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Background/purpose: Oral submucous fibrosis (OSF), characterized by excessive collagen deposition by myofibroblasts, is often linked to Areca nuts consumption. Probiotics consumption has shown protective effects against fibrotic diseases, and recently, their metabolic byproducts, known as postbiotics, have demonstrated superior advantages over probiotics. However, studies on the therapeutic impact of postbiotics on OSF have been scarce. Therefore, this study aims to examine the effect of PostBio GK4, a postbiotic derived from Lactobacillus pentosus GK4, on OSF and explore its underlying mechanisms. Materials and methods: The cytotoxicity of GK4 in normal buccal mucosal fibroblasts (BMFs) and fibrotic BMFs (fBMFs) were assessed. Following this, we evaluated the effects of GK4 on collagen contraction, migratory, and wound healing capacities in arecoline-induced fibrotic BMFs. Next, Western blotting and ELISA were employed to assess GK4's impact on fibrosis-related proteins such as COL1A1, and α-SMA, as well as on TGF-β and Smad2/3 signaling pathway. Results: Arecoline was shown to stimulate cell migratory, contractile and wound healing abilities as well as the expression of α-SMA and COL1A1 in BMFs. Treatment with GK4 reduced all arecoline-induced phenomena in BMFs. Moreover, GK4 diminished the increased expression of TGF-β and Smad2/3. Conclusion: Our findings proposed that GK4 may exert a suppressive effect on arecoline-induced myofibroblast activities via the inhibition of TGF-β and Smad2/3 signaling pathway. Therefore, GK4 holds promise as an adjunct therapeutic approach for intervening in OSF. Further in-vivo and clinical studies are warranted to validate these observations.

Abstract Background To evaluate whether the application of Dynamic tape to the pitching shoulder could result in reduced shoulder fatigue, reduced delayed onset muscle soreness, or improved performance. Methods This is a randomized crossover study, in which participants and investigators were blinded, included 20 amateur adult baseball players without shoulder pain. Sham taping and Dynamic taping were randomized, using an internal rotation support taping method in both groups. Bilateral shoulder strength and range of motion were measured with a handheld dynamometer and clinical goniometer before and after each test. The percentage of strength decrease, range of motion, pitch velocity, spin rate, and shoulder pain were recorded. The post-pitching decrease in strength and percentage of strength decrease were calculated by paired t-test and the pitching speed and spin rates in the innings for both the sham and Dynamic taping groups were analyzed using two-way ANOVA. Results Compared with the sham group, the Dynamic tape group showed a significant loss in the percentage of strength decrease in internal rotation compared to the sham group (-1.4% vs. 7.0%, p = 0.03). However, no significant differences were observed in other strength declines, shoulder range of motion, pain, pitching velocity, or spin rate. Conclusions Dynamic tape reduced direction-specific shoulder fatigue but did not significantly enhance pitching performance or prevent delayed onset muscle soreness. Trial registration ClinicalTrials: N201912094.

Abstract A two-dimensional (2D) Weyl semimetal, akin to a spinful variant of graphene, represents a topological matter characterized by Weyl fermion-like quasiparticles in low dimensions. The spinful linear band structure in two dimensions gives rise to distinctive topological properties, accompanied by the emergence of Fermi string edge states. We report the experimental realization of a 2D Weyl semimetal, bismuthene monolayer grown on SnS(Se) substrates. Using spin and angle-resolved photoemission and scanning tunneling spectroscopies, we directly observe spin-polarized Weyl cones, Weyl nodes, and Fermi strings, providing consistent evidence of their inherent topological characteristics. Our work opens the door for the experimental study of Weyl fermions in low-dimensional materials.

Abstract Background With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students’ surgical skills and career aspirations. Methods This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students’ interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training. Results Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p

Abstract Background Older patients are at risk for acute kidney injury and chronic kidney disease. Age-related increases in DNA methylation at CpG islands have been linked to aging-related diseases like cancer and cardiovascular disease, but the exact causal relationship between methylation in renal aging and other kidney diseases remains unclear. This study aimed to elucidate the methylation status of peripheral blood mononuclear cells (PBMCs) in the Asian population. Using human whole blood DNA methylation analysis from the Taiwan Biobank, we included participants with both whole blood genome-wide methylation data and follow-up data on serum creatinine. We investigated hyper- and hypomethylated genes in comparison of participants with higher and lower estimated glomerular filtration (eGFR) decline rate in overall cohort as well as in comparison of old and young participants in subgroup of participants with higher eGFR decline rate. Common genes and signaling pathways in both comparative analyses were identified. Results Among 1587 participants in the analysis, 187 participants had higher eGFR decline rate. According to the comparison of methylation in participants with different eGFR declines and at different ages, respectively, we identified common hypermethylated genes, including DNMT3A and GGACT, as well as hypomethylated genes such as ARL6IP5, CYB5D1, BCL6, RPRD2, ZNF451, and MIAT in both participants with higher eGFR decline and those of older age. We observed associations between the methylation status of signaling pathways and aging as well as renal function decline. These pathways notably included autophagy, p38 mitogen-activated protein kinases, and sirtuins, which were associated with autophagy process and cytokine production. Conclusions Through methylation analysis of PBMCs, we identified genes and signaling pathways which could play crucial roles in the interplay of renal aging and renal function decline. These findings contribute to the development of novel biomarkers for identifying at-risk groups and even for therapeutic agent discovery.

Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis.

Abstract Introduction The prognostic capability of targeted sequencing of primary tumors in patients with estrogen receptor‐positive, human epidermal growth factor receptor‐2‐negative early‐stage invasive breast cancer (EBC) in a real‐world setting is uncertain. Therefore, we aimed to determine the correlation between a 22‐gene mutational profile and long‐term survival outcomes in patients with ER+/ERBB2‐ EBC. Patients and Methods A total of 73 women diagnosed with ER+/ERBB2‐ EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse‐free survival (RFS) and overall survival (OS). The log‐rank test derived p‐value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. Results At follow‐up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty‐three missense mutations were detected in 14 genes. The median ages were 51 and 46 years in patients with and without mutations, respectively. Patients with any mutation had a 1.85‐fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60–5.69) compared to those without any mutation. Patients who harbored any of the six genes (MAP2K4, FGFR3, APC, KIT, RB1, and PTEN) had a nearly 6‐fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31–18.56; p = 0.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32–27.57) and 8.31 (p = 0.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (p = 0.0576) in the subcohort grouped by having a mutation in any of the six genes. Conclusions Our single‐institution tissue bank study of Taiwanese women with ER+/ERBB2‐ EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes.

Introduction To survey the potential correlation between the application of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the incidence of uveitis in individuals with type 2 diabetes mellitus (T2DM). Material and methods A retrospective cohort study using the National Health Insurance Research Database (NHIRD) was conducted. The T2DM patients using SGLT2 inhibitors and those taking other anti-diabetic medications were assigned to the SGLT2 group and the control group, respectively, with a 1 : 2 ratio via the propensity score-matching (PSM) method. The major outcome in this study is the development of uveitis according to the diagnostic codes. The Cox proportional hazard regression was adopted to yield the adjusted hazard ratio (aHR) with 95% confidence interval (CI) between the groups. Results There were 147 and 371 new uveitis episodes in the SGLT2 and control groups after the follow-up period up to 5 years. The incidence of uveitis in the SGLT2 group (aHR = 0.736, 95% CI: 0.602–0.899, p = 0.0007) was significantly lower than that in the control group after adjusting for the effect of all the confounders. In the subgroup analyses, the SGLT2 inhibitors showed a higher correlation with low uveitis incidence in T2DM patients aged under 50 than T2DM individuals aged over 50 years (p = 0.0012), while the effect of SGLT2 inhibitors on the incidence of anterior and posterior uveitis development was similar (p = 0.7993). Conclusions The use of SGLT2 inhibitors could be an independent protective factor for uveitis development in T2DM population.

Abstract Background Freezing of gait (FOG) is an episodic and highly disabling symptom of Parkinson’s Disease (PD). Traditionally, FOG assessment relies on time-consuming visual inspection of camera footage. Therefore, previous studies have proposed portable and automated solutions to annotate FOG. However, automated FOG assessment is challenging due to gait variability caused by medication effects and varying FOG-provoking tasks. Moreover, whether automated approaches can differentiate FOG from typical everyday movements, such as volitional stops, remains to be determined. To address these questions, we evaluated an automated FOG assessment model with deep learning (DL) based on inertial measurement units (IMUs). We assessed its performance trained on all standardized FOG-provoking tasks and medication states, as well as on specific tasks and medication states. Furthermore, we examined the effect of adding stopping periods on FOG detection performance. Methods Twelve PD patients with self-reported FOG (mean age 69.33 ± 6.02 years) completed a FOG-provoking protocol, including timed-up-and-go and 360-degree turning-in-place tasks in On/Off dopaminergic medication states with/without volitional stopping. IMUs were attached to the pelvis and both sides of the tibia and talus. A temporal convolutional network (TCN) was used to detect FOG episodes. FOG severity was quantified by the percentage of time frozen (%TF) and the number of freezing episodes (#FOG). The agreement between the model-generated outcomes and the gold standard experts’ video annotation was assessed by the intra-class correlation coefficient (ICC). Results For FOG assessment in trials without stopping, the agreement of our model was strong (ICC (%TF) = 0.92 [0.68, 0.98]; ICC(#FOG) = 0.95 [0.72, 0.99]). Models trained on a specific FOG-provoking task could not generalize to unseen tasks, while models trained on a specific medication state could generalize to unseen states. For assessment in trials with stopping, the agreement of our model was moderately strong (ICC (%TF) = 0.95 [0.73, 0.99]; ICC (#FOG) = 0.79 [0.46, 0.94]), but only when stopping was included in the training data. Conclusion A TCN trained on IMU signals allows valid FOG assessment in trials with/without stops containing different medication states and FOG-provoking tasks. These results are encouraging and enable future work investigating automated FOG assessment during everyday life.

Freezing of gait (FOG) is an episodic and highly disabling symptom of Parkinson’s disease (PD). Although described as a single phenomenon, FOG is heterogeneous and can express as different manifestations, such as trembling in place or complete akinesia. We aimed to analyze the efficacy of deep learning (DL) trained on inertial measurement unit data to classify FOG into both manifestations. We adapted and compared four state-of-the-art FOG detection algorithms for this task and investigated the advantages of incorporating a refinement model to address oversegmentation errors. We evaluated the model’s performance in distinguishing between trembling and akinesia, as well as other forms of movement cessation (e.g., stopping and sitting), against gold-standard video annotations. Experiments were conducted on a dataset of eighteen PD patients completing a FOG-provoking protocol in a gait laboratory. Results showed our model achieved an F1 score of 0.78 and segment F1@50 of 0.75 in detecting FOG manifestations. Assessment of FOG severity was strong for trembling (ICC=0.86, [0.66,0.95]) and moderately strong for akinesia (ICC=0.78, [0.51,0.91]). Importantly, our model successfully differentiated FOG from other forms of movement cessation during 360-degree turning-in-place tasks. In conclusion, our study demonstrates that DL can accurately assess different types of FOG manifestations, warranting further investigation in larger and more diverse verification cohorts.

Non-enzymatic dopamine (DA) sensors are important in diagnosing and treating human diseases. However, non-enzymatic sensors frequently encounter interference from other substances, posing a challenge of poor selectivity for such sensors. Herein, we prepared tungsten trioxide nanoparticles (WO3 NPs) via a simple hydrothermal method and immobilized them onto a cuprous oxide (Cu2O) film. The results demonstrate that WO3 NPs offer improved selectivity, thus avoiding interference from other substances. The DA sensor based on the Cu2O film modified with WO3 NPs exhibits excellent DA detection performance, with a wide linear range of $1~\mu \text{M}$ to 10 mM, a low limit of detection of $0.21~\mu \text{M}$ , and good selectivity against common interfering substances. This non-enzymatic DA sensor features a simple structure, easy fabrication, small size, and suitability for mass production.

In recent years, research in the field of sensors has been rapidly advancing. As a result, this study proposes a pH sensor based on a magnesium oxide (MgO) thin film. The MgO sensing layer of the pH sensor was deposited onto the electroless nickel immersion gold (ENIG) electrode using a radio frequency (RF) sputtering system, where the ENIG electrode is integrated as the working electrode and reference electrode on a Flexible Printed Circuit Board (FPCB). FPCB offers advantages such as flexibility, acid resistance, heat resistance, and low cost. Furthermore, the performance of the pH sensor is enhanced by modifying the sensing layer with Nafion and (3-Aminopropyl)triethoxysilane (APTES). This study utilized the potentiometric method to measure and analyze the performance of the pH sensor, and the measurement range of the pH sensor is from pH 3 to pH 11 with an average sensitivity of 46.48 mV/pH and linearity can reach 0.996. In terms of material analysis, this research utilizes atomic force microscopy (AFM) and energy dispersive X-ray spectroscopy (EDX) to analyze the surface morphology and elemental composition of the sensing layer to verify MgO film.

The ultimate goal of energy education is to cultivate citizens with energy literacy, which in turn influences the energy preferences of the general public. Various aspects, such as teaching, practice, publicity, and participation, all profoundly impact the formation of energy literacy. This study reviews the role of energy education in educational policy-making, the operation of educational systems, the design of innovative energy industry environments, and public participation. Through a systematic review, this study integrates empirical research across various contexts and environments. The relevant topics of empirical research include ‘energy education’, ‘energy literacy’, ‘energy preferences’, ‘energy education policy’, ‘operation of energy education systems’, ‘creation of a renewable energy industry environment’, and ‘public participation’. These studies indicate that energy education can enhance participants’ awareness of energy through knowledge transfer, enabling them to adopt more effective energy solutions and cultivate citizens with energy literacy. Energy education not only shapes the public’s energy literacy but also further influences energy preferences, which in turn can have profound effects on social interactions, market outcomes, and political and social systems. Finally, from the perspectives of ‘educational shaping’ and ‘cultural shaping’, the research explores the impact of energy education on the energy environment and people’s values. The findings reveal that society gradually forms a consensus on energy through long-term interactions, establishing a unique energy culture that subsequently influences the direction and implementation of national energy policies. There exist interactive cycles between energy education and energy policy: energy education influences public energy preferences, while energy culture, in turn, affects policy formulation.

Abstract Cancer is one of the most life‐threatening diseases worldwide. Numerous diagnostic and therapeutic techniques, such as nanomaterials‐based cancer detection and imaging‐guided focal therapy, are successfully developed to achieve highly precise cancer theranostic strategies. However, due to unpredictive alterations occurring in cancer cell morphology, a lack of sensitivity and selectivity is a critical challenge among most biomarkers’ detection. To address this issue, instead of targeting proteins or biomarkers, the detection of cancer using whole cell‐based biosensors are ubiquitously discovered through a selective oligonucleotide, so‐called aptamer. Aptamer‐based whole‐cell detection is concurrently engaged with various nanomaterials, such as magnetic beads, gold (Au) nanoparticles, and graphene family to establish a better performance of the biosensor. In this research review, the recent strategies and prospects on whole‐cell cancer detection platform based on electrochemical aptasensors integrated with nanomaterials are thoroughly discussed and summarized. Finally, future challenges and prospects are also provided.

This study examines the predictive value of elevated N-terminal-pro brain natriuretic peptide (NT-pro BNP) levels for mortality among patients with end-stage renal disease (ESRD). Data from 768 ESRD patients, excluding those with cancer or lost follow-up, were analyzed using Kaplan–Meier curves and Cox proportional hazards models over three years. Results indicated that patients with very high NT-pro BNP levels had shorter average survival times and a significantly higher risk of mortality (hazard ratio 1.43). Advanced age, ICU admission, and comorbidities like cerebrovascular diseases and chronic obstructive pulmonary disease also contributed to increased mortality risks. Thus, elevated NT-pro BNP is an independent risk factor for mortality in ESRD patients.

Objectives: To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC). Methods: Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models. Results: Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19 + lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A + and NKp30 + NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30 + NK cells (β ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model). Conclusions: Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.

Calcium titanium oxide has emerged as a highly promising material for optoelectronic devices, with recent studies suggesting its potential for favorable thermoelectric properties. However, current experimental observations indicate a low thermoelectric performance, with a significant gap between these observations and theoretical predictions. Therefore, this study employs a combined approach of experiments and simulations to thoroughly investigate the impact of structural and directional differences on the thermoelectric properties of two-dimensional (2D) and three-dimensional (3D) metal halide perovskites. Two-dimensional (2D) and three-dimensional (3D) metal halide perovskites constitute the focus of examination in this study, where an in-depth exploration of their thermoelectric properties is conducted via a comprehensive methodology incorporating simulations and experimental analyses. The non-equilibrium molecular dynamics simulation (NEMD) was utilized to calculate the thermal conductivity of the perovskite material. Thermal conductivities along both in-plane and out-plane directions of 2D perovskite were computed. The NEMD simulation results show that the thermal conductivity of the 3D perovskite is approximately 0.443 W/mK, while the thermal conductivities of the parallel and vertical oriented 2D perovskites increase with n and range from 0.158 W/mK to 0.215 W/mK and 0.289 W/mK to 0.309 W/mK, respectively. Hence, the thermal conductivity of the 2D perovskites is noticeably lower than the 3D ones. Furthermore, the parallel oriented 2D perovskites exhibit more effective blocking of heat transfer behavior than the perpendicular oriented ones. The experimental results reveal that the Seebeck coefficient of the 2D perovskites reaches 3.79 × 102 µV/K. However, the electrical conductivity of the 2D perovskites is only 4.55 × 10−5 S/cm, which is one order of magnitude lower than that of the 3D perovskites. Consequently, the calculated thermoelectric figure of merit for the 2D perovskites is approximately 1.41 × 10−7, slightly lower than that of the 3D perovskites.

Nerve injury can induce aberrant changes in the spine; these changes are due to, or at least partly governed by, transcription factors that contribute to the genesis of neuropathic allodynia. Here, we showed that spinal nerve ligation (SNL, a clinical neuropathic allodynia model) increased the expression of the transcription factor Tbx5 in the injured dorsal horn in male Sprague Dawley rats. In contrast, blocking this upregulation alleviated SNL-induced mechanical allodynia, and there was no apparent effect on locomotor function. Moreover, SNL-induced Tbx5 upregulation promoted the recruitment and interaction of GATA4 and Brd4 by enhancing its binding activity to H3K9Ac, which was enriched at the Trpv1 promotor, leading to an increase in TRPV1 transcription and the development of neuropathic allodynia. In addition, nerve injury-induced expression of Fbxo3, which abates Fbxl2-dependent Tbx5 ubiquitination, promoted the subsequent Tbx5-dependent epigenetic modification of TRPV1 expression during SNL-induced neuropathic allodynia. Collectively, our findings indicated that spinal Tbx5-dependent TRPV1 transcription signaling contributes to the development of neuropathic allodynia via Fbxo3-dependent Fbxl2 ubiquitination and degradation. Thus, we propose a potential medical treatment strategy for neuropathic allodynia by targeting Tbx5. [ABSTRACT FROM AUTHOR]