Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

Objective:To investigate the synergistic effect of astaxanthin and curcumin on assisted reproduc-tive technology(ART)outcomes in patients with poor ovarian response(POR).Methods:A prospective cohort study was conducted,involving 123 POR patients enrolled at the Reproductive & Women-Children Hospital,Chengdu University of Traditional Chinese Medicine between March 6,2023 to May 1,2024.According to patient preference,participants were divided into the treatment group(41 cases)and the control group(82 cases)at a ratio of 1∶2.The treatment group took astaxanthin and turmeric compound tablets orally for 60 to 90 days before ovulation induction treatment.The ovulation induction parameters and pregnancy outcomes were compared between the two groups,and a self-controlled analysis was conducted within the treatment group.Results:During the observation period,5 and 10 participants withdrew from the treatment and control groups,respectively,resul-ting in 108 patients included in the final analysis.There were no statistically significant differences between the two group in terms of endometrial thickness on the day of human chorionic gonadotropin(HCG),number of oocytes retrieved,oocyte maturation rate,normal fertilization rate,high-quality embryo rate,or cycle cancellation rate(P＞0.05).However,the treatment group demonstrated significantly higher clinical pregnancy rate(61.54％vs.28.57％),fresh embryo implantation rate(40.91％vs.18.97％),and cumulative clinical pregnancy rate(65.38％vs.33.33％)(P＜0.05).The early miscarriage rate was observed with no significant difference between groups(12.5％vs.10.0％)(P＞0.05).Furthermore,after treatment,basal FSH(bFSH),basal E2(bE2),antral follicles count(AFC),anti-Müllerian hormone(AMH),and the number of oocytes retrieved within the treatment group were significantly improved compared with those before treatment(P＜0.05).Conclusions:Pretreatment with astaxanthin and turmeric compound tablets in POR patients did not significantly improve the ovulation induction re-sponse,but was associated with increased fresh embryo clinical pregnancy rate,implantation rate,and cumulative pregnancy rate.The underlying mechanism may involve modulation of basal endocrine profiles and improvement of ovarian reserve function,though further investigation is required to elucidate precise pathways.

Objective:To investigate the synergistic effect of astaxanthin and curcumin on assisted reproduc-tive technology(ART)outcomes in patients with poor ovarian response(POR).Methods:A prospective cohort study was conducted,involving 123 POR patients enrolled at the Reproductive & Women-Children Hospital,Chengdu University of Traditional Chinese Medicine between March 6,2023 to May 1,2024.According to patient preference,participants were divided into the treatment group(41 cases)and the control group(82 cases)at a ratio of 1∶2.The treatment group took astaxanthin and turmeric compound tablets orally for 60 to 90 days before ovulation induction treatment.The ovulation induction parameters and pregnancy outcomes were compared between the two groups,and a self-controlled analysis was conducted within the treatment group.Results:During the observation period,5 and 10 participants withdrew from the treatment and control groups,respectively,resul-ting in 108 patients included in the final analysis.There were no statistically significant differences between the two group in terms of endometrial thickness on the day of human chorionic gonadotropin(HCG),number of oocytes retrieved,oocyte maturation rate,normal fertilization rate,high-quality embryo rate,or cycle cancellation rate(P＞0.05).However,the treatment group demonstrated significantly higher clinical pregnancy rate(61.54％vs.28.57％),fresh embryo implantation rate(40.91％vs.18.97％),and cumulative clinical pregnancy rate(65.38％vs.33.33％)(P＜0.05).The early miscarriage rate was observed with no significant difference between groups(12.5％vs.10.0％)(P＞0.05).Furthermore,after treatment,basal FSH(bFSH),basal E2(bE2),antral follicles count(AFC),anti-Müllerian hormone(AMH),and the number of oocytes retrieved within the treatment group were significantly improved compared with those before treatment(P＜0.05).Conclusions:Pretreatment with astaxanthin and turmeric compound tablets in POR patients did not significantly improve the ovulation induction re-sponse,but was associated with increased fresh embryo clinical pregnancy rate,implantation rate,and cumulative pregnancy rate.The underlying mechanism may involve modulation of basal endocrine profiles and improvement of ovarian reserve function,though further investigation is required to elucidate precise pathways.

Objective To create risk predictive models of healthcare-seeking delay among imported malaria patients in Jiangsu Province based on machine learning algorithms, so as to provide insights into early identification of imported malaria cases in Jiangsu Province. Methods Case investigation, first symptoms and time of initial diagnosis of imported malaria patients in Jiangsu Province in 2019 were captured from Infectious Disease Report Information Management System and Parasitic Disease Prevention and Control Information Management System of Chinese Center for Disease Control and Prevention. The risk predictive models of healthcare-seeking delay among imported malaria patients were created with the back propagation (BP) neural network model, logistic regression model, random forest model and Bayesian model using thirteen factors as independent variables, including occupation, species of malaria parasite, main clinical manifestations, presence of complications, severity of disease, age, duration of residing abroad, frequency of malaria parasite infections abroad, incubation period, level of institution at initial diagnosis, country of origin, number of individuals travelling with patients and way to go abroad, and time of healthcare-seeking delay as a dependent variable. Logistic regression model was visualized using a nomogram, and the nomogram was evaluated using calibration curves. In addition, the efficiency of the four models for prediction of risk of healthcare-seeking delay among imported malaria patients was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC). The importance of each characteristic was quantified and attributed by using SHAP to examine the positive and negative effects of the value of each characteristic on the predictive efficiency. Results A total of 244 imported malaria patients were enrolled, including 100 cases (40.98%) with the duration from onset of first symptoms to time of initial diagnosis that exceeded 24 hours. Logistic regression analysis identified a history of malaria parasite infection [odds ratio (OR) = 3.075, 95% confidential interval (CI): (1.597, 5.923)], long incubation period [OR = 1.010, 95% CI: (1.001, 1.018)] and seeking healthcare in provincial or municipal medical facilities [OR = 12.550, 95% CI: (1.158, 135.963)] as risk factors for delay in seeking healthcare among imported malaria cases. BP neural network modeling showed that duration of residing abroad, incubation period and age posed great impacts on delay in healthcare-seek among imported malaria patients. Random forest modeling showed that the top five factors with the greatest impact on healthcare-seeking delay included main clinical manifestations, the way to go abroad, incubation period, duration of residing abroad and age among imported malaria patients, and Bayesian modeling revealed that the top five factors affecting healthcare-seeking delay among imported malaria patients included level of institutions at initial diagnosis, age, country of origin, history of malaria parasite infection and individuals travelling with imported malaria patients. ROC curve analysis showed higher overall performance of the BP neural network model and the logistic regression model for prediction of the risk of healthcare-seeking delay among imported malaria patients (Z = 2.700 to 4.641, all P values < 0.01), with no statistically significant difference in the AUC among four models (Z = 1.209, P > 0.05). The sensitivity (71.00%) and Youden index (43.92%) of the logistic regression model was higher than those of the BP neural network (63.00% and 36.61%, respectively), and the specificity of the BP neural network model (73.61%) was higher than that of the logistic regression model (72.92%). Conclusions Imported malaria cases with long duration of residing abroad, a history of malaria parasite infection, long incubation period, advanced age and seeking healthcare in provincial or municipal medical institutions have a high likelihood of delay in healthcare-seeking in Jiangsu Province. The models created based on the logistic regression and BP neural network show a high efficiency for prediction of the risk of healthcare-seeking among imported malaria patients in Jiangsu Province, which may provide insights into health management of imported malaria patients.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

Animals ; Carrier Proteins/metabolism* ; Histidine/metabolism* ; Humans ; Methylation ; Methyltransferases/metabolism* ; Neoplasm Proteins/metabolism* ; Neoplasms/metabolism* ; Protein Processing, Post-Translational

Objective: To investigate the clinical features and pathogenic genes of a family with osteosclerosis. Methods: Six patients and six family members from a family in Jiangsu were tested for biochemical parameters, bone metabolic markers, bone mineral density, thoracolumbar anterior lateral slices, skull positive lateral radiographs, and pelvic plain films. Meanwhile, Sanger sequencing was performed to detect gene mutations of the proband and five other family members with high bone mass. The conformation of the mutational low-density lipoprotein receptor-related protein 5 (LRP5) protein was predicted by SWISS-MODEL. Results: Four adult patients (one male and three females) were tall, with mandibular enlargement and kyphosis in the center of the lower jaw, and none of the four had fractures. Their X ray examination revealed that the skull and long bone cortex was thickened, while the sella and mandible was enlarged. In addition, the absolute values of bone mineral density at each site of all patients were significantly higher as compared with the standard age- and sex-matched adults or adolescent mean reference values, with Z scores of L2-4, femoral neck and total hip being (6.31±4.03) SD, (6.56±2.36) SD, and (7.19±2.03) SD, respectively. The results of genetic sequencing revealed that all six patients carried a heterozygous mutation (c.331G>T; D111Y) in exon 2 of LRP5 gene, while other family members showed wild type (c.331G>G; D111D). Functional prediction indicated that this mutation was located at the amino acid terminal of exon 2 of LRP5 gene, which encodes the first β-helix-generating region of LRP5 protein. Conclusion The D111Y mutation in LRP5 gene leads to a clinical phenotype characterized by benign increased bone mineral density without increasing the risk of fracture. This mutation may further affect the downstream Wnt signaling pathway by altering the spatial structure of LRP5 protein, thereby promoting maturation and differentiation of osteoblasts and resulting in osteosclerosis.

Objective:To establish the quality standard for Qinzhu Liangxue mixture. Methods:Seutellaria baiealensis, glyeyrrhizae and jobstears seed were identified by TLC. Baicalin and glycyrrhizic acid were determined by HPLC. Results:Seutellaria baiealensis,glyeyrrhizae and jobstears seed could be identified by TLC. The linear range of baicalin was 0. 030- 0. 971 mg·ml -1(r = 1. 000 0),and the average recovery was 97. 74%(RSD = 2. 76% ,n = 9). The linear range of glycyrrhizic acid was 0. 013- 0. 220 mg·ml -1(r = 1. 000 0),and the average recovery was 99. 02%(RSD = 1. 79% ,n = 9)Glycyrrhizic acid. Conclusion:The method is specific,simple and accurate. It can be used for the quality control of Qinzhu Liangxue mixture.

Objective To investigate the relationships and types between pulmonary subsolid nodules and bronchi and vessels,and their diagnostic values in differentiating subsolid nodules.Methods MSCT images of 40 subsolid nodules were retrospectively reviewed.The relationships between subsolid nodules and bronchi were divided into five types.Type Ⅰ:the bronchi were “cutoff”in the solid part of nodules.Type Ⅱ:the bronchi were distortion and extension in the solid parts of nodules.Type Ⅲ:the bronchi were distortion and extension in the GGO parts of nodules.Type Ⅳ:the bronchi were normal course in the GGO parts of nodules.Type Ⅴ:the bronchi were circumvent nodule lesions.The relationships between subsolid nodules and vessels were categorized into four types.Type Ⅰ:vessels passing by SSNs;Type Ⅱ:intact vessels passing through SSNs;Type Ⅲ:distorted,dilated or tortuous vessels seen within SSNs;Type Ⅳ:more complicated vessels other than described above.The relationship types were correlated to pathologic and/or clinical findings of subsolid nodules.Results Of 40 subsolid nodules,4 were preinvasive nodules,6 micro infiltrating adeocarcinomas and 30 invasive ones that were pathologically proven.Types Ⅰ,Ⅱ,Ⅲ and Ⅳ vascular relationships were observed in 0,8,21 and 11 subsolid nodules,respectively.Type Ⅲ relationship was the dominating one.All 11 subsolid nodules were invasive adenocarcinomas,when the relationship between subsolid nodules and vessle was type Ⅳ.There were 17 invasive adenocarcinomas,2 preinvasive ones,and 2 infiltrating ones when the relationship between subsolid nodules and vessel was type Ⅲ.Correlation analysis showed strong correlation between invasive adenocarcinoma and type Ⅲ and Ⅳ relationships.There was significantly statistical significance among 3 groups of relationships between subsolid nodule and vessels(χ2 =1 5.1 90,P =0.004).Types Ⅰ,Ⅱ,Ⅲ,Ⅳ and V brochi relationships were observed in 20,5,6,9 and 0 subsolid nodules,respectively.Type I relationship was the dominating relationship.There were 1 7 invasive adenocarcinomas, 1 preinvasive one,2 micro invasive ones when the relationship between subsolid nodules and bronchi were typeⅠ.There was significantly statistical significance among 3 groups of relationships between subsolid nodule and bronchi (χ2 =23.81 1,P =0.001 ).Conclusion Different subsolid nodules have different relationships with bronchi and vessels.Understanding and recognizing the characteristic subsolid nodule-bronchi and subsolid nodule-vessel relationships may help to identify which nodules are more likely to be malignant.