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.

OBJECTIVES: To analyze the differential expression and biological functions of circRNAs in the anterior lens capsules of high myopic patients with cataract and their pathogenic roles in the development of this condition. METHODS: Anterior lens capsule specimens were collected intraoperatively from 36 patients with age-related cataract (ARC) and 36 high myopic patients with cataract. Among these, 18 specimens from each group were selected for whole transcriptome sequencing and biological analysis, and the remaining 36 specimens were used for validation of circPDGFRA, circFOXJ3, hsa_circ_0004767, hsa_circ_0007528, ciCRIM1, circMAN1A2, circSLC5A3, and circPTK2 expressions using RT-qPCR. hsa_circ_0007528 was selected for cell experiments to examine its effects on proliferation, migration, and apoptosis of lens epithelial cells (LECs). RESULTS: A total of 16 192 circRNAs were detected in the specimens from both groups, among which 62 circRNAs were differentially expressed (29 upregulated and 33 downregulated). GO and KEGG analyses revealed that the differentially expressed circRNAs were primarily localized in the cytoplasm, nucleoplasm, and endoplasmic reticulum, and were involved in signaling pathways associated with Gap junction and the PI3K-Akt, NF-κB, Jak-STAT, HIF-1, and MAPK signaling pathways. The ceRNA network predicted multiple target genes. RT-qPCR validation results were consistent with the sequencing data. In the LECs, upregulation of hsa_circ_0007528 significantly inhibited cell proliferation and migration and obviously promoted cell apoptosis. CONCLUSIONS The expression profile of circRNAs in the anterior lens capsule of high myopic patients with cataract differs from that of ARC patients. Upregulation of hsa_circ_0007528 inhibits LEC proliferation and migration and promotes cell apoptosis.
Humans ; Cataract/complications* ; RNA, Circular ; Myopia/genetics* ; Apoptosis ; Cell Proliferation ; Epithelial Cells ; Cell Movement ; Anterior Capsule of the Lens/metabolism* ; Male ; Female

Objective To investigate the effects and potential mechanisms of Marsdeniae Tenacissimae Caulis(Tongguanteng)injection and extract in human osteosarcoma cells proliferation,migration,invasion,and apoptosis.Methods MNNG/HOS,Saos-2 osteosarcoma cells,and normal bone marrow mesenchymal stem cells(BMSC)were cultured in vitro.Cells were incubated with different concentrations of Tongguanteng injection and Tongguanteng extract(40,60,80 mg/mL).Cell proliferation was evaluated by CCK-8 assay and plate colony formation assay.Cell migration and invasion were evaluated by scratch assay and Transwell assay.Cell apoptosis was evaluated by Hoechst33342 staining and Annexin-V/PI double staining assay.Bax,Bcl-2 and Caspase-3 mRNA expression were detected using RT-qPCR.The protein expressions of JAK1,p-JAK1,STAT3,p-STAT3 and MMP9 were detected by Western blot.Results Compared with the control group,both Tongguanteng injection and extract significantly decreased the survival rate of MNNG/HOS and Saos-2 cells,inhibited cell clone formation,migration,and invasion,induced cell apoptosis(P<0.05,P<0.01),promoted Bax mRNA and protein expression,inhibited Bcl-2 mRNA and protein expression,and up-regulated Caspase-3 mRNA and Cleaved Caspase-3 protein expression.Tongguanteng injection could significantly down-regulate the expressions of p-JAK1,p-STAT3 and MMP9 protein expression in Saos-2 cells(P<0.05,P<0.01).Conclusion Both Tongguanteng injection and Tongguanteng extract can significantly inhibit proliferation,migration and invasion of human osteosarcoma MNNG/HOS and Saos-2 cells,and induce apoptosis,with no significant difference in anti-tumor effect.The mechanism may be related to the inhibition of the activation of JAK1/STAT3 signaling pathway.

Objective:To explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders (NDDs) due to variants of TANC2 gene. Methods:Clinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. By using " TANC2 gene", "Neurodevelopmental disorders", "Nervous system development disorders", " TANC2" as the key words, similar cases were searched from the CNKI, Wanfang database platform and PubMed database, with the search time set as from the establishment of the database to December 2023. This study was approved by Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No. 2020-57). Results:Case 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures. Her epilepsy had resolved with the treatment of oxcarbazepine, which was stopped at the age of 2-year-and-7-month. Her language, movement and intelligence development were all normal. Case 2 was a 1-year-and-10-month-old boy, who had developed convulsions at 1 year old. His seizure type was myoclonus, and the frequency was dozens of times a day. His epilepsy had resolved with the treatment of sodium valproate. His language, movement and intelligence development was delayed for about half a year. Genetic analysis showed that both children had harbored novel variants of the TANC2 gene (NM_025185.4), including c. 3398G>A (p.Gly1133Glu) and c.2829+ 1G>A, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the former was rated as likely pathogenic (PS2+ PM2_Supporting+ PP3) and the latter was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Two previous reports were retrieved, which had involved 17 cases and 16 variants. Common features had included autism spectrum disorder (70.6%, 12/17), intellectual disability (94.1%, 16/17), language and motor retardation (88.2%, 15/17; 58.8%, 10/17), facial dysmorphism, epilepsy, ataxia, and thoracic and spinal deformities. Conclusion:Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.

Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.

Objective·To analyze the epidemiological characteristics of risk factors for cardiovascular diseases and malignant tumors based on the Shanghai community elderly cohort.Methods·The study subjects were selected from the Shanghai community elderly cohort established from February to August 2019,with a total of 17 948 people.The study subjects were divided into 4 groups according to self-reported presence or absence of tumors and/or cardiovascular diseases during the baseline survey:tumor-free and non-cardiovascular disease group,single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group.The differences among the four groups of subjects were collected and compared in terms of demographic characteristics and physiological indicators,daily living habits(smoking,drinking tea,drinking coffee,drinking carbonated drink,drinking alcohol,sedentary time,physical activity level and sleep quality),past medical history,psychological status(depression and anxiety)and dietary compliance.Results·Among the study subjects,60.1%of tumor patients were complicated with cardiovascular diseases.The differences among the four groups of subjects in age,gender,educational level,pre-retirement occupation,waist circumference,hip circumference and body mass index were statistically significant(all P<0.05).Compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group,single tumor group and tumor cardiovascular disease co-occurrence group all exhibited lower proportions of smoking and high physical activity levels(all P<0.05),and higher proportion of sedentary time exceeding 4 h/d and poor sleep quality(all P<0.05);the proportion of subjects with past medical histories including hyperlipidemia,peripheral vascular disease,endocrine system disease,respiratory system disease,urinary system disease and digestive system disease of the single cardiovascular disease group and the tumor cardiovascular disease co-occurrence group was higher(all P<0.05),and the proportion of subjects with depression and anxiety was also higher(all P<0.05).Furthermore,compared with the tumor-free and non-cardiovascular disease group,the single cardiovascular disease group had lower compliance rates of poultry,fish,fruit and liquid milk(all P<0.05).Among the four groups,only the compliance rate of vegetable intake exceeded 50%,while the compliance rates of poultry,fish,fruit,liquid milk and tubers were all below 20%.Conclusion·In the elderly population of Shanghai communities,over half of malignant tumor patients are concomitant with cardiovascular diseases.Unhealthy daily habits are prevalent among those with cardiovascular diseases,tumors and tumor-cardiovascular disease co-occurrence.The intake of many foods in the elderly of the community do not reach the levels recommended by Chinese Dietary Guidelines.

A clinically serious illness with a high death and morbidity rate is sepsis.Electro-acupuncture is a significant adjuvant treatment for sepsis,lowering the inflammatory response to sepsis,regulating the patient's immunological function,and preventing multi-system organ damage.However,no comprehensive study has been published.In order to review the clinical application of electro-acupuncture in the field of sepsis and its complications,analyze its clinical efficacy,and summarize effective acupuncture point prescriptions,we systematically compiled the clinical research literature on electro-acupuncture in the treatment of sepsis and its complications by searching PubMed,CNKI,and other databases.It was found that effective clinical evidence had been gathered for the administration of electro-acupuncture in uncomplicated sepsis as well as in sepsis aggravated by gastrointestinal,pulmonary,cardiac,and brain injury.The following successful acupoint prescriptions were indicated:①Simple sepsis was treated with"Zusanli+Guanyuan"or"Zusanli+Tianshu+Shangjuxu+Xiajuxu";②Combined gastrointestinal injury was treated with"Zusanli+Shangjuxu+Tianshu"or"Zusanli+Tianshu+Shangjuxu+Xiajuxu";③ Combined lung injury was treated with"Zusanli+Chize";④Combined myocardial injury was treated with"Neiguan+Zusanli+Shenmen+Taichong+Xuehai+Geshu+Sanyinjiao+Hegu";⑤Combined brain injury was treated with"Baihui+Shuigou".The study's findings can offer preliminary clinical direction for using electro-acupuncture to treat sepsis and associated complications in patients.

Objective:To explore the clinical and genetic characteristics of asparagine synthase deficiency.Methods:Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed.Results:All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor.Conclusions:Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Objective:To compare the clinical efficacy of endoscopic resection and laparoscopic surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) with a maximum diameter of 2 to 5 cm, and to analyze the influence of factors such as tumor surface, growth pattern and lesion origin on the choice of resection method, so as to provide a safer and more effective treatment for patients with gastric GIST.Methods:From January 2012 to November 2019, at the First Affiliated Hospital of Zhengzhou University, the clinical data of 301 patients with gastric GIST who underwent endoscopic resection (137 cases in the endoscopic resection group) or laparoscopic surgery (164 cases in the laparoscopic surgery group) were retrospectively analyzed, including age, gender, whether there was depression on the tumor surface (the local subsidence depth of the mucosa on the tumor surface was >5 mm), whether the tumor surface was irregular (non-hemispherical or non-elliptical tumor surface), whether there was combined ulcer, location, shape, origin of the lesion, growth pattern (intralumina growth or combined intraluminal and extraluminal growth), risk classification (very low risk, low risk, medium risk, high risk), whether the tumor was en bloc resection, operation time, whether bleeding or not, fasting time, indwelling time of gastric tube, time of hospitalization, time of postoperative hospital stay, postoperative complications and follow-up. Independent sample t test, chi-square test or Fisher′s exact test and Wilcoxon rank sum test were used for statistical analysis. Results:Among the 137 patients with gastric GIST in the endoscopic resection group, 85 cases (62.0%) underwent endoscopic submucosal dissection, 9 cases (6.6%) underwent endoscopic submucosal excavation, 42 cases (30.7%) underwent endoscopic full-thickness resection, and 1 case (0.7%) underwent submucosal tunnel endoscopic resection. There were no significant differences in gender, age, lesion location, tumor size, and risk classification between the endoscopic resection group and the laparoscopic surgery group (all P>0.05). The tumor surface was depressed, with ulcer or irregular in 1, 49, 26, and 2 cases of patients with gastric GIST of very low risk, low risk, medium risk and high risk, respectively. There was statistically significant difference in the proportion of depression, irregularity and ulcer on the tumor surface at different risk levels ( Z=-2.55, P=0.011). The complete tumor resection rate of the endoscopic resection group was lower than that of the laparoscopic surgery group (86.1%, 118/137 vs. 100.0%, 164/164), and the difference was statistically significant ( χ2=24.28, P<0.001). However the operation time, fasting time, the indwelling time of gastric tube, time of hospitalization, and the time of postoperative hospital stay of the endoscopic resection group were shorter than those of the laparoscopic surgery group, and the total hospitalization cost was lower than that of the laparoscopic surgery group (90.0 min (62.5 min, 150.0 min) vs. 119.5 min, (80.0 min, 154.2 min); 3 d (3 d, 4 d) vs. 5 d (4 d, 7 d); 3 d (2 d, 4 d) vs. 4 d (2 d, 6 d); 11 d (10 d, 14 d) vs. 16 d (12 d, 20 d); 7 d (6 d, 9 d) vs. 9 d (7 d, 11 d); (38 211.6±10 221.0) yuan vs. (59 926.1±17 786.1) yuan), and the differences were statistically significant ( Z=-2.46, -7.12, -4.44, -6.89 and -5.92, t=-13.24; all P<0.05). The incidence of postoperative abdominal pain and other severe postoperative complications (including shock, respiratory failure, pulmonary embolism, gastroparesis, etc.) of the endoscopic resection group were all lower than those of the laparoscopic surgery group (16.8%, 23/137 vs. 27.4%, 45/164; 0.7%, 1/137 vs. 4.9%, 8/164), and the differences were statistically significant ( χ2=4.84, Fisher′s exact test, P=0.028 and 0.043). There were no significant differences in the incidence of intraoperative bleeding, postoperative bleeding, fever and perforation between the two groups (all P>0.05). The incidence of operation-related complications of lesions with intraluminal growth and originating from muscularis propria in the endoscopic resection group were lower than those of the laparoscopic surgery group (19.5%, 25/128 vs. 32.6%, 45/138; 12.6%, 12/95 vs. 31.4%, 37/118), and the differences were statistically significant ( χ2=5.86 and 10.42, P=0.016 and 0.001). There was no significant difference in the postoperative tumor recurrent rate between the endoscopic resection group and the laparoscopic surgery group (0, 0/137 vs. 2.4%, 4/164; Fisher’s exact test, P=0.129). Conclusions:Endoscopic treatment is safe and effective for gastric GIST with a maximum diameter of 2 to 5 cm, which is superior to laparoscopic surgery. However, laparoscopic surgery is recommended for tumor with depressed, ulcerative, or irregular surface and combined intraluminal and extraluminal growth.

Cleft lip and/or palate (CLP) are the most common craniofacial malformations in humans. Speech problems often persist even after cleft repair, such that follow-up articulation training is usually required. However, the neural mechanism behind effective articulation training remains largely unknown. We used fMRI to investigate the differences in brain activation, functional connectivity, and effective connectivity across CLP patients with and without articulation training and matched normal participants. We found that training promoted task-related brain activation among the articulation-related brain networks, as well as the global attributes and nodal efficiency in the functional-connectivity-based graph of the network. Our results reveal the neural correlates of effective articulation training in CLP patients, and this could contribute to the future improvement of the post-repair articulation training program.
Brain/diagnostic imaging* ; Cleft Lip/surgery* ; Cleft Palate/surgery* ; Humans ; Magnetic Resonance Imaging ; Reading