KAT8 enhances the resistance of lung cancer cells to cisplatin by acetylation of PKM2.

Cisplatin (CDDP)-based chemotherapy resistance is a major challenge for lung cancer treatment. PKM2 is the rate-limiting enzyme of glycolysis, which is associated with CDDP resistance. KAT8 is an acetyltransferase that regulates lung cancer progression. Thus, we aimed to explore whether KAT8 regulates PKM2 acetylation to participate in CDDP resistance. CDDP resistance was analyzed by CCK-8, flow cytometry and western blotting. To explore the regulation of KAT8 on PKM2, coimmunoprecipitation (Co-IP), immunofluorescence and immunoprecipitation followed by western blotting were performed. Glycolysis was determined using glucose consumption, lactate production, ATP level detection kits and extracellular acidification rate assay. We observed that KAT8 levels were downregulated in CDDP-treated A549 and PC9 cells. Interference with KAT8 inhibited cell viability, promoted apoptosis and upregulated PARP1 and cleaved-PARP1 levels of A549 cells treated with CDDP, suggesting the sensitivity to CDDP was enhanced, while KAT8 overexpression attenuated the CDDP sensitivity. Moreover, KAT8 interacted with PKM2 to promote the PKM2 K433 acetylation. PKM2 K433 mutated plasmids inhibited the si-KAT8-regulated cell viability, apoptosis and glycolysis compared with PKM2-WT. Besides, KAT8 reversed the inhibition of tumor growth caused by CDDP. In conclusion, KAT8-mediated PKM2 K433 acetylation was associated with the resistance of lung cancer cells to CDDP. The findings may provide a new idea for the treatment of CDDP-resistant lung cancer.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Simultaneous and trace-level quantification of four benzene sulfonate potential genotoxic impurities in doxofylline active pharmaceutical ingredients and tablets using high-performance liquid chromatography with ultraviolet detection.

In the production of doxofylline, the common occurrence of toxic p-toluene sulfonate generation prompted the development and validation of a method using HPLC with ultraviolet detection (HPLC-UV). This method is designed for detecting four potential genotoxic impurities (PGIs) present in both doxofylline drug substance and tablets, with a focus on the UV-absorbing group p-toluene sulfonate. The four impurities were methyl 4-methylbenzenesulfonate (PGI-1), ethyl 4-methylbenzenesulfonate (PGI-2), 2-hydroxyethyl 4-methylbenzenesulfonate (PGI-3), and 2-(4-methylphenyl)sulfonyloxyethyl 4-methylbenzenesulfonate (PGI-4). In this method, chromatographic separation was achieved using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 µm). The mobile phases consisted of 20% acetonitrile as mobile phase A and pure acetonitrile as mobile phase B, operating in gradient elution mode at a flow rate of 1.0 mL/min. According to the guidelines of the International Conference on Harmonization, it was determined that this method could quantify four PGIs at 0.0225 µg/mL in samples containing 60 mg/mL. The validated approach demonstrated excellent linearity (R2 > 0.999) across the concentration range of 30%-200% (relative to 0.075 µg/mL doxofylline) for the four PGIs. The accuracy of this method for the four PGIs ranged from 94.8% to 100.4%. The reverse-phase-HPLC-UV analytical method developed in this study is characterized by its speed and precision, making it suitable for the sensitive analysis of benzene sulfonate PGIs in doxofylline drug substances and tablets.

Genome-wide identification and analysis of TCP family genes in Medicago sativa reveal their critical roles in Na+/K+ homeostasis.

BACKGROUND: Medicago sativa is the most important forage world widely, and is characterized by high quality and large biomass. While abiotic factors such as salt stress can negatively impact the growth and productivity of alfalfa. Maintaining Na+/K+ homeostasis in the cytoplasm helps reduce cell damage and nutritional deprivation, which increases a salt-tolerance of plant. Teosinte Branched1/ Cycloidea/ Proliferating cell factors (TCP) family genes, a group of plant-specific transcription factors (TFs), involved in regulating plant growth and development and abiotic stresses. Recent studies have shown TCPs control the Na+/K+ concentration of plants during salt stress. In order to improve alfalfa salt tolerance, it is important to identify alfalfa TCP genes and investigate if and how they regulate alfalfa Na+/K+ homeostasis. RESULTS: Seventy-one MsTCPs including 23 non-redundant TCP genes were identified in the database of alfalfa genome (C.V XinJiangDaYe), they were classified into class I PCF (37 members) and class II: CIN (28 members) and CYC/TB1 (9 members). Their distribution on chromosome were unequally. MsTCPs belonging to PCF were expressed specifically in different organs without regularity, which belonging to CIN class were mainly expressed in mature leaves. MsTCPs belongs to CYC/TB1 clade had the highest expression level at meristem. Cis-elements in the promoter of MsTCPs were also predicted, the results indicated that most of the MsTCPs will be induced by phytohormone and stress treatments, especially by ABA-related stimulus including salinity stress. We found 20 out of 23 MsTCPs were up-regulated in 200 mM NaCl treatment, and MsTCP3/14/15/18 were significantly induced by 10 µM KCl, a K+ deficiency treatment. Fourteen non-redundant MsTCPs contained miR319 target site, 11 of them were upregulated in MIM319 transgenic alfalfa, and among them four (MsTCP3/4/10A/B) genes were directly degraded by miR319. MIM319 transgene alfalfa plants showed a salt sensitive phenotype, which caused by a lower content of potassium in alfalfa at least partly. The expression of potassium transported related genes showed significantly higher expression in MIM319 plants. CONCLUSIONS: We systematically analyzes the MsTCP gene family at a genome-wide level and reported that miR319-TCPs model played a function in K+ up-taking and/ or transportation especially in salt stress. The study provide valuable information for future study of TCP genes in alfalfa and supplies candidate genes for salt-tolerance alfalfa molecular-assisted breeding.

A diagnostic approach integrated multimodal radiomics with machine learning models based on lumbar spine CT and X-ray for osteoporosis.

INTRODUCTION: The aim of this analysis is to construct a combined model that integrates radiomics, clinical risk factors, and machine learning algorithms to diagnose osteoporosis in patients and explore its potential in clinical applications. MATERIALS AND METHODS: A retrospective analysis was conducted on 616 lumbar spine. Radiomics features were extracted from the computed tomography (CT) scans and anteroposterior and lateral X-ray images of the lumbar spine. Logistic regression (LR), support vector machine (SVM), and random forest (RF) algorithms were used to construct radiomics models. The receiver operating characteristic curve (ROC) was employed to select the best-performing model. Clinical risk factors were identified through univariate logistic regression analysis (ULRA) and multivariate logistic regression analysis (MLRA) and utilized to develop a clinical model. A combined model was then created by merging radiomics and clinical risk factors. The performance of the models was evaluated using ROC curve analysis, and the clinical value of the models was assessed using decision curve analysis (DCA). RESULTS: A total of 4858 radiomics features were extracted. Among the radiomics models, the SVM model demonstrated the optimal diagnostic capabilities and accuracy, with an area under the curve (AUC) of 0.958 (0.9405-0.9762) in the training cohort and 0.907 (0.8648-0.9492) in the test cohort. Furthermore, the combined model exhibited an AUC of 0.959 (0.9412-0.9763) in the training cohort and 0.910 (0.8690-0.9506) in the test cohort. CONCLUSION: The combined model displayed outstanding ability in diagnosing osteoporosis, providing a safe and efficient method for clinical decision-making.

The mediating effect of distress tolerance on the relationship between stressful life events and suicide risk in patients with major depressive disorder.

BACKGROUND: Despite widespread acknowledgment of the impact of stressful life events on suicide risk, the understanding of the psychological mechanisms underlying the relationship between stressful life events and suicide risk in major depressive disorder (MDD) remain unclear. This study aim to examine whether the distress tolerance mediates the relationship between the stressful life events and suicide risk in patients with MDD. METHODS: A cross-sectional study was carried out among 125 Chinese patients with MDD, mean age was 27.05 (SD=0.68) and 68.8% were females. The 17-item Hamilton Depression Rating scale (HAMD-17), the validated Chinese version of the Mini International Neuropsychiatric Interview (MINI) suicide module, Life Events Scale (LES) and Distress Tolerance Scale (DTS) were utilized to evaluate depressive symptoms, stressful life events, levels of distress tolerance, and suicide risk, respectively. Mediation analyses was used to test the mediation effect of distress tolerance on the relationship between stressful life events and suicide risk. RESULTS: The ratio of suicide risk in patients with MDD was 75.2%. Pearson correlation analysis showed that stressful life events were positively correlated with suicide risk(r=0.182, p<0.05). Stressful life events(r=-0.323, p<0.01) and suicide risk(r=-0.354, p<0.01) were negatively correlated with distress tolerance. Mediation analyses showed that the direct path from stressful life events to suicide risk was not significant (B= 0.012, 95% confidence interval (CI) [-0.017, 0.042]). Stressful life events affected suicide risk indirectly through distress tolerance (B= 0.018, 95% CI [0.007, 0.031]), and the mediating effect accounted for 60.0% of the total effect. CONCLUSION: Distress tolerance completely played a mediating role between stressful life events and suicide risk. Further suicide prevention and intervention strategies should focus on increasing levels of distress tolerance in patients with MDD.

Correlation of gut dominant microbiota with hyperuricemia. / åŸºäºŽç²ªä¾¿è‚ é“ä¼˜åŠ¿èŒç¾¤æ£€æµ‹æ•°æ®çš„é«˜å°¿é ¸è¡€ç—‡ç›¸å ³å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To study the correlation of intestinal dominant flora with hyperuricemia, and to explore influencing factors of hyperuricemia. METHODS: Data of gut dominant microbiota were collected from subjects who underwent health check-up in Shulan (Hangzhou) Hospital from January 2018 to April 2020. Subjects with high uric acid and normal uric acid were matched by propensity score matching method according to age, gender and body mass index (BMI). This resulted in 178 pairs as hyperuricemia group and control group. The gut dominant microbiota between hyperuricemia and normal control group were compared. Pearson or Spearman correlation coefficient method was used to analyze the correlation between blood uric acid and intestinal dominant flora. Univariate and multivariate logistic regression were used to analyze the influencing factors of hyperuricemia. RESULTS: The abundance of Atopobium, Lactobacillus, Bacteroides, Enterococcus, Clostridium leptum, Fusobacterium prausnitzii, Bifidobacterium, Clostridium butyricum and the ratio of Bifidobacterium to Enterobacter (B/E) in the hyperuricemia group were significantly lower than those in the control group (all P<0.01). The correlation analysis showed that serum uric acid were negatively correlated with the abundance of Atopobium (r=－0.224, P<0.01), Bacteroides (r=－0.116, P<0.05), Clostridium leptum (r=－0.196, P<0.01), Fusobacterium prausnitzii (r=－0.244, P<0.01), Bifidobacterium (r=－0.237, P<0.01), Eubacterium rectale (r=－0.125, P<0.05), Clostridium butyricum (r=－0.176, P<0.01) and B/E value (r=－0.127, P<0.05). Multivariate logistic regression analysis showed that glutamyl transpeptidase was an independent risk factor for hyperuricemia (OR=1.007, 95%CI: 1.002-1.012, P<0.05), and the Atopobium was an independent protective factor for hyperuricemia (OR=0.714, 95%CI: 0.605-0.842, P<0.01). CONCLUSIONS: There are alterations in abundance of gut dominant microbiota in patients with hyperuricemia, and Atopobium abundance appears as a protective factor for hyperuricemia.

Quantitative Proteomic Analysis to Understand the Mechanisms of Zinc Oxide Nanoparticle Toxicity to Daphnia pulex (Crustacea: Daphniidae): Comparing with Bulk Zinc Oxide and Zinc Salt.

The widespread use of zinc oxide nanoparticles (ZnO NPs) has resulted in their release to the environment. There has been concern about the ecotoxicity of ZnO NPs, but little is known about their toxic mechanisms. In the present study, we conducted acute toxicity tests to show that ZnO NPs are more toxic to the freshwater crustacean Daphnia pulex compared to bulk ZnO or ZnSO4·7H2O. To provide an integrated and quantitative insights into the toxicity of ZnO NPs, we conducted isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis, which detected 262, 331, and 360 differentially expressed proteins (DEPs) in D. pulex exposed to ZnO NPs, bulk ZnO, and ZnSO4·7H2O, respectively. Among the DEPs, 224 were shared among the three treatments. These proteins were related to energy metabolism, oxidative stress, and endoplasmic reticulum stress. The three forms of Zn all caused D. pulex to downregulate Chitinase expression, disrupt Ca2+ homeostasis, and reduce expression of digestive enzymes. Nevertheless, 29 proteins were expressed only in the ZnO NP treatment. In particular, histone (H3) and ribosomal proteins (L13) were obviously influenced under ZnO NP treatment. However, increased expression levels of h3 and l13 genes were not induced only in ZnO NP treatment, they were sensitive to Zn ions under the same exposure concentration. These results indicate that the three zinc substances have a similar mode of action and that released zinc ions are the main contributor to ZnO NP toxicity to D. pulex under a low concentration. Further investigation is needed to clarify whether a small proportion of DEPs or higher bioavailability cause ZnO NPs to be more toxic compared to bulk ZnO or ionic zinc.

Psychotropic medication treatment patterns in community-dwelling schizophrenia in China: comparisons between rural and urban areas.

BACKGROUND: To date no study has compared more specifically the psychotropic medication treatment patterns for patients with schizophrenia living in community between rural and urban areas. This study examined the rural-urban differences of the use of psychotropic drugs among community-dwelling individuals with schizophrenia in China. METHOD: Data on 993 community-dwelling patients with schizophrenia (n = 479 in rural area and n = 514 urban area) were collected by interviews during 2013-2014, and 2015-2016 according to the diagnosis of DSM-IV or ICD-10. Data on patients' socio-demographic and clinical characteristics, prescriptions of psychotropic drugs were collected using a standardized protocol and data acquisition procedure. RESULTS: Multivariate analyses revealed that in comparison with the rural counterparts, the patients from the urban area were significantly more frequently prescribed antipsychotic polypharmacy, clozapine, and benzodiazepines, but the patients from the rural area had more frequently prescribed anticholinergics. CONCLUSIONS: Substantial variations in psychotropic medication treatment patterns for patients with schizophrenia living in community were found between rural and urban areas in China. Common use of antipsychotic polypharmacy, clozapine and benzodiazepines in urban area, and anticholinergics in rural area need to be further addressed.

CD44-Targeted Facile Enzymatic Activatable Chitosan Nanoparticles for Efficient Antitumor Therapy and Reversal of Multidrug Resistance.

Nanoparticles are attractive platforms for the delivery of various anticancer therapeutics. Nevertheless, their applications are still limited by the relatively low drug loading capacity and the occurrence of multidrug resistance (MDR) against chemotherapeutics. In this study, we report that the integration of d-α-tocopherol succinate (VES) residue with both chitosan and paclitaxel (PTX) led to significant improvement of drug loading capacity and drug loading efficiency through the enhancement of drug/carrier interaction. After the incorporation of hyaluronic acid containing PEG side chains (HA-PEG), higher serum stability and more efficient cellular uptake were obtained. Due to HA coating, VES residues and the enzymatic responsive drug release property, such facile nanoparticles actively targeted cancer cells that overexpress CD44 receptor and efficiently reversed the MDR of treated cells, but caused no significant toxicity to mouse fibroblast (NIH-3T3). More importantly, with HA-PEG coating, longer blood circulation and more effective tumor accumulation were achieved for prodrug nanoparticles. Finally, superior anticancer activity and excellent safety profile was demonstrated by HA-PEG coated enzymatically activatable prodrug nanoparticles compared to commercially available Taxol formulation.

Surface-coated probe nanoelectrospray ionization mass spectrometry for analysis of target compounds in individual small organisms.

Analysis of target compounds in individual small organisms is of significant importance for biological, environmental, medicinal, and toxicological investigation. In this study, we reported the development of a novel solid-phase microextraction (SPME) based ambient mass spectrometry (MS) method named surface-coated probe nanoelectrospray ionization (SCP-nanoESI)-MS for analysis of target compounds in individual small organisms with sizes at micrometer-to-millimeter level. SCP-nanoESI-MS analysis involves three procedures: (1) modification of adsorbent at the surface of a fine metal probe to form a specially designed surface-coated SPME probe with probe-end diameter at several-micrometer level, (2) application of the surface-coated SPME probe for enrichment of target analytes from individual small organisms, and (3) employment of a nanospray tip and some solvent to desorb the analytes and induce nanoESI for mass spectrometric analysis under ambient condition. A SCP-nanoESI-MS method for determination of the perfluorinated compounds (PFCs) in individual Daphnia magna was developed. The method showed satisfactory linearities for analysis of real Daphnia magna samples, with correlation coefficient values (R(2)) of 0.9984 and 0.9956 for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), respectively. The limits of detection were 0.02 and 0.03 ng/mL for PFOS and PFOA, respectively. By using the proposed method, the amount, bioaccumulation kinetics, and distribution of PFOS and PFOA in individual Daphnia magna were successfully investigated.

[The predictive factors of good glycaemic control in Chinese patients receiving biphasic insulin as part 30: a subgroup analyses from the A1 chieve study].

OBJECTIVE: To identify the baseline factors associated with achievement of glycosylated haemoglobin A1c (HbA1c) < 7.0% in Chinese patients receiving biphasic insulin as part 30 (BIAsp 30), who were previously inadequately controlled with oral anti-diabetic drugs (OADs). METHODS: A1 chieve was a multinational, prospective, open-label, 24-week non-interventional study in patients with type 2 diabetes initiating insulin analogues in 28 countries. The patients were enrolled to take BIAsp 30 according to physician's clinical judgments, who was also responsible for the treatment regimen and dosage adjustment. Primary safety endpoints were the incidence of serious drug adverse reactions (SADRs) including serious hypoglycaemia. Major efficacy endpoints were change in HbA1c, fasting plasma glucose (FPG), 2h post-prandial plasma glucose (2 hPG) from baseline. Relationships between baseline predictive baseline factors and achievement of HbA1c < 7.0% after treatment were examined using multivariate analysis. RESULTS: In China, 4 100 patients initiated BIAsp 30 [54.2% males, age (56.2 ± 13.6) years]. No SADRs were reported. Mean HbA1c was reduced from (9.3 ± 2.1)% to (7.0 ± 1.0)%; FPG was reduced from (10.2 ± 3.3) mmol/L to (6.8 ± 1.3) mmol/L. Changes in 2 hPG after breakfast, lunch and dinner were (-5.6 ± 4.7), (-4.9 ± 4.3) and (-4.2 ± 4.1) mmol/L, respectively (all P < 0.001). The proportion of patients achieving HbA1c < 7.0% increased from 9.7% at baseline to 54.2% at week 24. Multivariate analysis revealed a negative relationship between baseline HbA1c, FPG, 2 hPG and HbA1c < 7.0% after treatment. CONCLUSIONS: In the Chinese subgroup of the A1 chieve study, lower baseline HbA1c, FPG, 2 hPG were predictive factors for achieving HbA1c < 7.0% after 24-week treatment of BIAsp 30, indicating that the earlier initiation of BIAsp 30 in patients poorly controlled with OADs, the more helpful for them to achieve treatment target.

ABCA1 and ABCG1 expression in the small intestine of type 2 diabetic rats.

OBJECTIVE: Inflammation of the small intestine may occur in type 2 diabetes. This study aimed to investigate whether ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) were altered in chronic inflammation of the small intestine of type 2 diabetic rats. METHODS: Thirty-two male Sprague-Dawley rats were used. Eight rats in the control group were fed with regular chow, and 24 rats were fed a high-fat diet and injected with a single low dose of streptozotocin. All of the control rats and diabetic rats were bred for 10 months. Immunohistochemistry detected ABCA1 and ABCG1 in the small intestine in all the rats. RESULTS: Hematoxylin-eosin staining showed chronic inflammation in the small intestine of the diabetic rats. Immunohistochemistry staining showed that alteration of ABCA1 and ABCG1 was different in the inflammatory and epithelial cells. Quantitative analysis showed that the overall expression of ABCA1 and ABCG1 increased in the diabetic rats compared to the control rats. Both ABCA1 and ABCG1 were enriched in the inflammatory cells of the small intestine in diabetic rats. In the epithelial cells, ABCA1, but not ABCG1, was detected in significantly more diabetic rats than control rats. CONCLUSION: Both ABCA1 and ABCG1 are enriched in chronic inflammation of the small intestine of type 2 diabetic rats. ABCA1, but not ABCG1, is activated in the intestinal epithelial cells of type 2 diabetic rats.

Overexpression of miR-204-5p Alleviates Osteogenic Differentiation and Calcification of Human Aortic Vascular Smooth Muscle Cells by Targeting Calcium/Calmodulin-dependent Protein Kinase 1.

ABSTRACT: Vascular calcification (VC), a major complication in chronic kidney disease (CKD), is predominantly driven by osteoblastic differentiation. Recent studies have highlighted the crucial role of microRNAs in CKD's pathogenesis. Here, our research focused on the effects of miR-204-5p and its molecular mechanisms within VC. We initially found a notable decrease in miR-204-5p levels in human aortic vascular smooth muscle cells stimulated with inorganic phosphate, using this as a VC model in vitro. Following the overexpression of miR-204-5p, a decrease in VC was observed, as indicated by alizarin red S staining and measurements of calcium content. This decrease was accompanied by lower levels of the osteogenic marker, runt-related transcription factor 2, and higher levels of α-smooth muscle actin, a marker of contractility. Further investigation showed that calcium/calmodulin-dependent protein kinase 1 (CAMK1), which is a predicted target of miR-204-5p, promotes VC. Conversely, overexpressing miR-204-5p reduced VC by suppressing CAMK1 activity. Overexpressing miR-204-5p also effectively mitigated aortic calcification in an in vivo rat model. In summary, our research indicated that targeting the miR-204-5p/CAMK1 pathway could be a viable strategy for mitigating VC in CKD patients.

The causal relationship between diet habits and cholelithiasis: a comprehensive Mendelian randomization (MR) study.

Background: Epidemiological studies show dietary habits can have an impact on the risk of cholelithiasis, but the relationship is still unclear. We used a comprehensive Mendelian randomization (MR) study to explore the relationship between dietary habits and cholelithiasis. Methods: The 18 dietary habits were divided into six categories: meat foods, cereals, vegetables, fruits, dairy products, beverages, and condiments. Cholelithiasis data came from a GWAS meta-analysis and the FinnGen consortium. The inverse variance weighted (IVW), the weighted median (WM), and MR-Egger approaches were used as the main MR analysis methods. In addition, multiple sensitivity analysis and meta-analysis were performed to verify the robustness of the results. Results: Dried fruit intake [odds ratio (OR) = 0.568; 95% confidence interval (CI), 0.405-0.797; p = 0.001] was discovered to reduce the risk of cholelithiasis. The sensitivity analysis and meta-analysis showed reliable results for the relationship between dried fruit intake and cholelithiasis. Conclusion: Our study found that dried fruit intake is a protective factor in the development of cholelithiasis. However, the mechanisms of action need to be further explored.

Blocking miR396 activity by overexpression MIM396 improved switchgrass tiller number and biomass yield.

BACKGROUND: MicroRNA396 (miR396) plays an important role in the regulation of plant growth and development by repressing the expression level of its target growth-regulating factor (GRF) family genes. In our previous study, we found that overexpression of miR396 negatively regulated both tillering and biomass yield in switchgrass (Panicum virgatum L.). We, therefore, speculated that blocking the expression of miR396 could enhance switchgrass tillering and biomass yield. Here, we produced transgenic switchgrass plants overexpressing a target mimicry form of miR396 (MIM396) in wild type (WT) and Os-MIR319b overexpressing switchgrass plant (with higher enzymatic hydrolysis efficiency, but reduced tillering), in which the expression of miR396 was blocked. The phenotype and biological yields of these plants were analyzed. RESULTS: Blocking miR396 to improve its target PvGRFs expression in switchgrass improved the tiller number and dry weight of transgenic plants. Further morphological analysis revealed that MIM396 plants increased the number of aerial branches and basal tillers compared to those of wild-type plants. The enzymatic efficiency of MIM396 plants was reduced; however, the total sugar production per plant was still significantly higher than that of wild-type plants due to the increase in biomass. In addition, blocking miR396 in a transgenic switchgrass plant overexpressing Os-MIR319b (TG21-Ms) significantly increased the PvGRF1/3/5 expression level and tiller number and biomass yield. The miR156-target gene PvSPL4, playing a negative role in aerial and basal buds outgrowth, showed significant downregulated in MIM396 and TG21-Ms. Those results indicate that miR396-PvGRFs, through disrupting the PvSPL4 expression, are involved in miR319-PvPCFs in regulating tiller number, at least partly. CONCLUSIONS: MIM396 could be used as a molecular tool to improving tiller number and biomass yield in switchgrass wild type and miR319b transgenic plants. This finding may be applied to other graminaceous plants to regulate plant biological yield.

Characterization of gut dominant microbiota in obese patients with nonalcoholic fatty liver disease.

In obese patients, non-alcoholic fatty liver (NAFLD) is common. However, whether there is a connection between the gut microbiota and the onset of NAFLD in obese people is yet unknown. Using quantitative real-time PCR, the microbiota of feces of the eligible 181 obese individuals was identified to compare the differences in gut microbiota between obesity with NAFLD and simple obesity. According to the findings, the gut dominant microbiota was similar between obesity with NAFLD and simple obesity. Nonetheless, compared to the simple obesity group, the quantity of Faecalibacterium prausnitzii colonies was much lower in the obesity with the NAFLD group. Bacteroides were present in greater than 65% of both groups. Bacteroides, Clostridium leptum, and Clostridium butyricum accounted for more than 80% of the cases in the obesity with NAFLD group, whereas Bacteroides, Clostridium butyricum, and F. prausnitzii accounted for more than 80% of the cases in the simple obesity group. We look for potential contributing variables to obesity-related NAFLD and potential prevention measures for obese people. Based on a multi-factor logistic regression analysis, lymphocytes may be a risk factor for obesity with NAFLD while F. prausnitzii may be a protective factor. Additionally, F. prausnitzii is positively impacted by Bacteroides, Clostridium leptum, Clostridium butyricum, and Eubacterium rectale, yet adversely impacted by Enterobacteriaceae. Notably, lymphocytes and F. prausnitzii may help determine whether obese patients would develop NAFLD.

RPS15A Mediates PI3K/AKT Signaling-Induced Parathyroid Cell Proliferation in Rats with Secondary Hyperparathyroidism.

OBJECTIVE: Ribosomal protein S15A (RPS15A) has been identified as a new oncogene in several tumors, but its functional role in secondary hyperparathyroidism (SHPT) characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation remains unclear. METHODS: A rat model of SHPT was successfully established with a high-phosphorus diet plus 5/6 nephrectomy. ELISA assay was used to determine PTH, calcium and phosphorus and ALP activity. Cell proliferation was analyzed by Cell counting Kit-8 (CCK-8) assay. Flow cytometry assay was utilized to determine cell cycle distribution and apoptosis in parathyroid cells. LY294002, an inhibitor of PI3K/AKT signaling, was used to elucidate the relationship between RPS15A and PI3K/AKT signaling. Immunohistochemical (IHC) staining, quantitative real time PCR and western blot analysis were applied to determine related molecular levels. RESULTS: Our data showed an upregulation of RPS15A and activated PI3K/AKT signaling pathway in the parathyroid gland tissues of SHPT rats, accompanied with increased PTH, calcium and phosphorus levels. Knockdown of RPS15A decreased parathyroid cell proliferation, induced cell cycle arrest and apoptosis. Treatment with LY294002 reversed the effects of pcDNA3.1-RPSH15A in parathyroid cells. CONCLUSIONS: Our study demonstrated RPS15A-mediated PI3K/AKT pathway as a novel molecular mechanism in the pathogenesis of SHPT, which may provide a new drug target in the future.

Feasibility and safety of guidewire-balloon entrapment technique for recanalization of thoracic central vein occlusion in hemodialysis patients.

OBJECTIVE: To explore the feasibility and safety of Guidewire-Balloon Entrapment Technique (GBET) for the recanalization of thoracic central vein occlusions (TCVOs) in hemodialysis patients. METHODS: A retrospective observational study was conducted using data from 28 patients who required the establishment or maintenance of hemodialysis access and were treated with GBET for the recanalization of right-sided TCVOs from January 2017 to April 2021. Of the patients, 27 required tunneled cuffed catheter (TCC) placement or exchange, and 1 had an outflow tract occlusion of the Brescia-Cimino radio cephalic arteriovenous fistula (AVF). RESULTS: A total of 26 patients successfully underwent TCC exchange and placement using GBET; 1 patient underwent successful recanalization of an occlusion of the outflow tract of the right Brescia-Cimino AVF; and 1 patient underwent successful TCC placement in the left internal jugular vein (LIJV) after the failure of TCC placement in the right internal jugular vein (RIJV). The success rate for GBET was 27/28 (96.43%), and there were no major complications. CONCLUSION: GBET is a safe and effective method for the recanalization of right-sided TCVOs, especially for TCC exchange and placement, and can be used as a safe and easy approach for TCVO recanalization.