AMPK regulates immature boar Sertoli cell proliferation through affecting CDK4/Cyclin D3 pathway and mitochondrial function.

Sertoli cell (SC) proliferation plays an important role in sperm production and quality; however, the regulatory mechanism of SC proliferation is not well understood. This study investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in the regulation of immature boar SC activity. Cell counting kit-8, Seahorse XFe96, mitochondrial respiratory enzyme-related assay kits, and transmission electron microscopy were used to detect SC proliferative viability, oxygen consumption rate (OCR), mitochondrial respiratory enzyme activity, and the ultrastructure of primary cultured SCs in vitro from the testes of 21-day-old boars. A dual luciferase reporter assay was performed to determine the miRNA-mRNA target interaction. Western blotting was used to analyze cell proliferation-related protein expression of p38, p21, proliferating cell nuclear antigen (PCNA), Cyclin-dependent kinase 4 (CDK4), Cyclin D3, and phosphorylated retinoblastoma protein (Rb). Each experiment had a completely randomized design, with three replicates in each experiment. The results showed that the AMPK inhibitor (Compound C, 20 µM-24 h) increased cell proliferation viability, ATP production, and maximal respiration of SCs by 0.64-, 0.12-, and 0.08-fold (p < 0.05), respectively; increased the SC protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.13-, 0.09-, 0.88-, and 0.12-fold (p < 0.05), respectively; and decreased the SC protein expression of p38 and p21 by 0.36- and 0.27-fold (p < 0.05), respectively. The AMPK agonist AICAR (2 mM-6 h) significantly inhibited SC ultrastructure, OCR, mitochondrial respiratory enzyme activity, and cell proliferation-related protein levels. AMPK was validated to be a target gene of miR-1285 based on the result in which the miR-1285 mimic inhibited the luciferase activity of wild-type AMPK by 0.54-fold (p < 0.001). MiR-1285 mimic promoted the OCR of SCs, with 0.45-, 0.15-, 0.21-, and 0.30-fold (p < 0.01) increases in ATP production, basal and maximal respiration, and spare capacity, respectively. MiR-1285 mimic increased the mitochondrial respiratory enzyme activity of SCs, with 0.63-, 0.70-, and 0.97-fold (p < 0.01) increases in NADH-Q oxidoreductase, cytochrome c oxidase, and ATP synthase, respectively. Moreover, the miR-1285 mimic increased the protein expression of PCNA, CDK4, Cyclin D3, and p-Rb by 0.24-, 0.30-, 0.22-, and 0.13-fold (p < 0.05), respectively, and reduced the protein expression of p38 and p21 by 0.58- and 0.66-fold (p < 0.001). MiR-1285 inhibitor showed opposite effects on the above indicators and induced numerous autophagosomes and large lipid droplets in SCs. A high dose of estradiol (10 µM-6 h, showed a promotion of AMPK activation in a previous study) significantly inhibited SC ultrastructure, mitochondrial function, and proliferation-related pathways, while these adverse effects were weakened by Compound C treatment or miR-1285 mimic transfection. Our findings suggest that the activation and inhibition of AMPK induced by specific drugs or synthesized targeted miRNA fragments could regulate immature boar SC proliferative activity by influencing the CDK4/Cyclin D3 pathway and mitochondrial function; this helps to provide a basis for the prevention and treatment of male sterility in clinical practice.

Design, synthesis, and antibacterial activity of pleuromutilin derivatives.

This paper reports the design, synthesis, and antibacterial activity study of pleuromutilin derivatives with 2-methyl-4-nitroaniline and 2-methoxy-4-nitroaniline side chains at the C22 position. The structures of the new compounds were characterized by 1H-NMR, 13C-NMR and HRMS. The inhibitory activity of the compounds against MSSA, pyogeniccoccus, streptococcus, and MRSA strains was determined using the micro broth dilution method. The results showed that the compounds exhibited certain activity against Gram-positive bacteria, among which compounds A8a, A8b, A8c, A8d, and A7 demonstrated superior antibacterial activity against MSSA, MRSA, and pyogeniccoccus compared to tiamulin, although the derivatives showed lower antibacterial activity against streptococcus compared to the control drug. Based on the favorable in vitro activity of A8c, the time-kill kinetics against MRSA were evaluated, revealing that compound A8c could inhibit bacterial proliferation in a concentration-dependent manner.

Clinical and biochemical characteristics, and outcome in 33 patients with ceftriaxone-induced liver injury.

PURPOSE: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. METHODS: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. RESULTS: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. CONCLUSION: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.

Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

The Prognostic Value of D-Dimer in Patients with Acute Myocardial Infarction: A Retrospective Longitudinal Cohort Study in Taiwan.

Background: Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. Methods: We analyzed Tri-Service General Hospital-Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (≥ 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in-hospital mortality, and secondary endpoints were post-discharge mortality and post-discharge major adverse cardiovascular events. Results: Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non-cardiovascular causes. In-hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in-hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). Conclusions: This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in-hospital mortality, post-discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.

Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan.

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

Predictors of Remission or Combined Remission and Low Disease Activity in Rheumatoid Arthritis Patients in Taiwan: A Prospective Cohort Study.

Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ≦ 11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores.

Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

The mediating effect of health behaviors on the association between job strain and mental health outcome: a national survey of police officers.

Police officers often face emotionally challenging interpersonal situations and numerous studies have demonstrated that policing is a stressful occupation. A study revealed a significant positive correlation between emotional demands among police officers and emotional dissonance, as well as burnout. Health-promoting behaviors can contribute to better overall health outcomes and reduce the risk of developing health problems, but there is limited research evaluating the association of job strain and health behaviors with mental health outcomes in police officers. The objective of this study was to assess the job strain associated with mental health mediated by health behaviors in Taiwanese police officers. This was a cross-sectional quantitative study conducted in Oct 2016. A total of 41,871 police officers (response rate was 79.7%) participated questionnaire that consisted of demographic information, job characteristics, health behaviors, and mental component summary (MCS) scores of the Short-Form Health Survey. Independent t-tests and one-way analysis of variance (One-way ANOVA) were conducted to assess the differences in mean MCS scores across various demographics, health behavior, and job characteristics. Multivariate regression analyses were used to assess the relationship between job strain and health behaviors with mental health outcomes. MCS scores were associated with job characteristics and health behaviors among police officers except for gender. After adjusting for covariates, multivariate analysis indicated that police officers with high job demands and high job strain index exhibited poor MCS scores. Job strain was significantly associated with MCS mediated by health behaviors (consumption of fruits and vegetables, and physical activity) in Taiwanese police officers. Since regular physical activity and increased vegetable and fruit consumption might alleviate the effects of job strain on mental health status, it is recommended that institutional policies be established to promote health-enhancing behaviors among police officers.

N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance.

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.

Pancreatic mucinous adenocarcinoma has different clinical characteristics and better prognosis compared to non-specific PDAC: A retrospective observational study.

Background: Pancreatic mucinous adenocarcinoma (PMAC) is a rare malignant tumour, and there is limited understanding of its epidemiology and prognosis. Initially, PMAC was considered a metastatic manifestation of other cancers; however, instances of non-metastatic PMAC have been documented through monitoring, epidemiological studies, and data from the Surveillance, Epidemiology, and End Results (SEER) database. Therefore, it is crucial to investigate the epidemiological characteristics of PMAC and discern the prognostic differences between PMAC and the more prevalent pancreatic ductal adenocarcinoma (PDAC). Methods: The study used data from the SEER database from 2000 to 2018 to identify patients diagnosed with PMAC or PDAC. To ensure comparable demographic characteristics between PDAC and PMAC, propensity score matching was employed. Kaplan-Meier analysis was used to analyse overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were used to determine independent risk factors influencing OS and CSS. Additionally, the construction and validation of risk-scoring models for OS and CSS were achieved through the least absolute shrinkage and selection operator-Cox regression technique. Results: The SEER database included 84,857 patients with PDAC and 3345 patients with PMAC. Notably, significant distinctions were observed in the distribution of tumour sites, diagnosis time, use of radiotherapy and chemotherapy, tumour size, grading, and staging between the two groups. The prognosis exhibited notable improvement among married individuals, those receiving acceptable chemotherapy, and those with focal PMAC (p < 0.05). Conversely, patients with elevated log odds of positive lymph node scores or higher pathological grades in the pancreatic tail exhibited a more unfavourable prognosis (p < 0.05). The risk-scoring models for OS or CSS based on prognostic factors indicated a significantly lower prognosis for high-risk patients compared to their low-risk counterparts (area under the curve OS: 0.81-0.82, CSS: 0.80-0.82). Conclusion: PMAC exhibits distinct clinical characteristics compared to non-specific PDAC. Leveraging these features and pathological classifications allows for accurate prognostication of PMAC or PDAC.

MicroRNA bmo-miR-31-5p inhibits apoptosis and promotes BmNPV proliferation by targeting the CYP9e2 gene of Bombyx mori.

BACKGROUND: Bombyx mori nuclear polyhedrosis virus (BmNPV), as a typical baculovirus, is the primary pathogen that infects the silkworm B. mori, a lepidopteran species. Owing to the high biological safety of BmNPV in infecting insects, it is commonly utilized as a biological insecticide for pest control. Apoptosis is important in the interaction between the host and pathogenic microorganisms. MicroRNAs (miRNAs) influence immune responses and promote stability of the immune system via apoptosis. Therefore, the study of apoptosis-related miRNA in silkworms during virus infection can not only provide support for standardizing the prevention and control of diseases and insect pests, but also reduce the economic losses to sericulture caused by the misuse of biological pesticides. RESULTS: Through transcriptome sequencing, we identified a miRNA, miR-31-5p, and demonstrated that it can inhibit apoptosis in silkworm cells and promote the proliferation of BmNPV in BmE-SWU1 cells. We identified a target gene of miR-31-5p, B. mori cytochrome P450 9e2 (BmCYP9e2), and demonstrated that it can promote apoptosis in silkworm cells and inhibit the proliferation of BmNPV. Moreover, we constructed transgenic silkworm strains with miR-31-5p knockout and confirmed that they can inhibit the proliferation of BmNPV. CONCLUSION: These data indicate that miR-31-5p may exert functions of inhibiting apoptosis and promoting virus proliferation by regulating BmCYP9e2. The findings demonstrate how miRNAs influence host cell apoptosis and how they are involved in the host immune system response to viruses, providing important insights into the applications of biological insecticides for pest control. © 2024 Society of Chemical Industry.

Bombyx moriSuppressor of Hairless is involved in the regulation of the silkworm cell cycle and endoreplication of the silk glands.

The Notch signaling pathway is important in cell cycle regulation and cell proliferation. The transcriptional repressor Suppressor of Hairless [Su(H)] is a molecular switch for downstream target genes of the Notch signaling pathway but the regulatory mechanism of the Su(H) gene in the cell cycle is unclear. We determined the function of the Notch signaling pathway and Bombyx mori Su(H) [BmSu(H)] in the regulation of the silkworm cell cycle. Inhibition of Notch signaling promoted the replication of DNA in silkworm gland cells and expression of the BmSu(H) gene was significantly reduced. Overexpression of the BmSu(H) gene inhibited DNA replication and cell proliferation of silkworm cells, whereas knockout of the BmSu(H) gene promoted DNA replication and cell proliferation. Knockout of the BmSu(H) in silkworms improved the efficiency of silk gland cell endoreplication and increased important economic traits. We demonstrated that BmSu(H) protein can directly bind to the promoters of BmCyclinA, BmCyclinE and BmCDK1 genes, inhibiting or promoting their transcription at the cell and individual level. This study identified molecular targets for genetic improvement of the silkworm and also provided insights into the regulatory mechanism of the cell cycle.

Relative and absolute inequalities in cerebrovascular disease mortality rates: exploring the influence of socioeconomic status and urbanization levels in Taiwan.

BACKGROUND/OBJECTIVE: Limited evidence exists regarding the socioeconomic inequalities in cerebrovascular disease (CBD) mortality at different urbanization levels. Therefore, this study was conducted to assess the socioeconomic inequalities and urbanization levels in township-based CBD mortality in Taiwan. METHODS: Socioeconomic variables, including the percentages of low-income households, individuals with a university education and above, and tax payments, were measured at the township level from 2011 to 2020. Urbanization was also determined by the national survey and divided into seven levels. Age-standardized mortality rate (ASMR) of CBD was calculated using a Geographic Information System (GIS) in 358 townships. The effects of socioeconomic variables and urbanization levels on relative and absolute inequalities in township-based CBD mortality rates were examined. RESULTS: Significant differences in ASMR of CBD were observed across all socioeconomic status indicators over the years. Higher proportions of low-income households were associated with higher ASMR of CBD. Conversely, there were negative correlations between higher proportions of individuals with a university education and above and tax payments with ASMR of CBD. The regression analysis indicated significant impacts of relative and absolute socioeconomic inequalities on ASMR of CBD. Additionally, a moderation effect of socioeconomic variables and urbanization on CBD mortality rates was observed, with rural areas showing sensitivity to these factors. CONCLUSION: Although ASMR of CBD showed significant decreases over time, socioeconomic inequalities in CBD mortality rates persist. Interventions targeting socioeconomic inequalities in health outcomes, especially in rural areas, are needed to address this issue.

Bioinspired Quantum Oracle Circuits for Biomolecular Solutions of the Maximum Cut Problem.

Given an undirected, unweighted graph with n vertices and m edges, the maximum cut problem is to find a partition of the n vertices into disjoint subsets V1 and V2 such that the number of edges between them is as large as possible. Classically, it is an NP-complete problem, which has potential applications ranging from circuit layout design, statistical physics, computer vision, machine learning and network science to clustering. In this paper, we propose a biomolecular and a quantum algorithm to solve the maximum cut problem for any graph G. The quantum algorithm is inspired by the biomolecular algorithm and has a quadratic speedup over its classical counterparts, where the temporal and spatial complexities are reduced to, respectively, O(√2n/r) and O(m2). With respect to oracle-related quantum algorithms for NP-complete problems, we identify our algorithm as optimal. Furthermore, to justify the feasibility of the proposed algorithm, we successfully solve a typical maximum cut problem for a graph with three vertices and two edges by carrying out experiments on IBM's quantum simulator.

Antibacterial activity of lysozyme after association with carboxymethyl konjac glucomannan.

The unique high isoelectric point of lysozyme (LYZ) restricts its application in composite antibacterial coating due to the unfavorable liability to electrostatic interaction with other components. In this work, the antibacterial activity of a dispersible LYZ-carboxymethyl konjac glucomannan (CMKGM) polyelectrolyte complex was evaluated. Kinetic analysis revealed that, compared with free LYZ, the complexed enzyme exhibited decreased affinity (Km) but markedly increased Vmax against Micrococcus lysodeikticus, and QCM and dynamic light scattering analysis confirmed that the complex could bind with the substrate but in a much lower ratio. The complexation with CMKGM did not alter the antibacterial spectrum of LYZ, and the complex exerted antibacterial function by delaying the logarithmic growth phase and impairing the cell integrity of Staphylococcus aureus. Since the LYZ-CMKGM complex is dispersible in water and could be assembled easily, it has great potential as an edible coating in food preservation.

Twenty years' experience of midgut malrotation and volvulus in a tertiary center in northern Taiwan: A retrospective study.

BACKGROUND: Early diagnosis and surgical intervention for midgut malrotation with bowel obstruction are crucial. We aimed to identify risk factors for adverse outcomes in infants with midgut malrotation and to develop a prediction model. METHODS: We reviewed the operation records of infants surgically diagnosed with midgut malrotation at Chang Gung Children's Medical Center between January 2000 and December 2020. Patients were classified into the poor-outcome group (PO) if they underwent bowel resection or experienced mortality; all others were categorized as the favorable-outcome group (FO). Data on demographics, initial presentations, laboratory results, radiographic or sonographic findings, maternal conditions, and outcomes were collected and analyzed. Fisher's exact test, the independent sample t-test, and the Mann-Whitney test were utilized for comparative analysis when suitable. RESULTS: The study included 103 infants. Eleven were in the PO group, and 92 were in the FO group. Initial presentations such as respiratory distress, poor activity, and shock status were notably more prevalent in the PO group. The INR, hemoglobin, HCO3, base excess, and aspartate transaminase values showed significant variation between the two groups. Multivariate analysis identified that lower hemoglobin (OR 0.677, p = 0.043) and higher AST (OR 1.036, p = 0.044) were independent predictors of adverse outcomes. An AST/Hb ratio of <3.78 demonstrated a high negative predictive value (98.6%) for an adverse outcome in midgut malrotation. CONCLUSIONS: Prompt diagnosis and surgical treatment of midgut malrotation are vital to prevent bowel resection or mortality. The independent predicting factors for poor outcomes include low hemoglobin and elevated AST levels.

NTRK3 exhibits a pro-oncogenic function in upper tract urothelial carcinomas.

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan-Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the overexpression of NTRK3 in UM-UC-14 cells promoted AKT-mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT-mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

Promotion of 14-3-3ζ/Heme Oxygenase-1 Axis on Endotoxin-Induced Uveitis and Microglia Ferroptosis in Mice.

PURPOSE: Uveitis is a common, sight-threatening inflammatory ocular disease and is the main cause of blindness, which is caused by autoimmune response, infection, and injury. The contribution of 14-3-3ζ in uveitis remains obscure. This study aims to investigate the role of 14-3-3ζ in regulating ferroptosis in retinal inflammation and its contribution to uveitis. METHODS: A lipopolysaccharide (LPS)-induced uveitis mouse model and BV-2 cell line were used to examine the effect of LPS stimulation on the expression of 14-3-3ζ and ferroptosis in microglia. The expression of heme oxygenase-1 (HO-1) was also analyzed to understand its role in promoting microglial ferroptosis. RESULTS: We found that LPS stimulation increased the expression of 14-3-3ζ and promoted ferroptosis in microglia. Additionally, 14-3-3ζ was found to promote microglial ferroptosis by stabilizing the expression of HO-1. These findings suggest that the 14-3-3ζ/HO-1 axis plays a crucial role in promoting microglial ferroptosis in retinal inflammation. CONCLUSION: The study provides valuable insights into the mechanisms underlying uveitis and highlights the potential of the 14-3-3ζ/HO-1 axis as a therapeutic target for the disease. Further research in this area could lead to the development of preventive and therapeutic strategies for uveitis.