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Background: Links have been reported between the airflow limitation and both metabolic syndrome (MetS) and fatty liver (FL). Additionally, associations between genetic factors and risks of MetS, FL, and airflow limitation have been identified separately in different studies. Our study aims to simultaneously explore the association between specific single nucleotide polymorphisms (SNPs) of certain genes and the risk of the three associated diseases., Methods: In this retrospective cross-sectional nationwide study, 150,709 participants from the Taiwan Biobank (TWB) were enrolled. We conducted a genotype-phenotype association analysis of nine SNPs on seven genes (ApoE-rs429358, MBOAT7-rs641738, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, TM6SF2-rs58542926, and IFNL4-rs368234815) using data from the TWB1.0 and TWB2.0 genotype dataset. Participants underwent a series of assessments including questionnaires, blood examinations, abdominal ultrasounds, and spirometry examinations., Results: MetS was associated with FL and airflow limitation. ApoE-rs429358, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, and TM6SF2-rs58542926 were significantly associated with the risk of MetS. The cumulative impact of T alleles of ApoE-rs429358 and TM6SF2-rs58542926 on the risk of FL was observed (p-value for trend < 0.001). Individuals without MetS and airflow limitation carrying LEPR-rs1805096 G&#95;G genotype exhibited a reduction in the forced expiratory volume in 1 s percentage prediction (Coefficient -35, 95 % confidence interval (CI) -69.7- -0.4), low forced vital capacity percentage prediction (Coefficient -41.6, 95 % CI -82.6- -0.6), and low vital capacity percentage prediction (Coefficient -42.2, 95 % CI -84.2- -0.1)., Conclusions: MetS significantly correlated with FL and airflow limitation. Multiple SNPs were notably associated with MetS. Specifically, T alleles of ApoE-rs429358 and TM6SF2-rs58542926 cumulatively increased the risk of FL. LEPR-rs1805096 shows a trend-wise association with pulmonary function, which is significant in patients without MetS or airflow limitation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metabolic-associated fatty liver disease (MAFLD) induced-severe hepatic steatosis poses significant health risks. Early prediction of this condition is crucial for prompt intervention. Short-chain fatty acids (SCFAs) and tryptophan are gut metabolites correlated with MAFLD pathogenesis in the gut-liver axis. This study aims to construct prediction models for severe hepatic steatosis by including SCFAs and tryptophan metabolites. This study enrolled 83 participants from the outpatient department in 2023. Physical measurements, serum metabolic and inflammatory markers, metabolites of serum SCFAs and tryptophan were collected. Severe hepatic steatosis was diagnosed using vibration-controlled transient elastography and abdominal sonography. All 40 (48.2%) participants diagnosed with severe hepatic steatosis had MAFLD, while approximately three-quarters of those without severe hepatic steatosis had MAFLD. In comparison to the non-severe hepatic steatosis group, individuals with severe hepatic steatosis exhibited higher levels of waist and arm circumference, serum triglyceride (TG), and lower levels of serum high-density lipoprotein cholesterol (HDL-C) and AST/ALT ratio. They also had higher serum levels of lipopolysaccharide-binding protein, isovaleric acid, and propionic acid, and lower levels of 3-methylvaleric acid, indole-3-propionic acid, and indoxyl sulfate. Models incorporating these markers predicted severe hepatic steatosis. One model additionally included waist circumference and triglyceride-glucose index, while the other incorporated arm circumference and TG/HDL-C ratio. The area under the curve reached 0.958 and 0.938, respectively (p < 0.001). SCFAs and tryptophan metabolites are valuable in predicting severe hepatic steatosis. Further research is needed to investigate the roles of these metabolites in MAFLD., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

This study explores the mechanisms and combined effects of chronic peroxisome proliferator-activated receptor (PPAR)α/γ and cannabinoid receptor 2 (CB 2 R) agonists on visceral adipose tissue (VAT)-derived extracellular vesicle (EVs) release and associated systemic/VAT inflammation, decreased VAT capillary density/fibrosis, and intestinal inflammation/hyperpermeability in nonalcoholic steatohepatitis (NASH) mice. NASH mice receiving 1 month of PPARα/γ agonist aleglitazar (10 mg/kg/day), CB 2 R agonist JWH015 (3 mg/kg/day) alone or combined. High EV release from VAT of NASH mice was associated with severe systemic/VAT/intestinal inflammation, reduced capillary network of VAT, and intestinal hyperpermeability. Combined JWH015 with aleglitazar treatment significantly suppressed HFD-induced obesity/adiposity, inhibited VAT expansion, reduced VAT inflammation/fibrosis, normalized VAT capillary network, and attenuated intestinal mucosal injury, inflammation, and hyperpermeability in NASH+aleg+JWH015 mice. The inhibition of AT-derived EV release and hypoxia inducible factor (HIF)1α levels in AT-derived EV, normalization of CB 2 R, PPARα, PPARγ, PPARγ1, PPARγ2, tight junction proteins, VEGF/CD31 expression, and downregulations of HIF1α, MCP-1 and TGFβ1 were observed in the VAT and intestine of the NASH+aleg+jwh015 group. In vitro experiments revealed that PPARα/γ and CB 2 R activation attenuated NASH AT-derived EV (EVnash)-induced pathogenic changes in the J774/SVEC4-10/Caco2 /3T3-L1 cell system. This study suggested that VAT-derived EVs contribute to the pathogenesis of NAFLD and that combined PPARα/γ and CB 2 R agonist treatment reduces VAT-released EV release and HIF1/MCP-1 signals to ameliorate hepatic steatosis and VAT/intestine abnormalities of NASH mice., (Copyright © 2024. Published by Elsevier Inc.)

Background: Objective structured clinical examination (OSCE) is used worldwide. This study aims to explore potential alternatives to the OSCE by using entrustable professional activities (EPA)-based assessments in the workplace., Methods: This study enrolled 265 six-year undergraduate medical students (UGY) from 2021 to 2023. During their rotations, students were assessed using 13 EPAs, with the grading methods modified to facilitate application. Before graduation, they participated in two mock OSCEs and a National OSCE. We used generalized estimating equations to analyze the associations between the EPA assessments and the OSCE scores, adjusting for age and sex, and developed a prediction model. EPA8 and EPA9, which represent advanced abilities that were not significant in the regression models, were removed from the prediction model., Results: Most EPAs were significantly correlated with OSCE scores across the three cohorts. The prediction model for forecasting passing in the three OSCEs demonstrated fair predictive capacity (area under curve = 0.82, 0.66, and 0.71 for students graduated in 2021, 2022, and 2023, respectively all p  < 0.05)., Conclusions: The workplace-based assessments (EPA) showed a high correlation with competency-based assessments in simulated settings (OSCE). EPAs may serve as alternative tools to formal OSCE for medical students.

In deserts, sedimentation from frequent dust activities on solar cells poses a substantial technical challenge, reducing efficiency and necessitating advanced cost-inefficient cleaning mechanisms. Herein, a novel sandfish scale-inspired self-healing fluorinated copolymer-based triboelectric layer is directly incorporated on top of the polysilicon solar cell for sustained hybrid energy harvesting. The transparent biomimetic layer, with distinctive saw-tooth microstructured morphology, exhibits ultra-low sand adhesion and high abrasion-resistant properties, inhibits sedimentation deposition on solar cells, and concurrently harvests kinetic energy from wind-driven sand particles through triboelectric nanogenerator (TENG). The film exhibits a low friction coefficient (0.149), minimal sand adhesion force (27 nN), and a small wear area (327 µm 2 ). In addition, over 2 months, a solar cell with the sandfish scale-inspired structure demonstrates only a 16% decline in maximum power output compared to the bare solar cell, which experiences a 60% decline. Further, the sandfish scale-based TENG device's electrical output is fully restored to its original value after a 6-h self-healing cycle and maintains consistent stable outputs. These results highlight the exceptional advantages of employing biomimetic self-healing materials as robust triboelectric layers, showcasing sustained device stability and durability for prolonged use in harsh desert environments, ultimately contributing to a low cost-of-electricity generation paradigm., (© 2024 Wiley‐VCH GmbH.)

Wastewater-Based Epidemiology (WBE) is widely used to monitor the progression of SARS-CoV-2 pandemic. While there is a clear correlation between the number of COVID patients in a sewershed and the viral load in the wastewater, there is notable variability across different treatment plants. In particular, some facilities consistently exhibit higher viral content per diagnosed patient, implying a potential underestimation of the number of COVID patients, while others show a low viral load per diagnosed case, indicating potential attenuation of genetic material from the sewershed. In this study, we investigated the impact of nonylphenol ethoxylate (NPHE), linear alkylbenzene sulfonic acid (LABS), bisoctyl dimethyl ammonium chloride (BDAC), and didecyldimethylammonium chloride (DDAC), the surfactants that have been commonly used as detergents, emulsifiers, wetting agents on the stability of SARS-CoV-2 in wastewater. The results showed multiple and dynamic mechanisms, including degradation and desorption, can occur simultaneously during the interaction between SARS-CoV-2 and different chemicals depending on the physicochemical properties of each chemical. Through the elucidation of the dynamic interactions, the findings from this study could help the state health organizations and scientific community to optimize the SARS-CoV-2 wastewater-based epidemiology strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chung-Ho Lin reports financial support was provided by The Centers for Disease Control and prevention and the National Institute on Drug Abuse of the National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Celiac patients are required to strictly adhere to a gluten-free diet because even trace amounts of gluten can damage their small intestine and leading to serious complications. Despite increased awareness, gluten can still be present in products due to cross-contamination or hidden ingredients, making regular monitoring essential. With the goal of guaranteeing food safety for consuming labeled gluten-free products, a capacitive aptasensor was constructed to target gliadin, the main allergic gluten protein for celiac disease. The success of capacitive aptasensing was primarily realized by coating a Parylene double-layer (1000 nm Parylene C at the bottom with 400 nm Parylene AM on top) on the electrode surface to ensure both high insulation quality and abundant reactive amino functionalities. Under the optimal concentration of aptamer (5 μM) used for immobilization, a strong linear relationship exists between the amount of gliadin (0.01-1.0 mg/mL) and the corresponding Δ C response (total capacitance decrease during a 20 min monitoring period after sample introduction), with an R 2 of 0.9843. The detection limit is 0.007 mg/mL (S/ N > 5), equivalent to 0.014 mg/mL (14 ppm) of gluten content. Spike recovery tests identified this system is free from interferences in corn and cassava flour matrices. The analytical results of 24 commercial wheat flour samples correlated well with a gliadin ELISA assay ( R 2 = 0.9754). The proposed label-free and reagentless capacitive aptasensor offers advantages of simplicity, cost-effectiveness, ease of production, and speediness, making it a promising tool for verifying products labeled as gluten-free (gluten content <20 ppm).

Background: Social detachment includes the subjective aspect "loneliness" and the objective aspect "social isolation," but tools to assess both dimensions are limited. This study aims to develop a questionnaire, the Social Detachment Questionnaire for Older Population (SDQO), that considers multiple dimensions of social detachment simultaneously., Methods: The study collected 600 valid samples from individuals aged 55 and above to examine the psychometric properties of the developed SDQO. Item analysis was conducted to assess the performance of each item, and exploratory factor analysis (EFA) was employed to analyze its initial structure and eliminate less ideal items. Subsequently, confirmatory factor analysis (CFA) was used to examine the model fit of the suggested structure by EFA, using different subsamples. Internal consistency, concurrent validity, and other analyses were also performed., Results: The original 27-item SDQO was reduced to 17 items after removing 4 questions in item analysis and 6 questions in EFA. The Cronbach's alpha for the 17-item version of SDQO was 0.80. Both EFA and CFA supported its 6-factor structure, with factors identified as community activities, loneliness, personal resources, leisure activities, friendship, and family resources. SDQO also demonstrated expected performance in concurrent validity., Conclusion: The 17-item version of SDQO exhibited good reliability and validity, measuring various aspects of social detachment behavior, feelings, and resources. It holds value for future research applications., Competing Interests: Declaration of competing interest The authors report no conflicts with any product mentioned or concept discussed in this article., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Formation of programmed DNA double-strand breaks is essential for initiating meiotic recombination. Genetic studies on Arabidopsis thaliana and Mus musculus have revealed that assembly of a type IIB topoisomerase VI (Topo VI)-like complex, composed of SPO11 and MTOPVIB, is a prerequisite for generating DNA breaks. However, it remains enigmatic if MTOPVIB resembles its Topo VI subunit B (VIB) ortholog in possessing robust ATPase activity, ability to undergo ATP-dependent dimerization, and activation of SPO11-mediated DNA cleavage. Here, we successfully prepared highly pure A. thaliana MTOPVIB and MTOPVIB-SPO11 complex. Contrary to expectations, our findings highlight that MTOPVIB differs from orthologous Topo VIB by lacking ATP-binding activity and independently forming dimers without ATP. Most significantly, our study reveals that while MTOPVIB lacks the capability to stimulate SPO11-mediated DNA cleavage, it functions as a bona fide DNA-binding protein and plays a substantial role in facilitating the dsDNA binding capacity of the MOTOVIB-SPO11 complex. Thus, we illustrate mechanistic divergence between the MTOPVIB-SPO11 complex and classical type IIB topoisomerases., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes., Methods: This retrospective cohort study from 2011 to 2019 enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (DXA, for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes, and the effect of different ranges of BMI (18.5-24, 24-27, and ≥27 kg/m2 in women; 18.5-24, 24-27, 27-30 and ≥30 kg/m2 in men) on the risk of future fractures in FL patients., Results: The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors for osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24-27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5-24 kg/m2., Conclusion: The protective effect of a higher BMI against future fractures in middle-aged and elderly women and men with FL is not uniform and decreases beyond certain BMI ranges.

A 9 yr old male miniature poodle presented with acute diarrhea, vomiting, and a distended abdomen. A large and firm mass was palpated in the caudal abdomen. Radiography showed a large soft-tissue mass in the mid ventral abdomen. The mass was mildly contrast-enhancing and in contact with the right cranial aspect of the bladder on computed tomography. The mass was heterogeneous with minimal blood flow on Doppler examination. Surgery confirmed its origin of the urinary bladder, and it was diagnosed leiomyosarcoma on pathology. This is the first report of extraluminal leiomyosarcoma of the bladder wall with imaging characteristics using various modalities., (© 2024 by American Animal Hospital Association.)

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, HCO 3 , 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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Surface coating technology is broadly demanded across various fields, including marine and biomedical materials; therefore, a facile and versatile approach is desired. This study proposed an attractive surface coating strategy using photo-crosslinkable benzophenone (BP) moiety for biomaterials application. BP-containing "bioglue" polymer can effectively crosslink with all kinds of surfaces and biomolecules. Upon exposure to ultraviolet (UV) light, free radical reaction from the BP glue facilitates the immobilization of diverse molecules onto different substrates in a straightforward and user-friendly manner. Through either one-step, mixing the bioglue with targeted biomolecules, or two-step methods, pre-coating the bioglue and then adding targeted biomolecules, polyacrylic acid (PAA), cyclic RGD-containing peptides, and proteins (gelatin, collagen, and fibronectin) were successfully immobilized on substrates. After drying the bioglue, targeted biomolecules can still be immobilized on the surfaces preserving their bioactivity. Cell culture on biomolecule-immobilized surfaces using NIH 3T3 fibroblasts and human bone marrow stem cells (hBMSCs) showed significant improvement of cell adhesion and activity compared to the unmodified control in serum-free media after 24 hours. Furthermore, hBMSCs on the fibronectin-immobilized surface showed an increased calcium deposition after 21 days of osteogenic differentiation, suggesting that the immobilized fibronectin is highly bioactive. Given the straightforward protocol and substrate-independent bioglue, the proposed coating strategy is promising in broad-range fields., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Injection molding is a highly nonlinear procedure that is easily influenced by various external factors, thereby affecting the stability of the product's quality. High-speed injection molding is required for production due to the rapid cooling characteristics of thin-walled parts, leading to increased manufacturing complexity. Consequently, establishing appropriate process parameters for maintaining quality stability in long-term production is challenging. This study selected a hot runner mold with a thin wall fitted with two external sensors, a nozzle pressure sensor and a tie-bar strain gauge, to collect data regarding the nozzle peak pressure, the timing of peak pressure, the viscosity index, and the clamping force difference value. The product weight was defined as the quality indicator, and a standardized parameter optimization process was constructed, including injection speed, V / P switchover point, packing, and clamping force. Finally, the optimized process parameters were applied to the adaptive process control experiments using the developed control system operated within the micro-controller unit (MCU). The results revealed that the control system effectively stabilized the product weight variation and standard deviation of 0.677% and 0.0178 g, respectively.

Campylobacter jejuni is the leading foodborne bacterial pathogen that causes human gastroenteritis worldwide linked to the consumption of undercooked broiler livers. Application of bacteriophages during poultry production has been used as an alternative approach to reduce contamination of poultry meat by Campylobacter. To make this approach effective, understanding the presence of the bacteriophage sequences in the CRISPR spacers in C. jejuni is critical as they may confer bacterial resistance to bacteriophage treatment. Therefore, in this study, we explored the distribution of the CRISPR arrays from 178 C. jejuni isolated from chicken livers between January and July 2018. Genomic DNA of C. jejuni isolates was extracted, and CRISPR type 1 sequences were amplified by PCR. Amplicons were purified and sequenced by the Sanger dideoxy sequencing method. Direct repeats (DRs) and spacers of CRISPR sequences were identified using the CRISPRFinder program. Further, spacer sequences were submitted to the CRISPRTarget to identify potential homology to bacteriophage types. Even though CRISPR-Cas is reportedly not an active system in Campylobacter, a total of 155 (87%) C. jejuni isolates were found to harbor CRISPR sequences; one type of DR was identified in all 155 isolates. The CRISPR loci lengths ranged from 97 to 431 nucleotides. The numbers of spacers ranged from one to six. A total of 371 spacer sequences were identified in the 155 isolates that could be grouped into 51 distinctive individual sequences. Further comparison of these 51 spacer sequences with those in databases showed that most spacer sequences were homologous to Campylobacter bacteriophage DA10. The results of our study provide important information relative to the development of an effective bacteriophage treatment to mitigate Campylobacter during poultry production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

A 2A R-disrupted mice is characterized by severe systemic and visceral adipose tissue (VAT) inflammation. Increasing adenosine cyclase (AC), cAMP, and protein kinase A (PKA) formation through A 2A R activation suppress systemic/VAT inflammation in obese mice. This study explores the effects of 4 wk A 2A R agonist PSB0777 treatment on the VAT-driven pathogenic signals in hepatic and cardiac dysfunction of nonalcoholic steatohepatitis (NASH) obese mice. Among NASH mice with cardiac dysfunction, simultaneous decrease in the A 2A R, AC, cAMP, and PKA levels were observed in VAT, liver, and heart. PSB0777 treatment significantly restores AC, cAMP, PKA, and hormone-sensitive lipase (HSL) levels, decreased SREBP-1/FASN , MCP-1, and CD68 levels, reduces infiltrated CD11b +  F4/80 + cells and adipogenesis in VAT of NASH + PSB0777 mice. The changes in VAT were accompanied by the suppression of hepatic and cardiac lipogenic/inflammatory/injury/apoptotic/fibrotic markers, the normalization of cardiac contractile [sarco/endoplasmic reticulum Ca 2+  ATPase (SERCA2)] marker, and cardiac dysfunction. The in vitro approach revealed that conditioned media (CM) of VAT of NASH mice (CMnash) trigger palmitic acid (PA)-like lipotoxic (lipogenic/inflammatory/apoptotic/fibrotic) effects in AML-12 and H9c2 cell systems. Significantly, A 2A R agonist pretreatment-related normalization of A 2A R-AC-cAMP-PKA levels was associated with the attenuation of CMnash-related upregulation of lipotoxic markers and the normalization of lipolytic (AML-12 cells) or contractile (H9C2 cells) marker/contraction. The in vivo and in vitro experiments revealed that A 2A R agonists are potential agent to inhibit the effects of VAT inflammation-driven pathogenic signals on the hepatic and cardiac lipogenesis, inflammation, injury, apoptosis, fibrosis, hypocontractility, and subsequently improve hepatic and cardiac dysfunction in NASH mice. NEW & NOTEWORTHY Protective role of adenosine A 2A R receptor (A 2A R) and AC-cAMP-PKA signaling against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) possibly via its actions on adipocytes is well known in the past decade. Thus, this study evaluates pharmacological activities of A 2A R agonist PSB0777, which has already demonstrated to treat NASH. In this study, the inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A 2A R with A 2A R agonist PSB0777 improves the hepatic and cardiac dysfunction of high-fat diet (HFD)-induced NASH mice.

Background: Diffusion tensor imaging (DTI) biomarkers can be used to quantify microstructural changes in the cerebral white matter (WM) following injury., Objectives: This prospective single-center study aimed to evaluate whether atlas-based DTI-derived metrics obtained within 1 week after stroke can predict the motor outcome at 3 months., Methods: Forty patients with small acute stroke (2-7 days after onset) involving the corticospinal tract were included. Each patient underwent magnetic resonance imaging (MRI) within 1 week and at 3 months after stroke, and the changes based on DTI-derived metrics were compared by performing WM tract atlas-based quantitative analysis., Results: A total of 40 patients were included, with median age 63.5 years and a majority of males (72.5%). Patients were classified into good-prognosis group (mRS 0-2, n  = 27) and poor-prognosis group (mRS 3-5, n  = 13) by outcome. The median (25 th -75 th percentile) of MD (0.7 (0.6-0.7) vs. 0.7 (0.7-0.8); p  = 0.049) and AD (0.6 (0.5, 0.7) vs. 0.7 (0.6, 0.8); p  = 0.023) ratios within 1 week were significantly lower in the poor-prognosis group compared to the good-prognosis group. The ROC curve of the combined DTI-derived metrics model showed comparable Youden index (65.5% vs. 58.4%-65.4%) and higher specificity (96.3% vs. 69.2%-88.5%) compared to clinical indexes. The area under the ROC curve of the combined DTI-derived metrics model is comparable to those of the clinical indexes (all p  > 0.1) and higher than those of the individual DTI-derived metrics parameters., Conclusions: Atlas-based DTI-derived metrics at acute stage provide objective information for prognosis prediction of patients with ischemic or lacunar stroke.

Background: Cognitive-behavioral therapy (CBT) and biofeedback therapy are commonly regarded as effective treatment modalities for panic disorder. The aim of this study was to establish a Taiwanese version of an integrated cognitive-behavioral and biofeedback therapy (ICB) and examine its effects on panic disorder using psychological and physiological indicators., Methods: Thirty patients with panic disorder were enrolled in this study. They were randomly assigned to either the ICB group (n = 15) or the treatment as usual (TAU) group (n = 15). The intervention consisted of six sessions, conducted once a week. Psychological indicators were measured at baseline (prior to intervention), week 3, and week 6, while physiological indicators were measured at baseline and week 6. The psychological indicators included five scales, with the Panic Disorder Severity Scale (PDSS) being the primary measure. The physiological indicators included respiratory sinus arrhythmia (RSA) and skin conductance, which respectively represent parasympathetic and sympathetic activity., Results: Considering all participants, PDSS scores significantly decreased over time, but the difference between the ICB and TAU groups did not reach statistical significance. Among the physiological indicators, resting-state RSA and RSA under relaxation showed significant between-group differences over time, with the ICB group demonstrating a more pronounced improvement in RSA., Conclusion: In the context of existing pharmacological treatments, the benefits of ICB for panic disorder may not be observable through psychological indicators. However, it can lead to enhancement of parasympathetic activity as evidenced by the physiological indicators., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Aim: Campylobacter is the leading bacterial pathogen that causes foodborne illnesses worldwide. Pasture farming is regarded as an important source of agricultural production for small farming communities. Consumer preference for pasture-raised animal products has increased; however, there is a paucity of information on the microbiological quality of pasture-raised poultry products. The purpose of this study was to explore genetic relatedness of thermophilic Campylobacter isolates, to assess antibiotic resistance phenotypically and genotypically, and to screen the presence of virulence determinants of Campylobacter isolates from pasture-raised poultry farms from southeastern United States., Methods: Ninety-seven Campylobacter isolates previously identified by Q7 BAX ® System Real-Time PCR were genotyped by multilocus sequence typing (MLST). Campylobacter isolates were then evaluated for their phenotypic antimicrobial susceptibility against nine antimicrobial agents using Sensititre plates. Additionally, Campylobacter isolates were tested for the presence of antimicrobial resistance-associated elements. Furthermore, Campylobacter isolates were screened for the presence of 13 genes encoding putative virulence factors by PCR. These included genes involved in motility ( flaA and flhA ), adhesion and colonization ( cadF , docC , racR , and virB11 ), toxin production ( cdtA , cdtB , cdtC , wlaN , and ceuE ) and invasion ( ciaB and iamA )., Results: Among 97 Campylobacter isolates, Campylobacter jejuni ( n  = 79) and Campylobacter coli ( n  = 18) were identified. By MLST, C. jejuni isolates were assigned to seven clonal complexes. Among them, ST-353, ST-607 and ST-21 were the most common STs recognized. All C. coli ( n  = 18) isolates were included in CC-828. Interestingly, eight STs identified were not belonging any previous identified clonal complex. Campylobacter isolates displayed a high resistance rate against tetracycline (81.4%), while a low rate of resistance was observed against macrolides (azithromycin and erythromycin), quinolones and fluoroquinolones (nalidixic acid and ciprofloxacin), aminoglycosides (gentamicin), ketolide (telithromycin), amphenicol (florfenicol) and lincomycin (clindamycin). Thirteen isolates (13.54%) were pan-susceptible to all tested antibiotics, while nine isolates were multi-antimicrobial resistant (MAR; resist to three or more antimicrobial classes). Interestingly, there were no isolates resistant to all antimicrobial classes. Thr86Ile mutation was identified in all quinolones resistant strains. Erythromycin encoding gene ( ermB ) was identified in 75% of erythromycin resistant isolates. The A2075 mutation was detected in one erythromycin resistant strain, while A2074 could not be identified. The tet O gene was identified in 93.7% of tetracycline resistant isolates and six tetracycline susceptible isolates. In conclusion, the results of this study revealed that Campylobacter isolates from pasture-raised poultry farms showed the ST relatedness to Campylobacter isolates commonly associated with humans, indicating pasture-raised broiler flocks, similar to conventionally-reared broiler flocks, as a potential vector for antibiotic-resistant and pathogenic strains of thermophilic Campylobacter to humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Awad, Yeh, Ramadan and Rothrock.)

This study investigates a cultivation strategy for the macroalga Colaconema formosanum by determining optimal inorganic carbon concentration and salinity for maximizing biomass and photosynthetic pigment production while also facilitating carbon sequestration. The response surface method was used with a central composite design (CCD-RSM) to determine the optimal conditions. Results showed that adding 1.2 g/L of carbon increased the specific growth rate to 18%-19% per day. The maximum amount of pigment, including phycobiliprotein and chlorophyll, was achieved by adjusting both carbon content and salinity. This strategy enables mass pigment production and offers an eco-friendly approach to carbon sequestration while reducing culture period. This study also sheds light on algal mechanisms against enriched inorganic carbon and salinity content, contributing to an enhanced understanding of these vital processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glansreginin A has been reported to be an indicator of the quality of walnuts (Juglans spp.). However, bioactive properties of glansreginin A have not been adequately explored. In the present study, we quantified concentrations of glansreginin A in black walnuts (Juglans nigra) using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and performed an array of in vitro bioassays to characterize biological activities (e.g., antibacterial, antioxidant, anticancer capacities) of this compound. Results from HPLC-MS/MS analysis indicated that glansreginin A was presented in all 12 black cultivars examined and its contents were variable among black walnut cultivars, ranged from 6.8 mg/kg (Jackson) to 47.0 mg/kg (Hay). Glansreginin A possessed moderate antibacterial activities against Gram-positive pathogens (Staphylococcus aureus and Bacillus anthracis). This compound exhibited no antioxidant activities, did not induce the activity of antioxidant response element signaling pathways, and exerted no antiproliferative effects on tumorigenic alveolar epithelial cells and non-tumorigenic lung fibroblast cells., (© 2023. The Author(s).)

The superhydrophobic properties of material surfaces have attracted significant research and practical development in a wide range of applications. In the present study, a superhydrophobic coating was fabricated using a vapor-phase sublimation and deposition process. This process offers several advantages, including a controllable and tunable superhydrophobic property, a dry and solvent-free process that uses well-defined water/ice templates during fabrication, and a coating technology that is applicable to various substrates, regardless of their dimensions or complex geometric configurations. The fabrication process exploits time-dependent condensation to produce ice templates with a controlled surface morphology and roughness. The templates are sacrificed via vapor sublimation, which results in mass transfer of water vapor out of the system. A second vapor source of a polymer precursor is then introduced to the system, and deposition occurs upon polymerization on the iced templates, replicating the same topologies from the iced templates. The continuation of the co-current sublimation and deposition processes finally renders permanent hierarchical structures of the polymer coatings that combine the native hydrophobic property of the polymer and the structured property by the sacrificed ice templates, achieving a level of superhydrophobicity that is tunable from 90° to 164°. The experiments demonstrated the use of [2,2]paracyclophanes as the starting materials for forming the superhydrophobic coatings of poly( p -xylylenes) on substrate surfaces. In comparison to conventional vapor deposition of poly( p -xylylenes), which resulted in dense thin-film coatings with only a moderate water contact angle of approximately 90°, the reported superhydrophobic coatings and fabrication process can achieve a high water contact angle of 164°. Demonstrations furthermore revealed that the proposed coatings are durable while maintaining superhydrophobicity on various substrates, including an intraocular lens and a cardiovascular stent, even against harsh treatment conditions and varied solution compositions used on the substrates.

Aims: Epidemiological evidence suggests that comorbidity of obesity and depression is extremely common and continues to grow in prevalence. However, the mechanisms connecting these two conditions are unknown. In this study, we explored how treatment with K ATP channel blocker glibenclamide (GB) or the well-known metabolic regulator FGF21 impact male mice with high-fat diet (HFD)-induced obesity and depressive-like behaviors., Materials and Methods: Mice were fed with HFD for 12 weeks and then treated with recombinant FGF21 protein by infusion for 2 weeks, followed by intraperitoneal injection of 3 mg/kg recombinant FGF21 once per day for 4 days. Measurements were made of catecholamine levels, energy expenditure, biochemical endpoints and behavior tests, including sucrose preference and forced swim tests were. Alternatively, animals were infused with GB into brown adipose tissue (BAT). The WT-1 brown adipocyte cell line was used for molecular studies., Key Findings: Compared to HFD controls, HFD + FGF21 mice exhibited less severe metabolic disorder symptoms, improved depressive-like behaviors, and more extensive mesolimbic dopamine projections. FGF21 treatment also rescued HFD-induced dysregulation of FGF21 receptors (FGFR1 and co-receptor β-klotho) in the ventral tegmental area (VTA), and it altered dopaminergic neuron activity and morphology in HFD-fed mice. Importantly, we also found that FGF21 mRNA level and FGF21 release were increased in BAT after administration of GB, and GB treatment to BAT reversed HFD-induced dysregulation of FGF21 receptors in the VTA., Significance: GB administration to BAT stimulates FGF21 production in BAT, corrects HFD-induced dysregulation of FGF21 receptor dimers in VTA dopaminergic neurons, and attenuates depression-like symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

ATP-dependent RAD51 recombinases play an essential role in eukaryotic homologous recombination by catalyzing a four-step process: 1) formation of a RAD51 single-filament assembly on ssDNA in the presence of ATP, 2) complementary DNA strand-exchange, 3) ATP hydrolysis transforming the RAD51 filament into an ADP-bound disassembly-competent state, and 4) RAD51 disassembly to provide access for DNA repairing enzymes. Of these steps, filament dynamics between the ATP- and ADP-bound states, and the RAD51 disassembly mechanism, are poorly understood due to the lack of near-atomic-resolution information of the ADP-bound RAD51-DNA filament structure. We report the cryo-EM structure of ADP-bound RAD51-DNA filaments at 3.1 Å resolution, revealing a unique RAD51 double-filament that wraps around ssDNA. Structural analysis, supported by ATP-chase and time-resolved cryo-EM experiments, reveals a collapsing mechanism involving two four-protomer movements along ssDNA for mechanical transition between RAD51 single- and double-filament without RAD51 dissociation. This mechanism enables elastic change of RAD51 filament length during structural transitions between ATP- and ADP-states., (© 2023. Springer Nature Limited.)

The development of acute kidney injury (AKI) and hepatorenal syndrome-acute kidney injury (HRS-AKI) in cirrhosis has been associated with intestinal barrier dysfunction and gut-kidney crosstalk. We use the related markers such as zonulin, lipopolysaccharides (LPS), and lipopolysaccharide-binding protein (LBP) to predict AKI and HRS-AKI in cirrhotic patients and evaluate their in vitro effects on intestinal (Caco-2) cells and renal tubular (HK-2) cells. From 2013 to 2020, we enrolled 70 cirrhotic patients and developed prediction models for AKI and HRS-AKI over a six-month period. There were 13 (18.6%) and 8 (11.4%) cirrhotic patients developed AKI and HRS-AKI. The prediction models incorporated zonulin, LPS, LBP, C-reactive protein, age, and history of hepatitis B for AKI, and zonulin, LPS, LBP, total bilirubin, and Child-Pugh score for HRS-AKI. The area under curve (AUC) for the prediction of AKI and HRS-AKI was 0.94 and 0.95, respectively. Furthermore, the conditioned medium of LPS+hrLBP pre-treated Caco-2 cells induced apoptosis, necrosis, and zonulin release in HK-2 cells, demonstrating the communication between them. This study found that zonulin, LPS, and LBP are potential practical markers for predicting AKI and HRS-AKI in cirrhotic patients, which may serve as potential targets for renal outcomes in cirrhotic patients., (© 2023. Springer Nature Limited.)

The classic immunoblot technique is an important tool for identification and characterization of target proteins. However, a standard protocol for this classic immunoblot assay involves many steps that may cause experimental variations in each step and make quantification of antibodies in sera difficult. A capillary electrophoresis-based immunoblot system was developed to reduce potential problems in variations during the experimental process, enable protein identification in an automatic manner and quantitate various isotypes of antibodies in sera. In the present study, we used this system to examine the purity of the recombinant proteins and measure amounts of various isotypes of immunoglobins in chicken sera after immunization with two recombinant Salmonella FliD and FimA proteins. A single band of each protein was detected in the gel like images by this system after purification by nickel-chelated affinity chromatography. A good linear range of the protein concentrations was also obtained for each recombinant protein. This automated capillary immunoblot system was successfully used for detection and quantification of various immunoglobin isotypes against two recombinant Salmonella proteins from the immunized chicken sera, but not the un-immunized chicken sera. The chicken immunoglobin G (IgG) antibody response to the FliD protein from the immunized group was 1110- and 51,400-fold higher than that from the un-immunized chickens both two- and three-weeks post-vaccination, respectively. It was also observed that IgM antibody against the FliD protein from the immunized chickens was 1030-fold higher than that from the un-immunized chickens two weeks post-vaccination, but the IgM response declined to 120-fold between two groups from two weeks to three weeks after immunization. The IgM antibody response to the FimA protein from the immunized group was 1.84- and 1.12-fold higher than that from the un-immunized group, respectively, both two- and three-weeks post-vaccination, while the IgG antibody response from the immunized group was 8.07- and 27.6-fold higher than that from the un-immunized group, respectively, during the same period. These results suggest that this capillary-based immunoblot assay can be an alternative method for analyses and quantitation of chicken humoral immune response before and after immunization with any antigens and/or for investigation in Salmonella outbreaks., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Published by Elsevier B.V.)

Background: A increasing number of studies have revealed associations between country-level determinants and coronavirus disease 2019 (COVID-19) outcomes. This ecological study was conducted to analyze country-level parameters related to COVID-19 infections and deaths during the first year of the pandemic., Methods: The examined predictors comprised demographics, economic factors, disease prevalence and healthcare system status, and the relevant data were obtained from public databases. The index dates were set to 15 July 2020 (Time 1) and 15 December 2020 (Time 2). The adjusted spatial autoregression models used a first-order queen contiguity spatial weight for the main analysis and a second-order queen contiguity spatial weight for a sensitivity analysis to examine the predictors associated with COVID-19 case and mortality rates., Results: Obesity was significantly and positively associated with COVID-19 case and mortality rates in both the main and sensitivity analyses. The sensitivity analysis revealed that a country's gross domestic product, population density, life expectancy and proportion of the population older than 65 y are positively associated with COVID-19 case and mortality rates., Conclusions: With the increasing global prevalence of obesity, the relationship between obesity and COVID-19 disease at the country level must be clarified and continually monitored., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Bacillus anthracis is the zoonotic causal agent of anthrax. Its infectious form is the spore, which can persist in soil. Herbivores usually acquire the disease from grazing in spore-contaminated sites. There are two schools of thought regarding B. anthracis activities in soil. One contends the bacteria are obligate animal parasites and soil-based spores remain inert until taken up by another animal host. Others contend that spores can germinate in soil and the bacteria replicate and re-sporulate to maintain and/or increase spore numbers. This review discusses whether soil replication of B. anthracis is an important part of its life cycle., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Earlier detection of aortic calcification can facilitate subsequent cardiovascular care planning. Opportunistic screening based on plain chest radiography is potentially feasible in various population. We used multiple deep convolutional neural network (CNN) transfer learning by fine-tuning pre-trained models followed by ensemble technique for aortic arch calcification on chest radiographs from a derivation and two external databases with distinct features. Our ensemble approach achieved 84.12% precision, 84.70% recall, and an area under the receiver-operating-characteristic curve (AUC) of 0.85 in the general population/older adult's dataset. We also obtained 87.5% precision, 85.56% recall, and an AUC of 0.86 in the pre-end-stage kidney disease (pre-ESKD) cohort. We identified discriminative regions for identifying aortic arch calcification between patients without and with pre-ESKD. These findings are expected to optimize cardiovascular risk prediction if our model is incorporated into the process of routine care., Competing Interests: The authors declared no competing interests., (© 2023 The Author(s).)

Objective: Septic arthritis is not commonly reported in paleopathology. This study aims to provide a differential diagnosis of septic arthritis by looking at a case from ancient China. We also aim to add to the current literature on septic arthritis in paleopathology., Materials: One adult male skeleton recovered from the Dapuzi Cemetery, Shaanxi, dating to the Western Han Dynasty (3rd century BCE-1st century CE)., Methods: Macroscopic observations were conducted., Results: The lytic appearance and massive new bone formation on the left acetabulum of M142 are compatible with septic arthritis. The hip pathology greatly influenced his stature. The two femur shafts present different degrees of robusticity. He also showed severe osteoarthritis., Conclusions: The individual suffered from septic arthritis of the hip, of unknown cause, for a long period, which greatly influenced his daily life. Complications included osteoarthritis, shortened stature, and difficulties in walking., Significance: This study offers a new case of septic arthritis and provides insight into the people who guarded the royal tombs in the West Han Dynasty., Limitations: The skeleton is not well-preserved, limiting observations of bony changes to other areas of the body., Competing Interests: Conflicts of interest statement The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in 2019 and became a pandemic in 2020. Since then, vaccines have been approved to prevent severe illness. However, vaccines are associated with the risk of neurological complications ranging from mild to severe. Severe complications such as vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with acute ischaemic stroke have been reported as rare complications post-COVID-19 vaccination. During the pandemic era, VITT evaluation is needed in cases with a history of vaccination within the last month prior to the event. Cerebral venous sinus thrombosis (CVST) should be suspected in patients following immunization with persistent headaches who are unresponsive to analgesics. In this article, we investigated neurological complications after COVID-19 vaccination and provided more subsequent related clinical studies of accurate diagnosis, pathophysiological mechanisms, incidence, outcome, and management.

Background: Vascular calcification (VC) constitutes an important vascular pathology with prognostic importance. The pathogenic role of transforming growth factor-β (TGF-β) in VC remains unclear, with heterogeneous findings that we aimed to evaluate using experimental models and clinical specimens., Methods: Two approaches, exogenous administration and endogenous expression upon osteogenic media (OM) exposure, were adopted. Aortic smooth muscle cells (ASMCs) were subjected to TGF-β1 alone, OM alone, or both, with calcification severity determined. We evaluated miR-378a-3p and TGF-β1 effectors (connective tissue growth factor; CTGF) at different periods of calcification. Results were validated in an ex vivo model and further in sera from older adults without or with severe aortic arch calcification., Results: TGF-β1 treatment induced a significant dose-responsive increase in ASMC calcification without or with OM at the mature but not early or mid-term VC period. On the other hand, OM alone induced VC accompanied by suppressed TGF-β1 expressions over time; this phenomenon paralleled the declining miR-378a-3p and CTGF expressions since early VC. TGF-β1 treatment led to an upregulation of CTGF since early VC but not miR-378a-3p until mid-term VC, while miR-378a-3p overexpression suppressed CTGF expressions without altering TGF-β1 levels. The OM-induced down-regulation of TGF-β1 and CTGF was also observed in the ex vivo models, with compatible results identified from human sera., Conclusions: We showed that TGF-β1 played a context-dependent role in VC, involving a time-dependent self-regulatory loop of TGF-β1/miR-378a-3p/CTGF signaling. Our findings may assist subsequent studies in devising potential therapeutics against VC.

Polysaccharide from Laminaria japonica (LJPS) exhibits multiple biological functions. However, we found that crude LJPS doesn't show good anti-lung cancer activity in this study. We therefore used tangential flow filtration (TFF) system to optimize the anticancer activity of LJPS. We divided the crude LJPS into two fractions by TFF system with a 10 kDa filter and denoted as retentate (10K-R) and filtration (10K-F). The chemical assay revealed that the main molecular mass of 10K-R and 10K-F is about 985 and 3 kDa, respectively. The main components of 10K-R include fucose (19.3 %), and glucose (59.5 %); while glucose (88.6 %) is a major component of 10K-F. Biological functions showed that 10K-R but not 10K-F inhibited the viability and mobility of cancer cells. 10K-R downregulated expressions of transforming growth factor β receptor and Slug, and inhibited intracellular signaling molecules, including FAK, AKT, ERK1/2, and Smad2. This study is the first concept to purify the polysaccharide by TFF system and showed the potential mechanism of 10K-R inhibited cancer cells., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The injection-molding process is a non-linear process, and the product quality and long-term production stability are affected by several factors. To stabilize the product quality effected by these factors, this research establishes a standard process parameter setup procedure and an adaptive process control system based on the data collected by a nozzle pressure sensor and a tie-bar strain gauge to achieve this goal. In this research, process parameters such as the V/P switchover point, injection speed, packing pressure, and clamping force are sequentially optimized based on the characteristics of the pressure profile. After the optimization process, this research defines the standard quality characteristics through the optimized process parameters and combines it with the adaptive process control system in order to achieve the purpose of automatic adjustment of the machine and maintain high-quality production. Finally, three different viscosity materials are used to verify the effectiveness of the optimization procedure and the adaptive process control system. With the system, the variation of product weight was reduced to 0.106%, 0.092%, and 0.079%, respectively.

Transcription factor EB (TFEB) plays a very important role in the maintenance of cellular homeostasis. TFEB is a transcription factor that regulates the expression of several genes in the Coordinated Lysosomal Expression and Regulation (CLEAR) network. The CLEAR network genes are known to regulate many processes associated with the autophagy pathway and lysosome biogenesis. Lysosomes, which are degradative organelles in the cell, are associated with several cellular mechanisms, such as autophagy and phagocytosis. Recent studies have shown that TFEB dysregulation and lysosomal dysfunction are associated with several degenerative diseases. Thus, enhancing TFEB activity and accompanied induction of lysosomal function and autophagy can have tremendous therapeutic potential for the treatment of several degenerative diseases including age-related macular degeneration (AMD). In this chapter, we briefly illustrate the expression and regulation of TFEB in response to several cellular stressors and discuss the effects of TFEB overexpression to induce cellular clearance functions., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Direct neuronal reprogramming of somatic cells into induced neurons (iNs) has been recently established as a promising approach to generating neuron cells. Previous studies have reported that the biophysical cues of the in vitro microenvironment are potent modulators in the cell fate decision; thus, the present study explores the effects of a customized pattern (named colloidal self-assembled patterns, cSAPs) on iN generation from human fibroblasts using small molecules. The result revealed that the cSAP, composed of binary particles in a hexagonal-close-packed (hcp) geometry, is capable of improving neuronal reprogramming efficiency and steering the ratio of the iN subtypes. Cells exhibited distinct cell morphology, upregulated cell adhesion markers (i.e., SDC1 and ITGAV), enriched signaling pathways (i.e., Hippo and Wnt), and chromatin remodeling on the cSAP compared to those on the control substrates. The result also showed that the iN subtype specification on cSAP was surface-dependent; therefore, the defined physicochemical cue from each cSAP is exclusive. Our findings show that direct cell reprogramming can be manipulated through specific biophysical cues on the artificial matrix, which is significant in cell transdifferentiation and lineage conversion.

BxpB (also known as ExsFA) and ExsFB are an exosporium basal layer structural protein and a putative interspace protein of Bacillus anthracis that are known to be required for proper incorporation of the BclA collagen-like glycoprotein on the spore surface. Despite extensive similarity of the two proteins, their distribution in the spore is markedly different. We utilized a fluorescent fusion approach to examine features of the two genes that affect spore localization. The timing of expression of the bxpB and exsFB genes and their distinct N-terminal sequences were both found to be important for proper assembly into the exosporium basal layer. Results of this study provided evidence that the BclA nap glycoprotein is not covalently attached to BxpB protein despite the key role that the latter plays in BclA incorporation. Assembly of the BxpB- and ExsFB-containing outer basal layer appears not to be completely abolished in mutants lacking the ExsY and CotY basal layer structural proteins despite these spores lacking a visible exosporium. The BxpB and, to a lesser extent, the ExsFB proteins, were found to be capable of self-assembly in vitro into higher-molecular-weight forms that are stable to boiling in SDS under reducing conditions. IMPORTANCE The genus Bacillus consists of spore-forming bacteria. Some species of this genus, especially those that are pathogens of animals or insects, contain an outermost spore layer called the exosporium. The zoonotic pathogen B. anthracis is an example of this group. The exosporium likely contributes to virulence and environmental persistence of these pathogens. This work provides important new insights into the exosporium assembly process and the interplay between BclA and BxpB in this process.

Objective: To investigate symptom-relief and comorbid drug uses at the end of life for older people with different dying trajectories (cancer, organ failure, frailty and sudden death) in Taiwan., Methods: In a retrospective observational study of older people aged 65 years and older who died in hospitals between 2008 and 2012, we used NHIRD to measure numbers, incremental changes and determinants of symptom-relief and comorbid drug use in the last month of outpatient care and last hospitalisation before death., Results: We included 59 407 older adults (cancer 37%, organ failure 26%, frailty 35% and sudden death 2%) who died in hospitals for this study. In the last hospitalisation before death, individuals who died of cancer received greatest number of symptom-relief drugs (mean: 4.65, [SD 2.77]) and increased most the average change in the number of symptom-relief drug use (+1.60; SD 3.36). However, individuals who died of organ failure received the highest number of comorbid drugs (mean 2.88, [SD 1.95]) and also increased most the average change in the number of comorbid drug use (+0.17; SD 2.28) at last hospitalisation. Different dying trajectories were key determinants of receiving symptom-relief and comorbid drugs in our study., Conclusions: Our study suggests that the drug use of older adults at the end of life in the cancer group is different from that in the organ failure and frailty groups. Policymakers and health professionals should consider the different strategies to optimise drug use for older people with different dying trajectories near their end of life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To examine factors that affect the severity of pyloric hypertrophy, post-operative feeding and nutritional recovery in infantile hypertrophic pyloric stenosis (IHPS)., Methods: Medical records of infants diagnosed with IHPS at a single tertiary center between 2009 and 2018 were retrospectively reviewed. Clinical characteristics, biochemistry data and outcome were assessed for their association with the severity of pyloric hypertrophy and post-operative recovery. Nutritional recovery was assessed using weight-for-age status improvement after surgery., Results: Eighty-five patients were recruited in this study. The mean pre-operative weight-for-age percentile was 18.2. Elevated bicarbonate was positively correlated with symptom duration (p = 0.007). Pyloric muscle thickness was significantly correlated with age, weight, and symptom duration (p = 0.004, 0.003, 0.008, respectively). The mean weight-for-age percentile increased to 41.6 by post-operative weeks 6-8. Pyloric muscle thickness was negatively correlated with nutritional recovery by post-operative weeks 6-8 (p = 0.003). In multivariable analysis, pyloric length related to nutritional recovery at week 1-2 postoperatively (OR = 1.42, p = 0.030, 95% CI = 0.03-1.94), and pyloric muscle thickness related to nutritional recovery at week 6-8 postoperatively (OR = 4.08, p = 0.032, 95% CI = 1.13-14.7)., Conclusion: Our study indicated that favorable nutritional outcome and successful weight gain was observed 6-8 weeks after surgery in children with IHPS. Pyloric muscle thickness positively correlated with age, weight, symptom duration, and favorable nutritional recovery. Serum bicarbonate showed a positive correlation with symptom duration., Competing Interests: Conflicts of interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has circulated in Taiwan since late 2019. Healthcare facilities are vulnerable to COVID-19 outbreaks due to clusters of symptomatic patients and susceptible hosts. Prompt control of outbreaks is crucial. In May 2021, an index case of COVID-19 was detected at Far Eastern Memorial Hospital (FEMH) in New Taipei City, Taiwan, 3 days after hospital admission, spreading to 26 patients and staff. Herein we evaluate control of this COVID-1 outbreak., Methods: To control the outbreak, the index case ward was closed, and large-scale COVID-19 testing (RT PCR) was performed for all inpatients, caregivers and healthcare workers (HCWs). All exposed persons were quarantined. Thorough investigation was conducted to analyze the transmission route., Results: The outbreak comprised 12 patients, 12 caregivers, and 3 HCWs. Seven patients expired and the remaining cases recovered. Overall, 456 patients/caregivers and 169 HCWs were quarantined. Analysis showed that longer exposure time was the main cause of HCW infection; all three infected HCWs were primary-care nurses related to the index case. To diminish hidden cases, all hospitalized patients/caregivers received PCR examinations and all results were negative. Thereafter, all patients/caregivers routinely received PCR examination on admission. Hospital-wide PCR screening for HCW detected 4 positive HCWs unrelated to this outbreak, and a second-round of screening detected 2 more cases, with no additional cases during the following 6 months., Conclusion: Prompt infection control measures and large-scale PCR screening can control a COVID-19 outbreak within 2 weeks. Exposure time is the major risk factor for HCW infection., (Copyright © 2022. Published by Elsevier B.V.)

Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are the major pathogens of the spore-forming genus Bacillus and possess an outer spore layer, the exosporium, not found in many of the nonpathogenic species. The exosporium consists of a basal layer with the ExsY, CotY, and BxpB proteins being the major structural components and an exterior nap layer containing the BclA glycoprotein. During the assembly process, the nascent exosporium basal layer is attached to the spore coat by a protein linker that includes the CotO and CotE proteins. Using transmission electron microscopy, Western blotting, immunofluorescence, and fluorescent fusion protein approaches, we examined the impact of single, double, and triple mutants of the major exosporium proteins on exosporium protein content and distribution. Plasmid-based expression of exsY and cotE resulted in increased production of exosporium lacking spores, and the former also resulted in outer spore coat disruptions. The exosporium bottlecap produced by exsY null spores was found to be more stable than previously reported, and its spore association was partially dependent on CotE. Deletion mutants of five putative spore genes ( bas1131 , bas1142 , bas1143 , bas2277 , and bas3594 ) were created and shown not to have obvious effects on spore morphology or BclA and BxpB content. The BclC collagen-like glycoprotein was found to be present in the spore and possibly localized to the interspace region. IMPORTANCE B. anthracis is an important zoonotic animal pathogen causing sporadic outbreaks of anthrax worldwide. Spores are the infectious form of the bacterium and can persist in soil for prolonged periods of time. The outermost B. anthracis spore layer is the exosporium, a protein shell that is the site of interactions with both the soil and with the innate immune system of infected hosts. Although much is known regarding the sporulation process among members of the genus Bacillus , significant gaps in our understanding of the exosporium assembly process exist. This study provides evidence for the properties of key exosporium basal layer structural proteins. The results of this work will guide future studies on exosporium protein-protein interactions during the assembly process.