibits various pharmacological activities, such as anticancer activity, anti-oxidation, antimicrobial activity, anti-inflammation, protection of cardiovascular, neural, respiratory and digestive systems, antidiabetic effects, and protection of the liver and kidney, and other activities. In clinical practice, ASA can be used as a single drug or in combination with other traditional Chinese medicines, forming ASA-containing formulas, to treat various afflictions. However, it is important to consider the potential adverse reactions and pharmacokinetic properties of ASA during its clinical use. Overall, with various bioactive components, diversified pharmacological actions and potent efficacies, ASA is a promising drug that merits in-depth study on its functional mechanisms to facilitate its clinical application.

Drugs targeting structural and nonstructural proteins of the chikungunya virus: A review.

Chikungunya virus (CHIKV) is a single positive-stranded RNA virus of the Togaviridae family and Alphavirus genus, with a typical lipid bilayer envelope structure, and is the causative agent of human chikungunya fever (CHIKF). The U.S. Food and Drug Administration has recently approved the first chikungunya vaccine, Ixchiq; however, vaccination rates are low, and CHIKF is prevalent owing to its periodic outbreaks. Thus, developing effective anti-CHIKV drugs in clinical settings is imperative. Viral proteins encoded by the CHIKV genome play vital roles in all stages of infection, and developing therapeutic agents that target these CHIKV proteins is an effective strategy to improve CHIKF treatment efficacy and reduce mortality rates. Therefore, in the present review article, we aimed to investigate the basic structure, function, and replication cycle of CHIKV and comprehensively outline the current status and future advancements in anti-CHIKV drug development, specifically targeting nonstructural (ns) proteins, including nsP1, nsP2, nsP3, and nsP4 and structural proteins such as capsid (C), E3, E2, 6K, and E1.

Transcriptome and proteomics conjoint analysis reveal anti-alcoholic liver injury effect of Dianhong Black Tea volatile substances.

Dianhong Black Tea, a fermented tea containing various bioactive ingredients, has been found to have a significant role in alleviating alcoholic liver injury (ALI). One of its main unique components, Dianhong Black Tea volatile substances (DBTVS), may have potential anti-ALI effects. However, its effects and underlying molecular mechanisms are still unknown. In this study, we aimed to investigate the potential of DBTVS as an anti-ALI agent using alcohol-fed rats. We assessed the effect of DBTVS on ALI by analyzing serum transaminase and lipid levels, as well as conducting hematoxylin-eosin and oil red O staining. Additionally, GC-MS was used to detect the components of DBTVS, while transcriptome, proteomics analysis, Western blot, and molecular docking were employed to uncover the underlying mechanisms. Our results demonstrated that DBTVS significantly reduced serum ALT and AST levels and improved lipid metabolism disorders. Moreover, we identified 14 components in DBTVS, with five of them exhibiting strong binding affinity with key proteins. These findings suggested that DBTVS could be a promising agent for the prevention and treatment of ALI. Its potential therapeutic effects may be attributed to its ability to regulate lipid metabolism through the PPAR signaling pathway.

Nomogram for the prediction of tigecycline-induced hypofibrinogenaemia in a Chinese population.

BACKGROUND: Tigecycline has been widely used for multi-drug-resistant bacterial infections in China. Although many studies have reported the risk factors for tigecycline-induced hypofibrinogenaemia, it remains unknown whether valproic acid or voriconazole in combination with tigecycline is associated with the decrease in fibrinogen, as both drugs could lead to coagulation disorders. The aim of this study was to develop a nomogram for the prediction of tigecycline-induced hypofibrinogenaemia. METHODS: This was a multi-centre retrospective case-control study. The primary outcome was the accurate prediction of tigecycline-induced hypofibrinogenaemia. Nomograms were developed from logistic regression models with least absolute shrinkage and selection operator regression for variable selection. Model performance was assessed via calibration plots, and models were validated internally using bootstrapping on a validation cohort. RESULTS: In total, 2362 patients were screened, of which 611 were eligible for inclusion in this study. These 611 patients were divided into the training cohort (n=488) and the validation cohort (n=123). Predictors included in the nomogram for the total population were total dose, age, fibrinogen, prothrombin time (PT), comorbidity, and concomitant use of voriconazole. Total dose, fibrinogen, PT, activated partial thromboplastin time, white blood cell count, and concomitant use of voriconazole were selected to predict hypofibrinogenaemia in patients with malignant haematologic diseases. Both models were calibrated adequately, and their predictions were correlated with the observed outcome. The cut-offs for treatment duration in the total population and the subgroup were 10 and 6 days, respectively. CONCLUSIONS: Tigecycline in combination with voriconazole could increase the risk of hypofibrinogenaemia, and tigecycline-induced hypofibrinogenaemia is more likely to occur in patients with malignant haematologic diseases.

Rapid AMR prediction in Pseudomonas aeruginosa combining MALDI-TOF MS with DNN model.

BACKGROUND: Pseudomonas aeruginosa is a significant clinical pathogen that poses a substantial threat due to its extensive drug resistance. The rapid and precise identification of this resistance is crucial for effective clinical treatment. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used for antibiotic susceptibility differentiation of some bacteria in recent years, the genetic diversity of P. aeruginosa complicates population analysis. Rapid identification of antimicrobial resistance (AMR) in P. aeruginosa based on a large amount of MALDI-TOF-MS data has not yet been reported. In this study, we employed publicly available datasets for P. aeruginosa, which contain data on bacterial resistance and MALDI-TOF-MS spectra. We introduced a deep neural network model, synergized with a strategic sampling approach (SMOTEENN) to construct a predictive framework for AMR of three widely used antibiotics. RESULTS: The framework achieved area under the curve values of 90%, 85%, and 77% for Tobramycin, Cefepime, and Meropenem, respectively, surpassing conventional classifiers. Notably, random forest algorithm was used to assess the significance of features and post-hoc analysis was conducted on the top 10 features using Cohen's d. This analysis revealed moderate effect sizes (d = 0.5-0.8) in Tobramycin and Cefepime models. Finally, putative AMR biomarkers were identified in this study. CONCLUSIONS: This work presented an AMR prediction tool specifically designed for P. aeruginosa, which offers a hopeful pathway for clinical decision-making.

Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation.

Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.

Determination of ochratoxin A in licorice extract based on modified immunoaffinity column clean-up and HPLC analysis.

Contamination of ochratoxin A (OTA) is a common concern for the quality and safety of licorice and its derivatives, while their complex sample matrices always restrict the monitoring and regulation of OTA. Taking the much more concentrated and complicated licorice extract as the representative, a modified analysis method was established for OTA by HPLC. Parameters were comprehensively investigated based on liquid-liquid extraction and immunoaffinity column clean-up. In comparison to other methods, the developed method achieved effective clean-up efficiency and selectivity without tedious procedures and specialized instrumentation. Good linearity (R2 ≥0.9995), low LOD/LOQ (0.10 µg/kg/0.33 µg/kg), and satisfactory recovery (90.0%-96.4%, RSDs <7.0%) indicated the satisfactory sensitivity and reliability of the method. In addition, the applicability and robustness of the method was demonstrated by the analysis of large numbers of licorice extract samples. It is noteworthy that 66.5% of 176 samples were contaminated with OTA, while the concentrations of 9.1% of samples exceeded the maximum limit (ML, 80 µg/kg) defined by the EU. On account of the high contamination frequency and broad concentration range of OTA, the daily intake limit of licorice extract was preliminarily determined to be 123.18-123.93 g/day (chronic exposure) and 24.24 g/day (acute exposure), indicating a potential of acute risk through daily exposure. This calls for improved supervision and regulation for OTA contamination in licorice samples. This study suggests a prospective option for the efficient determination and routine monitoring of OTA in licorice and its derivatives, simultaneously providing a valuable data base for its health risk assessment.

Risk Factors for Cefoperazone/Sulbactam-Induced Coagulation Disorder.

Purpose: Cefoperazone/sulbactam is a ß-lactam/ß-lactamase inhibitor combination effective against intra-abdominal, urinary tract, and respiratory infections. Although some studies have suggested that cefoperazone/sulbactam is associated with coagulation disorders, it remains debatable whether the combination of cefoperazone/sulbactam with tigecycline or valproic acid increases the risk of bleeding, as both drugs can lead to coagulation disorders. This study aimed to explore the risk factors of cefoperazone/sulbactam-induced coagulopathy. Patients and Methods: This was a single-center, retrospective, nested case-control study. The sample groups were derived from individuals registered at the Department of Neurosurgery, Shanxi Provincial People's Hospital. Propensity score matching (PSM) was used to adjust for demographic data. Conditional logistic regression was used to estimate the matched odds ratios representing the odds of cefoperazone/sulbactam-induced coagulopathy (CIC), and a receiver operating characteristic curve was used to determine the optimal cut-off conditions. Results: After PSM, 155 and 56 patients were included in the control and case groups, respectively. Multivariate analysis revealed that advanced age, treatment duration, and total dose were independent risk factors of cefoperazone/sulbactam-induced coagulation disorders. Concomitant use of vitamin K was an independent protective factor against CIC. The optimal cut-off for the length of treatment was 5 d, and the cut-off for the total dose was 48 g. Conclusion: Tigecycline and valproic acid were not associated with CIC. Advanced age and long treatment duration are risk factors for CIC. Supplementation with vitamin K during cefoperazone/sulbactam treatment was associated with a reduced risk.

FBXW7 in breast cancer: mechanism of action and therapeutic potential.

Breast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin-proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.

Intra-abdominal infection after tumor surgery: tigecycline combined with ß-lactam antibiotics versus tigecycline alone.

BACKGROUNDS: Tigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus ß-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery. METHODS: This was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student's t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication. RESULTS: In total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time. CONCLUSIONS: Tigecycline plus ß-lactam wasn't superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.

Polysaccharides from natural resource: ameliorate type 2 diabetes mellitus via regulation of oxidative stress network.

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia that can occur in children, adults, elderly people, and pregnant women. Oxidative stress is a significant adverse factor in the pathogenesis of DM, especially type 2 diabetes mellitus (T2DM), and metabolic syndrome. Natural polysaccharides are macromolecular compounds widely distributed in nature. Some polysaccharides derived from edible plants and microorganisms were reported as early as 10 years ago. However, the structural characterization of polysaccharides and their therapeutic mechanisms in diabetes are relatively shallow, limiting the application of polysaccharides. With further research, more natural polysaccharides have been reported to have antioxidant activity and therapeutic effects in diabetes, including plant polysaccharides, microbial polysaccharides, and polysaccharides from marine organisms and animals. Therefore, this paper summarizes the natural polysaccharides that have therapeutic potential for diabetes in the past 5 years, elucidating their pharmacological mechanisms and identified primary structures. It is expected to provide some reference for the application of polysaccharides, and provide a valuable resource for the development of new diabetic drugs.