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Tick-borne severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the SFTS virus (SFTSV). Serological assays based on the nucleocapsid protein and partial glycoprotein of this virus have been used for detecting SFTSV infections in humans and animals. However, whether the complete SFTSV glycoprotein (Gn/Gc) can induce the assembly of virus-like particles (VLPs) which can be used for serological surveillance and vaccine production remains unclear. In this study, we successfully expressed and secreted SFTSV Gn/Gc antigens by using a single plasmid encoding the complete glycoprotein sequence of the dominant genotype B virus. HEK293T and COS-1 cells were transfected with the aforementioned plasmid; cultivating these cells at 32 °C, instead of 37 °C, led to 4.0- and 3.3-fold higher antigen recovery, respectively. The secreted Gn/Gc antigens at 32 °C retained epitopes resembling those of the virion; these epitopes were recognized by a SFTS human-derived monoclonal antibody. Sucrose density gradient centrifugation, followed by transmission electron microscopy, confirmed the formation of VLPs with a diameter of approximately 100 nm. Overall, our findings highlight the potential of SFTSV VLPs for serological surveillance and vaccine development. KEY POINTS: • Cultivating transfected cells at 32 °C boosts SFTSV glycoprotein production. • Complete SFTSV glycoprotein expression facilitates virus-like particle assembly. • The assembly does not require any other viral proteins or RNA., Competing Interests: Declarations. Ethical approval: This study included no human participants or animals. Consent to participate: Not applicable. Consent for publication: All authors approved the final version of the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: To characterize multistate oral carcinogenesis, we conducted a cohort study of patients with oral precancer and a parallel case-control study of oral cancers and controls in Taiwan., Methods: During 2013-2019, we recruited patients with oral precancer (n = 1998) or invasive oral cancer (n = 768) and hospital-based controls (n = 717). Precancer patients were followed up biannually for up to five years; questionnaire data and biospecimens were collected at multiple timepoints. Precancer natural history (regression/persistence, incidence, progression) was evaluated through follow-up visits and linkages with Taiwan's Cancer Registry., Cohort Updates: Cross-sectionally, 71 % of oral precancers and 62 % of cancers were attributable to betel-quid chewing, smoking, and alcohol. Precancer patients had substantially elevated risk of oral cancer (standardized-incidence-ratio vs. Taiwan general population = 14.1; 95 %CI = 12.0-16.6). Among precancer patients, 156 incident invasive oral cancers occurred (median follow-up = 6.4 years; incidence rate = 1,221/100,000 person-years; annual incidence = 1.2 %; 1-year cumulative-incidence = 1.8 %; 5-year cumulative-incidence = 6.9 %; 10-year cumulative-incidence = 9.5 %). Baseline precancer histopathology strongly predicted risk of progression to oral cancer (5-year cumulative-incidence: no-dysplasia = 5.2 %, mild-dysplasia = 7.1 %, moderate-dysplasia = 32.8 %, severe-dysplasia = 45.9 %). Most oral cancers (88.5 %) were preceded by precancers identified during the study. The study has established a resource of >63,500 biospecimens, including biopsies (n = 6,012), oral cytology (n = 18,422), oral rinses (n = 15,054), saliva (n = 15,066), and blood (n = 8,990). Ongoing investigations are characterizing oral carcinogenesis at the epidemiologic, macroscopic, microscopic, microbiomic, and genomic levels., Conclusions: A majority of oral precancers/cancers in Taiwan are caused by betel-quid chewing, smoking, and alcohol. Patients with oral precancer have substantially elevated risk of site-concordant oral cancer. We highlight our study as a resource to collaboratively address questions regarding oral precancer/cancer natural history and clinical management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘J. Silvio Gutkind reports consulting fees from Radionetics Oncology, BTB Therapeutics, Pangea Therapeutics, and io9 and is the founder of Kadima Pharmaceuticals, all unrelated to the current study. None of the other authors have any relevant conflicts of interest to report.’., (Published by Elsevier Ltd.)

Background: Exercise is the most effective method of reducing visceral adipose tissue (VAT). However, the optimal exercise modality and strategy for reducing VAT have yet to be determined., Purpose: This study was designed to identify the optimal sequence exercise strategy for reducing VAT in community residents with obesity., Methods: A sequential multiple assignment randomized trial design was used to conduct a two-stage (8 weeks each) adaptive exercise for 40- to 64-year-old residents with obesity. In the first stage, the participants were randomly allocated into two groups, one of which did 30 minutes of moderate-intensity continuous training (MICT; n = 58) and the other which did 20 minutes of high-intensity interval training (HIIT; n = 58) three times per week. In the second stage, the nonresponders (with VAT decreases < 3%) were randomly reallocated into a group that performed MICT combined with an additional 10 minutes of resistance exercise or one that performed the opposite of the first-stage treatment (HIIT or MICT). Those who responded to the first-stage intervention (with VAT decreases of ≥ 3%) continued the same exercise treatment until 16 weeks., Results: The MICT intervention was found to be more efficacious than the HIIT intervention in reducing VAT during the first 8 weeks (β = -4.10, p = .029). Among the nonresponders to MICT, the HIIT outperformed MICT combined with resistance exercise as the alternative choice in the second stage (β = -7.36, p = .006). On the contrary, there were no significant differences between MICT and MICT combined with resistance exercise for the nonresponders to HIIT (β = 1.34, p = .626). Those participants who repeated the same exercise modality (either MICT or HIIT) in both stages exhibited superior VAT reduction to those who changed exercise modalities after the first stage., Conclusions/implications for Practice: The optimal sequence exercise strategy for reducing VAT is captured by a two-stage sequential multiple assignment randomized trial design. Community residents with obesity are advised to reduce VAT efficiently through participation in an 8-week MICT program. For those preferring HIIT rather than MICT, a 16-week program without changing the modality midway is recommended., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc.)

This study investigated water vapor condensation on superhydrophobic surfaces (SHSs) featuring micropillars enclosed by wall lattices and having three-tier hierarchical roughness. A total of five samples were created with three (NW-J, W200-J and W400-J samples) having large micropillar depth (∼6 μm) and two (NW-S and W200-S samples) having small micropillar depth (∼1 μm). Two distinct condensate removal modes were observed during condensation: coalescence-induced jumping on samples with large micropillar depth and coalescence-induced shedding on samples with small micropillar depth. The results showed that the diameter of the shedding droplet on the W200-S sample having small micropillar depth could be as small as 107 μm, as compared to the theoretical critical diameter of 267 μm for gravitational shedding on the same sample. The enhanced functionality of the three-tier nanotextures on the W200-S sample could effectively suppress localized pinning of the three-phase contact line and Wenzel neck formation during the growth of condensate droplets. Consequently, during multidroplet coalescence, the released surface energy easily overcomes the solid-liquid adhesion, leading to spontaneous shedding of merged droplets. The inclusion of the wall lattice aids condensate growth by the droplet self-alignment along the walls and promoting coalescence. As a result, the W200-S sample exhibited the highest condensate collection as well. The proposed surface design has great potential for scaling up and implementation in heating, ventilation, and air-conditioning equipment due to the simplicity of the surface morphology and the facile spray-coating method used to achieve hierarchical roughness.

Elephant endotheliotropic herpesvirus (EEHV), a persistent threat, has caused significant mortality among young Asian elephants (Elephas maximus), raising serious concerns for the conservation of this endangered species. Given the urgent need for protective measures, research into EEHV vaccine development has become increasingly critical. This study evaluated the immune response in mice following immunization with an EEHV1A-glycoprotein B (gB) subunit vaccine. The vaccine incorporated gBF1 and gBF2, corresponding to segments of the gB ectodomains I and IV, respectively, along with emulsion adjuvants Montanide™ ISA 206 VG and incomplete Freund's adjuvant (IFA). The findings revealed that both gBF1 and gBF2, when paired with these adjuvants, were capable of inducing strong humoral immune responses against EEHV-gB, as demonstrated by the ability of sera from immunized mice to detect EEHV-gB ex vivo. Additionally, in terms of cellular immunity, the vaccine formulations predominantly activated CD4+ T cells, including both Th1 (IFN-γ+) and Th2 (IL-4+) cells, with no significant activation of CD8+ T cells. If also applicable in elephants, gB-based vaccines would be a significant step forward in the fight against EEHV., Competing Interests: Declaration of competing interest The authors declare that they hold no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Orf virus (ORFV) is gaining attention as a promising viral vector for cancer therapy because of its unique properties. Recent studies have shown that ORFV could be effective against various cancers, particularly nasopharyngeal carcinoma. This research explores the ability of wild-type ORFV and recombinant ORFVs, which lack specific virulence factors, to kill NPC cells and modulate the immune response., Methods: Two NPC cell lines, HK1 (from Hong Kong) and TW02 (from Taiwan), were infected with wild-type ORFV and two recombinant ORFVs lacking either vascular endothelial growth factor (VEGF) or chemokine binding protein (CBP) virulence factors. The oncolytic effects were evaluated by assessing cell death pathways, particularly pyroptosis, which was monitored through the cleavage of gasdermin E (GSDME). The activation of survival pathways, such as focal adhesion kinase (FAK) and AKT, was also analyzed. In addition, the influence of ORFV infection on natural killer (NK) cell recruitment and cytotoxicity was investigated. In vivo experiments were conducted in a xenograft mouse model in which HK1 tumors were used to evaluate the antitumor activity of wild-type ORFV and two deletion-mutant ORFVs., Results: Wild-type ORFV effectively killed NPC cells, especially HK1 cells. The recombinant ORFVs, despite being attenuated by the loss of VEGF or CBP, retained the ability to infect and cause NPC cell death, with the CBP-deleted virus showing notable effectiveness in HK1 cells. Early ORFV infection led to pyroptosis via GSDME cleavage, causing cell detachment and a reduction in FAK and AKT activation. ORFV also enhanced NK cell recruitment and boosted NK cell-mediated cytotoxicity in infected NPC cells. In the HK1 xenograft model, CBP-deleted ORFV significantly inhibited tumor growth., Conclusion: ORFV, particularly the wild-type and CBP-deleted variants, has significant potential as an oncolytic viral vector for NPC therapy. It induces cell death via pyroptosis and enhances immune-mediated tumor cell destruction through NK cells. The attenuated CBP-deleted ORFV offers a safer and effective option for cancer treatment, making it a promising candidate for future therapeutic applications., Competing Interests: Declarations. Ethical approval: All applicable international, national, and institutional guidelines for the care and use of animals were followed. The use of animals and experimental protocols were approved by the IACUC of National Chung Hsing University (approval number: 110 − 106). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

We investigated anti-EBV IgA and IgG responses by sex among 387 cancer-free individuals in Asia. Antibody responses were measured using an EBV proteome array to assess age-adjusted sex-specific associations with 404 EBV-antigens in 86 protein sequences via meta-analysis and pathway analysis by EBV stage. Males were more likely to have elevated IgA responses (P=0.001) and females had higher IgG responses (P=0.003). Significant sex associations were observed across stages of lytic replication. The largest sex differences were seen in latent IgA, but no differences were observed in latent IgG antibodies. Higher IgA responses suggest higher rates of EBV reactivation in males., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2025.)

Gating is a fundamental process in ion channels configured to open and close in response to specific stimuli such as voltage across cell membranes thereby enabling the excitability of neurons. Here we report on voltage-gated solid-state nanopores by electrically tunable chemical reactions. We demonstrate repetitive precipitation and dissolution of metal phosphates in a pore through manipulations of cation flow by transmembrane voltage. Under negative voltages, precipitates grow to reduce ionic current by occluding the nanopore, while inverting the voltage polarity dissolves the phosphate compounds reopening the pore to ionic flux. Reversible actuation of these physicochemical processes creates a nanofluidic diode of rectification ratio exceeding 40000. The dynamic nature of the in-pore reactions also facilitates a memristor of sub-nanowatt power consumption. Leveraging chemical degrees of freedom, the present method may be useful for creating iontronic circuits of tunable characteristics toward neuromorphic systems., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: While common variants have been studied for head and neck cancer (HNC) risk and exome sequencing has been conducted for head and neck tumor tissue samples, large-scale studies of exome sequencing on head and neck cancer risk have not been conducted. Our study aimed to identify head and neck cancer predisposition genes with exome sequencing and to assess interactions between the head and neck cancer susceptibility genes and tobacco use., Methods: We conducted a case-control analysis to identify germline susceptibility genes for HNC risk. We used whole-exome sequencing data in Phase 1, targeted gene sequencing data in Phase 2 (2,134 HNC cases and 2,072 controls), and publicly available whole-exome sequencing data from the UK Biobank database. We conducted a gene-based association analysis and estimated the effect size of known and novel HNC susceptibility genes and pathways., Results: Six known cancer predisposition genes reached nominal significance (p < 0.05), including BRCA1 , BRCA2 , RAD51B , BAP1 , APC , and MUTYH . Additionally, we identified 21 novel HNC risk genes with meta p-value < 0.05. LoF variants in BRCA1 (OR=5.0, 95% CI: 1.72-14.57), BRCA2 (OR=2.56, 95% CI: 1.22-5.41), and MUTYH (OR=4.84, 95% CI: 1.01-13.86) exhibited significantly elevated effect sizes. APC, BRCA2 , and the DNA repair gene set exhibited borderline interactions with smoking, with synergy indices and 95% confidence intervals of 1.92 [0.98, 3.75], 1.77 [0.91, 3.46], and 1.57 [0.97, 2.54], respectively., Conclusions: We observed associations with HNC risk for DNA repair pathway genes associated with breast cancer and polyposis colorectal cancer predisposition genes. Potential interactions between these genes and tobacco smoking were also identified. Our study utilized targeted gene sequencing and whole-exome sequencing approaches to identify cancer susceptibility genes, while further studies are needed to confirm the associations observed with HNC risk.

Bovine viral diarrhea virus (BVDV) significantly impacts cattle worldwide, causing respiratory, gastrointestinal, and reproductive disorders that lead to substantial economic losses. Despite its high global prevalence and various genotypes, the infection status of BVDV in Taiwan has not been reported. This study conducted large-scale surveillance in 2014, analyzing 460 bovine serum samples collected from 49 dairy herds across Taiwan. The results revealed a herd-level seroprevalence of 59.2 % (29/49), with significant regional variations: 16.7 % in the northern region and 77.8 % in the southern region. At the animal level, the overall BVDV-positive rate was 32.4 % (148/460), ranging from 3.3 % (northern region) to 41.5 % (central region), with significant regional differences as analyzed by the mixed-effects logistic regression model. Five-year surveillance of a single dairy farm revealed persistent BVDV circulation, with the seroprevalence starting at 89 % in 2019 and remaining between 82 % and 100 % among the cohort of 27 cattle monitored from 2020 to 2023. In contrast, a study of three farms revealed that while the two high-prevalence farms maintained high infection rates, the low-prevalence farm experienced a gradual decline in infections, indicating varied infection dynamics. Moreover, this study identified BVDV-1b as the predominant genotype in Taiwan, along with BVDV-1a and BVDV-2a, which were detected in mosquito samples. These findings emphasize the high prevalence of BVDV in Taiwan, ongoing viral circulation within herds, and the need for continuous surveillance and robust control measures to mitigate the spread of BVDV in Taiwan's cattle industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2025. Published by Elsevier Ltd.)

Ethnopharmacological Relevance: The dried fruit of Ligustrum lucidum Ait. (FLL), known as Nuzhenzi, is traditionally recognized for its anti-aging properties in Chinese medicine. Nuezhenide, a water-soluble secoiridoid present in FLL, has demonstrated various pharmacological activities including neuroprotection, enhancement of learning and memory, antiosteoporotic, and antiviral activities. These therapeutic benefits align with the anti-aging effects attributed to ghrelin, particularly in the modulation of growth hormone secretagogue receptor type 1a (GHSR-1a) signaling., Aim of the Work: This study aimed to investigate the potential of FLL extracts, particularly its major compound nuezhenide, as agonists of GHSR-1a, a receptor implicated in anti-aging mechanisms, utilizing a stable GHSR-1a-expressing cell line., Materials and Methods: HEK293T cells expressing GHSR-1a-mCherry were used to assess the effects of FLL extract and its major compound, nuezhenide, on cell viability and ERK1/2 signaling. Molecular docking simulations predicted the interaction between nuezhenide and the GHSR-1a binding pocket. The impact of nuezhenide on ERK1/2 phosphorylation was evaluated, along with the involvement of phospholipase C and calcium signaling in this process., Results: Molecular docking simulations indicated that nuezhenide could interact with the GHSR-1a receptor, similar to teaghrelin, another known ghrelin analog. Experimental data showed that FLL extracts and nuezhenide enhanced cell viability and ERK1/2 activation in GHSR1a-mCherry HEK293T cells. The effect was specifically mediated by GHSR-1a, as confirmed by SP-analog treatment. Further analysis revealed that nuezhenide-induced ERK1/2 activation is likely mediated through a phospholipase C-dependent pathway involving intracellular calcium release., Conclusion: This study demonstrated for the first time that nuezhenide acts as a putative GHSR-1a agonist, promoting cell proliferation and activating ERK1/2 signaling via phospholipase C and calcium pathways. These findings support the traditional use of FLL as an anti-aging herbal remedy and suggest that nuezhenide could be developed as a therapeutic agent targeting GHSR-1a-mediated pathways., 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. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for Journal of Ethnopharmacology and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cancer has consistently been the leading cause of death worldwide, with head and neck cancer (HNC) being one of the top ten causes of cancer-related death. Nasopharyngeal carcinoma (NPC), in particular, is a cancer that is unique to East Asia. Numerous studies have shown that the Epstein-Barr virus (EBV) DNA load and the systemic immune inflammation (SII) index can serve as prognostic indicators for NPC patients. However, no studies have compared different predictive models of inflammatory factors. This study combines the SII and the EBV virus load in patients with stage I to IV NPC and compares different inflammatory factor models to determine the best predictive model., Materials and Methods: We reviewed 240 patients with stage I to IV NPC who were diagnosed between January 2016 and July 2023. We collected data from adult patients who were diagnosed with NPC and included those who completed the definitive staging workup and treatment in this analysis. We tested various inflammatory markers and the EBV DNA load via Cox regression for survival analysis., Results: We found that the EBV viral load, the SII, and the SIRI are related to the severity of nasopharyngeal cancer. In the univariate Cox regression analysis, clinical stage, EBV virus load (HR: 2.15, 95 % CI: 1.19-3.90), NLR (2.37, 1.29-4.34), PLR (2.7, 1.06-6.87), SIRI (2.02, 1.11-3.68), and SII (2.45, 1.251-4.89) were prognostic factors for overall survival. In the multivariate analysis, after adjusting for sex, age and clinical stage, a higher EBV virus load and SII were associated with a worse prognosis (HR: 4.71, 1.95-11.41)., Conclusion: The combination of the EBV viral load and the SII was a better predictor of NPC prognosis., Competing Interests: Declaration of competing interest The authors declare that no conflicts of interest exist., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Environmental chemicals and toxins are known to impact human health and contribute to cancer developments. Among these, genotoxins induce genetic mutations critical for cancer initiation. In the liver, proliferation serves not only as a compensatory mechanism for tissue repair but also as a potential risk factor for the progression of premalignant lesions. The role of Human Liver DnaJ-Like Protein (DNAJB4/HLJ1), a stress-responsive heat shock protein 40, in genotoxin-induced liver carcinogenesis remains unexplored. Using whole-genome transcriptomic analysis, we demonstrate that HLJ1 deficiency in mice results in altered gene signatures enriched in pathways associated with chemically induced liver cancer and IL-6/STAT3 signaling activation. Employing diethylnitrosamine (DEN) as a carcinogen, we further reveal that STAT3 and H2AX phosphorylation induced by short-term DEN treatment are amplified in HLJ1-deficient mice. In long-term DEN experiments, HLJ1 deletion enhances tumor proliferation and progression, accompanied by pronounced STAT3 phosphorylation in normal tissues rather than in tumor regions. The tumor-suppressive role of peritumoral HLJ1 is validated through the transplantation of HLJ1-wildtype B16F1 and LLC cancer cell lines into syngeneic HLJ1-deficient mice, which exhibits an augmented tumorigenic phenotype compared to wildtype controls. This study uncovers a previously unrecognized role of HLJ1 in suppressing liver carcinogenesis via the downregulation of STAT3 signaling in peritumoral normal cells. These findings suggest that HLJ1 reinforcement represents a promising strategy for liver cancer treatment and prevention., Competing Interests: Declarations. Ethical approval: All experimental procedures performed were approved by the Institutional Animal Care and Use Committee (IACUC), College of Medicine, National Taiwan University with IACUC number 20180126. Competing interest: The authors declare no competing interests., (© 2024. The Author(s).)

Treating metastatic brain tumors remains a significant challenge. This study introduces and applies the Patient-Derived Tumor Spheroid (PDTS) system, an ex vivo model for precision drug testing on metastatic brain tumor. The PDTS system utilizes a decellularized extracellular matrix (dECM) derived from adipose tissue, combined with the tumor cells, to form tumor spheroids. These spheroids were subsequently used to test anticancer drugs, with results compared to the clinical outcomes observed after administering these treatments to patients. To assess the validity of the data, the correlation between the drug responses observed in the PDTS model and actual patient outcomes was analyzed. Chi-square tests evaluated the significance of associations between lab predictions and clinical outcomes, using a significance threshold of p < 0.05. In preliminary data, 17 patients met the criteria for final analysis, which showed an overall 57% accuracy (p-value = 0.463), with improvements to 73% accuracy (p-value = 0.072) when patients receiving certain treatments were excluded. This PDTS offers real-time results within three weeks, simultaneous testing of multiple drugs, and the ability to culture and store tumor cells for reproducibility. Despite some limitations, further development of this model could enhance its clinical application and improve patient outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Hypoxia-inducible factors (HIF) regulate gene transcription, which aids hypoxia adaptation while promoting renal fibrosis. Non-transferrin-bound iron (NTBI) is a catalytic form of iron that can lead to oxidative damage. However, NTBI in cat biofluids has rarely been evaluated., Aims: We assessed cat plasma and urine HIF-1α (pHIF-1α/uHIF-1α) concentrations and urine NTBI (uNTBI) concentrations to investigate their relationship with chronic kidney disease (CKD) severity., Methods: pHIF-1α and uHIF-1α concentrations were measured using commercial ELISA kits, while uNTBI concentrations were detected by inductively coupled plasma mass spectrometry., Results: Healthy cats ( n  = 35) and cats with CKD ( n  = 84) formed the study cohorts. pHIF-1α concentrations increased from 9.48 pg./mL (median) in the healthy cohort to 11.42 pg./mL in early-stage CKD cats but decreased to 8.50 pg./mL in late-stage CKD cats. uHIF-1α concentrations gradually decreased with a significant difference between the control group (44.61 pg./mL) and the late-stage CKD group (36.79 pg./mL, p  < 0.001). Cats with proteinuria had significantly higher uNTBI concentrations (35.61 ppb) than non-proteinuric cats (25.13 ppb, p  = 0.019). Finally, the concentrations of pHIF-1α and uHIF-1α were positively correlated independent of renal function., Conclusion and Clinical Importance: Overall, pHIF-1α and uHIF-1α concentrations are lower in advanced CKD cats, while uNTBI concentrations are significantly higher in proteinuric cats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Hsu, Tsai, Lai, Wu and Lee.)

The Jun dimerization protein (Jdp2) gene is active in mouse cerebellar granule cells and its protein product plays a crucial role in the formation of the cerebellum lobes through programmed cell death. However, the role of Jdp2 in cellular differentiation and pluripotency in the cerebellum, and the effect of the antioxidation reaction on cell plasticity, remain unknown. N-acetyl-L-cysteine (NAC) induced the early commitment of the differentiation of granule cell precursors (GCPs) to neurons, especially Purkinje cells, via the γ-aminobutyric acid type A receptor α6 subunit (Gabra6) axis; moreover, Jdp2 depletion enhanced this differentiation program of GCPs. The antioxidative effect of NAC was the main driving force of this decision toward the neural differentiation of the GCP population in the presence of Gabra6 in vitro. This implies that antioxidative drugs are effective agents for rescuing oxidative-stress-induced GCP damages in the cerebellum and commit this Gabra6-positive cell population toward differentiation into Purkinje cells., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: The animal welfare guidelines published by the Animal Care Committee of the RIKEN BioResource Research Center (BRC) in Japan (Kiteisv.intra.riken.jp/JoureiV5HTMLContents/act/print/print110000514.htm), the National Laboratory Animal Center (NLAC)(106022), and the Kaohsiung Medical University in Taiwan (106189; 107128; 108244) were used for the care of laboratory animals [10, 11]. Various organs were isolated from the Jdp2-KO mice (RIKEN Modified SHIRPA; https://ja.brc.riken.jp/lab/jmc/shirpa/en/ ) and evaluated for LacZ expression. The strategy used to produce the Jdp2-KO mouse has been described elsewhere [42, 43]. Primary GCPs were prepared as described previously [10, 11]., (© 2024. The Author(s).)

Background/Objectives : There remain several challenges to the acceptance and standardization of active surveillance (AS) in patients with early thyroid cancer. The purpose of this study was to update the evidence of tumor progression outcomes in AS to support resolution of clinical concerns and to examine the effect of follow-up duration, period context such as diagnostic techniques, and tumor size at baseline on outcomes. Methods : PubMed, Web of Science, and Embase were used to search for original articles in English until January 2024. The main outcomes were the pooled proportion of patients who showed tumor growth ≥ 3 mm, metastasis to cervical lymph nodes, and conversion to delayed thyroid surgery. A single-arm meta-analysis was performed using a random-effects model. Results : Fourteen studies with 7291 patients were included in the analysis. Pooled results showed that 5.6% (95% CI: 4.2-7.4) of patients increased tumor diameter by more than 3 mm, 1.1% (95% CI: 0.9-1.4) developed cervical lymph node metastases by clinical diagnosis and 3.6% (95% CI: 3.1-4.2) by pathology, 12.7% (95% CI: 9.9-16.1) of patients converted to delayed surgery, with 31.6% (95% CI: 25.3-38.7) of those conversions being due to tumor progression. Subgroup analysis showed a small difference in the proportion of outcomes by baseline tumor size but no increase in the proportion of tumor progression or conversion to surgery due to other factors. Conclusions : This meta-analysis suggests long-term stability in the proportion of tumor progression in AS and less susceptibility to external influences.

Ambient fine particulate matter (PM 2.5 ), a vital environmental toxicant, not only adversely affects the cardiovascular and respiratory systems but also potentially exhibits an association with intestinal inflammation and colorectal cancer (CRC). The underlying molecular mechanisms of PM2.5 impacts on CRC are still unclear. In this study, we utilized collected ambient PM 2.5 and standard reference material SRM2786 to investigate the toxic effects on the colon through in vivo chronic exposure mouse and in vitro cell culture models. We employed a chronic mouse exposure model to clarify the colonic injury and gut microbiome biomarkers. Prolonged exposure to PM 2.5 via oropharyngeal aspiration led to a significant rise in colonic epithelial proliferation and reduced colon length in mice. It triggered characteristics indicative of gut microbiota dysbiosis linked to inflammatory bowel disease. The gut microbiome alternations may serve as a biomarker indicating the colonic health impacts of PM 2.5 exposure. PM 2.5 and SRM2786-induced cytotoxicity manifested as autophagy dysregulation-mediated abnormal proliferation, IL-8 production, p62/SQSTM1 accumulation, and lysosomal membrane damage in human colon cells WiDr and Caco-2. Both PM 2.5 and SRM2786 exposures led to the accumulation of p62/SQSTM1 and compromised lysosomal membrane integrity, showing impaired autophagic flux in WiDr and Caco-2 cells. Finally, we examined the correlations between atmospheric PM 2.5 data and biomarkers of colonic inflammation in human population. The serum level of IL-8 was significantly correlated with regional anthropogenic pollutants. In conclusion, our findings elucidate that ambient PM 2.5 exhibits adverse effects on colon health manifested as inflammation, aberrant proliferation, and gut dysbiosis, potentially mediated through autophagy dysregulation, thereby highlighting the importance of further research on the impact of environmental pollutants on gastrointestinal health., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yueh-Hsia Luo's report was supported by the National Science and Technology Council and the NCU-Landseed joint research grant of Taiwan. Pinpin Lin's report was funded by the National Health Research Institutes of Taiwan. Any additional authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objectives: We investigated the therapeutic effects of exercise in patients with obstructive sleep apnea, aiming to identify the subgroups that benefit the most and determine the optimal exercise protocol., Methods: Major databases were searched for randomized controlled trials involving patients with obstructive sleep apnea performing aerobic exercise and/or resistance training. The investigated outcomes included apnea-hypopnea index (AHI), Epworth Sleepiness Scale, body mass index, and peak oxygen consumption during exercise (VO 2 peak). The pre- and postintervention unstandardized mean difference (USMD) of these parameters was compared between the exercise and control groups., Results: Twelve studies involving 526 patients were included. Exercise training significantly reduced AHI (USMD = -7.08 events/h, 95% confidence interval: -9.98 to -4.17, P < .00001), Epworth Sleepiness Scale (USMD = -2.37, 95% confidence interval: -3.21 to -1.54, P < .00001), and body mass index (USMD = -0.72 kg/m 2 , 95% confidence interval: -1.22 to -0.22, P = .005) and enhanced VO 2 peak (USMD = 3.46 ml·kg -1 ·min -1 , 95% confidence interval: 1.20 to 5.71, P = .003). Subgroup analyses revealed that in continuous positive airway pressure-adherent patients, exercise significantly improved VO 2 peak but did not reduce AHI and Epworth Sleepiness Scale. A trend was observed that combining resistance training with aerobic exercise resulted in greater AHI reduction and VO 2 peak enhancement. Notably, exercise improved AHI, Epworth Sleepiness Scale, body mass index, and VO 2 peak regardless of the baseline AHI or body mass index., Conclusions: Exercise, including resistance and aerobic training, should be part of treatment for patients with obstructive sleep apnea of all severities, regardless of obesity status, and even for those who are already under continuous positive airway pressure., Citation: Lin C-F, Ho N-H, Hsu W-L, Lin C-H, Wang Y-H, Wang Y-P. Effects of aerobic exercise and resistance training on obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med. 2024;20(11):1839-1849., (© 2024 American Academy of Sleep Medicine.)

Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions., (© 2024 UICC.)

Background: Repetitive motion can alter joint angles and subsequently affect the control of the center of mass (CoM). While the CoM has been studied as a fatigue indicator in various sports, the control of the whole-body CoM during repetitive pitching in baseball pitchers has not been examined. This study aimed to investigate changes in lower-extremity joint angles and CoM control in collegiate baseball pitchers after repetitive pitching., Hypothesis: Baseball pitchers would exhibit significant increase in lower-extremity flexion angles, CoM position, and CoM variability after repetitive pitching., Study Design: Descriptive laboratory study., Level of Evidence: Level 3., Methods: A total of 23 pitchers from the Collegiate Baseball League were recruited. A motion analysis system was employed to assess lower-extremity joint angles and CoM position during the simulated game, while pitching accuracy and velocity were also recorded., Results: The results revealed a significant forward and downward shift in CoM position ( P < 0.05), along with increased CoM variability in all directions ( P < 0.05) after the simulated game. Furthermore, there was a significant increase in flexion angles of the knee and hip ( P < 0.05); however, pitching velocity and accuracy did not demonstrate significant changes., Conclusion: Repetitive pitching leads to kinematic changes that should be monitored to prevent sports injuries., Clinical Relevance: Baseball pitchers have the ability to modify the control of their CoM and angles of their lower-extremity joints to sustain their pitching performance. It is crucial to monitor compensatory strategies closely to avoid shoulder and elbow injuries among these pitchers., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.This work was supported by the National Science and Technology Council, Ministry of Science and Technology, Taiwan, (NSTC 112-2425-H-028-002).

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis-that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva-higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03-3.97]; P = .04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI, .35-1.32]; P = .26). These findings underscore the complexity of virus-host interactions and emphasize the need for further investigations into their role in EBV-associated diseases., Competing Interests: Potential conflicts of interest. Z. L. is currently an employee at Merck & Co, Inc, Rahway, New Jersey. The views and opinions expressed in this article do not represent the views and opinions of any public or private entity (e.g. agency, government, organization, institution, or company). All other authors report no conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Osteoarthritis (OA) is a leading cause of pain and disability worldwide in elderly people. There is a critical need to develop novel therapeutic strategies that can effectively manage pain and disability to improve the quality of life for older people. Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for age-related disorders due to their multilineage differentiation and strong paracrine effects. Notably, MSC-derived exosomes (MSC-Exos) have gained significant attention because they can recapitulate MSCs into therapeutic benefits without causing any associated risks compared with direct cell transplantation. These exosomes help in the transport of bioactive molecules such as proteins, lipids, and nucleic acids, which can influence various cellular processes related to tissue repair, regeneration, and immune regulation. In this review, we have provided an overview of MSC-Exos as a considerable treatment option for osteoarthritis. This review will go over the underlying mechanisms by which MSC-Exos may alleviate the pathological hallmarks of OA, such as cartilage degradation, synovial inflammation, and subchondral bone changes. Furthermore, we have summarized the current preclinical evidence and highlighted promising results from in vitro and in vivo studies, as well as progress in clinical trials using MSC-Exos to treat OA.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has caused significant transformations in healthcare. Many countries began the rapid development and adoption of telemedicine to avoid the spread of the pandemic and created an innovative model for healthcare delivery. This study identified the critical antecedents that affected the considered healthcare outcomes via teleophthalmology in Eastern Taiwan during the COVID-19 pandemic., Methods: This study's participants included residents of five towns in Taitung County who had experience with teleophthalmology. This study analyzed the structured questionnaires completed by the participants to validate the proposed research framework. Statistical methods were used to verify the research models, including descriptive statistical analysis, confirmatory factor analysis, and structural equation modeling. The date of this study was from 1 October 2020 to 31 July 2023., Results: The results of this study reveal that the average monthly use of teleophthalmology by individuals in rural areas increased annually. Females tended to utilize teleophthalmology services more than males. There were no significant differences across any of the constructs with respect to age or educational level. Additionally, the patients' awareness of healthcare accessibility via and the communication quality of teleophthalmology simultaneously affected teleophthalmology's adoption and service quality, which in turn jointly affected health outcomes. Both healthcare accessibility and communication quality were the antecedents of the healthcare outcomes. The health outcomes refer to the impact of teleophthalmology on the quality of the patients' health and well-being. Additionally, teleophthalmology's adoption and service quality acted as mediators., Conclusions: This study's findings are expected to increase attention to the healthcare outcomes and antecedents of teleophthalmology to promote better telemedicine practices and services for rural residents.

Objectives: Head-and-neck cancer is a major cancer in Taiwan. Most patients are in the advanced stage at initial diagnosis. In addition to primary surgery, adjuvant therapy, including chemotherapy and radiotherapy, is also necessary to treat these patients. We used a machine learning tool to determine the factors that may be associated with and predict treatment outcome., Materials and Methods: We retrospectively reviewed 187 patients diagnosed with advanced-stage head-and-neck cancer who received surgery and adjuvant radiotherapy with or without chemotherapy. We used eXtreme Gradient Boosting (XGBoost) - a gradient tree-based model - to analyze data. The features were extracted from the entries we recorded from the electronic health-care system and paper medical record. The patient data were categorized into training and testing datasets, with labeling according to their recurrence status within the 5-year follow-up. The primary endpoint was to predict whether the patients had recurrent disease. The risk factors were identified by analyzing the feature importance in the model. For comparison, we also used regression to perform the variate analysis to identify the risk factors., Results: The accuracy, sensitivity, and positive predictive value of the model were 57.89%, 57.14%, and 44.44%, respectively. Pathological lymph node status was the most important feature, followed by whether the patient was receiving chemotherapy. Fraction size, early termination, and interruption were the important factors related to radiotherapy and might affect treatment outcome. The area under the curve of the receiver operating characteristic curve was 0.58. The risk factors identified by XGBoost were consistent with those found by regression., Conclusion: We found that several factors were associated with treatment outcome in advanced-stage head-and-neck cancer. In future, we hope to collect the data according to the features introduced in this study and to construct a stronger model to explain and predict outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)

Objective: Verbal instruction is one of the most commonly used methods that therapists use to correct walking pattern for people with Parkinson disease. This study aimed to compare the long-term training effects of two different verbal instructions that either asked the participants to "take big steps" or "strike the ground with the heel" on walking ability in individuals with Parkinson disease., Design: Forty-five participants with Parkinson disease were randomized into the big-step or heel strike group. The participants underwent 12 sessions of treadmill and overground gait training. Throughout the interventions, the big-step group received an instruction to "take big steps," while the heel strike group received an instruction to "strike the ground with your heel." The primary outcome was gait performance, including velocity, stride length, cadence, and heel strike angle. The participants were assessed before, immediately after, and 1 mo after training., Results: Both groups showed significant improvements in gait performance after training. The heel strike group showed continuous improvements in velocity and stride length during the follow-up period; however, the big-step group showed slightly decreased performance., Conclusions: A verbal instruction emphasizing heel strike can facilitate long-term retention of walking performance in people with Parkinson disease., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Thyroid cancer incidence has increased globally in recent decades, especially in females, although its trends in Taiwan have not been studied extensively. This study aimed to investigate changes in female incidence and possible causes of thyroid cancer in Taiwan., Methods: Using the Taiwan Cancer Registry (TCR) Database, age-standardized incidence rates, age-specific incidence rates and birth cohorts were calculated. Correlation between female thyroid cancer incidence and cohort fertility rates were examined., Results: Thyroid cancer incidence increased in Taiwanese female, with age-adjusted rates per 100,000 people increasing from 7.37 during 1995-1999 to 20.53 during 2015-2019; the annual percentage change (APC) was 5.9% (95% CI, 5.3-6.5). Age-specific incidence rates increased with age, with peak rates occurring at younger ages. The APCs in the 50-54 age group were the highest (6.8%, 95% CI, 6.1-7.5). Incidence rates also increased with later birth cohorts. We observed a significant negative correlation between thyroid cancer incidence and fertility rates in the same birth cohort., Conclusions: We hypothesize that overdiagnosis may be a main reason for the rapidly increasing thyroid cancer incidence in Taiwanese females. Notably, we observed a strong negative correlation between fertility and thyroid cancer incidence. However, our study is limited by the absence of individual-level cancer data in the TCR database. These associations with fertility will be an important subject for future thyroid cancer research.

Introduction: Degenerative lumbar disease (DLD) is a prevalent disorder that predominantly affects the elderly population, especially female. Extensive research has demonstrated that overweight individuals (categorized by body fat distribution) have a higher susceptibility to developing DLD and an increased risk of falling. However, there is limited research available on the standing balance and functional performance of overweight females with DLD. Aims: To determine the impact of body fat distribution on standing balance and functional performance in overweight females with DLD. Methods: This cross-sectional study evaluated thirty females with DLD were categorized into three types of body fat distribution based on body mass index (BMI) and waist-hip ratio, specifically as android-type, gynoid-type, and normal weight groups. In addition, a control group of ten age-matched females with normal weight was recruited. The Visual Analogue Scale, Roland Morris Disability Questionnaire, Cobb angle (Determined using x-ray), and body composition (Determined using the InBody S10), were conducted only on the DLD groups. All participants were assessed standing balance in the anteroposterior and mediolateral directions. The functional assessments included timed-up-and-go and 5-times-sit-to-stand tests. Results: There were 10 people in each group. Android-type (Age = 65.00 ± 6.34 years; BMI = 26.87 ± 2.05 kg/m 2 ), Gynoid-type (Age = 65.60 ± 4.99 years; BMI = 26.60 ± 1.75 kg/m 2 ), Normal weight (Age = 65.70 ± 5.92 years; BMI = 22.35 ± 1.26 kg/m 2 ), and Control (Age = 65.00 ± 5.23 years; BMI = 22.60 ± 1.12 kg/m 2 ). The android-type group had higher body fat, visceral fat, and lower muscle mass ( p < 0.05), along with an increased Cobb angle ( p < 0.05). They showed greater ellipse area, total excursion, and mean distance in the anteroposterior direction ( p < 0.05). During the functional performance assessments, the android-type group had longer durations in both the 5-times-sit-to-stand and timed-up-and-go tasks ( p < 0.05). Conclusion: Our study found that android-type overweight individuals showed postural instability, reduced functional performance, and insufficient lower limb muscle strength and mass. These findings might help physical therapists in planning interventions, as they imply that patients with DLD may require specific types of standing balance training and lower extremities muscle-strengthening based on their body fat distribution. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05375201., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Chen, Kantha, Tsai, Lai and Hsu.)

Long-term memory formation requires de novo RNA and protein synthesis. Using differential display PCR, we found that the NCoR1 cDNA fragment is differentially expressed between fast learners and slow learners, with fast learners showing a lower expression level than slow learners in the water maze learning task. Fast learners also show lower NCoR1 mRNA and protein expression levels. In addition, spatial training decreases both NCoR1 mRNA and protein expression, whereas NCoR1 conditional knockout (cKO) mice show enhanced spatial memory. In studying the molecular mechanism, we found that spatial training decreases the association between NCoR1 and DEC2. Both NCoR1 and DEC2 suppress the expression of BDNF, integrin α3 and SGK1 through C/EBPα binding to their DNA promoters, but overexpression of DEC2 in NCoR1 cKO mice rescues the decreased expression of these proteins compared with NCoR1 loxP mice overexpressing DEC2. Further, spatial training decreases DEC2 expression. Spatial training also enhances C/EBPα binding to Bdnf, Itga3 and Sgk1 promoters, an effect also observed in fast learners, and both NCoR1 and DEC2 control C/EBPα activity. Whereas knockdown of BDNF, integrin α3 or SGK1 expression impairs spatial learning and memory, it does not affect Y-maze performance, suggesting that BDNF, integrin α3 and SGK1 are involved in long-term memory formation, but not short-term memory formation. Moreover, NCoR1 expression is regulated by the JNK/c-Jun signaling pathway. Collectively, our findings identify DEC2 as a novel interacting protein of NCoR1 and elucidate the novel roles and mechanisms of NCoR1 and DEC2 in negative regulation of spatial memory formation., (© 2024. The Author(s).)

Nanofluidic channels in a membrane represent a promising avenue for harnessing blue energy from salinity gradients, relying on permselectivity as a pivotal characteristic crucial for inducing electricity through diffusive ion transport. Surface charge emerges as a central player in the osmotic energy conversion process, emphasizing the critical significance of a judicious selection of membrane materials to achieve optimal ion permeability and selectivity within specific channel dimensions. Alternatively, here we report a field-effect approach for in situ manipulation of the ion selectivity in a nanopore. Application of voltage to a surround-gate electrode allows precise adjustment of the surface charge density at the pore wall. Leveraging the gating control, we demonstrate permselectivity turnover to enhanced cation selective transport in multipore membranes, resulting in a 6-fold increase in the energy conversion efficiency with a power density of 15 W/m 2 under a salinity gradient. These findings not only advance our fundamental understanding of ion transport in nanochannels but also provide a scalable and efficient strategy for nanoporous membrane osmotic power generation.

Background: Central metatarsal pressure is increased in patients with hallux valgus, but the pedographic outcomes after hallux valgus (HV) correction are inconclusive. No known literature has reported the pedographic outcomes after HV correction with Minimally Invasive Chevron and Akin Osteotomy (MICA)., Methods: A prospective cohort of 31 feet from 25 patients with moderate-to-severe symptomatic HV but without metatarsalgia underwent MICA and was evaluated using radiographic parameters and pedographic measurements (Footscan ® , RSscan International, Olen, Belgium). Data were collected preoperatively and 3 months after surgery., Results: The radiographic parameters of the hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, first metatarsal head lateral shape, and lateral sesamoid grade significantly improved after MICA. The corrected first metatarsal length was significantly shortened by 2.3 mm, with consistent second metatarsal protrusion distance, lateral Meary's angle, and calcaneal pitch angle. Max force, max pressure, cumulative force, and cumulative pressure on the central metatarsals did not show significant changes between pre- and post-operative measurements, while these parameters significantly decreased in the hallux and first metatarsal area., Conclusion: MICA effectively corrects radiographic parameters but does not reduce central metatarsal loading in patients with moderate-to-severe HV without metatarsalgia.

High-entropy materials emerged as a field of research in 2004, when the first research on high-entropy alloys was published. The scope was soon expanded from high-entropy alloys to medium-entropy alloys, as well as to ceramics, polymers and composite materials. A fundamental understanding on high-entropy materials was proposed in 2006 by the 'four core effects' - high-entropy, severe-lattice-distortion, sluggish-diffusion and cocktail effects - which are often used to describe and explain the mechanisms of various peculiar phenomena associated with high-entropy materials. Throughout the years, the effects have been examined rigorously, and their validity has been affirmed. This Perspective discusses the fundamental understanding of the four core effects in high-entropy materials and gives further insights to strengthen the understanding for these effects. All these clarifications are believed to be helpful in understanding low-to-high-entropy materials as well as to aid the design of materials when studying new compositions or pursuing their use in applications., (© 2024. Springer Nature Limited.)

The leopard cat (Prionailurus bengalensis) is an endangered wildlife that is protected under Taiwan's regulations. The body of a road-killed leopard cat was found to contain sequences of feline calicivirus (FCV), designated W109-1443. Analysis of the complete genomic sequence revealed that it shared approximately 81% similarity with a Chinese strain of FCV found in a domestic cat. Phylogenetic analysis of the VP1 gene indicated that the W109-1443 isolate belonged to genogroup II. Recombination analysis revealed that the W109-1443 isolate may have resulted from recombination between two FCV strains. Given the potential impact of FCV on the health and survival of wild felids, further investigation is necessary to assess its pathogenicity in the leopard cat population.

Background: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood., Methods: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period., Results: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001)., Conclusions: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops., (© 2024. The Author(s).)

Background: This study validates real-time biofeedback for lumbopelvic control training in baseball. The lumbopelvic region is crucial for generating kinetic energy in pitching. Real-time biofeedback enhances training effectiveness and reduces injury risk. The validity and reliability of this system were examined., Purpose: This study was to investigate the validity and reliability of the real-time biofeedback system for lumbopelvic control training., Methods: Twelve baseball players participated in this study, with data collected in two sessions separated by a week. All participants needed to do the lateral slide exercise and single-leg squat exercise in each session. Pelvic angles detected by the real-time biofeedback system were compared to the three-dimensional motion capture system (VICON) during training sessions. Additionally, pelvic angles measured by the biofeedback system were compared between the two training sessions., Results: The real-time biofeedback system exhibited moderate to strong correlations with VICON in both exercises: lateral slide exercise ( r = 0.66-0.88, p < 0.05) and single-leg squat exercise ( r = 0.70-0.85, p < 0.05). Good to excellent reliability was observed between the first and second sessions for both exercises: lateral slide exercise (ICC = 0.76-0.97) and single-leg squat exercise (ICC = 0.79-0.90)., Conclusions: The real-time biofeedback system for lumbopelvic control training, accurately providing the correct pelvic angle during training, could enhance training effectiveness.

Background: Degenerative lumbar spine disease (DLD) is a prevalent condition in middle-aged and elderly individuals. DLD frequently results in pain, muscle weakness, and motor impairment, which affect postural stability and functional performance in daily activities. Simulated skateboarding training could enable patients with DLD to engage in exercise with less pain and focus on single-leg weight-bearing. The purpose of this study was to investigate the effects of virtual reality (VR) skateboarding training on balance and functional performance in patients with DLD., Methods: Fourteen patients with DLD and 21 age-matched healthy individuals completed a 6-week program of VR skateboarding training. The motion capture and force platform systems were synchronized to collect data during a single-leg stance test (SLST). Musculoskeletal simulation was utilized to calculate muscle force based on the data. Four functional performance tests were conducted to evaluate the improvement after the training. A Visual Analogue Scale (VAS) was also employed for pain assessment., Results: After the training, pain intensity significantly decreased in patients with DLD (p = 0.024). Before the training, patients with DLD took longer than healthy individuals on the five times sit-to-stand test (p = 0.024). After the training, no significant between-group differences were observed in any of the functional performance tests (p > 0.05). In balance, patients with DLD were similar to healthy individuals after the training, except that the mean frequency (p = 0.014) was higher. Patients with DLD initially had higher biceps femoris force demands (p = 0.028) but shifted to increased gluteus maximus demand after the training (p = 0.037). Gluteus medius strength significantly improved in patients with DLD (p = 0.039), while healthy individuals showed consistent muscle force (p > 0.05)., Conclusion: This is the first study to apply the novel VR skateboarding training to patients with DLD. VR skateboarding training enabled patients with DLD to achieve the training effects in a posture that relieves lumbar spine pressure. The results also emphasized the significant benefits to patients with DLD, such as reduced pain, enhanced balance, and improved muscle performance., (© 2024. The Author(s).)

Introduction: Angiotensin-converting enzyme 2 (ACE2) played an important role in the renin-angiotensin-aldosterone system (RAAS) and it was proved to be renoprotective in renal disease. Urinary angiotensin-converting enzyme 2 (uACE2) has been shown to reflect renal injury in human and experimental studies, but its role in feline kidney disease remains unknown., Aims: Our objectives involve comparing uACE2 concentrations and activities in cats across CKD stages with healthy controls, investigating the relationship between uACE2 concentrations, activities, and clinicopathological data in feline CKD patients, and assessing the predictive abilities of both for CKD progression., Methods: A retrospective, case-control study. The concentration and activity of uACE2 were measured by commercial ELISA and fluorometric assay kits, respectively. The concentration was adjusted to give uACE2 concentration-to-creatinine ratios (UACCRs)., Results: In total, 67 cats consisting of 24 control and 43 chronic kidney disease (CKD), including 24 early-stage CKD and 19 late-stage CKD, were enrolled in this study. UACCR values were significantly higher in both early-stage (2.100 [1.142-4.242] x 10 -6 ) and late-stage feline CKD (4.343 [2.992-5.0.71] x 10 -6 ) compared to healthy controls (0.894 [0.610-1.076] x 10 -6 ; p  < 0.001), and there was also significant difference between-early stage group and late-stage group ( p = 0.026). Urinary ACE2 activity (UAA) was significantly lower in CKD cats (1.338 [0.644-2.755] x pmol/min/ml) compared to the healthy cats (7.989 [3.711-15.903] x pmol/min/ml; p  < 0.001). UACCR demonstrated an independent, positive correlation with BUN ( p  < 0.001), and UAA exhibited an independent, negative correlation with plasma creatinine ( p  < 0.001). Both UACCR and UAA did not yield significant results in predicting CKD progression based on the ROC curve analysis., Conclusion and Clinical Importance: uACE2 concentration and activity exhibit varying changes as renal function declines, particularly in advanced CKD cats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kuo, Hsu, Wu, Jan, Tsai and Lee.)

Nonlocal effects originating from interactions between neighboring meta-atoms introduce additional degrees of freedom for peculiar characteristics of metadevices, such as enhancement, selectivity, and spatial modulation. However, they are generally difficult to manipulate because of the collective responses of multiple meta-atoms. Here, we experimentally demonstrate the nonlocal metasurface to realize the spatial modulation of dark-field emission. Plasmonic asymmetric split rings (ASRs) are designed to simultaneously excite local dipole resonance and nonlocal quasi-bound states in the continuum and spatially extended modes. With one type of unit, nonlocal effects are tailored by varying array periods. ASRs at the metasurface's edge lack sufficient interactions, resulting in stronger dark-field scattering and thus edge emission properties of the metasurface. Pixel-level spatial control is demonstrated by simply erasing some units, providing more flexibility than conventional local metasurfaces. This work paves the way for manipulating nonlocal effects and facilitates applications in optical trapping and sorting at the nanoscale.

Severe fever with thrombocytopenia syndrome virus (SFTSV) causes the highly fatal disease in humans. To facilitate diagnosis, the native form of subunit glycoprotein (Gn), a prime target for potential vaccines and therapies, was produced in Nicotiana benthamiana using a Bamboo mosaic virus-based vector system. By fusion with secretory signal tags, SS Ext , derived from the extension protein, and the (SP) 10 motif, the yield of the recombinant Gn (rGn) was remarkably increased to approximately 7 mg/kg infiltrated leaves. Ultimately, an rGn-based ELISA was successfully established for the detection of SFTSV-specific antibodies in serum samples from naturally infected monkeys. As validated with the reference method, the specificity and sensitivity of rGn-ELISA were 94% and 96%, respectively. In conclusion, utilizing well-suited fusion tags facilitates rGn production and purification in substantial quantities while preserving its antigenic properties. The rGn-ELISA, characterized by its commendable sensitivity and specificity could serve as a viable alternative diagnostic method for assessing SFTSV seroprevalence. KEY POINTS: • SFTSV Gn, fused with secretory signal tags, was expressed by the BaMV-based vector. • The plant fusion tags increased expression levels and eased the purification of rGn. • The rGn-ELISA was established and validated; its specificity and sensitivity > 94%., (© 2024. The Author(s).)

Natural language processing (NLP) has become an essential technique in various fields, offering a wide range of possibilities for analyzing data and developing diverse NLP tasks. In the biomedical domain, understanding the complex relationships between compounds and proteins is critical, especially in the context of signal transduction and biochemical pathways. Among these relationships, protein-protein interactions (PPIs) are of particular interest, given their potential to trigger a variety of biological reactions. To improve the ability to predict PPI events, we propose the protein event detection dataset (PEDD), which comprises 6823 abstracts, 39 488 sentences and 182 937 gene pairs. Our PEDD dataset has been utilized in the AI CUP Biomedical Paper Analysis competition, where systems are challenged to predict 12 different relation types. In this paper, we review the state-of-the-art relation extraction research and provide an overview of the PEDD's compilation process. Furthermore, we present the results of the PPI extraction competition and evaluate several language models' performances on the PEDD. This paper's outcomes will provide a valuable roadmap for future studies on protein event detection in NLP. By addressing this critical challenge, we hope to enable breakthroughs in drug discovery and enhance our understanding of the molecular mechanisms underlying various diseases., (© The Author(s) 2024. Published by Oxford University Press.)

In this paper, we present the design, optimization, and implementation of a sub-wavelength grating (SWG) multi-mode interference coupler (MMI) on the silicon nitride photonic integrated circuit (PIC) platform with a significantly enhanced bandwidth compared to the conventional MMI. We extend the SWG MMI theory, previously presented for the silicon-on-insulator platform, to the Si 3 N 4 /SiO 2 platform. Our approach involves an initial parameter optimization for a non-paired design, followed by a shift to a paired design that offers a smaller footprint and a broader bandwidth. The optimized SWG MMI exhibits a 1 dB bandwidth of 300 nm for both the insertion loss and power imbalance, making it a significant addition to silicon nitride photonics.

Flavivirus virus-like particles (VLPs) exhibit a striking structural resemblance to viral particles, making them highly adaptable for various applications, including vaccines and diagnostics. Consequently, increasing VLPs production is important and can be achieved by optimizing expression plasmids and cell culture conditions. While attempting to express genotype III (GIII) Japanese encephalitis virus (JEV) VLPs containing the G104H mutation in the envelope (E) protein, we failed to generate VLPs in COS-1 cells. However, VLPs production was restored by cultivating plasmid-transfected cells at a lower temperature, specifically 28 °C. Furthermore, we observed that the enhancement in JEV VLPs production was independent of amino acid mutations in the E protein. The optimal condition for JEV VLPs production in plasmid-transfected COS-1 cells consisted of an initial culture at 37 °C for 6 h, followed by a shift to 28 °C (37/28 °C) for cultivation. Under 37/28 °C cultivation conditions, flavivirus VLPs production significantly increased in various mammalian cell lines regardless of whether its expression was transiently transfected or clonally selected cells. Remarkably, clonally selected cell lines expressing flavivirus VLPs consistently achieved yields exceeding 1 μg/ml. Binding affinity analyses using monoclonal antibodies revealed similar binding patterns for VLPs of genotype I (GI) JEV, GIII JEV, West Nile virus (WNV), and dengue virus serotype 2 (DENV-2) produced under both 37 °C or 37/28 °C cultivation conditions. In summary, our study demonstrated that the production of flavivirus VLPs can be significantly improved under 37/28 °C cultivation conditions without affecting the conformational structure of the E protein. KEYPOINTS: • Low-temperature culture (37/28 °C) enhances production of flavivirus VLPs. • Flavivirus VLPs consistently achieved yields exceeding 1 μg/ml. • 37/28 °C cultivation did not alter the structure of flavivirus VLPs., (© 2024. The Author(s).)

Diazepam and zolpidem are the most widely used medications for managing insomnia. However, significant concerns regarding the potential risks of misuse and abuse problems arose in many literatures. While urine analysis is a valuable diagnostic tool, a challenge arises from the fact that some parent drugs may remain undetectable in urine. This necessitates concurrent monitoring of their metabolites. Here, we described an innovative on-line sample preconcentration technique known as micelle to solvent stacking (MSS) for the analysis of diazepam, zolpidem, and their main metabolites in urine. Several key parameters warrant further discussion to optimize the MSS model, enhancing its performance in terms of sensitivity and resolution. After optimizing the conditions, we conducted a validation test, achieving high correlation coefficients (greater than 0.9977) for intra-day and inter-day regression lines. Additionally, both the relative standard deviation (RSD) and relative error (RE) remained below 6.10% and 12.55%, respectively. The limits of detection (LODs, S/N = 3) for all five analytes ranged from 2.0 to 56 ng/mL. Compared to the conventional capillary zone electrophoresis method, this new approach exhibited remarkable sensitivity enhancements, ranging from 123 to 235-fold. Upon applying this method to actual urine samples from patients, we successfully detected nordiazepam, zolpidem, and its metabolites. This simple and sensitive approach has promising applications in supporting patient medication safety and bolstering forensic investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A pregnancy booster dose significantly reduces the risk and severity of COVID-19, and it is widely recommended. A prospective cohort study was conducted to compare the transplacental passage of maternal antibodies from vaccination or infection during three trimesters against both the vaccine-targeted Wuhan strain and the Omicron strain of SARS-CoV-2. Maternal-infant dyads from vaccinated mothers were collected between 6 June 2022 and 20 September 2022. We analyzed 38 maternal-infant dyads from mothers who had been infected with COVID-19 and 37 from mothers without any previous infection. Pregnant women who received their last COVID-19 vaccine dose in the third trimester exhibited the highest anti-spike protein antibody levels and neutralizing potency against both the Wuhan strain and Omicron BA.2 variant in their maternal and cord plasma. Both second- and third-trimester vaccination could lead to a higher level of neutralization against the Wuhan and Omicron strains. COVID-19 infection had a negative effect on the transplacental transfer ratio of SARS-CoV-2 antibodies. A booster dose during the second or third trimester is encouraged for the maximum transplacental transfer of humoral protection against COVID-19 for infants.

Macrophages play a pivotal role in the response to injury, contributing significantly to the repair and regrowth of damaged tissues. The external lateral line system in aquatic organisms offers a practical model for studying regeneration, featuring interneuromast cells connecting sensory neuromasts. Under normal conditions, these cells remain dormant, but their transformation into neuromasts occurs when overcoming inhibitory signals from Schwann cells and posterior lateral line nerves. The mechanism enabling interneuromast cells to evade inhibition by Schwann cells remains unclear. Previous observations suggest that macrophages physically interact with neuromasts, nerves, and Schwann cells during regeneration. This interaction leads to the regeneration of neuromasts in a subset of zebrafish with ablated neuromasts. To explore whether macrophages achieve this effect through secreted cytokines, we conducted experiments involving tail amputation in zebrafish larvae and tested the impact of cytokine inhibitors on neuromast regeneration. Most injured larvae remarkably regenerated a neuromast within 4 days post-amputation. Intriguingly, removal of macrophages and inhibition of the anti-inflammatory cytokine transforming growth factor-beta (TGF-β) significantly delayed neuromast regeneration. Conversely, inhibition of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) had minor effects on the regeneration process. This study provides insights into how macrophages activate interneuromast cells, elucidating the pathways underlying neuromast regeneration., (© 2024 Japanese Society of Developmental Biologists.)

Introduction: Patients with head and neck cancer may develop a second primary neoplasm (SPN) of the esophagus due to field cancerization. This study investigated the impacts of esophageal cancer screening using magnifying endoscopy with narrow-band imaging (ME-NBI) on the outcomes of hypopharyngeal cancer patients., Methods: Patients with hypopharyngeal cancer diagnosed from 2008 to 2021 in a tertiary hospital were reviewed retrospectively. Screening and surveillance using ME-NBI examination of the esophagus were divided into three patterns: (1) ME-NBI never performed or more than 6 months after diagnosis of index primary hypopharyngeal cancer, (2) ME-NBI within 6 months only, and (3) ME-NBI within 6 months and regular surveillance., Results: A total of 261 were reviewed and 21 (8%) patients were in stage I, 20 (8%) in stage II, 27 (10%) in stage III, 116 (44%) in stage IVA, 65 (25%) in stage IVB, and 12 (5%) in stage IVC. Sixty-seven (26%) patients had SPN (50 esophagus, 10 oral cavity, 3 oropharynx, 2 nasopharynx, 1 larynx and 1 lung). Among esophageal SPN, 35 (70%) and 15 (30%) patients developed synchronous and metachronous neoplasia, respectively. In multivariate Cox regression analysis, advanced stages III and IV (compared with stages I and II, HR: 1.86, 1.18-2.95, p=0.008), ME-NBI examination of the esophagus received within 6 months and regular surveillance (HR: 0.53, 0.36-0.78, p=0.001) were independent factors affecting the overall survival of patients with hypopharyngeal cancer., Discussion: Our findings demonstrated that screening and surveillance of esophageal SPN by ME-NBI improves the survival of patients with hypopharyngeal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chung, Wu, Lin, Lo, Cheng, Hsu and Liao.)

Plants offer a promising platform for cost-effective production of biologically active therapeutic glycoproteins. In previous studies, we have developed a plant expression system based on Bamboo mosaic virus (BaMV) by incorporating secretory signals and an affinity tag, which resulted in notably enhanced yields of soluble and secreted fusion glycoproteins (FGs) in Nicotiana benthamiana . However, the presence of fusion tags on recombinant glycoproteins is undesirable for biomedical applications. This study aimed to develop a refined expression system that can efficiently produce tag-free glycoproteins in plants, with enhanced efficacy of mature interferon gamma (mIFNγ) against viruses. To accommodate the specific requirement of different target proteins, three enzymatically or chemically cleavable linkers were provided in this renovated BaMV-based expression system. We demonstrated that Tobacco etch virus (TEV) protease could process the specific cleavage site (L TEV ) of the fusion protein, designated as SS Ext His(SP) 10 L TEV -mIFNγ, with optimal efficiency under biocompatible conditions to generate tag-free mIFNγ glycoproteins. The TEV protease and secretory-affinity tag could be effectively removed from the target mIFNγ glycoproteins through Ni 2+ -NTA chromatography. In addition, the result of an antiviral assay showed that the tag-free mIFNγ glycoproteins exhibited enhanced biological properties against Sindbis viru s, with comparable antiviral activity of the commercialized HEK293-expressed hIFNγ. Thus, the improved BaMV-based expression system developed in this study may provide an alternative strategy for producing tag-free therapeutic glycoproteins intended for biomedical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Hsu, Tseng, Lin, Hsu and Hu.)

Artificial nanofluidic networks are emerging systems for blue energy conversion that leverages surface charge-derived permselectivity to induce voltage from diffusive ion transport under salinity difference. Here the pivotal significance of electrostatic inter-channel couplings in multi-nanopore membranes, which impose constraints on porosity and subsequently influence the generation of large osmotic power outputs, is illustrated. Constructive interference is observed between two 20 nm nanopores of 30 nm spacing that renders enhanced permselectivity to osmotic power output via the recovered electroneutrality. On contrary, the interference is revealed as destructive in two-dimensional arrays causing significant deteriorations of the ion selectivity even for the nanopores sparsely distributed at an order of magnitude larger spacing than the Dukhin length. Most importantly, a scaling law is provided for deducing the maximal membrane area and porosity to avoid the selectivity loss via the inter-pore electrostatic coupling. As the electric crosstalk is inevitable in any fluidic network, the present findings can be a useful guide to design nanoporous membranes for scalable osmotic power generations., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)

An analysis of the optical response of a GaN-based metalens was conducted alongside the utilization of two sequential artificial intelligence (AI) models in addressing the occasional issues of blurriness and color cast in captured images. The optical loss of the metalens in the blue spectral range was found to have resulted in the color cast of images. Autoencoder and CodeFormer sequential models were employed in order to correct the color cast and reconstruct image details, respectively. Said sequential models successfully addressed the color cast and reconstructed details for all of the allocated face image categories. Subsequently, the CIE 1931 chromaticity diagrams and peak signal-to-noise ratio analysis provided numerical evidence of the AI models' effectiveness in image reconstruction. Furthermore, the AI models can still repair the image without blue information. Overall, the integration of metalens and artificial intelligence models marks a breakthrough in enhancing the performance of full-color metalens-based imaging systems.