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Objective: The objective of this study is to use parametric human modeling and machine learning methods to identify representative occupants that can account for injury variations among a more diverse population with a limited simulation budget., Method: A maximal projection method was used to sample 100 occupants, considering the variations in stature, weight, and sitting height. An automated mesh morphing method was used to morph the THUMS v4.1 midsize male model into the target geometries. US-NCAP frontal crash simulations were conducted with morphed human models and validated vehicle/restraint models. Surrogate models based on the Gaussian Process (GP) method were trained to find inducing points (IP), here defined as a small number of representative occupants whose outcomes could be used to accurately estimate the variations in the injury risks and patterns throughout the population. Statistical analysis was conducted to validate the IPs' coverage of total variation by illustrating the IP distribution. Restraint optimization was performed at IPs to yield an enhanced restraint system. The method was validated through comparisons among the predicted injury risks under the optimal and baseline designs., Results: Only 20 IPs were needed to sufficient to properly represent the variations in the injury risks and patterns in the whole population with acceptable accuracy. Compared to the surrogate model built from 100 crash simulations, the IP-based surrogate models incurred only 0.4% and 1.8% errors in head injury risks for males and females, respectively. Regarding the injury risks on the chest and lower extremities, the IP-based surrogate models resulted in less than 0.1% and 0.5% errors for males and females, respectively. The FE simulations indicated that the optimal restraint system design reduced the injury risk by relatively 16% and 13% for male and female respectively when delta- V  = 25 (mph), and 47% and 27% for male and female when delta- V  = 35 (mph)., Significance of Results: The study proposed a method to generate more accurate injury risk predictions for a more diverse population under a limited simulation budget. Simulations using IPs may enable restraint system optimization to be conducted more efficiently while reducing injury risks across a more diverse population.

Cancer research is continuously exploring new avenues to improve treatments, and ferroptosis induction has emerged as a promising approach. However, the lack of comprehensive analysis of the ferroptosis sensitivity in different cancer types has limited its clinical application. Moreover, identifying the key regulator that influences the ferroptosis sensitivity during cancer progression remains a major challenge. In this study, we shed light on the role of ferroptosis in colorectal cancer and identified a novel ferroptosis repressor, NUDT16L1, that contributes to the ferroptosis insensitivity in this cancer type. Mechanistically, NUDT16L1 promotes ferroptosis insensitivity in colon cancer by enhancing the expression of key ferroptosis repressor and mitochondrial genes through direct binding to NAD-capped RNAs and the indirect action of MALAT1. Our findings also reveal that NUDT16L1 localizes to the mitochondria to maintain its proper function by preventing mitochondrial DNA leakage after treatment of ferroptosis inducer in colon cancer cells. Importantly, our orthotopic injection and Nudt16l1 transgenic mouse models of colon cancer demonstrated the critical role of NUDT16L1 in promoting tumor growth. Moreover, clinical specimens revealed that NUDT16L1 was overexpressed in colorectal cancer, indicating its potential as a therapeutic target. Finally, our study shows the therapeutic potential of a NUDT16L1 inhibitor in vitro, in vivo and ex vivo. Taken together, these findings provide new insights into the crucial role of NUDT16L1 in colorectal cancer and highlight its potential as a promising therapeutic target., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: β,β-Dimethylacrylalkannin (DMAKN), a natural naphthoquinone found in Zicao, a traditional Chinese medicine (TCM), serves as the designated quantitative marker in the Chinese Pharmacopoeia. Despite its established role in assessing Zicao quality, DMAKN's biological potential remains underexplored in research., Methods: We investigated DMAKN's involvement in Zicao's anti-hepatocellular carcinoma (HCC) properties using a combination of HPLC content analysis and comprehensive bioinformatics. Subsequently, both in vitro and in vivo experiments were conducted to evaluate DMAKN's efficacy against HCC. Mechanistic investigations focused on elucidating DMAKN's impact on cell cycle regulation and induction of cell death., Results: Integrated HPLC analysis and bioinformatics identified DMAKN as the primary active compound responsible for Zicao's anti-HCC activity. In vitro and in vivo studies confirmed DMAKN's potent efficacy against HCC. Notably, DMAKN demonstrated dual effects on HCC cells: inhibiting proliferation at lower doses and inducing rapid cell death at higher doses. Mechanistic insights revealed that low-dose DMAKN induced G2/M phase cell cycle arrest through modulation of CDK1 and Cdc25C phosphorylation, while high-dose DMAKN triggered necrosis. Importantly, high-dose DMAKN caused a sharp increase in intracellular ROS levels in a short time, while low-dose DMAKN gradually increased ROS levels over a long period. Additionally, low-dose DMAKN-induced ROS activated the JNK pathway, crucial for cell cycle arrest, whereas high-dose DMAKN-induced necrosis was ROS-dependent but JNK-independent., Conclusion: This study underscores DMAKN's pivotal role as the principal anti-HCC compound in Zicao, delineating its differential effects and underlying mechanisms. These results demonstrate the potential of DMAKN as a therapeutic agent for the treatment of HCC, providing important information for further study and advancement in cancer therapy., Competing Interests: Declaration of competing interest 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 © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Abstract: Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs' involvement in chronic pain pathways. However, animal studies have predominantly examined epigenetic modulation within the spinal cord after pain induction, which may not fully reflect the complexity of chronic pain in humans. Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [ 11 C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [ 11 C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP., (Copyright © 2024 International Association for the Study of Pain.)

cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions., (© 2024. The Author(s).)

The study uses Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH)-MS in conjunction with secretome proteomics to identify key proteins that Pseudomonas aeruginosa secretes against methicillin-resistant Staphylococcus aureus (MRSA). Variations in the inhibition zones indicated differences in strain resistance. Multivariate statistical methods were applied to filter the proteomic results, revealing five potential protein biomarkers, including Peptidase M23. Gene ontology (GO) analysis and sequence alignment supported their antibacterial activity. Thus, SWATH-MS provides a comprehensive understanding of the secretome of P. aeruginosa in its action against MRSA, guiding future antibacterial research., (© 2024 Wiley‐VCH GmbH.)

Background: Barcode information management systems (BIMS) have been implemented in operating rooms to improve the quality of medical care and administrative efficiency. Previous research has demonstrated that the Agile development model is extensively used in the development and management of information systems. However, the effect of information systems on staff acceptance has not been examined within the context of clinical medical information management systems., Objective: This study aimed to explore the effects and acceptance of implementing a BIMS in comparison to the original information system (OIS) among operating and supply room staff., Methods: This study was a comparative cohort design. A total of 80 staff members from the operating and supply rooms of a Northern Taiwan medical center were recruited. Data collection, conducted from January 2020 to August 2020 using a mobile-based structured questionnaire, included participant characteristics and the Information Management System Scale. SPSS (version 20.0, IBM Corp) for Windows (Microsoft Corporation) was used for data analysis. Descriptive statistics included mean, SD, frequency, and percentage. Differences between groups were analyzed using the Mann-Whitney U test and Kruskal-Wallis test, with a P value <.05 considered statistically significant., Results: The results indicated that the BIMS generally achieved higher scores in key elements of system success, system quality, information quality, perceived system use, perceived ease of use, perceived usefulness, and overall quality score; none of these differences were statistically significant (P>.05), with the system quality subscale being closest to significance (P=.06). Nurses showed significantly better perceived system use than technicians (1.58, SD 4.78 vs -1.19, SD 6.24; P=.02). Significant differences in perceived usefulness were found based on educational level (P=.04) and experience with OIS (P=.03), with junior college-educated nurses and those with over 6 years of OIS experience reporting the highest perceived usefulness., Conclusions: The study demonstrates that using the Agile development model for BIMS is advantageous for clinical environments. The high acceptance among operating room staff underscores its practicality and broader adoption potential. It advocates for continued exploration of technology-driven solutions to enhance health care delivery and optimize clinical workflows., (©Chia-Yen Li, Mei-Hui Huang, Yu-Shiue Lin, Chi-Ming Chu, Hsueh-Hsing Pan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.10.2024.)

This study reports the methodology for reconstructing anomalous temperature index series of China in 1368-1911 based on the REACHES database which digitizes the Chinese records quoted in the Compendium of Meteorological Records of China in the Last 3000 Years. The reconstruction adopts an ordinal scale index approach ranging from -2 (very cold) to 1 (warm). Based on the grading criteria, a total of 12,871 records were retrieved through a standard coding system established at REACHES. Sensitivity experiments were performed to test robustness of the index system and a reasonability test was conducted to develop an appropriate method for deriving areal mean temperature index. The reconstructed series were validated through comparison with early instrumental data from Global Historical Climatology Network which shows good correlations and reliability of the REACHES reconstructed index data. Annual and semi-annual (winter and summer) temperature index data series were released for the whole domain as well as the 3- and 15-subregion geographical domains in China., (© 2024. The Author(s).)

Home blood pressure monitoring (HBPM) has been proven to be reliable for both diagnosis and treatment of hypertension. Experts from 11 Asian countries collaborated to design a questionnaire aimed at healthcare workers, seeking to understand the current status of HBPM. A cross-sectional survey was conducted among healthcare professionals from Taiwan between November 2019 and June 2021. A total of 779 physicians in Taiwan participated in the survey. Nearly all physicians (97.7%) reported recommending HBPM to their patients. There was a 14.6% difference between the HBPM device ownership rate (60.2%) and the proportion of patients who measured their home blood pressures (45.6%). Among physicians who recommended HBPM, only 15.5% cited HBPM diagnostic threshold values consistent with the guidelines. Among all respondents, 85.9% and 48.9% viewed HBPM as highly recognized by physicians and patients, respectively. Lack of guidelines for HBPM and concern to reliability and accuracy of the HBPM devices were identified as key barriers to HBPM recognition. This study indicates that there is still room for improvement among healthcare providers in their understanding and implementation of HBPM in Taiwan., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

A carboxylate-directed regioselective Heck-type alkenylation and alkenylative lactonization of ( E )-β,γ-unsaturated carboxylic acids by simply substrate control is reported. ( E )- and ( Z )-alkenyl bromides reacted to give energetically more favorable palladacyles, allowing access to fully stereocontrolled conjugated 1,3-dienes and alkenyled γ-lactones. Mechanistic studies suggest that excellent regioselectivity may be strongly influenced by the steric factors of reactants involved in the palladacycle intermediates.

Objective: The purpose of this systematic review was to characterize methodologies reported in the literature to elicit and record pudendal somatosensory evoked potentials (SEPs) in human adults., Methods: We conducted an electronic literature search in MEDLINE, Embase, CENTRAL, and CINAHL for studies that elicited pudendal SEPs via electrical stimulation and recorded responses though electroencephalography. From included studies, we extracted methodological details of how the SEPs were evoked and recorded., Results: 132 studies were included in our review. The majority of participants were male (n = 6742/8526, 79%). Almost all studies stimulated the dorsal nerve of penis/clitoris. Stimulus parameters varied, with most standardizing stimulus intensity to 2-4x perceptual threshold, pulse duration to 0.1-0.2 ms, and frequency to 3 Hz. The number of stimuli recorded varied by clinical population., Conclusions: Our results demonstrate the inconsistencies of pudendal SEP methodology in the literature, with the majority (77%) of publications not reporting enough detail to reasonably replicate their protocol. Most research to date has been conducted in males, highlighting the paucity of female pelvic neurophysiology research., Significance: We propose a Pudendal SEP Reporting Checklist for adequate reporting of pudendal SEP protocols. Optimal sex- and patient-specific methodologies to investigate all branches of the pudendal nerve need to be established., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Novel D-A 1 -A 2 -π-A organic sensitizers (FZ-sensitizer), utilizing spiro [fluorene-9,9'-phenanthren]-10'-one and benzo [c][1,2,5]thiadiazole moiety as two auxiliary acceptors, are synthesized and applied in dye-sensitized solar cells (DSSCs) and hydrogen production. By incorporating a bulky spiro [fluorene-9,9'-phenanthrene]-10'-one (A 1 ) and benzo[c][1,2,5]thiadiazole (A 2 ) between the donor (D) and π-bridge moiety, structural modifications inhibit molecular aggregation, while the carbonyl group enhances the capture of Li + ions, thereby delaying charge recombination. Furthermore, the extended π-conjugation broadens the light absorption range and enhances the power conversion efficiency (PCE) of FZ-2 under AM1.5 conditions, achieving up to 5.72%. Co-sensitization with N719 and FZ-2 shows PCE of 9.60% under one sun. Under TL84 indoor light conditions, the efficiency is 29.69% at 2500 lux. The superior co-sensitization performance of N719 and FZ-2 can be attributed to FZ-2's high absorptivity at short wavelengths, compensating for N719's shortcomings in this range. FZ-sensitizers also exhibit high efficiency in photocatalytic hydrogen production. The hydrogen production activities of FZ-2 are 9190 μmol/g (1 hour) and 76582 μmol/g (12 hours) respectively, while those of FZ-1 are 7430 μmol/g (1 hour) and 64004 μmol/g (12 hours), indicating that FZ-2 can inject charges into TiO 2 more efficiently and utilize them for water splitting. Stability testing of photocatalytic water splitting after 12 hours shows a turnover number (TON) of 4249 for FZ-1 and 5378 for FZ-2., (© 2024 Wiley-VCH GmbH.)

Background: Triple-negative breast cancer is a breast cancer subtype characterized by its challenging prognosis, and establishing prognostic models aids its clinical treatment. PANoptosis, a recently identified type of programmed cell death, influences tumor growth and patient outcomes. Nonetheless, the precise impact of PANoptosis-related genes on the prognosis of triple-negative breast cancer has yet to be determined., Methods: Clinical information for the triple-negative breast cancer samples was collected from the Gene Expression Omnibus and The Cancer Genome Atlas databases, while 19 PANoptosis-related genes were sourced from previous studies. We first categorized PANoptosis-related subtypes and determined the differentially expressed genes between them. Subsequently, we developed and validated a PANoptosis-associated predictive model using LASSO and Cox multivariate regression analyses. Statistical evaluations were conducted using R software, and the mRNA expression levels of the genes were quantified using real-time PCR., Results: Using consensus clustering analysis, we divided triple-negative breast cancer patients into two clusters based on PANoptosis-related genes and identified 1054 differentially expressed genes between these clusters. Prognostic-related genes were subsequently selected to re-cluster patients, validating their predictive ability. A prognostic model was then constructed based on four genes: BTN2A2, CACNA1H, PIGR, and S100B. The expression and enriched cell types of these genes were examined and the expression levels were validated in vitro. Furthermore, the model was validated, and a nomogram was created to enhance personalized risk assessment. The risk score, proven to be an independent prognostic indicator for triple-negative breast cancer, showed a positive correlation with both age and disease stage. Immune infiltration and drug sensitivity analyses suggested appropriate therapies for different risk groups. Mutation profiles and pathway enrichment were analyzed, providing insights into potential therapeutic targets., Conclusion: A PANoptosis-related prognostic model was successfully developed for triple-negative breast cancer, offering a novel approach for predicting patient prognosis and guiding treatment strategies., Competing Interests: 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., (© 2024 The Authors.)

Background: Personalized medicine remains an unmet need in ovarian cancer due to its heterogeneous nature and complex immune microenvironments, which has gained increasing attention in the era of immunotherapy. A key obstacle is the lack of reliable biomarkers to identify patients who would benefit significantly from the therapy. While conventional clinicopathological factors have exhibited limited efficacy as prognostic indicators in ovarian cancer, multi-omics profiling presents a promising avenue for comprehending the interplay between the tumor and immune components. Here we aimed to leverage the individual proteomic and transcriptomic profiles of ovarian cancer patients to develop an effective protein-based signature capable of prognostication and distinguishing responses to immunotherapy., Methods: The workflow was demonstrated based on the Reverse Phase Protein Array (RPPA) and RNA-sequencing profiles of ovarian cancer patients from The Cancer Genome Atlas (TCGA). The algorithm began by clustering patients using immune-related gene sets, which allowed us to identify immune-related proteins of interest. Next, a multi-stage process involving LASSO and Cox regression was employed to distill a prognostic signature encompassing five immune-related proteins. Based on the signature, we subsequently calculated the risk score for each patient and evaluated its prognostic performance by comparing this model with conventional clinicopathological characteristics., Results: We developed and validated a protein-based prognostic signature in a cohort of 377 ovarian cancer patients. The risk signature outperformed conventional clinicopathological factors, such as age, grade, stage, microsatellite instability (MSI), and homologous recombination deficiency (HRD) status, in terms of prognoses. Patients in the high-risk group had significantly unfavorable overall survival (p < 0.001). Moreover, our signature effectively stratified patients into subgroups with distinct immune landscapes. The high-risk group exhibited higher levels of CD8 T-cell infiltration and a potentially greater proportion of immunotherapy responders. The co-activation of the TGF-β pathway and cancer-associated fibroblasts could impair the ability of cytotoxic T cells to eliminate cancer cells, leading to poor outcomes in the high-risk group., Conclusions: The protein-based signature not only aids in evaluating the prognosis but also provides valuable insights into the tumor immune microenvironments in ovarian cancer. Together our findings highlight the importance of a thorough understanding of the immunosuppressive tumor microenvironment in ovarian cancer to guide the development of more effective immunotherapies., (© 2024. The Author(s).)

Tonsillitis, the inflammation of the palatine tonsils, is a common cause of throat pain. It is most often due to viruses but can also be related to bacteria. Necrotizing tonsillitis is a rare complication of acute tonsillitis with relatively few cases reported in the literature. We present a case of necrotizing tonsillitis in a patient with mononucleosis related to infection by Epstein-Barr virus, with superinfection with Streptococcus pyogenes , or group A streptococcus. To our knowledge, this is the first case of this nature to be reported in the medical literature. While the role of radiologic imaging is generally of limited diagnostic utility in cases of uncomplicated tonsillitis, its use was invaluable in ascertaining the nature and scope of necrotizing tonsillitis in this case. Further research remains to determine whether viral or bacterial superinfection can be used to further stratify patients who present with sore throat., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Adenocarcinoma is the most common subtype of prostate cancer. Prostatic urothelial carcinoma (UC) typically originates from the prostatic urethra. The concurrent occurrence of adenocarcinoma and UC of the prostate gland is uncommon., Case Summary: We present the case of an 82-year-old male patient with simultaneous adenocarcinoma and UC of the prostate gland. The patient underwent a transrectal ultrasound-guided biopsy, and the pathology test revealed UC. Subsequently, transurethral laser prostatectomy was performed, and the pathology test indicated adenocarcinoma of the prostate with a Gleason score of 3 + 4 and high-grade UC. Therefore, the patient was treated with androgen deprivation therapy, systemic chemotherapy, and immunotherapy. Magnetic resonance imaging performed during follow-up revealed a prostate tumor classified as cT2cN1M0, stage IVA. Therefore, the patient underwent robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection. The final pathology test of the prostate gland revealed acinar-type adenocarcinoma, Gleason pattern 4 + 3, pT2N0M0, and high-grade UC. The patient regularly presented to the clinic for postoperative follow-up evaluations. He did not experience any urinary discomfort., Conclusion: According to our literature review, this is the first reported case of coexisting adenocarcinoma and UC of the prostate gland., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study utilized a large-scale representative sample to explore the prevalence of sexting and its associated factors among adolescents in Taiwan. A total of 12,954 students in grade 5-12 countrywide were randomly selected to answer the sexting module of an online survey. 13.7% of the respondents reported having ever received sexts on cellphone, and 2.0% had sent sexts to others. The prevalence was higher among older adolescents. Gender differences were also found, in which female students were more likely to receive sexts (15.8% vs. 11.7%), while male students were at higher risk of sending sexts to others (2.9% vs. 1.1%). A series of hierarchical logistic regression were further performed to examine the associations between potential factors and receiving/sending sexts as the outcome variables. Age, gender, and time spending on texting were significantly associated with receiving and ending sexts. Online respect was found positively associated with receiving sexts but negatively associated with sending them. Privacy awareness was found not significantly associated with sexting. As the first national survey on this growing issue in Taiwan, the results of the present study highlighted the existence of sexting among local youth. Practice and policy implications were discussed., (© 2024 John Wiley & Sons Ltd.)

Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases., (© 2024. The Author(s).)

Background: Pneumoconiosis is associated with pulmonary and cardiovascular diseases; however, the link between pneumoconiosis and sleep disorders is not well understood. This study aimed to investigate the connection between pneumoconiosis and subsequent risk of sleep disorders., Methods: This population-based retrospective cohort study used data from the National Health Insurance database in Taiwan. The pneumoconiosis cohort consisted of 13,329 patients newly diagnosed between 2000 and 2015. The comparison group included 53,316 age-, sex-, and diagnosis date-matched individuals without pneumoconiosis. The development of sleep disorders was monitored until the end of 2018. Cox proportional hazard regression models were used for risk assessment., Results: The incidence of sleep disorders was 1.31 times higher in the pneumoconiosis cohort than in the comparison cohort (22.8 vs. 16.2 per 1000 person-years). After controlling for age, sex, comorbidity, and medication, the adjusted hazard ratio (aHR) was 1.24 (95% confidence interval [CI] = 1.17-1.32). Stratified analyses by age group, sex, and comorbidity status showed significant associations between pneumoconiosis and sleep disorders (aHRs, 1.19-1.64). In addition, patients with pneumoconiosis had a significantly increased risk of developing sleep apnea (aHR = 1.71, 95% CI = 1.31-2.22)., Conclusion: This study demonstrates that patients with pneumoconiosis are at a higher risk of developing sleep disorders and sleep apnea. Healthcare professionals should pay close attention to sleep quality and disturbances in patients with pneumoconiosis., (© 2024. The Author(s).)

Toxoplasma gondii (T. gondii) is an intracellular protozoan that can cause toxoplasmosis in all warm-blooded hosts. This study focused on the prevalence and genetic characterize of T. gondii in ducks from Fujian province, China. Genomic DNA was extracted from duck tissue samples (heart, liver, lung, and muscle). To assess the genetic diversity of the T. gondii isolates, it was determined by using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. A total of 586 ducks from 5 cities in Fujian province were tested, and 35 (6.0%) of which were found to be positive for the T. gondii B1 gene. Further genotyping of these positive samples at 10 genetic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using PCR-RFLP revealed that one tissue samples (heart samples from Fuzhou ducks) were identified as Type I (ToxoDB#10). This study is the first report on the prevalence and genetic characterization of T. gondii in ducks in Fujian province, and Type I (ToxoDB#10) is found in ducks in China for the first time. The findings document the genetic characterization of T. gondii in free-range ducks from Fujian Province, thereby enriching the understanding of T. gondii genetic diversity in China. Moreover, these results provide essential data support for further prospective studies and underscores the "One Health" concept, emphasizing the integral link among human, animal, and environmental health., Competing Interests: DISCLOSURES The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dong-Hui Zhou reports financial support was provided by Industry-university-research Cooperation Project in Fujian Province University and enterprise (Grant No. 2022N5005). Dong-Hui Zhou reports financial support was provided by Natural Science Foundation of Fujian Province of China (2022J01131). Dong-Hui Zhou reports was provided by Special Fund for Science and Technology Innovation of Fujian Agriculture and Forestry University (KFb22059XA). 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 Inc. All rights reserved.)

Adenosine triphosphate (ATP) can be released into the extracellular milieu from various types of cells in response to a wide range of physical or chemical stresses. In the respiratory tract, extracellular ATP is recognized as an important signal molecule and trigger of airway inflammation. Chlorine (Cl 2 ), sulfur dioxide (SO 2 ), and ammonia (NH 3 ) are potent irritant gases and common industrial air pollutants due to their widespread uses as chemical agents. This study was carried out to determine if acute inhalation challenges of these irritant gases, at the concentration and duration simulating the accidental exposures to these chemical gases in industrial operations, triggered the release of ATP in the rat respiratory tract; and if so, whether the level of ATP in bronchoalveolar lavage fluid (BALF) evoked by inhalation challenge of a given irritant gas was elevated by chronic allergic airway inflammation. Our results showed: 1 ) inhalation of these irritant gases caused significant increases in the ATP level in BALF, and the magnitude of evoked ATP release was in the order of Cl 2 > SO 2 > NH 3 . 2 ) Chronic airway inflammation induced by ovalbumin-sensitization markedly elevated the ATP level in BALF during baseline (breathing room air) but did not potentiate the release of ATP in the lung triggered by inhalation challenges of these irritant gases. These findings suggested a possible involvement of the ATP release in the lung in the regulation of overall airway responses to acute inhalation of irritant gases and the pathogenesis of chronic allergic airway inflammation. NEW & NOTEWORTHY Extracellular adenosine triphosphate (ATP) is a contributing factor and signaling molecule of airway inflammation. This study demonstrated for the first time that the ATP release in the lung was markedly elevated after acute inhalation challenges of three common industrial air pollutants; the order of the response magnitude was chlorine > sulfur dioxide > ammonia. These findings provided new information and improved our understanding of the adverse pulmonary effects caused by accidental inhalation exposures to these irritant gases.

Background: Breast cancer-related lymphedema (BCRL) is one of the debilitating complications after breast cancer treatment. Several forms of patient-reported outcome measures (PROMs) were developed to evaluate the severity of BCRL based on the patients' perspective. LYMPH-Q Upper Extremity Module is a newly developed questionnaire for BCRL. This study aimed to demonstrate the process of translation and cultural adaption from English to Mandarin Chinese., Methods and Results: The translation process followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines for the translation and cultural adaption of PROM. The process included four steps: forward translation, back translation, back translation review, and patient interviews. In total, five patients with BCRL were recruited for patient interviews. The forward translation step involved two professional translators whose native language was Mandarin Chinese. A reconciled translated version was produced. In the back translation step, the reconciled translated version in Mandarin Chinese was sent to another professional translator whose native language was English. The back-translated version in English was sent back to the developer of LYMPH-Q for review. In this step, 22 items were revised. In the final step of patient interviews, 15 items were revised based on the patients' feedback., Conclusion: The development of Mandarin Chinese version of LYMPH-Q Upper Extremity Module and its utilization in conjunction with the existing objective measures could provide a more well-rounded picture of the status of patients with BCRL worldwide., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Ethical bonds transformation is a cultural phenomenon in Taiwanese bereaved families. When the death event occurs, the absent status of the deceased invokes spontaneous change in whole family to cope with the irreparable loss. In the present study, 283 bereaved individuals were recruited to develop the ethical bonds transformation scale. Exploratory factor analysis has generated two factors: ethical bonds and symbolic bonds. Partial correlation has shown that ethical bonds was positively correlated with post-grief growth and negatively correlated with most of the grief related symptoms, indicating that ethical bonds might be a protective factor in the family grief process., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Older chronic kidney disease (CKD) patients frequently face unrecognized cognitive impairment and excess mortality. Physical activity (PA) reduces cognitive decline but whether PA modifies cognitive impairment-associated mortality remains unknown., Methods: From 2005 to 2011, 30,561 older Taiwanese CKD patients were enrolled. Patients were divided into intact cognition (≥8 scores), mild (6-7 scores), and severe (≤5 scores) cognitive impairment groups by the Short Portable Mental Status Questionnaire (SPMSQ), and were also categorized into high-PA (≥60 min/week of moderate-intensity PA), low-PA (20-60 min/week) or inactive (<20 min/week) groups. Cox regression was conducted to evaluate the individual and joint associations of cognitive impairment and PA on all-cause and cardiovascular mortality., Results: After a median follow-up of 4.52 years, the all-cause mortality were higher in CKD patients with severe (multivariable-adjusted hazard ratio [aHR] 2.31; 95% confidence interval [CI] 2.05-2.60) and mild (aHR 1.74; CI 1.51-1.99) cognitive impairment than cognitively intact ones. Remarkably, decreased PA amount interacted and amplified the cognitive impairment-associated mortality risks. Notably, the high-PA status linked to lower overall mortality risks both in mild (aHR 0.65; CI 0.45-0.93) and severe (aHR 0.73; CI 0.54-0.99) cognitively-impaired patients as compared to inactivity. Survival tree analysis indicated the least mortality in those with high PA and >8 SPMSQ scores. Similar associations were found in the cardiovascular mortality., Limitations: Residual confounding and single ethnicity., Conclusions: Cognitive impairment defined by SPMSQ was progressively associated with higher mortality among elderly CKD. Higher PA linked to lower cognitive impairment-associated death risks, and could be promoted for longevity benefits., 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.)

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, continues to pose significant global health challenges. The results demonstrated that GB-2 at 200 μg/mL effectively increased the population of 293T-ACE2 cells with low RBD binding for both SARS-CoV-2 Omicron EG.5.1 and HV.1 variants by dual-color flow cytometry, indicating its ability to inhibit virus attachment. Further investigation revealed that (+)-catechin at 25 and 50 μg/mL did not significantly alter the ACE2-RBD interaction for the EG.5.1 variant. In contrast, theaflavin showed inhibitory effects at both 25 and 50 μg/mL for EG.5.1, while only the higher concentration was effective for HV.1. Notably, theaflavin 3-gallate exhibited a potent inhibition of ACE2-RBD binding for both variants at both concentrations tested. Molecular docking studies provided insight into the binding mechanisms of theaflavin and theaflavin 3-gallate with the RBD of EG.5.1 and HV.1 variants. Both compounds showed favorable docking scores, with theaflavin 3-gallate demonstrating slightly lower scores (-8 kcal/mol) compared to theaflavin (-7 kcal/mol) for both variants. These results suggest stable interactions between the compounds and key residues in the RBD, potentially explaining their inhibitory effects on virus attachment. In conclusion, GB-2, theaflavin, and theaflavin 3-gallate demonstrate significant potential as inhibitors of the ACE2-RBD interaction in Omicron variants, highlighting their therapeutic promise against COVID-19. However, these findings are primarily based on computational and in vitro studies, necessitating further in vivo research and clinical trials to confirm their efficacy and safety in humans.

The terahertz (THz) metamaterials integrated with microelectromechanical systems (MEMS) have led to the realization of dynamic control in amplitude, phase, polarization, and spin angular momentum of the THz wave. In this study, we demonstrate an MEMS-based reconfigurable THz metamaterial (RTM) composed of a split ring resonator (SRR) for real-time modulation of THz wave. By gradually increasing the polarization angle of the incident THz wave, the resonant frequency of SRR switches from 0.74 to 1.16 THz, and the maximum modulation depth is more than 70%. When the MEMS-based RTM is actuated by different DC bias voltages, the polarization-dependent transmission intensity and resonant frequency of the device can be actively tuned. MEMS-based RTM shows logical function characteristics that can be used for logic modulators by performing the driving voltages and polarization states as 2-bit input signals and quantizing the transmission response as "on" and "off" states. The logic gates of "NAND" are at 0.439 THz and "AND" is at 0.732 THz. These results offer potential applications for the proposed MEMS-based RTM in tunable and reconfigurable polarization filters, optical switches, programmable logic modulators, and so on.

Managing pneumonia, especially when complicated by underlying anatomical anomalies, presents unique challenges that require a nuanced and multidisciplinary approach. Dysphagia lusoria, a rare vascular anomaly where the right subclavian artery originates aberrantly, can coexist with other thoracic conditions, complicating both diagnosis and treatment. Understanding the interplay between such anomalies and common infections like pneumonia is crucial for optimal patient outcomes. This case report describes a 33-year-old male with a history of recurrent pneumonia in the past who presented to the emergency department (ED) with right flank pain and dyspnea persisting for one week. Initial investigations revealed moderate parapneumonic pleural effusion and right lower lobe pneumonia. At the time, an aberrant origin of the right subclavian artery (ARSA) (dysphagia lusoria) was incidentally detected on imaging. The patient's management included antibiotic therapy tailored for pneumonia and the placement of a chest tube for pleural effusion drainage. Despite intermittent dysphagia, surgical intervention for dysphagia lusoria was deferred due to its minimal impact on daily functioning. The patient improved significantly with supportive care and antibiotics, highlighting the complexity of managing pneumonia complicated by anatomical anomalies. This case underscores the importance of multidisciplinary management and tailored treatment strategies in addressing intricate clinical scenarios., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kyaw et al.)

Aims: The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant (EnzaR) cells remain largely elusive., Methods: Drug-resistant prostate cancer cell lines, animal models, and organoids were utilized to examine NUDT21 function by transcriptomic and metabolomic analyses through loss-of-function and gain-of-function assays. Notably, a mono-methylation monoclonal antibody and conditional-knockin transgenic mouse model of NUDT21 were generated for evaluating its function., Results: NUDT21 overexpression acts as a crucial alternative polyadenylation (APA) mediator, supported by its oncogenic role in prostate cancer. PRMT7-mediated mono-methylation of NUDT21 induces a shift in 3'UTR usage, reducing oncogenicity. In contrast, its un-methylation promotes cancer growth and cuproptosis insensitivity in EnzaR cells by exporting toxic copper and suppressing docosahexaenoic acid (DHA) biosynthesis. Crucially, NUDT21 inhibition or DHA supplementation with copper ionophore holds therapeutic promise for EnzaR cells., Conclusions: The un-methylation of NUDT21-mediated 3'UTR shortening unveils a novel mechanism for enzalutamide resistance, and our findings offer innovative strategies for advancing the treatment of prostate cancer patients experiencing enzalutamide resistance., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We propose a meta-emitter based on micro-electro-mechanical system (MEMS) technology. The main structure of the meta-emitter unit cell is composed of four symmetrically split crosses of Au and SiO 2 bilayer cantilevers. By changing the size of the cantilevers, this MEMS-based meta-emitter can realize the tunable perfect absorption, and the absorption spectrum is within the longwave infrared (LWIR) wavelength from 8.90 to 11.90 µm. When the surface temperature of the meta-emitter rises, the electrothermal actuation mechanism is performed through the different thermal expansion coefficient (TEC) of the bilayer cantilevers. Therefore, the cantilevers will be bent downward and the bending height of the cantilevers decreases linearly. In such case, the peak value of thermal radiation power can be tuned from the wavelength of 9.52 µm to 10.48 µm when the temperature of meta-emitter is increased from 293 to 1290 K. This proposed MEMS-based meta-emitter is an excellent LWIR light source and has potential application prospects in gas sensing, infrared spectroscopy analysis, medical care and so on., (© 2024. The Author(s).)

Tumor-associated macrophages (TAMs) are pivotal in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC), influencing various stages from initiation to metastasis. Understanding the role of TAMs in HCC is crucial for developing novel therapeutic strategies. Macrophages exhibit plasticity, resulting in M1 and M2 phenotypes, with M1 macrophages displaying antitumor properties and M2 macrophages promoting tumor progression. Targeting TAMs to alter their polarization could offer new avenues for HCC treatment. β,β-dimethylacrylalkannin (DMAKN), a natural naphthoquinone, has gained attention for its antitumor properties. However, its impact on TAMs modulation remains unclear. This study investigates DMAKN's modulation of TAMs and its anti-HCC activity. Using an in vitro model with THP-1 cells, we induced M1 macrophages with LPS/IFN-γ and M2 macrophages with IL-4/IL-13, confirming polarization with specific markers. Co-culturing these macrophages with HCC cells showed that M1 cells inhibited HCC growth, while M2 cells promoted it. Screening for non-toxic DMAKN concentrations revealed its ability to induce M1 polarization and enhance LPS/IFN-γ-induced M1 macrophages, both showing anti-HCC effects. Conversely, DMAKN suppressed IL-4/IL-13-induced M2 polarization, inhibiting M2 macrophages' promotion of HCC cell viability. In summary, DMAKN induces and enhances M1 polarization while inhibiting M2 polarization of macrophages, thereby inhibiting HCC cell growth. These findings suggest that DMAKN has the potential to regulate TAMs in HCC, offering promise for future therapeutic development.

The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play important physiological roles. Stabilized agonists of the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR) for the management of diabetes and obesity have generated widespread enthusiasm and have become blockbuster drugs. These therapeutics are refractory to the action of dipeptidyl peptidase-4 (DPP4), that catalyzes rapid removal of the two N-terminal residues of the native peptides, in turn severely diminishing their activity profiles.  Here we report that a single atom change from carbon to nitrogen in the backbone of the entire peptide make them refractory to DPP4 action while still retaining full potency and efficacy at their respective receptors.  This was accomplished by use of aza-amino acids, that are bioisosteric replacements for a-amino acids that perturb the structural backbone and local side chain conformations.  Molecular dynamics simulations reveal that aza-amino acid can populate the same conformational space that GLP-1 adopts when bound to the GLP-1R. The insertion of an aza-amino acid at the second position from the N-terminus in semaglutide and in a dual agonist of GLP-1R and GIPR further demonstrates its capability as a viable alternative to current DPP4 resistance strategies while offering additional structural variety., (© 2024 Wiley‐VCH GmbH.)

Lung cancer is the leading cause of cancer deaths, where the metastasis often causes chemodrug resistance and leads to recurrence after treatment. Desmethylclomipramine (DCMI), a bioactive metabolite of clomipramine, shows the therapeutic efficacy with antidepressive agency as well as potential cytostatic effects on lung cancer cells. Here, we demonstrated that DCMI effectively caused transforming growth factor (TGF)-β1-mediated mesenchymal type of A549 cells to undergo mitochondrial death via myeloid cell leukemia-1 (Mcl-1) suppression and activation of truncated Bid (tBid). TGF-β1 induced epithelial mesenchymal transition in A549 cells with the increase of fibronectin and decrease of E-cadherin, the activation of Akt/glycogen synthase kinase-3β (GSK-β)/Mcl-1 axis, and the hypo-responsiveness to cisplatin. DCMI initiated a dose-dependent cytotoxicity on TGF-β1-mediated mesenchymal type of A549 cells through inactivating Akt/GSK-β/Mcl-1 axis, in which mitochondria instability and caspase-9/3 activation also occurred concurrently. Pharmacological inhibition of caspase-8 and cathepsin B partly reversed tBid expression and mitochondrial damage to further attenuate DCMI-mediated cytotoxicity. Additionally, DCMI presented partial therapeutic effects in treating mesenchymal type of A549 tumor bearing nude mice through an acceleration of cancer cell death. Taken together, DCMI exerts antitumor effects via initiating the mechanisms of Akt/GSK-β/Mcl-1 inactivation and cathepsin B/caspase-8-regulated mitochondrial death, which suggests its potential role in mesenchymal type of cancer cell therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have demonstrated significant clinical benefits in progression-free and overall survival. This study investigates the outcomes associated with two kinds of CDK4/6i in patients with hormone receptor (HR)-positive metastatic and relapsed breast cancer to inform real-world evidence of treatment strategies., Methods: This retrospective study included 340 Taiwanese patients with HR-positive advanced breast cancer from the Taipei Veterans General Hospital, between 2018 and 2023. We analyzed patient characteristics, treatment strategies and outcomes associated with two CDK4/6i. The efficacy of patients who experienced economic burden and interrupted CDK4/6i treatment after 2 years of National Health Insurance (NHI) reimbursement was also investigated., Results: Patients receiving ribociclib and palbociclib showed no significant differences in age, histology, body mass index(BMI), or pathologic status. The distribution of disease status and endocrine therapy partners was comparable between the two groups. Dose reduction was similar, while patients with palbociclib tended to discontinue CDK4/6i usage, and those with ribociclib tended to switch to the other CDK4/6i or endocrine partners. There was no significant difference in progression-free survival (PFS) between the two CDK4/6i in the first-line setting. Adverse prognostic factors were increasing HER2 IHC score, higher Ki-67 levels, visceral and liver metastasis, prior chemotherapy, and endocrine therapy resistance, while higher BMI, bone-only metastasis, and letrozole treatment were associated with a lower risk of progression. The limited follow-up time in our study was insufficient to assess the outcomes of patients treated with interrupted CDK4/6i for up to two years under the NHI reimbursement policy., Conclusion: Treatment outcomes between the two types of CDK4/6i did not differ significantly, indicating the safety and efficacy of CDK4/6i for the Asian population. Ribociclib and palbociclib showed similar efficacy in PFS in the real-world setting., (© 2024. The Author(s).)

Prostate cancer rarely metastasizes to the stomach and kidneys. We report a 73-year-old male with such spread, highlighting significant clinical challenges. Initially diagnosed via biopsy and imaging, he received hormone therapy and cytoreductive radical prostatectomy. Despite initial management, the cancer progressed to metastatic castration-resistant prostate cancer, with gastric and renal metastases confirmed by imaging and biopsy. This case emphasizes the need for awareness of rare metastatic sites, comprehensive diagnostic evaluations, and further research into these atypical metastases to improve patient outcomes and develop better treatment strategies for managing advanced prostate cancer effectively., Competing Interests: The authors declare that they have no conflict of interest to disclose., (© 2024 The Authors.)

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA , de novo lipogenesis-related genes ACACA and FASN , and MYC . FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis. NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).