Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. METHOD: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. RESULTS: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. CONCLUSION: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Faecalibacterium taiwanense sp. nov., isolated from human faeces.

Two Gram-stain-negative, straight rods, non-motile, asporogenous, catalase-negative and obligately anaerobic butyrate-producing strains, HLW78T and CYL33, were isolated from faecal samples of two healthy Taiwanese adults. Phylogenetic analyses of 16S rRNA and DNA mismatch repair protein MutL (mutL) gene sequences revealed that these two novel strains belonged to the genus Faecalibacterium. On the basis of 16S rRNA and mutL gene sequence similarities, the type strains Faecalibacterium butyricigenerans AF52-21T(98.3-98.1 % and 79.0-79.5 % similarity), Faecalibacterium duncaniae A2-165T(97.8-97.9 % and 70.9-80.1 %), Faecalibacterium hattorii APC922/41-1T(97.1-97.3 % and 80.3-80.5 %), Faecalibacterium longum CM04-06T(97.8-98.0% and 78.3 %) and Faecalibacterium prausnitzii ATCC 27768T(97.3-97.4 % and 82.7-82.9 %) were the closest neighbours to the novel strains HLW78T and CYL33. Strains HLW78T and CYL33 had 99.4 % both the 16S rRNA and mutL gene sequence similarities, 97.9 % average nucleotide identity (ANI), 96.3 % average amino acid identity (AAI), and 80.5 % digital DNA-DNA hybridization (dDDH) values, indicating that these two strains are members of the same species. Phylogenomic tree analysis indicated that strains HLW78T and CYL33 formed an independent robust cluster together with F. prausnitzii ATCC 27768T. The ANI, AAI and dDDH values between strain HLW78T and its closest neighbours were below the species delineation thresholds of 77.6-85.1 %, 71.4-85.2 % and 28.3-30.9 %, respectively. The two novel strains could be differentiated from the type strains of their closest Faecalibacterium species based on their cellular fatty acid compositions, which contained C18 : 1 ω7c and lacked C15 : 0 and C17 : 1 ω6c, respectively. Phenotypic, chemotaxonomic and genotypic test results demonstrated that the two novel strains HLW78T and CYL33 represented a single, novel species within the genus Faecalibacterium, for which the name Faecalibacterium taiwanense sp. nov. is proposed. The type strain is HLW78T (=BCRC 81397T=NBRC 116372T).

Blocking Gremlin1 inhibits M1 macrophage polarization through Notch1/Hes1 signaling pathway in apical periodontitis.

BACKGROUND: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment. METHODS: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western-blot, immunofluorescence staining were performed. RESULTS: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results. CONCLUSION: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.

[Ethical Reflections on Preimplantation Genetic Diagnoses].

With fertility rates at an all-time low, children have become even more the 'treasures' of their families. Progress in genetic selection technology has made preimplantation genetic diagnosis an increasingly common practice in clinics. However, the practice of purposively selecting genes for future children remains controversial. In this article, the process of preimplantation genetic diagnosis is introduced and related philosophical and social perspectives are reviewed. Finally, the ethics related to this practice are discussed in the contexts of obligation theory, utility theory, and four ethical principles. The authors hope this article sheds light on the diverse perspectives used to consider and discuss the ethical issues surrounding gene selection and, importantly, helps nurses provide care grounded in ethics and humanity in ethically uncertain circumstances.

[Mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in treating cardiovascular diseases with syndrome of combined phlegm and stasis based on serum metabolomics].

This study aimed at investigating the mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus(GX) in treating cardiovascular diseases in rats with the syndrome of combined phlegm and stasis. The rat model was established by a high-fat diet, ice-water bath combined with subcutaneous injection of adrenalin hydrochloride, and the syndrome score was determined. The serum samples of rats in the control, model, and GX groups were collected. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to analyze the metabolic profiles of the serum samples. The differential metabolites were screened and identified by partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). The intervention targets of GX-regulated metabolites and their metabolic pathways were searched against MetaboAnalyst. Gene Ontology enrichment was carried out to predict the biological pathways associated with the intervention targets of metabolic pathways. A total of 129 potential biomarkers were detected in the rat model with the syndrome of combined phlegm and stasis via metabolomics, and GX regulated 54 metabolites in several metabolic pathways such as linoleic acid metabolism, sphingolipid metabolism, and tricarboxylic acid cycle. The further screening against MetaboAnalyst showed that GX recovered the levels of nine metabolites associated with cardiovascular diseases with the syndrome of combined phlegm and stasis, which involved 69 targets in the pathways regarding cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism. The above-mentioned results suggested that GX can alleviate the symptoms of the rat model of cardiovascular diseases with the syndrome of combined phlegm and stasis by regulating the metabolism of linoleic acid, sphingosine, docosahexaenoic acid, rosemary acid, succinic acid, adenine, L-phenylalanine, L-valine and modulating the biological pathways such as cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism.

[Mechanism of Huangqin Qingre Chubi Capsules in improving rheumatoid arthritis based on METTL3-SFRP4/Wnt/ß-catenin pathway].

The effect and mechanism of Huangqin Qingre Chubi Capsules(HQC) on rheumatoid arthritis(RA) were studied.Seventy male SPF rats were randomly divided into normal group, model group, low-(0. 18 g·kg~(-1)), middle-(0. 36 g·kg~(-1)), and high-(0. 72 g·kg~(-1)) dose groups of HQC, methotrexate group(MTX, 0. 75 mg·kg~(-1)), and negative control group(NC group, model +saline). Adjuvant arthritis fibroblast-like synoviocytes(AA-FLS) were divided into normal group, model group, low-, middle-, and high-dose groups of HQC, and negative control group. RT-qPCR and Western blot were used to detect the m RNA and protein expressions of METTL3, SFRP4, ß-catenin, CCND1, c-Myc, MMP3, and fibronectin. The protein expression of MMP3 and ß-catenin was detected by immunofluorescence. The gene expression level of METTL3 on AA-FLS was knocked down to further examine the expression of each gene. ELISA measured the levels of IL-1ß, IL-6, and IL-8. The results showed that compared with the normal group, rats in the model group found redness and swelling in their limbs and significantly increased joint swelling. Compared with the model group, the joint swelling degree of each treatment group significantly decreased(P<0. 05). The paw retraction threshold and body weight mass index both significantly increased(P<0. 05). METTL3 was highly expressed on AA and negatively correlated with the expression of SFRP4. After treatment, the m RNA and protein expression of METTL3, ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 were significantly decreased on AA-FLS(P< 0. 05). Compared with the model group, knocking down METTL3 resulted in reduced m RNA and protein expression of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3(P< 0. 05). At the same time, the m RNA and protein expressions of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 in the HQC+METTL3 knockdown group were significantly lower than those in the METTL3 knockdown group(P<0. 05). HQC could reduce the levels of IL-1ß, IL-6, and IL-8 to varying degrees(P<0. 05). The results indicate that HQC has a significant improvement effect on arthritis in AA rats. The expression of METTL3 is significantly increased in synovial tissue and AA-FLS of AA rats, which may be a potential target for the diagnosis and treatment of RA. HQC improves RA through the METTL3-SFRP4/Wnt/ß-catenin signaling pathway and has significant antiinflammatory and anti-rheumatic effects.

Progresses on genetic susceptibility of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). Genetic factors might influence susceptibility to the SARS-CoV-2 infection or disease severity. Genome-wide association studies (GWASs) have identified multiple susceptible genes related to COVID-19 phenotypes, providing the scientific basis for the COVID-19 prevention and treatment. In this review, we summarize the recent progresses of COVID-19 susceptible genes, including the GWASs on multiple phenotypes of COVID-19, GWASs of COVID-19 in multiple ethnic populations, GWASs of COVID-19 based on multiple types of genetic variations, and the fine-mapping of the regions surrounding the susceptible genes.

Multiple Eruptive Dermatofibroma: A Case Report.

Background: Multiple eruptive dermatofibroma (MEDF) is a rare presentation of dermatofibroma which is frequently associated with underlying diseases such as human immunodeficiency virus infection or systemic lupus erythematosus. It generally presents a characteristic histology with hyperplasia of the epidermis, prominent bundles of collagen and a diffuse proliferation of fibrocytes. Case Summary: We report a case of MEDF in a 30-year-old man who presented with a large number of dark brownish red maculopapules distributed over the trunk and extremities for more than 10 years. According to the pathology, the patient was diagnosed with MEDF. Infections and autoimmune diseases were ruled out. As he had no clinical symptoms, and presented with lesions widely distributed over the body, we gave no special treatment, but suggested a regular examination. Conclusion: Patients with MEDF usually have no pain and pruritus. If human immunodeficiency virus infection and systemic lupus erythematosus and other causes are ruled out, and lesions are widely distributed over the body, regular check-up is recommended without specific treatment.

Efficacy of the spirit-regulation method of Jin's three-needle therapy for post-stroke anxiety and its effect on the hypothalamus-pituitary-adrenal axis. / 靳三针调神针法治疗卒中后焦虑的疗效观察及对下丘脑-垂体-è‚¾ä¸Šè ºè½´çš„å½±å“.

OBJECTIVES: To observe the clinical efficacy of the spirit-regulation method of Jin's three-needle therapy on post-stroke anxiety and its effects on the hypothalamus-pituitary-adrenal (HPA) axis. METHODS: Fifty-four patients with post-stroke anxiety were divided into spirit regulation (Jin's three needle therapy) group and sham-acupuncture group according to the random number table method, 28 cases in the spirit regulation and 26 cases in the sham-acupuncture group. The patients of the two groups received the same regimen of basic medication and rehabilitation, and the same acupoint prescription was adopted, including Sishenzhen (extra points, 1.5 cun to Baihui ［GV20］ at 3, 6, 9 and 12 o'clock positions), Shenting (GV24), Yintang (EX-HN3), and bilateral Shenmen (HT7), Sanyinjiao (SP6), Hegu (LI4) and Taichong (LR3). The true acupuncture was delivered in the spirit regulation group and the sham acupuncture operated in the sham-acupuncture group. One treatment lasted for 30 min, once daily, 5 times a week. The duration of treatment was 3 weeks in the trial. Before treatment and on day 10 and day 21 of treatment, the changes in the score of Hamilton anxiety scale (HAMA) and that of National Institutes of Health Stroke Scale (NIHSS) were compared between the two groups separately. Using ELISA, the contents of adrenocorticotropin (ACTH) and cortisol (CORT) in the serum were detected, and the adverse reactions were recorded. RESULTS: In the within-group comparison before and after treatment, HAMA score and NIHSS score dropped on day 10 and day 21 after treatment in the spirit regulation group (P<0.05)；HAMA score and NIHSS score in the sham-acupuncture group were decreased on day 21 of treatment (P<0.05). After 21 days of treatment, HAMA score and NIHSS score in the spirit-regulation group were decreased significantly than those in the sham-acupuncture group (P<0.05) and the contents of ACTH and CORT in the serum decreased when compared with those before treatment and those of the sham-operation group (P<0.05). No obvious adverse events occurred in the spirit-regulation group and the sham-acupuncture group. CONCLUSIONS: Using sham acupuncture as a control, it is preliminarily confirmed that the spirit regulation method of Jin's three-needle therapy is effective on post-stroke anxiety. In association of the downtrend of serological indicators, it is speculated that the underlying mechanism of this therapy is related to HPA axis.

Serum activin A as a prognostic biomarker for community acquired pneumonia.

BACKGROUND: It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia (CAP) predictors. AIM: To evaluate the association between serum activin A levels and prognosis in CAP patients. METHODS: A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition, and 48 healthy individuals as the control group were enrolled in this study. Circulating concentrations of activin A were measured using enzyme-linked immunoassays. The interaction between activin A levels and etiologies of CAP was determined. Based on the severity of CAP, 110 patients (65.48%) were categorized into group-I, 42 (25%) cases were grouped into group-II, and 16 (9.52%) cases were categorized into group-III. RESULTS: Serum activin A levels were higher in patients with CAP than controls, but independent of etiology. Moreover, the scores of Pneumonia Severity Index (PSI) and CURB-65 positively correlated with the increasing levels of serum activin A, and were at their highest peak in individuals in group-III (P < 0.001). Combining activin A with CURB-65 or PSI was more effective in improving predictive property (P < 0.01). According to Cox proportional regression analysis, after adjusting clinical parameters, we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients (P < 0.001). CONCLUSION: Higher level of serum activin A was associated with poor prognosis of CAP. Activin A can be used as a more valuable biomarker of prognosis in CAP patients.

Identification of key sensory and chemical factors determining flavor quality of Xinyu mandarin during ripening and storage.

Xinyu mandarin is popular for its good flavor, but its flavor deteriorates during postharvest storage. To better understand the underlying basis of this change, the dynamics of the sensory profiles were investigated throughout fruit ripening and storage. Sweetness and sourness, determined especially by sucrose and citric acid content, were identified as the key sensory factors in flavor establishment during ripening, but not in flavor deterioration during storage. Postharvest flavor deterioration is mainly attributed to the reduction of retronasal aroma and the development of off-flavor. Furthermore, sugars, acids and volatile compounds were analyzed. Among the 101 detected volatile compounds, 10 changed significantly during the ripening process. The concentrations of 15 volatile components decreased during late postharvest storage, among which α-pinene and d-limonene were likely to play key roles in the reduction of aroma. Three volatile compounds were found to increase during storage, associated with off-flavor development.

Endoscopic retrograde cholangiopancreatography using a pediatric colonoscope in patients with Roux­en­Y gastrectomy and an intact major duodenal papilla.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastrectomy and an intact major duodenal papilla is challenging and difficult, with unsatisfactory outcomes using various endoscopes. Limited data are available regarding the outcomes of ERCP using a pediatric colonoscope in such patients. To evaluate the efficacy of a pediatric colonoscope in patients with Roux-en-Y gastrectomy and an major duodenal intact papilla, 93 consecutive patients with Roux-en-Y gastrectomy and an intact major duodenal papilla who underwent ERCP using a pediatric colonoscope at the Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, (Nanjing, China) between January 2018 and December 2022 were retrospectively reviewed. Following the failure of bile duct cannulation, a double-guidewire or precut technique was utilized for advanced cannulation. Interventions were performed using standard ERCP therapeutic accessories. The results indicated that distal gastrectomy with Roux-en-Y reconstruction was performed in 38 out of 93 patients, while 55 patients underwent total gastrectomy with Roux-en-Y reconstruction. The success rates associated with endoscope insertion, endoscopic cannulation and therapeutic ERCP were 88.17% (82/93), 85.37% (70/82) and 95.71% (67/70), respectively, while the clinical intervention success and complication rates were 72.04% (67/93) and 7.53% (7/93), respectively. The endoscope insertion time was 40.78±10.04 min, and the ERCP procedure time was 88.55±16.38 min. Student's t-test showed that the endoscope insertion time and the ERCP procedure time in patients undergoing distal gastrectomy were longer than those in patients undergoing total gastrectomy (P<0.05). Binary logistic regression analysis showed that age and number of previous abdominal surgeries were independent risk factors associated with endoscope insertion failure. In conclusion, the present study demonstrated that the use of a pediatric colonoscope is efficacious and safe for patients with Roux-en-Y gastrectomy and an intact major duodenal papilla undergoing ERCP.

Clinical efficacy of rhGM-CSF gel and medical collagen sponge on deep second-degree burns of infants: A randomized clinical trial.

BACKGROUND: This study aimed to observe clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel, medical collagen sponge and rhGM-CSF gel in combination with medical collagen sponge on deep second-degree burns of head, face or neck in infants. METHODS: A total of 108 infants with deep second-degree burns on head, face or neck were randomly divided into rhGM-CSF group, medical collagen sponge group, and rhGM-CSF + medical collagen sponge group. The scab dissolving time, healing time, bacterial positive rate and Vancouver scar scale were evaluated and analyzed. RESULTS: The data analysis showed that scab dissolving time and healing time were shorter in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group, and the difference was statistically significant (P < .05). Bacterial positive rate was lower in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). After 3 months, score of Vancouver scar scale (scar thickness, pliability, pigmentation and vascularity) was less in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). CONCLUSION: rhGM-CSF gel in combination with medical collagen sponge is significantly effective in treating deep second-degree burns of head, face or neck in infants. This combination is beneficial for infection control, acceleration of scab dissolving and wound healing, and reduction of scar hyperplasia and pigmentation, which is worthy of clinical application and promotion.

Development and validation of a clinical prediction model for early ventilator weaning in post-cardiac surgery.

Background: Weaning patients from mechanical ventilation is a critical clinical challenge post cardiac surgery. The effective liberation of patients from the ventilator significantly improves their recovery and survival rates. This study aimed to develop and validate a clinical prediction model to evaluate the likelihood of successful extubation in post-cardiac surgery patients. Method: A predictive nomogram was constructed for extubation success in individual patients, and receiver operating characteristic (ROC) and calibration curves were generated to assess its predictive capability. The superior performance of the model was confirmed using Delong's test in the ROC analysis. A decision curve analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. Results: Among 270 adults included in our study, 107 (28.84%) experienced delayed extubation. A predictive nomogram system was derived based on five identified risk factors, including the proportion of male patients, EuroSCORE II, operation time, pump time, bleeding during operation, and brain natriuretic peptide (BNP) level. Based on the predictive system, five independent predictors were used to construct a full nomogram. The area under the curve values of the nomogram were 0.880 and 0.753 for the training and validation cohorts, respectively. The DCA and clinical impact curves showed good clinical utility of this model. Conclusion: Delayed extubation and weaning failure, common and potentially hazardous complications following cardiac surgery, vary in timing based on factors such as sex, EuroSCORE II, pump duration, bleeding, and postoperative BNP reduction. The nomogram developed and validated in this study can accurately predict when extubation should occur in these patients. This tool is vital for assessing risks on an individual basis and making well-informed clinical decisions.

Application of neutrophil-to-lymphocyte-to-monocyte ratio in predicting mortality risk in adult patients with septic shock: A retrospective cohort study conducted at a single center.

Background: Sepsis is a life-threatening condition characterized by an aberrant host response to infection, resulting in multi-organ dysfunction. The application of currently available prognostic indicators for sepsis in primary hospitals is challenging. In this retrospective study, we established a novel index, the neutrophil-to-lymphocyte-to-monocyte ratio (NLMR), based on routine blood examination upon admission, and assessed its prognostic value for early mortality risk in adult patients with septic shock. Methods: This study included clinical data from adult patients with septic shock who were admitted to the hospital between January 1, 2018, and December 31, 2022. Training and validation sets were constructed, and patients were categorized into "survival" and "death" groups based on their survival status within the 28-day hospitalization period. Baseline data, including demographic characteristics and comorbidities, and laboratory results, such as complete blood count parameters, were collected for analysis. The Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were documented.The NLMR was determined through the utilization of multivariate binary logistic regression analysis, leading to the development of a risk model aimed at predicting early mortality in adult patients suffering from septic shock. Results: Overall, 112 adult patients with septic shock were enrolled in this study, with 84 and 28 patients in the training and validation sets, respectively. Multivariate binary logistic analysis revealed that the neutrophil, lymphocyte, and monocyte counts independently contributed to the mortality risk (odds ratios = 1.22, 0.08, and 0.16, respectively). The NLMR demonstrated an area under the receiver operating characteristic curve (ROC-AUC) of 0.83 for internal validation in the training set and 0.97 for external validation in the validation set. Both overall model quality values were significantly high at 0.74 and 0.91, respectively (P < 0.05). NLMR exhibited a higher ROC-AUC value of 0.88 than quick SOFA (ROC-AUC = 0.71), SOFA (ROC-AUC = 0.83), and APACHE II (ROC-AUC = 0.78). Conclusion: NLMR may be a potential marker for predicting the risk of early death in adult patients with septic shock, warranting further exploration and verification.

Staphylococcus hsinchuensis sp. nov., Isolated from Soymilk.

A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were <95% and <70%, respectively. The H164T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).

Inhibition of colon C5a/C5a receptor signalling pathway confers protection against LPS-induced acute kidney injury via gut microbiota-kidney axis.

Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway. Additionally, C5a receptor blockade resulted in the inhibition of colonic inflammation and the reconstruction of the intestinal mucosal barrier. Furthermore, W54011 administration significantly impacted the composition and stability of the gut microbiota, restoring the abundance of dominant bacteria to levels observed in the normal state of the intestinal flora and reducing the abundance of potentially harmful bacterial groups. In conclusion, W54011 alleviates LPS-induced AKI by modulating the interplay between the colon, gut microbiota, and kidneys. It preserves the integrity of the intestinal barrier and reinstates gut microbiota, thereby mitigating AKI symptoms. These findings suggest that targeting the colon and gut microbiota could be a promising therapeutic strategy for AKI treatment.

BRAFV600E/ p-ERK/ p-DRP1(Ser616) Promotes Tumor Progression and Reprogramming of Glucose Metabolism in Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid cancer (PTC) with the BRAFV600E mutation is associated with a poorer prognosis. BRAF inhibitors may demonstrate limited efficacy due to emerging drug resistance. The Warburg effect may have cancer therapeutic implications. It is not known if the BRAFV600E mutation is associated with altered glucose metabolism in PTC. METHODS: This study examined the effect of the BRAFV600E and DRP1 on various cellular processes in PTC cells, including: cell proliferation, migration, invasion, mitochondrial fission, glucose metabolism, reactive oxygen species (ROS) generation and apoptosis. We used RT-qPCR to assess the expression of key glycolytic enzymes in thyroid cancer tissues. Additionally, the regulatory interaction between BRAFV600E and DRP1 was investigated through Western Blot and immunohistochemical staining. We further evaluated the impact of DRP1 in PTC and inhibitory effects of Dabrafenib and 2-DG in vitro and in vivo. RESULTS: We found that the BRAFV600E mutation significantly augments aerobic glycolysis while suppressing oxidative phosphorylation in PTC. We identified the BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway as a critical mediator in PTC progression. The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway enhances cell proliferation by upregulating HK2 expression and thereby increasing aerobic glycolysis. Secondly, it inhibits apoptosis by promoting mitochondrial fission and reducing ROS levels. Moreover, we demonstrated that the combination therapy of 2-DG and Dabrafenib markedly impedes the progression of BRAFV600E-positive PTC. CONCLUSION: The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway plays a pivotal role in glucose metabolism reprogramming, contributing to the aggressiveness and progression of BRAFV600E-positive PTC. Our findings suggest that a combined therapeutic approach using 2-DG and Dabrafenib has potential to improve the outcome of PTC patients with BRAFV600E.

Sesquiterpenoid derivatives isolated from a liquid culture of Hypholoma capnoides 819.

Nine previously undescribed sesquiterpenoids, named as capnoidones A-G (1-6 and 8) and capnoidols A and B (7 and 9), along with three known sesquiterpenoids, fascicularones A, B, and G (12, 11 and 10), were isolated from the fermentation products of the mushroom Hypholoma capnoides 819 (Strophariace). The structures of these compounds were determined through MS and NMR experiments along with electronic circular dichroism analysis. Optical rotation calculations and X-ray diffraction experiments were also conducted for confirmation of the structures. Compounds 1 and 4 displayed mild cytotoxicity towards BV2 microglial cells in mice, while compound 4 exhibited mild cytotoxicity against breast cancer MCF-7 cells. However, none of the compounds demonstrated antibacterial activity against Staphylococcus aureus or Escherichia coli.

Regulation of primary cilia disassembly through HUWE1-mediated TTBK2 degradation plays a crucial role in cerebellar development and medulloblastoma growth.

Development of the cerebellum requires precise regulation of granule neuron progenitor (GNP) proliferation. Although it is known that primary cilia are necessary to support GNP proliferation, the exact molecular mechanism governing primary cilia dynamics within GNPs remains elusive. Here, we establish the pivotal roles for the centrosomal kinase TTBK2 (Tau tubulin kinase-2) and the E3 ubiquitin ligase HUWE1 in GNP proliferation. We show that TTBK2 is highly expressed in proliferating GNPs under Sonic Hedgehog (SHH) signaling, coinciding with active GNP proliferation and the presence of primary cilia. TTBK2 stabilizes primary cilia by inhibiting their disassembly, thereby promoting GNP proliferation in response to SHH. Mechanistically, we identify HUWE1 as a novel centrosomal E3 ligase that facilitates primary cilia disassembly by targeting TTBK2 degradation. Disassembly of primary cilia serves as a trigger for GNP differentiation, allowing their migration from the external granule layer (EGL) of the cerebellum to the internal granule layer (IGL) for subsequent maturation. Moreover, we have established a link between TTBK2 and SHH-type medulloblastoma (SHH-MB), a tumor characterized by uncontrolled GNP proliferation. TTBK2 depletion inhibits SHH-MB proliferation, indicating that TTBK2 may be a potential therapeutic target for this cancer type. In summary, our findings reveal the mechanism governing cerebellar development and highlight a potential anti-cancer strategy for SHH-MB.