Search

Abstract The global obesity problem is becoming increasingly serious, with eight of the top ten causes of death in Taiwan in 2020 being related to obesity. Morbid obesity poses a significant threat to one’s health and well-being. In recent years, bariatric surgery has emerged as a more effective treatment option for patients with morbid obesity. However, the procedure is not without risks. This study aims to examine the factors that impact the postoperative efficacy evaluation of patients with morbid obesity. This study uses a retrospective cross-sectional design, with medical records being collected retrospectively. The data was collected from patients who underwent bariatric surgery between July 1, 2017 and June 30, 2020 at a hospital in southern Taiwan. A total of 663 patients were included in the study and were observed for 1 year after the surgery. The independent variables included demographic variables, perceived symptoms variables, perceived lifestyle variables, and surgery-related variables, while the dependent variables included weight loss outcomes and complications. The prognostic factors affecting the postoperative efficacy evaluation of patients with pathological obesity were determined using multiple regression analysis and binary regression analysis. The study found that 65.6% of the participants were female, with an average age of 36.8 years. The results of the multiple regression and binary logistic regression showed that gender, age, BMI, diabetes, and smoking habit were the predictors of postoperative weight loss. Hypertension, diabetes, liver disease, kidney disease, smoking habit, drinking habit, and operation time were the predictors of postoperative complications. The study found that the presence of the aforementioned 12 significant factors can affect the success of weight loss after surgery and the incidence of postoperative complications. This information can serve as a reference for clinical care institutions and patients to improve the postoperative efficacy evaluation.

Abstract Purpose The purpose of this study is to examine whether leisure activities can help reduce years lived with disability and increase healthy life expectancy of diabetics aged 50 years and above. Methods Analysis was based on five waves of follow-up survey data (Taiwan Longitudinal Study of Aging, TLSA) from 1996 to 2011. A total of 5131 participants aged 50 years and above in 1996 were included in the analysis, and gender, leisure activity participation, and diabetes mellitus were used as primary variables to examine the variation trend in health status in the participants. The health status in the various waves of surveys was measured using the activities of daily living scale, and nondisabled was defined as healthy. A multivariate logistic regression model was used to calculate the life expectancy (LE) and healthy life expectancy (HLE) of the people aged 50 years and above. Results The diabetes older people with a high frequency of leisure activities have longer HLE than those with lower activity frequency. Using 50-year-old diabetic women as an example, the LE (HLE) of those with six or more leisure activities and those with three or fewer leisure activities was 30.40 (25.34) and 24.90 (20.87), respectively. The LE (HLE) of men with the same conditions was 24.79 (22.68) and 20.30 (18.45), respectively. Conclusions This study used life expectancy and healthy life expectancy as markers to evaluate health benefits and provided evidence that leisure activities can help extend the life span and maintain the health status of middle-aged and older diabetics.

Abstract Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti‐ vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real‐world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR‐TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first‐line EGFR‐TKI with anti‐VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high‐grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti‐VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR‐TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large‐scale registry‐based cohort studies may be needed to validate our findings.

In the pursuit of establishing a unified model for fine-grained access control and secure data communication within a distributed microservices architecture, a verifier-policy attributed-based signature (VP-ABS) scheme, augmented with attribute revocation and an authenticated key agreement protocol, was proposed. This scheme was underpinned by Type-3 pairing. In this scheme, signatures generated by signers were linked solely to a subset of the signer's attributes and were disassociated from the access policy. This decoupling allowed for the reusability of the signer's signature across multiple access policies. Additionally, an attribute-Hash filter algorithm was introduced to facilitate a direct attribute revocation mechanism within the proposed VP-ABS scheme. This mechanism was designed to prevent users from authenticating with expired attributes. To further secure data communication, a mutually authenticated key agreement protocol was also proposed. This protocol was secure within the framework of the extended Canetti-Krawczyk (eCK) model and was built upon the foundation of the VP-ABS scheme. A rigorous unforgeability proof for the VP-ABS scheme was provided. Ultimately, theoretical comparisons and simulation experiments conducted at a 128-bit advanced encryption standard (AES) security level demonstrated that the proposed attribute-based authentication and secure communication scheme outperforms other contemporary schemes in terms of efficiency.

The conjugate of rhein and artesunate have shown promising effects in inducing immunogenic cell death (ICD) and inhibiting tumor growth. Rhein, a natural anthraquinone derivative found in various medicinal plants such as Rheum palmatum, possesses diverse pharmacological properties including anti-inflammatory and anticancer activities. Artesunate, a sesquiterpene lactone extracted from Artemisia annua, exhibits potent antimalarial efficacy and has garnered attention for its potential anticancer properties. Through rational drug design, the conjugation of rhein with artesunate has yielded compounds capable of selectively targeting mitochondria of cancer cells, inducing oxidative stress-mediated ICD, and enhancing the immunogenicity of tumor cells. The conjugate leverages the inherent cytotoxicity of artesunate while incorporating the capability to selectively target the mitochondria of rhein, thereby fostering a special approach to immunotherapy for cancer. Upon accumulation in the mitochondria, these compounds induce the generation of reactive oxygen species (ROS), leading to mitochondrial membrane potential (ΔΨm) reduction and endoplasmic reticulum (ER) stress. Notably, the conjugate exhibits far more potent ICD-inducing properties than their parent compounds. In vivo studies have demonstrated that the vaccine, when treated with the conjugate, effectively suppresses tumor growth.

Abstract This study aimed to establish an astaxanthin-rich strain of the calanoid copepod Pseudodiaptomus annandalei, through selective breeding based on RGB (red, green and blue) value, a parameter indicating color intensity. We evaluated the RGB value frequency distributions of the copepod populations, and selected individuals with the highest 10% and the lowest 10% RGB value over six generations. The RGB value, nauplii production, clutch interval and clutch number were assessed, and the genetic gain was calculated across generations (G0-G5). Two strains of copepods were selected and defined as dark body copepod strain (DBS) and light body copepod strain (LBS) at the end of experiment. Results revealed significantly lower RGB values (male: 121.5 ± 14.1; female: 108.8 ± 15) in the G5 DBS population compared to the G0 (male: 163.9 ± 13.1; female: 162.2 ± 14.6), with higher genetic gains of RGB values during G0 to G2. While DBS females exhibited longer clutch intervals in the G3 and G4, there was no significant difference in nauplii production between the two strains across all generations. Significantly higher astaxanthin content was found in the DBS copepods (0.04 μg/ ind.) compared to the LBS copepods (0.01 μg/ ind.) and the non-selective copepods (0.02 μg/ ind.) 20 months post selective breeding, validating the stability of the desired trait in the DBS strain. This study successfully established an astaxanthin-rich strain of P. annandalei, which provides implications for enhancing marine and brackish larviculture production.

Background/purpose: Periodontal ligament stem cells (PDLSCs) have the potential for regenerating periodontal tissue. The study aims to investigate the impact of demographics (ages, gender, disease) and culture techniques (shipping storage time and culture method) on the success of primary culture. Materials and methods: PDLSCs were collected from 51 teeth of 26 patients and cultured via outgrowth (OG) and enzymatic digestion (ED) methods. Cells characteristics were confirmed by flow cytometry, MTT, and ARS. The primary culture success rate was evaluated with a serial chi-square test to determine the relationship with culture technique (ED/OG and ≤4 h/prolonged culture) and patient demographics (Young/Old, Female/Male, and Health/Periodontitis). Results: The overall success rate of Health group (69.7%) was higher than Periodontitis (38.9%). Culturing within 4 h possessed a higher success rate (71.8%) than prolonged group (16.7%) regardless of patient demographics, and using OG method (81.5%) revealed more promising. Subgroup analysis of 39 cases (culture within 4 h) found that the success rate of OG was higher than ED in the Old group (87.5%–25.0%) and in the Periodontitis group (83.3%–25.0%). Conclusion: Primary culturing of PDLSCs within 4 h and using the outgrowth method led to higher success rates regardless of patient demographics. It can achieve successful PDLSCs culture of older patients or patients with periodontal disease by appropriate culture technique.

Purpose:. The purpose of this study is to demonstrate the feasibility and safety of the Senhance robotic system in urologic surgeries. Materials and methods:. Patients were included prospectively from July 2018 to December 2020. The exclusion criteria included severe cardiopulmonary diseases and previous extensive abdominal surgeries. Institutional approval and informed consent were obtained. We used the Clavien-Dindo classification system to evaluate the complications that occurred within 30 days after surgery. Common technical and mechanical events encountered were also recorded. Results:. A total of 173 patients were recruited. The median age was 65 (58–74) years, and the median body mass index was 24.7 (16.5–35.6) kg/m2. Seventeen (9.8%) patients had previously undergone abdominal surgeries. Eighty-three (48%) cases had total extraperitoneal hernioplasty and 32 (18.5%) cases radical prostatectomy, which were the largest 2 surgeries in our study. Sixty-one (35.3%) patients received surgeries due to malignancy. The median docking time was 5 (1–35) minutes. There were 28 (16.2%) cases with grade I complications and 9 (5.2%) cases with grade II complications. Only one case of a grade IIIb complication occurred during radical prostatectomy. No grade IV complications or mortalities were noted. Robotic arm collisions and forces exceeding the limit were the most commonly encountered problems intraoperatively. Conclusion:. In our initial experiences, the Senhance robotic system was feasible in oncologic and nononcologic urologic surgeries and had acceptable outcomes. The haptic feedback system is unique and requires a learning period. This system may serve as an alternative tool for robotic urologic surgeries.

Abstract Familial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, whereas the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry–based non‐targeted metabolomics, we analyzed pre‐ and post‐BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways, including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post‐BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.

Class IIa histone deacetylases (HDACs) have been linked to tumorigenesis in various cancers. Previously, we designed phenylhydroxamic acid LH4f as a potent class IIa HDAC inhibitor. However, it also unselectively inhibited class I and class IIb HDACs. To enhance the compound’s selectivity towards class IIa HDACs, the ortho-phenyl group from the selective HDAC7 inhibitor 1 is incorporated into ortho position of the phenylhydroxamic acid in LH4f. Compared to LH4f, most resulting compounds displayed substantially improved selectivity towards the class IIa HDACs. Notably, compound 7 g exhibited the strongest HDAC9 inhibition with an IC50 value of 40 nM. Molecular modelling further identified the key interactions of compound 7 g bound to HDAC9. Compound 7 g significantly inhibited several human cancer cells, induced apoptosis, modulated caspase-related proteins as well as p38, and caused DNA damage. These findings suggest the potential of class IIa HDAC inhibitors as lead compounds for the development of cancer therapeutics.

AbstractThe phytochemical investigation of the methanol extract of the seeds of Magydaris pastinacea afforded two undescribed benzofuran glycosides, furomagydarins A-B (1, 2), together with three known coumarins. The structures of the new isolates were elucidated after extensive 1D and 2D NMR experiments as well as HR MS. Compound 1 was able to inhibit the COX-2 expression in RAW264.7 macrophages exposed to lipopolysaccharide, a pro-inflammatory stimulus. RT-qPCR and luciferase reporter assays suggested that compound 1 reduces COX-2 expression at the transcriptional level. Further studies highlighted the capability of compound 1 to suppress the LPS-induced p38MAPK, JNK, and C/EBPβ phosphorylation, leading to COX-2 down-regulation in RAW264.7 macrophages.

Increasingly deployment of distributed renewable energy sources has driven the emergence of peer-to-peer (P2P) energy trading, which refers to trading energy directly among the end energy customers. This paper studies the feasibility and mechanism of establishing cooperation among different types of energy prosumers in a community microgrid environment with uncertainty. In particular, a coalitional game-based P2P energy trading framework is proposed, through which participating prosumers are enabled to form a coalition to share the energy trading profit by sufficiently considering the renewable energy and load uncertainties. To incentivize prosumers to participate in energy trading cooperation, some contract constraint rules are designed to ensure that the risk of the prosumer energy systems is controllable, and a theoretical analysis framework is presented to strictly prove the benefit of the prosumer coalition. A Shapely value-based payoff distribution scheme is designed to allocate profit for each prosumer in the coalition. Comprehensive numerical simulation is conducted to validate the proposed method.

Background: A previous phase 1 dose-escalation study in Taiwan indicated CAN008 (asunercept) with standard concurrent chemoradiotherapy (CCRT) improved progression-free survival (PFS) in newly diagnosed glioblastoma (GBM) patients. This study evaluates the efficacy of CAN008 in promoting overall survival (OS) and identifies genetic alterations associated with treatment responses. Methods: We compared OS of 5-year follow-ups from 9 evaluable CAN008 cohort patients (6 received high-dose and 3 received low-dose) to a historical Taiwanese GBM cohort with 164 newly diagnosed patients. CAN008 treatment response-associated genetic alterations were identified by whole-exome sequencing and comparing variant differences between response groups. Associations among patient survival, tumor mutational burden (TMB), and genetic alterations were analyzed using CAN008 cohort and TCGA-GBM dataset. Results: OS for high-dose CAN008 patients at 2 and 5 years was 83% and 67%, respectively, and 40.1% and 8.8% for the historical GBM cohort, respectively. Better OS was observed in the high-dose CAN008 cohort (without reaching the median survival) than the historical GBM cohort (median OS: 20 months; p = 0.0103). Five high-dose CAN008 patients were divided into good and poor response groups based on their PFS. A higher variant count and TMB were observed in good response patients, whereas no significant association was observed between TMB and patient survival in the newly diagnosed TCGA-GBM dataset, suggesting TMB may modulate patient CAN008 response. Conclusion: CAN008 combined with standard CCRT treatment prolonged the PFS and OS of newly diagnosed GBM patients compared to standard therapy alone. Higher treatment efficacy was associated with higher TMB.

Summary: The dentate gyrus plays a key role in the discrimination of memories by segregating and storing similar episodes. Whether hilar mossy cells, which constitute a major excitatory principal cell type in the mammalian hippocampus, contribute to this decorrelation function has remained largely unclear. Using two-photon calcium imaging of head-fixed mice performing a spatial virtual reality task, we show that mossy cell populations robustly discriminate between familiar and novel environments. The degree of discrimination depends on the extent of visual cue differences between contexts. A context decoder revealed that successful environmental classification is explained mainly by activity difference scores of mossy cells. By decoding mouse position, we reveal that in addition to place cells, the coordinated activity among active mossy cells markedly contributes to the encoding of space. Thus, by decorrelating context information according to the degree of environmental differences, mossy cell populations support pattern separation processes within the dentate gyrus.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5–14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167–7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922–41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374–12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780–10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771–0.894) and 0.821 (95 % CI 0.720–0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

The intestinal tract plays an important role in digestion and absorption, nutrient metabolism, and immune anti-stress. At the same time, the intestine is also the major site for pathogens and various harmful substances to invade. Probiotics, as living microbial agents, improve animal health by maintaining the microecological balance of the host's intestinal flora. To explore the protective effect of Clostridium butyricum (CB) on the gut, we investigated the changes in digestion, antioxidant, and gut microbiota in juvenile largemouth bass. The fish were fed with diets containing 0 (control, CB0), 4.3×108 (CB1), 7.5×108 (CB2), 1.5×109 (CB3), and 3.2×109 (CB4) CFU/kg Clostridium butyricum for 56 days. After 56 days of dietary supplementation with 4.3×108 and 3.2×109 CFU/kg of CB, significant growth promotion and feed utilization improvement were observed in largemouth bass (P < 0.05). The activities of digestive enzymes (trypsin, protease and amylase) and intestinal functional indicators (sodium-potassium ATP, γ-GT and CK) were significantly increased in the intestine of largemouth bass (P < 0.05). The contents of intestinal short-chain fatty acids (acetic acid, propionic acid, isobutyric acid, N-butyric acid and isovaleric acid) in largemouth bass were significantly increased (P < 0.05). CB significantly increased the activities of antioxidant enzymes (T-AOC, CAT, POD, GSH-Px and SOD) and decreased the content of MDA in the intestine of largemouth bass (P < 0.05). It was also observed that CB significantly increased the activities of immune-related markers lysozyme and alkaline phosphatase (P < 0.05). High-throughput sequencing of the 16 S rRNA gene in largemouth bass revealed a significant increase in gut microbial richness. KEGG pathway analysis showed that CB had significant effects on intestinal microbiota functions, such as nutrient metabolism and energy conversion. The results showed that CB could stimulate intestine to produce the organic product butyric acid, which was customized in the gut to enhance digestive performance, promote nutrient metabolism, and protect microbial homeostasis in the intestinal tract of largemouth bass. These results provide new insights into the protective effects of CB on the intestinal tract of aquatic animals.

Purpose: This study used the Taiwan Longitudinal Study in Aging from 1996 to 2011 to investigate the effects of diabetes, hypertension, and healthy living behaviors of those aged over 50 years on the survival status in Taiwan. Methods: Among the 5,131 participants aged 50 years and above in the 1996 survey were included in this study. Cox’s proportional hazards model was used to examine the incidence of diabetes, hypertension, and related mortality risk in those aged over 50 years. Results: After adjusting for age, gender, education level, diabetes, hypertension, health behavior, and leisure activity, results from the Cox model show that the elderly without diabetes have a lower mortality risk than those with diabetes. Regular exercise was associated with a lower risk of mortality. The hazard ratios of elderly with regular exercise were 0.78 (95 % CI: 0.64–0.96) for two times a week or less, 0.81 (95 % CI: 0.69–0.96) for 3–5 times a week, and 0.84 (95 % CI: 0.77–0.93) for 6 + times a week, respectively. On the other hand, leisure activity positively reduces mortality risk. For example, the hazard ratios of the elderly with watching TV and reading were 0.63 (95 % CI: 0.55–0.72) and 0.80 (95 % CI: 0.72–0.89), respectively. Moreover, smoking can increase mortality risk 23 % whether the elderly are with diabetes or hypertension or not. Conclusions: Regarding preventing and controlling chronic diseases in the future, continuously encouraging improvement in health behavior and engaging in leisure activities for the middle-aged and over should be considered essential markers.

Dengue virus (DENV) causes approximately 390 million dengue infections worldwide every year. There were 22,777 reported DENV infections in Tainan, Taiwan in 2015. In this study, we sequenced the C-prM-E genes from 45 DENV 2015 strains, and phylogenetic analysis based on C-prM-E genes revealed that all strains were classified as DENV serotype 2 Cosmopolitan genotype. Sequence analysis comparing different DENV-2 genotypes and Cosmopolitan DENV-2 sequences prior to 2015 showed a clade replacement event in the DENV-2 Cosmopolitan genotype. Additionally, a major substitution C-A314G (K73R) was found in the capsid region which may have contributed to the clade replacement event. Reverse genetics virus rgC-A314G (K73R) showed slower replication in BHK-21 and C6/36 cells compared to wildtype virus, as well as a decrease in NS1 production in BHK-21-infected cells. After a series of passaging, the C-A314G (K73R) mutation reverted to wildtype and was thus considered to be unstable. Next generation sequencing (NGS) of three sera collected from a single DENV2-infected patient at 1-, 2-, and 5-days post-admission was employed to examine the genetic diversity over-time and mutations that may work in conjunction with C-A314G (K73R). Results showed that the number of haplotypes decreased with time in the DENV-infected patient. On the fifth day after admission, two new haplotypes emerged, and a single non-synonymous NS4A-L115I mutation was identified. Therefore, we have identified a persistent mutation C-A314G (K73R) in all of the DENV-2 isolates, and during the course of an infection, a single new non-synonymous mutation in the NS4A region appears in the virus population within a single host. The C-A314G (K73R) thus may have played a role in the DENV-2 2015 outbreak while the NS4A-L115I may be advantageous during DENV infection within the host.

Abstract Objectives To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre‐operation. Methods From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT‐derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application. Results Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145). Conclusions ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.

Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy of copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with a short blood half‐life, face challenges in transporting enough amounts of Cu ions into tumor cells. This work describes the construction of carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by the coordination of Cu2+ with the sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination of cuproptosis and ferroptosis. Ce6@Cu NPs internalized by U87MG cells induce a sonodynamic effect and glutathione (GSH) depletion capability, promoting lipid peroxidation and eventually inducing ferroptosis. Furthermore, Cu+ concentration in tumor cells significantly increases as Cu2+ reacts with reductive GSH, resulting in the downregulation of ferredoxin‐1 and lipoyl synthase. This induces the oligomerization of lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress and irreversible cuproptosis. Ce6@Cu NPs possess a satisfactory ability to penetrate the blood‐brain barrier, resulting in significant accumulation in orthotopic U87MG‐Luc glioblastoma. The sonodynamic‐triggered combination of ferroptosis and cuproptosis in the tumor by Ce6@Cu NPs is evidenced both in vitro and in vivo with minimal side effects. This work represents a promising tumor therapeutic strategy combining ferroptosis and cuproptosis, potentially inspiring further research in developing logical and effective cancer therapies based on cuproptosis.

Abstract This study aimed to investigate the relationship between the utilization of household water treatment devices (UHWTD) and both overall and cause-specific mortality, addressing the lack of comprehensive prospective research in this area. The study was a population-based prospective cohort study using data from the US National Health and Nutrition Examination Survey (NHANES 1999–2010). Among the 30,322 participants included in the study, the group without UHWTD (No UHWTD) was younger but reported worse baseline health compared to the UHWTD group. During an average follow-up period of 14.3 years, 6811 participants died. After adjusting for age, sex, and other covariates, No UHWTD was significantly associated with a higher risk of overall (adjusted hazard ratio [aHR]: 1.221, 95% Confidence Interval [CI]: 1.147–1.300), heart (aHR: 1.405, 95% CI: 1.241–1.589), cancer (aHR: 1.176, 95% CI: 1.003–1.379), Alzheimer’s disease (aHR: 1.404, 95% CI: 1.027–1.919), and nephrosis (aHR: 1.613, 95% CI: 1.026–2.537) mortality compared to UHWTD. Moreover, those main association almost remained after further adjustment for water source. Additionally, we observed a lower detection rate of bromoform, chloroform, bromodichloromethane, and dibromochloromethane in tap water when household water treatment devices was used compared to No UHWTD. The utilization of household water treatment devices in this prospective cohort was associated with modest reductions in the risk of overall, heart, cancer, Alzheimer’s disease, and nephrosis mortality. These findings suggest that the use of household water treatment devices may have the potential to influence health outcomes and extend life expectancy.

Abstract Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Background: Antimicrobial resistance (AMR) is a growing worldwide public health issue due to the overuse and inappropriate use of antibiotics. AMR has been more prevalent during the coronavirus pandemic of 2019 (COVID-19) compared to previous periods. Therefore, this study was conducted to evaluate the AMR profile of common bacteria that were isolated for routine analysis during the pandemic of COVID-19 in Central Taiwan. The main goal of this study was to examine and analyze the AMR patterns both before and after the start of the COVID-19 pandemic. Methods: We conducted a retrospective analysis of clinical samples collected from two different time periods: the 1-year period before the onset of the COVID-19 pandemic (January 2019 to December 2019) and the 2-year period following the start of the pandemic (September 2020 to September 2022). The data for this study were obtained from clinical records, and both bacterial identification and antibiotic susceptibility testing were performed using the Phoenix identification system. Results: Among the 8152 bacterial isolates obtained during the study period from September 2020 to September 2022, 4022 (49.3%) were Escherichia coli, 1346 (16.5%) were Klebsiella pneumoniae, 1156 (14.2%) were Staphylococcus aureus, 887 (10.9%) were Pseudomonas aeruginosa, 376 (4.6%) were Enterococcus faecium, and 365 (4.5%) were Acinetobacter baumannii. The overall prevalence of resistant bacteria during the COVID-19 pandemic was as follows: vancomycin-resistant Enterococcus, 69%; carbapenem-resistant A. baumannii, 65%; methicillin-resistant S. aureus, 49%; carbapenem-resistant K. pneumoniae, 29%; carbapenem-resistant P. aeruginosa, 17%; and carbapenem-resistant E. coli, 2%. Carbapenem-resistant A. baumannii, vancomycin-resistant Enterococcus, carbapenem-resistant K. pneumoniae, and carbapenem-resistant E. coli increased by 19%, 10%, 2%, and 1%, respectively. On the other hand, carbapenem-resistant P. aeruginosa and methicillin-resistant S. aureus decreased by 6%, respectively. Conclusion: This study provides a comprehensive assessment of AMR during the COVID-19 pandemic in Central Taiwan. Understanding the prevalence of AMR is crucial for preventing infection and formulating disease prevention policies. Further research is warranted to elucidate the correlation between AMR and the severity of infection in COVID-19 patients.

Bidirectional interlinking converter (BIC) is the core equipment in a hybrid AC/DC microgrid connected between AC and DC sub-grids. However, the variety of control modes and flexible bidirectional power flow complicate the influence of AC faults on BIC itself and on DC sub-grid, which potentially threaten both converter safety and system reliability. This study first investigates AC fault influence on the BIC and DC bus voltage under different BIC control modes and different pre-fault operation states, by developing a mathematical model and equivalent sequence network. Second, based on the analysis results, a general accommodative current limiting strategy is proposed for BIC without limitations to specific mode or operation condition. Current amplitude is predicted and constrained according to the critical requirements to protect the BIC and relieving the AC fault influence on the DC bus voltage. Compared with conventional methods, potential current limit failure and distortions under asymmetric faults can also be avoided. Finally, experiments verify feasibility of the proposed method.

Abstract Objective The outbreak of the COVID-19 pandemic has drawn attention from all sectors of society to the level of public health services. This study aims to investigate the level of public health service supply in the four major regions of Guangdong Province, providing a basis for optimizing health resource allocation. Methods This article uses the entropy method and panel data of 21 prefecture-level cities in Guangdong Province from 2005 to 2021 to construct the evaluation index system of public health service supply and calculate its supply index. On this basis, the standard deviation ellipse method, kernel density estimation, and Markov chain are used to analyze the spatiotemporal evolution trend of the public health service supply level in Guangdong Province. The Dagum Gini coefficient and panel regression model are further used to analyze the relative differences and the key influencing factors of difference formation. Finally, the threshold effect model is used to explore the action mechanism of the key factors. Results Overall, the level of public health service supply in Guangdong Province is on an upward trend. Among them, polarization and gradient effects are observed in the Pearl River Delta and Eastern Guangdong regions; the balance of public health service supply in Western Guangdong and Northern Mountainous areas has improved. During the observation period, the level of public health services in Guangdong Province shifted towards a higher level with a smaller probability of leapfrogging transition, and regions with a high level of supply demonstrated a positive spillover effect. The overall difference, intra-regional difference and inter-regional difference in the level of public health service supply in Guangdong Province during the observation period showed different evolutionary trends, and spatial differences still exist. These differences are more significantly positively affected by factors such as the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate. Under different economic development threshold values, the degree of fiscal decentralization and urbanization rate both have a double threshold effect on the role of public health service supply level. Conclusion The overall level of public health service supply in Guangdong Province has improved, but spatial differences still exist. Key factors influencing these differences include the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate, all of which exhibit threshold effects. It is suggested that, in view of the actual situation of each region, efforts should be made to build and maintain their own advantages, enhance the spatial linkage of public health service supply, and consider the threshold effects of key factors in order to optimize the allocation of health resources.

Abstract Human papillomavirus (HPV) infection poses a significant threat to public health worldwide. Targeting the function of HPV E6 and E7 proteins and activating the host immune response against these proteins represent promising therapeutic strategies for combating HPV-related diseases. Consequently, the efficient production of soluble, high-purity E6 and E7 proteins is crucial for function and host immune response studies. In this context, we selected the pMCSG19 protein expression vector for Escherichia coli to produce soluble MBP-His6 tagged HPV11/16 E6/E7 proteins, achieving relatively high purity and yield. Notably, these proteins exhibited low toxicity to peripheral blood mononuclear cells (PBMCs) and did not compromise their viability. Additionally, the recombinant proteins were capable of inducing the secretion of multiple cytokines by immune cells in peripheral blood, indicating their potential to elicit immune responses. In conclusion, our study offers a novel approach for the production of HPV11/16 E6/E7 fusion proteins with relatively high purity and yield. The fusing HPV11/16 E6/E7 proteins to MBP-His6 tag may serve as a valuable method for large-scale protein production in future research endeavors.

Abstract The recently discovered kagome superconductors offer a promising platform for investigating intertwined orders and novel states, including topology, superconductivity, charge density waves, and more. The interplay among these orders can spontaneously break rotational symmetry, giving rise to exotic phenomena such as nematicity or even nematic superconductivity. Here we present our findings on the two-fold symmetric superconductivity in thin-flake RbV3Sb5 in response to direction-dependent in-plane magnetic fields, in contrast to the inherent six-fold structural symmetry of the crystal lattice. The two-fold symmetry was evidenced through a combination of magnetoresistance transport experiments, critical magnetic field measurements, and observations of anisotropic superconducting gaps. Additionally, by altering the experimental configuration, we also detected the presence of six-fold symmetric components superimposed on the two-fold symmetry at the boundary between normal and superconducting states. Our results underscore the correlation-driven symmetry-breaking phenomena and emphasize the potential of this correlated kagome family as a promising platform for investigating intertwined orders, including unconventional superconductivity.

In order to further understand the characteristics of phytoplankton community in the sea area near Changbiao Island in Xiapu, the data of phytoplankton and water environment from four cruises in May (spring), September (summer), December (autumn) and February (winter) in 2019—2020 were analyzed, and the characteristics of phytoplankton community structure were analyzed. The main environmental factors affecting the structure of phytoplankton community were studied by redundancy analysis. The results showed that there were 170 species of phytoplankton in 60 genera, 48 genera and 131 species of diatoms, 26 species of dinoflagellates in 10 genera, 2 species of cyanobacteria in 1 genera and 1 species of diatoms in 1 genera. Phytoplankton are mainly coastal wide-temperature and wide-salt species and warm water species. There are 13 dominant species throughout the year. In spring, Prorocentrum donghaiense and Noctiluca are the main species, and Skeletonema costatum and Siegesbeckia qiongshi are the main species in summer, autumn and winter. The spatial distribution of phytoplankton abundance shows a trend of high nearshore, low farshore, low in the south, and high in the north. Seasonal variation of phytoplankton is mainly affected by water temperature. Appropriate temperature and nutrients in spring and summer promote a large increase in phytoplankton, while autumn and winter are mainly affected by temperature. Now in spring and summer, the coastal nuclear power station of Changbiao Island in Xiapu should focus on monitoring the occurrence of red tide in spring and summer.

Abstract The hippocampus is the brain’s center for episodic memories. Its subregions, the dentate gyrus and CA1-3, are differentially involved in memory encoding and recall. Hippocampal principal cells represent episodic features like movement, space, and context, but less is known about GABAergic interneurons. Here, we performed two-photon calcium imaging of parvalbumin- and somatostatin-expressing interneurons in the dentate gyrus and CA1-3 of male mice exploring virtual environments. Parvalbumin-interneurons increased activity with running-speed and reduced it in novel environments. Somatostatin-interneurons in CA1-3 behaved similar to parvalbumin-expressing cells, but their dentate gyrus counterparts increased activity during rest and in novel environments. Congruently, chemogenetic silencing of dentate parvalbumin-interneurons had prominent effects in familiar contexts, while silencing somatostatin-expressing cells increased similarity of granule cell representations between novel and familiar environments. Our data indicate unique roles for parvalbumin- and somatostatin-positive interneurons in the dentate gyrus that are distinct from those in CA1-3 and may support routing of novel information.

Aim: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous clinical studies. This trial evaluates the pharmacokinetics of 400 μg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 μg. Methods: Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 μg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed. Results: Tmax was 154.003 h and T1/2 was 114.273 h. The Cmax was 29.823 ng mL−1. AUClast was 9364.292 h∗ng mL−1 and AUCinf was 11084.317 h∗ng mL−1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL−1. Conclusion: Ropeginterferon alfa-2b at 400 μg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 μg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.

Abstract Objective To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). Methods Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. Results Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P

Abstract Background Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. Materials We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. Results In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. Conclusion The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

本文整理三位文化人類學家對教育的觀點。C. Geertz認為教育即文化限 縮，J. Henry認為教育即文化綑綁，G. D. Spindler則認為教育即文化干預、 文化壓縮，三者皆強調文化依賴教育擔負傳遞的功能，卻同時框限教育的內涵與運作。延伸討論的結果指出，教育的框限並非絕對的，教育不會被全然的文化所決定，在特定文化範圍內仍允許學校實施的彈性與個人抉擇的自由，也容許相對程度的創造；從文化相對論推論出教育的相對論，教育皆有其文化框限，各有其優缺點；每種教育模式都只是適應文化環境的文化選擇，沒有優劣差別，亦無放諸四海皆準的教育。在結論中，引用Spindler創用之文化治療概念，期待教育工作者從文化觀點進行質疑與批判，不需盲從於特定時空的教育模式，勇於發掘文化框限的機制與效應，以獲得教育的相對主體性，促成文化與教育的覺醒來支持合理教育的運作。 This article synthesizes the viewpoints of three cultural anthropologists on education. C. Geertz regards education as cultural reduction, J. Henry views it as cultural binding or fettering, and G. D. Spindler sees it as cultural intervention and compression. They all emphasize the reliance of culture on education for its transmission, yet at the same time, note how cultural also confines the operation of education. The extended discussion suggests that the limitations of education are not absolute. Education is not entirely determined by culture; there is still room for flexibility in implementation within the broader cultural space and freedom for individual choice, as well as opportunities for relative creativity. Derived from cultural relativism, the perspective adopted in this paper argues that all forms of education have their own cultural limitations, each with its advantages and disadvantages, and that every educational model is merely a cultural choice, adapted to its environment, with no superior or inferior models. In conclusion, drawing on Spindler’s concept of ‘cultural therapy,’ the paper calls for educators to critically question educational models from a cultural perspective, and to avoid blind adherence to specific educational models found in a particular time or place. It encourages the exploration of the mechanisms and effects of cultural constraints, with the goal of achieving relative subjectivity in education, and thereby fostering a better understanding of the interplay between culture and education that supports the rational operation of education.

Background: SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1–7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1–7)/Mas receptor axis. Methods: HPAEpiC were treated with SARS-CoV-2 SP in the presence or absence of ACE2 antagonist-dalbavancin and Mas receptor agonist-angiotensin-(1–7). Proinflammatory cytokine production (IL-6 and IL-8) were measured at mRNA and protein levels. MAP kinase phosphorylation and transcription factor activation was determined by Western Blot. Mas receptor was blocked by either antagonist (A779) or knockdown (specific SiRNA). Experiments were replicated using A549 cells. Findings: SARS-CoV-2 SP (5 μg/mL) significantly induced MAP kinase (ERK1/2) phosphorylation, downstream transcription factor (activator protein-1, AP-1) activation and cytokine production (IL-6 and IL-8) at both mRNA and protein levels. Pretreatment with dalbavancin (10 μg/mL), or angiotensin-(1–7) (10 μM) significantly reduced ERK1/2 phosphorylation, AP-1 activation, and cytokine production. However, these angiotensin-(1–7)-related protective effects were significantly abolished by blocking Mas receptor with either antagonist (A799,10 μM) or SiRNA knockdown. Interpretation: SARS-CoV-2 SP can induce proinflammatory cytokine production, which can be inhibited by either ACE2 antagonist or Mas receptor agonist-angiotensin-(1–7). Angiotensin-(1–7)-related protective effect on cytokine reduction can be abolished by blocking Mas receptor. Our findings suggest that ACE2/angiotensin-(1–7)/Mas axis may serve as a therapeutic target to control inflammatory response triggered by SARS-CoV-2 SP.