Ubiquitylation activates a peptidase that promotes cleavage and destabilization of its activating E3 ligases and diverse growth regulatory proteins to limit cell proliferation in Arabidopsis.

The characteristic shapes and sizes of organs are established by cell proliferation patterns and final cell sizes, but the underlying molecular mechanisms coordinating these are poorly understood. Here we characterize a ubiquitin-activated peptidase called DA1 that limits the duration of cell proliferation during organ growth in Arabidopsis thaliana The peptidase is activated by two RING E3 ligases, Big Brother (BB) and DA2, which are subsequently cleaved by the activated peptidase and destabilized. In the case of BB, cleavage leads to destabilization by the RING E3 ligase PROTEOLYSIS 1 (PRT1) of the N-end rule pathway. DA1 peptidase activity also cleaves the deubiquitylase UBP15, which promotes cell proliferation, and the transcription factors TEOSINTE BRANCED 1/CYCLOIDEA/PCF 15 (TCP15) and TCP22, which promote cell proliferation and repress endoreduplication. We propose that DA1 peptidase activity regulates the duration of cell proliferation and the transition to endoreduplication and differentiation during organ formation in plants by coordinating the destabilization of regulatory proteins.

Enhanced Broadband Manipulation of Acoustic Vortex Beams Using 3-bit Coding Metasurfaces through Topological Optimization.

The acoustic coding metasurfaces (ACMs) have the ability to manipulate complex acoustic behavior by reconstructing the coding sequence. In particular, the design of broadband coding enhances the versatility of ACMs. ACMs offer significant advantages over traditional metasurfaces, including a limited number of units and flexible wave control performance. The unit quantity is determined by 2n, with 1-bit utilizing 2 units, 2-bit using 4 units, and 3-bit employing 8 units. Utilizing multiple bits allows for precise control over the phase of sound waves and enables the realization of more intricate acoustic functions. To address the requirements of broadband multi-bit applications, this paper presents the development of novel 3-bit broadband reflected acoustic coding metasurfaces (BACMs) with eight coding units. These metasurfaces are systematically designed using the bottom-up topology optimization method. A constant phase difference of 45° can be achieved across all eight coding units within a broad frequency range. Additionally, the spiral distribution of phase differences enables the construction of an acoustic vortex metasurface. Moreover, by combining the convolution method, the strategies are outlined for constructing vortex-focusing metasurfaces and vortex beam manipulation metasurfaces. These 3-bit coding metasurfaces possess significant potential in the fields of acoustic particle suspension and acoustic communication.

Roles of natural products on myokine expression and secretion in skeletal muscle atrophy.

Skeletal muscles serve both in movement and as endocrine organs. Myokines secreted by skeletal muscles activate biological functions within muscles and throughout the body via autocrine, paracrine, and/or endocrine pathways. Skeletal muscle atrophy can influence myokine expression and secretion, while myokines can impact the structure and function of skeletal muscles. Regulating the expression and secretion of myokines through the pharmacological approach is a strategy for alleviating skeletal muscle atrophy. Natural products possess complex structures and chemical properties. Previous studies have demonstrated that various natural products exert beneficial effects on skeletal muscle atrophy. This article reviewed the regulatory effects of natural products on myokines and summarized the research progress on skeletal muscle atrophy associated with myokine regulation. The focus is on how small-molecule natural products affect the regulation of interleukin 6 (IL-6), irisin, myostatin, IGF-1, and FGF-21 expression. We contend that the development of small-molecule natural products targeting the regulation of myokines holds promise in combating skeletal muscle atrophy.

Characteristics of blood clotting on thromboelastography in patients with early burns.

BACKGROUND: Thromboelastography (TEG) is a viscoelastic test that may be used to evaluate the hemostatic function of whole blood, and it may be useful for burn patients with multiple hemostatic defects. METHODS: We retrospectively recruited patients with burns between January 2019 and July 2021. Blood samples were drawn on admission and subjected to coagulation parameter assessment, including conventional coagulation tests and TEG assessment. Receiver operating characteristic (ROC) analysis was performed to predict the occurrence of complications in patients with early burns. RESULTS: Ninety-three patients with early burns met the inclusion criteria. Patients with minor, moderate, severe, and extremely severe burns accounted for 19.4 %, 36.6 %, 16.1 %, and 27.9 % of all patients, respectively. Compared with the healthy controls, patients with early burns showed significant reductions in the R and K values, and significant elevation in the maximum amplitude (MA), coagulation index (CI), and alpha angle. Compared with minor and moderate burn patients, patients with severe and extremely severe burns had lower K values and thrombin time and higher alpha angle, CI, prothrombin time, international normalized ratio, D-dimer, and fibrin degradation products. Patients with hypercoagulation had lower R and K values, longer MA, longer CI, and greater alpha angle. After ROC analysis, the areas under the ROC curve for acute lung injury, acute kidney injury, and bleeding were 0.789, 0.802, and 0.900, respectively. CONCLUSION: TEG provides insight into the hemostatic state of patients with early burns, and can predict complications in early burn patients when combined with conventional coagulation tests.

The use of human-derived feeder layers for the cultivation of transplantable human epidermal cell sheet to repair second degree burn wounds.

BACKGROUND AND OBJECTIVES: Human epidermal cell sheet (human-ECS) is a feasible treatment option for wound injury. Traditionally, researchers often use murine 3T3 fibroblast cells as feeder layer to support human epidermal cell sheet grafts, thus increase risk to deliver animal-borne infection. To overcome the potential risks involved with xenotransplantation, we develop human foreskin fibroblast cell as feeder layer culture system and investigate the effects of human-ECS on second-degree burn wound healing in mini-pig in order to develop more effective and safer therapies to enhance wound healing in human. MATERIALS AND METHODS: Human epidermal keratinocytes and fibroblasts were isolated from foreskin tissue and were co-cultured to manufacture human-ECS. The cell morphology was monitored with phase-contrast microscopy, the stem cell markers were assessed by flow cytometry, and by colony-forming efficiency (CFE) assay. The structure of human-ECS was observed by hematoxylin and eosin staining. Expression of cytokines in human-ECS was confirmed by enzyme-linked immunosorbent assay. Second-degree burn wounds were created on the dorsal of miniature pig to evaluate the effect of oil gauze, oil gauze combined with commercial epidermal growth factor (EGF) cream, and oil gauze combined with human-ECS. Wound healing rate, histological examination, and Masson staining were measured to observe the wound repair efficacy. Real-time PCR and Western blot were utilized to detect the expression level of EGF and interleukin 6 (IL-6). RESULTS: Stratified human-ECS with 6-7 layers of epidermal cells was successfully cultivated with human-derived feeder cells, in which epidermal cell highly expressed CD49f and CFE was 3% ± 0.45%. Application of human-ECS induced a higher wound healing rate than commerical EGF cream and oil gauze control. The expression of EGF in human-ECS group was higher than those in the other groups; however, the expression of IL-6 was significantly decreased at day 14 by human-ECS treatment group. CONCLUSIONS: Human-derived feeder cells are suitable for cultivation of human-ECS, avoiding pathogen transmission. Human-ECS could enhance second-degree burn wound healing, and its promoting effect involved secreting a variety of cytokines to regulate tissue reparative process.

Comparison of Human Eukaryotic Translation Initiation Factors 5A1 and 5AL1: Identification of Amino Acid Residues Important for EIF5A1 Lysine 50 Hypusination and Its Protein Stability.

The human eukaryotic translation initiation factor 5A (EIF5A) family consists of three members, namely EIF5A1, EIF5A2, and EIF5AL1. Recent studies have shown that the expression of EIF5As is related to many human diseases, such as diabetes, viral infection, central nervous system injury, and cancer. Among them, EIF5A1 plays different functions in various cancers, possibly as a tumor-suppressor or oncogene, while EIF5A2 promotes the occurrence and development of cancer. Yet, the biological function of EIF5AL1 is not being studied so far. Interestingly, although there are only three amino acid (at residues 36, 45, and 109) differences between EIF5A1 and EIF5AL1, we demonstrate that only EIF5A1 can be hypusinated while EIF5AL1 cannot, and EIF5AL1 has a tumor-suppressor-like function by inhibiting cell proliferation and migration. We also show that EIF5AL1 protein turnover is mediated through the proteasomal pathway, and EIF5AL1 protein turnover is much faster than that of EIF5A1, which may explain their differential protein expression level in cells. By engineering single and double mutations on these three amino acids, we pinpoint which of these amino acids are critical for hypusination and protein stability. The data of this work should fill in the gaps in EIF5As research and pave the way for future studies on EIF5AL1.

[Association between early-life factors and pubertal timing in girls]. / ç”Ÿå‘½æ—©æœŸå› ç´ ä¸Žå¥³ç”Ÿé’æ˜¥å‘åŠ¨æ—¶ç›¸çš„å ³è”åˆ†æž.

OBJECTIVES: To study the association between early-life factors (including birth weight, method of birth, gestational age, and history of gestational metabolic disorders) and pubertal timing in girls. METHODS: The stratified cluster sampling method was used to select the girls in grades 2-3 and 7-8 from three primary schools and three middle schools in Guangzhou, China from March to December, 2019, and breast development was examined for all girls. A questionnaire survey was performed to collect the information on early-life factors. The multivariate logistic regression model was used to evaluate the association of gestational metabolic disorders, birth weight, method of birth, and gestational age with pubertal timing in girls. The Bootstrap method was used to assess the mediation effect of body mass index (BMI) (Z score) between high birth weight (≥4 000 g) and pubertal timing. RESULTS: A total of 1 665 girls were enrolled, among whom 280 (16.82%) were judged to have early pubertal timing. The multivariate logistic regression analysis showed that high birth weight was associated with the increased risk of early pubertal timing (OR=2.12, 95%CI: 1.19-3.66, P=0.008). Nevertheless, no significant association was observed between other early-life factors and pubertal timing (P>0.05). The OR for the mediation effect of BMI (Z score) between high birth weight and early pubertal timing was 1.25 (95%CI: 1.09-1.47), accounting for 29.33% of the total effect of high birth weight on early pubertal timing. CONCLUSIONS: High birth weight is associated with the increased risk of early pubertal timing in girls, and overweight/obesity may play a partial mediating role in the association between high birth weight and early pubertal timing in girls.

Exploitation of a Half-Conjugate Polydentate Salamo-Salen Hybrid Ligand and Its Two Phenoxide-Bridged Heterohexanuclear 3d-s Double-Helical Cluster Complexes.

A half-conjugate polydentate Salamo-Salen hybrid ligand, H5L, containing two unique N2O2 pockets was first designed so that these metal ions in the complexes appear in different coordination modes. Two heterohexanuclear 3d-s double-helical cluster complexes, [Zn4Ca2L2(µ1-OAc)2(EtOH)2]·2EtOH (1; EtOH = ethanol) and [Zn4Sr2L2(µ2-OAc)2(MeOH)2]·2CH2Cl2 (2; MeOH = methanol), are reported that are formed through the reaction of H5L with zinc(II) and calcium(II) acetate or strontium(II) acetate, respectively. IR spectral analysis of the two complexes showed the existence of monodentate- and bidentate-coordinated acetate ions. The fluorescence properties of the ligand and its two heterohexanuclear complexes were explored in MeOH and water solutions, separately. In addition, theoretical calculations (density functional theory, interaction region indicator, and bond order) were performed to further understand the formation of a single-molecular double helix and the electron distribution characteristics of the two complexes.

Effect of Implantation and Fixation of Mirena in the Treatment of Adenomyosis and its Influence on Serum Inflammatory Factors.

This experiment was carried out to analyze the placement and fixation of Mirena in the treatment of adenomyosis (AM) and its influence on the level of serum inflammatory factors in patients. For this purpose, the subjects of this study were 100 AM patients hospitalized in our hospital from June 2019 to June 2021. They were divided into two groups according to the lottery method (n=50 for each group). The control group was treated with intramuscular triptorelin after the operation, and the observation group was treated with Mirena during the operation. Sex hormone indexes, VAS score, uterine volume, serum inflammatory indexes, the total incidence of adverse reactions, WHOQOL-BREF score and recurrence rate were compared between the two groups. Results showed that in the observation group after treatment E2VAS score and uterine volume were lower, serum IL-8 and TNF-A were lower, the whoqOL-BREf score was higher, and the recurrence rate (0) was lower than that in the control group (12.00%). The total incidence of adr in the observation group (4.00%) was lower than in the control group (8.00%). Then intraoperative placement of Mirena can effectively regulate sex hormone indexes of AM patients, reduce uterine volume, relieve dysmenorrhea symptoms, reduce the inflammatory response, improve quality of life, and reduce recurrence rate, without obvious adverse reactions.

Early Diagnosis of Abnormal Left Ventricular Systolic Functions of Rare Pathogenic Titin Mutation Gene Carriers in FHCM by Three-Dimensional Speckle Tracking Echocardiography Combined with Gene Detection.

Objective: This study aimed to explore the early diagnosis of abnormal left ventricular systolic function of rare pathogenic titin (TTN) mutation gene carriers in familial hypertrophic cardiomyopathy (FHCM) by three-dimensional speckle tracking echocardiography (3D-STE) combined with gene detection. Methods: Eighteen members of a Hui nationality family in Ningxia province of China were enrolled in this study in July 2019. The proband was tested with high-throughput sequencing of gene detection technology to detect the whole exome, and the mutation locus of pathogenic TTN gene was analyzed. According to the result, 16 subjects were divided into two groups: carrier group (n = 4) and noncarrier group (n = 12). Related indicators from 2DE were obtained, and myocardial strain indicators from 3D-STE were analyzed by postprocessing software of Tomtec. Strain indicators included global longitudinal strain (GLS), global circumference strain (GCS), global radial strain (GRS), regional longitudinal strain (RLS), regional circumference strain (RCS), and regional radial strain (RRS). All those indicators were compared between the two groups, and a receiver operating characteristic (ROC) curve was used for further analysis. Results: There were 4 subjects diagnosed as asymptomatic TTN gene carriers with the mutation locus of Val135643Ile. Compared with the noncarrier group, GLS and partial RLS were significantly reduced in the carrier group. The ROC curve shows that GLS has the largest AUC, and its sensitivity was better than LVPWD and specificity was better than IVSD and LVMI obtained from 2DE in the carrier group. Conclusions: There were 4 subjects diagnosed as asymptomatic TTN gene carriers with the mutation locus of Val135643Ile, and their GLS and partial RLS were significantly reduced; GLS had the better sensitivity and specificity than LVPWD, IVSD, and LVMI.

Capabilities and mechanisms of microalgae on nutrients and florfenicol removing from marine aquaculture wastewater.

The regulations governing the discharge of marine aquaculture wastewater are becoming increasingly stringent, and the problems of nitrogen and phosphorus pollution and antibiotic residues in wastewater are serious. Microalgae-based treatment with the dual benefits of wastewater purification and microalgae resource recycling was regarded as the most promising technology in aquaculture wastewater treatment. Isochrysis galbana and Chlorella sp. were chosen to investigate antibiotic and nutrient removal mechanisms from aquaculture wastewater. FLO addition stimulated microalgae growth at low FLO concentrations (0.1 and 1 mg/L) but inhibited growth at 10 mg/L. The removal efficiency of DIN by Chlorella sp. and I. galbana after 7 days of cultivation was 66.4% and 25.8%, respectively. Linear curves were obtained between DIN concentration and cultivation duration, remove constant (k) increased as FLO concentration increased from 0 to 10 mg/L, and the highest value of k was obtained in both the Chlorella sp. and I. galbana groups at 10 mg/L. DIP concentrations in FLO-contained simulated aquaculture wastewater decreased sharply with the cultivation of Chlorella sp. and I. galbana, and DIP removal rate increased as FLO concentration increased. When the initial concentration of FLO was 0.1 mg/L, biodegradation by I. galbana accounted for 86.67% of FLO removal. In contrast, FLO removal with biodegradation and biosorption by Chlorella sp. was 89.74% and 3.72%, respectively. Furthermore, Chlorella sp. grown in MPBR demonstrated superior capability for antibiotic-containing marine aquaculture wastewater purification, with average removal rates of DIN and DIP of 81.2% and 100%, respectively. The high removal rate is related to membranes which can improve microalgae performance by decoupling SRT and HRT. For microalgae-based aquaculture wastewater, ammonia was the most crucial nitrogen source, followed by nitrate. These findings serve as a theoretical foundation for developing microalgae-based aquaculture wastewater treatment technology and eliminating antibiotics in aquaculture.

Clinical features and diagnostic approaches for abdominal tuberculosis: five-year experience from a non-tuberculosis-designated hospital in China.

BACKGROUND AND PURPOSE: abdominal tuberculosis (TB) is a common form of extrapulmonary TB but it is still a diagnostic dilemma in clinical practice. This study aimed to highlight the clinical features and diagnostic approaches for abdominal TB. METHODS: seventy cases of diagnosed abdominal TB were retrospectively collected between August 1st, 2015 and June 30th, 2020. They were classified as peritoneal TB, lymph node TB, gastrointestinal TB, visceral TB or mixed TB. RESULTS: eighteen patients were diagnosed with peritoneal TB, nine with lymph node TB, five with gastrointestinal TB, two with visceral TB and 36 with mixed TB. More than 65 % of the patients had tuberculosis of other sites except the abdomen. The median diagnosis time was 60 days. Ascites (58.6 %), abdominal distension (48.6 %), weight loss (44.3 %) and fever (42.9 %) were the most common symptoms. The overall microbiological and histological detection rates were 70.0 % and 38.6 %, respectively. The non-ascite samples yielded a higher microbiological confirmation rate (63.6 %) than the total samples (40.8 %). Diagnosis was confirmed histologically in 18 patients (69.2 %). Forty-five cases (64.3 %) were clinically diagnosed. Invasive procedures such as surgery (6/7), percutaneous biopsy (7/7) and endoscopy in lymph node TB (4/5) had high confirmation rates. CONCLUSIONS: the diagnosis of abdominal TB should be reached by a combination of clinical, laboratory, radiological, microbiological and pathological findings.

HMG20A was identified as a key enhancer driver associated with DNA damage repair in oral squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the main type of oral cancer. Disturbing DNA repair is an invaluable way to improve the effectiveness of tumor treatment. Here, we aimed to explore the key enhancer drivers associated with DNA damage repair in OSCC cells. METHODS: Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA) and Kaplan-Meier analysis were applied to explore the relationship among DNA repair-related genes expression and clinical phenotypes based on The Cancer Genome Atlas (TCGA) database. HOMER software and Integrative Genomics Viewer were applied to identify and visualize enhancers using GSE120634. Toolkit for Cistrome Data Browser was applied to predict transcription factors. Human Protein Atlas Database was used to analyze the protein levels of transcription factors in OSCC and control tissues. Seventy-two OSCC patients were included in this study. qRT-PCR was used to detect transcription factor expression in OSCC and adjacent control tissues collected in this study. qRT-PCR and ChIP-qPCR were used to verify the binding of transcription factors to enhancers, and regulation of target genes transcription. Transcription factor knockdown and control cells were treated with cisplatin. CCK8 was used to detect cell viability and proliferation. Western blotting was implemented to detect the levels of DNA repair-related proteins. Transwell assay was used to detect cell invasion. RESULTS: DNA repair was positively associated with the OSCC metastatic phenotype. Patients in the cluster with high expression of DNA repair-related genes had a worse prognosis and a higher proportion of advanced stage, low-differentiation, alcohol consumption and smoking compared to the cluster with low DNA repair-related gene expression. Seventeen metastasis-specific enhancer-controlled upregulated DNA repair-related genes, with the top two upregulated genes being ADRM1 26 S proteasome ubiquitin receptor (ADRM1) and solute carrier family 12 member 7 (SLC12A7) were screened. High mobility group 20 A (HMG20A) was the key prognostic enhancer driver regulating metastasis-specific DNA repair-related genes, with higher expression in OSCC tissues than normal control tissues, and higher expression in metastatic OSCC tissues than non-metastatic OSCC tissues. HMG20A bound to the metastasis-specific enhancers of ADRM1 and SLC12A7, thereby promoting ADRM1 and SLC12A7 expression. Knockdown of HMG20A enhanced cisplatin sensitivity of cells, and inhibited OSCC cells from repairing DNA damage caused by cisplatin, as well as proliferation and invasion of OSCC cells. CONCLUSION: HMG20A was identified as the key prognostic enhancer driver regulating DNA repair in OSCC cells, providing a new therapeutic target for OSCC.

Gray water footprint evaluation of arsenic in Central China: from the perspective of health risk theory.

Central China is one of the areas with the most serious arsenic (As) pollution in the world. However, the local controlling standards of arsenic are not unique, and its toxicities to humans have gender differences, which brings challenges to gray water footprint (GWF) evaluation. The GWF model is improved on the basis of health risk theory to address the abovementioned problems. According to the gender differences in health parameters, the assessment is further divided into male and female GWFs (i.e., GWF (As-M) and GWF (As-F), respectively). The results show that (1) the average annual GWF (As-M) and GWF (As-F) values in Central China from 2011 to 2015 are 97.27 and 105.11 billion m3, respectively. Hunan Province accounts for about 77% of the total GWF (As-M) and GWF (As-F) in Central China (2). The carcinogenic hazard of arsenic load in Hunan Province is the most serious among the three provinces in central China. The water pollution levels of arsenic for male and female in Hunan Province are 0.917 and 0.843 in 2011, both of which belong to the "high" grade. The carcinogenic hazards of arsenic loads in Hubei Province and Jiangxi Province are the second and third highest in Central China (3). For the females, the average daily dose to arsenic is about 1.03 times larger than the male's, and the female carcinogenic risk of arsenic is higher than that of males. Therefore, women are the main protection group of arsenic pollution in Central China (4). The decrease in the GWF (As-M) and GWF (As-F) risk factors in Central China is primarily caused by the closure of Shimen realgar mine in Hunan Province. The leaching of historical slag is a key source to be controlled to further improve water safety of Central China.

[Value of three-dimensional speckle-tracking imaging in evaluating left ventricular systolic function and its correlation with peripheral arterial elasticity in children with simple obesity: a prospective study]. / ä¸‰ç»´æ–‘ç‚¹è¿½è¸ªæˆåƒæŠ€æœ¯å¯¹å•çº¯æ€§è‚¥èƒ–å„¿ç«¥å·¦å¿ƒå®¤æ”¶ç¼©åŠŸèƒ½çš„è¯„ä»·åŠå ¶ä¸Žå¤–å‘¨åŠ¨è„‰å¼¹æ€§ç›¸å ³æ€§çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the application of three-dimensional speckle-tracking imaging in evaluating left ventricular systolic function and its correlation with peripheral arterial elasticity in children with simple obesity. METHODS: Random sampling combined with convenience sampling was used to obtain research samples, and then the samples were divided into an obesity group (23 cases), an overweight group (21 cases), and a normal group (24 cases). Three-dimensional speckle-tracking imaging was used to measure the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of the left ventricle. An automatic arteriosclerosis tester was used to measure ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). These parameters were compared among the three groups. The correlation of three-dimensional speckle-tracking parameters with ABI and baPWV was evaluated. RESULTS: There were no significant differences in GLS, GRS, and GCS between the obesity and normal groups (P>0.05). The overweight group had a significantly higher GLS than the normal group [(-24±7) vs (-19±12), P<0.05]. The obesity and overweight groups had a significantly lower ABI than the normal group [(1.00±0.09)/(1.09±0.13) vs (2.25±0.13), P<0.05). The obesity group had a significantly higher baPWV than the normal group [(978±109) vs (905±22), P<0.05]. In the children with obesity, GLS was positively correlated with baPWV (r=0.516, P<0.05) , but not correlated with ABI (P>0.05), and GCS and GRS had no significant correlation with ABI or baPWV (P>0.05). CONCLUSIONS: There are varying degrees of changes in left ventricular systolic function and peripheral arterial elasticity in children with simple obesity, and there is a certain correlation between them.

[Detection of drug-resistance genes of Mycoplasma pneumoniae in bronchoalveolar lavage fluid of children with refractory Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To study the drug resistance of Mycoplasma pneumoniae (MP) in the bronchoalveolar lavage fluid (BALF) of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and the distribution of drug-resistance genes, as well as the association of alleles at 2063 locus of 23SrRNA V region central ring with resistance to antimicrobial drugs. METHODS: BALF specimens were collected from 245 children with RMPP who were admitted to the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2020. A rapid cultured drug sensitivity assay was used to detect the resistance of MP isolates to nine commonly used antimicrobial drugs. The real-time PCR was used to measure MP DNA. The direct sequencing was used to detect gene mutations in MP 23SrRNA V region central ring. RESULTS: Among the 245 BALF specimens, 207 tested positive for MP DNA, with a positive rate of 84.5%. The results of drug susceptibility test showed that the children with RMPP had a resistance rate of > 70% to macrolide antimicrobial drugs, with the highest resistance rate to clarithromycin, followed by roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin, and these children had a resistance rate of < 5% to quinolone antimicrobial drugs. Among the 207 MP DNA-positive specimens, 41 (19.8%) had no drug-resistance gene mutations and 166 (80.2%) had drug-resistance gene mutations, among which 154 (74.4%) had an A→G mutation at 2063 locus of 23SrRNA V region central ring, 7 (3.4%) had an A→G mutation at 2064 locus, and 5 (2.4%) had mutations in both 2063 and 2064 loci. Among the 166 specimens with point mutations of the MP 23SrRNA gene, 159 (95.8%) had point mutations at 2063 locus. The A→G point mutation at 2063 locus of 23SrRNA V region central ring had a great impact on resistance to macrolide antimicrobial drugs. There was a significant difference in the distribution of alleles at 2063 locus between the children with resistance to clarithromycin, roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin (P < 0.05). CONCLUSIONS: MP in the BALF of children with RMPP has a relatively high resistance rate to macrolide antimicrobial drugs. Resistance to macrolide antimicrobial drugs is closely associated with the A→G point mutation in the 23SrRNA gene, and the point mutation at 2063 locus of 23SrRNA V region central ring may affect the drug-resistance mechanism of MP.

Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma.

BACKGROUND: The ability to treat glioblastoma (GBM) using the chemotherapeutic agent temozolomide (TMZ) has been hampered by the development of therapeutic resistance. In this study, we assessed the ability of the isoquinoline alkaloid berberine to alter GBM TMZ resistance using two different TMZ-resistant cell lines to mimic a physiologically relevant GBM experimental system. METHODS: By treating these resistant cell lines with berberine followed by TMZ, we were able to assess the chemosensitivity of these cells and their parental strains, based on their performance in the MTT and colony formation assays, as well as on the degree of detectable apoptosis that was detected in the strains. Furthermore, we used Western blotting to assess autophagic responses in these cell lines, and we extended this work into a xenograft mouse model to assess the in vivo efficacy of berberine. RESULTS: Through these experiments, our findings indicated that berberine enhanced autophagy and apoptosis in TMZ-resistant cells upon TMZ treatment in a manner that was linked with ERK1/2 signaling. Similarly, when used in vivo, berberine increased GBM sensitivity to TMZ through ERK1/2 signaling pathways. CONCLUSIONS: These findings demonstrate that berberine is an effective method of increasing the sensitization of GBM cells to TMZ treatment in a manner that is dependent upon the ERK1/2-mediated induction of autophagy, thus making berberine a potentially viable therapeutic agent for GBM treatment.

Clinical study of argatroban for preventing vascular thrombosis in the early period after pediatric living-related donor liver transplantation.

OBJECTIVE: To evaluate the effect of heparin and argatroban on coagulation function and vascular thrombosis in the early period after pediatric LRDLT. METHOD: Eighty-four congenital biliary atresia pediatric patients who had undergone LRDLT were studied. Patients were divided into two groups according to the method of anticoagulation (heparin or argatroban). AT-Ⅲ activity, APTT, and INR of the two groups were measured in the first 5 days after LRDLT. Vascular thrombosis was investigated by Doppler ultrasound daily. RESULTS: There were no significant differences in gender, age, weight, graft-recipient weight ratio, and Kasai procedure between the two groups. The AT-Ⅲ activity of the two groups was low and increased gradually after surgery, with no significant difference between the two groups. There was no significant difference of APTT between the two groups immediately after and in the first day after surgery. After anticoagulation treatment, a significant difference in APTT between the two groups was observed. The incidences of vascular thrombosis were 4.76% (3/63) and 0% (0/21) in the heparin and argatroban groups, respectively, with no significant difference between the two groups. During the treatment, no serious complications such as active hemorrhage or drug allergy were observed in the two groups. CONCLUSION: Argatroban is a direct anticoagulant, which is independent of AT-Ⅲ activity. Argatroban might be an alternative to heparin in uncomplicated LRDLT with recovered hepatic and coagulation function.

The relationship between sleep onset time and cardiometabolic biomarkers in Chinese communities: a cross-sectional study.

BACKGROUND: Late sleep onset time (SOT) is a common social phenomenon in modern society, and it was associated with a higher risk of obesity. However, the literature gap exists about the SOT and cardiometabolic biomarkers which closely associated with obesity. The present study aimed to explore the association of SOT with cardiometabolic biomarkers in Chinese communities. METHODS: A cross-sectional study enrolled a total of 2418 participants was conducted in Ningxia province of China. The cardiometabolic biomarkers included triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein and fasting plasma glucose were measured quantitatively using the standard method. The SOT and sleep duration were acquired by a self-report questionnaire. The multiple mixed-effect linear regression model was employed to examine the association. RESULTS: Binary analysis found an inverse association of SOT with high-density lipoprotein (ß = - 0.05, 95%CI: - 0.06, - 0.03), with 1 h delayed in SOT the high-density lipoprotein decreased 0.05 mmol/L. After controlling for demographic variables, health-related behaviors, and physical health covariates, late SOT was associated with a higher level of triglyceride (ß = 0.12, 95%CI: 0.06, 0.18), a higher level of low-density lipoprotein (ß = 0.06, 95% CI: 0.02, 0.09), and a lower level of high-density lipoprotein (ß = - 0.05, 95% CI: - 0.06, - 0.03). when stratified by sleep duration (less than eight hours vs. eight and longer hours), a positive association between SOT and LDL (ß = 0.08, 95% CI: 0.04, 0.12) was found among participants with sleep duration eight hours and longer. CONCLUSION: Late sleep onset time with the negative effect on the cardiometabolic biomarkers, and individuals with late SOT coupled with longer sleep duration may take risk of a higher level of low-density lipoprotein which in turn lead to increase the risk of cardiovascular disease.