Search

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.

Abstract There is little research about the stress, quality of life (QOL) and gut microbiota in newly diagnosed breast cancer patients. In this study addressing the dearth of research on stress, quality of life (QOL), and gut microbiota in newly diagnosed breast cancer patients, 82 individuals were prospectively observed. Utilizing the Functional Assessment of Chronic Illness Therapy (FACT)-Breast questionnaire to assess health-related quality of life (HRQOL) and the Distress Thermometer (DT) to gauge distress levels, the findings revealed a mean FACT-B score of 104.5, underscoring HRQOL's varied impact. Significantly, 53.7% reported moderate to severe distress, with a mean DT score of 4.43. Further exploration uncovered compelling links between distress levels, FACT-B domains, and microbial composition. Notably, Alcaligenaceae and Sutterella were more abundant in individuals with higher DT scores at the family and genus levels (p = 0.017), while Streptococcaceae at the family level and Streptococcus at the genus level were prevalent in those with lower DT scores (p = 0.028 and p = 0.023, respectively). This study illuminates the intricate interplay of stress, QOL, and gut microbiota in newly diagnosed breast cancer patients, offering valuable insights for potential interventions of biomarker or probiotics aimed at alleviating stress and enhancing QOL in this patient cohort.

Abstract Objective Metabolic and morphological adaptations of the intestine have been suggested to play a role in the various therapeutic benefits of Roux‐en‐Y Gastric Bypass (RYGB) surgery. However, the precise underlying mechanisms remain unclear. In this study, the effects of physical properties of ingested food and redirection of biliopancreatic secretions on intestinal remodeling were investigated in RYGB operated rats. Methods RYGB employing two different Roux Limb (RL) lengths was performed on high fat diet induced obese rats. Post‐operatively, rats were fed either Solid or isocaloric Liquid diets. Metabolic and morphological remodeling of intestine was compared across both diet forms (Solid and Liquid diets) and surgical models (Short RL and Long RL). Results RYGB surgery in rats induced weight loss and improved glucose tolerance which was independent of physical properties of ingested food and biliopancreatic secretions. Intestinal glucose utilization after RYGB was not determined by either food form or biliopancreatic secretions. The GLUT‐1 expression in RL was not influenced by physical properties of food. Furthermore, both physical properties of food and biliopancreatic secretions showed no effects on intestinal morphological adaptations after RYGB. Conclusion Results of this study demonstrate that physical properties of food and bile redirection are not major determinants of intestinal remodeling after RYGB in rats.

IntroductionThe failure of remodeling the spiral arteries is associated with the pathogenesis of preeclampsia. Estradiol (E2) plays a crucial role in placentation and may be involved in the development of preeclampsia. However, there is a lack of data in this area. This study aims to assess the association between serum estradiol levels in early pregnancy and the risk of preeclampsia.MethodsWe conducted a retrospective cohort study on patients who conceived after frozen embryo transfer (FET) using data from a database at a university-affiliated in vitro fertilization center. The study period spanned from January 1, 2010, to December 31, 2020. Multivariable logistic regression analyses were performed to determine the adjusted effect of E2 levels on the risk of preeclampsia. We compared the odds ratios of preeclampsia across quartiles of E2 levels and assessed their significance.ResultsSerum E2 levels at the fifth gestational week were significantly different between women with and without preeclampsia after FET programmed cycles (607.5 ± 245.4 vs. 545.6 ± 294.4 pg/ml, p=0.009). A multivariable logistic regression model demonstrated that E2 levels in early pregnancy were independent risk factors for preeclampsia. We observed an increased odds ratio of preeclampsia with increasing quartiles of estradiol levels after adjusting for potential confounders in FET programmed cycles. When comparing quartiles 3 and 4 (E2 > 493 pg/ml at the fifth gestational week) to quartiles 1 and 2, the odds ratios of preeclampsia were significantly higher.ConclusionWe found that serum E2 levels in early pregnancy may impact the risk of preeclampsia, particularly following FET programmed cycles. The association between E2 levels in early pregnancy and preeclampsia deserves further investigation.

This study investigated the effects of weight reduction and/or calcitriol administration on regulating CD4 T cell subsets and renin-angiotensin system (RAS)-associated acute lung injury (ALI) in obese mice with sepsis. Half of the mice were fed a high-fat diet for 16 weeks, half of them had high-fat diet for 12 weeks then were transferred to a low-energy diet for 4 weeks. After feeding the respective diets, cecal ligation and puncture (CLP) were performed to induce sepsis. There were four sepsis groups: OSS group, obese mice injected with saline; OSD group, obese mice given calcitriol; WSS group, mice with weight reduction and saline; WSD group, mice with weight reduction and calcitriol. Mice were sacrificed after CLP. The findings showed that CD4 T subsets distribution did not differ among the experimental groups. Calcitriol-treated groups had higher RAS-associated AT2R, MasR, ACE2, and angiopoietin 1–7 (Ang(1–7)) levels in the lungs. Also, higher tight junction proteins were noted 12 h after CLP. At 24 h post-CLP, weight reduction and/or calcitriol treatment reduced plasma inflammatory mediator production. Calcitriol-treated groups had higher CD4/CD8, T helper (Th)1/Th2 and lower Th17/regulatory T (Treg) ratios than the groups without calcitriol. In the lungs, calcitriol-treated groups had lower AT1R levels, whereas the RAS anti-inflammatory protein levels were higher than those groups without calcitriol. Lower injury scores were also noted at this time point. These findings suggested weight reduction decreased systemic inflammation. However, calcitriol administration produced a more-balanced Th/Treg distribution, upregulated the RAS anti-inflammatory pathway, and attenuated ALI in septic obese mice.

In this study, the titanium dioxide (TiO2) thin film prepared by radio frequency magnetron sputtering system (R.F. sputtering) was used as the blocking layer (BL) of DSSCs. TiO2 blocking layer (TBL) is used to reduce the recombination reaction caused by contacting the oxidized electrolyte with the fluorine-doped tin oxide (FTO) substrate through the active layer with porous structure. We analyzed the effect of TBL introduction on the electrochemical impedance between photoanodes by potentiostat and calculated the electron lifetime, which proved that TBL can effectively improve the process of electron transfer. In addition, the direct impact of TBL on the photovoltaic performance of DSSC was determined through the quantum efficiency (QE) measurement system and current density-voltage (J-V) measurement system, and it was found that the short-circuit current density ( $\text{J}_{\mathrm {SC}}$ ), external quantum efficiency (EQE), fill factor (FF) and photoelectric conversion efficiency (PCE) were all improved. DSSCs with TBL also exhibited better performance under low illumination due to the reduced recombination reaction. Further improves the applicability of DSSCs under low illumination.

This study prepared an enzymatic potentiometric uric acid sensor based on zinc oxide (ZnO) and uricase. Also, we develop a potentiometric differential measurement system. We applied Nafion, APTES, and glutaraldehyde to immobilize the enzyme and increase sensitivity to prevent enzyme leakage. Thus, the uric acid sensor was integrated into FPCB which could provide flexibility to the sensor. In the uric acid concentration range of 2 mg/dL-10 mg/dL, we analyzed the characteristics of sensors with the voltage-time measurement system, measuring the average sensitivity, linearity, response time, limit of detection (LOD), and interference effects. The modification of Nafion and uricase improved the performance of the uric acid sensor.

Abstract Background Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach that includes targeted agents and immunotherapy. Although the response to targeted therapies for unresectable hepatocellular carcinoma (HCC) is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects continue to be problematic. Given that immune checkpoint inhibitor alone are not robust enough to improve survival in unresectable HCC, growing evidence supports the combination of targeted therapy and immunotherapy with synergistic effect. Methods Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (version 1.1) for unresectable HCC patients, an Eastern Cooperative Oncology Group performance status of 0–2, and a Child–Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). Results Three phase II/III randomized controlled trials were included in this study. The pooled results showed that combination therapy significantly improved survival than targeted monotherapy, in terms of OS (hazard ratio (HR) = 0.67; 95% confidence interval [CI]: 0.50–0.91) and PFS (HR = 0.58; 95% CI: 0.51–0.67), respectively. In the incidence of grade 3–5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (odds ratio = 1.98; 95% CI: 1.13–3.48). Conclusion For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared with targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.

Objective: This study aims to compare the efficacy, tolerability and patient satisfaction between aqueous subcutaneous progesterone (Prolutex, 25 mg/vial; IBSA) and vaginal progesterone (Crinone, 90 mg/tube; Merck) as luteal support for fresh embryo transfers in in-vitro fertilization (IVF). Materials & Methods: In this prospective randomized study, 65 patients who underwent IVF were recruited and randomly assigned to either the Prolutex (25 mg daily, n = 33) or Crinone (90 mg daily, n = 32) group. The luteal support regimens were given daily, starting from two days after oocyte pickup. If the serum pregnancy test was positive, luteal support was continued until 7 weeks of gestation. Primary outcomes were clinical pregnancy rate and serum progesterone level at the mid-luteal phase and at 4 weeks of gestation. Secondary outcomes were drug tolerability and patient satisfaction assessed by questionnaire. Results: There were no significant differences in clinical pregnancy rates (Prolutex 25.0% versus Crinone 33.3%, p = 0.699), serum progesterone levels and patient satisfaction between Prolutex and Crinone group. Although the patients that had received Prolutex complained of more local pain at the injection sites, they also had less annoying vaginal discharges and vulvar discomforts. Conclusion: Prolutex is of comparable efficacy and patient satisfaction to Crinone, and its availability means patients have more options in regards to the routes of progesterone administration as luteal phase support during IVF.

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.

Background/Purpose: To assess the relationship between gene expressions of the magnesium transporters and glucose parameters in pregnant women. Methods: A cohort of women without ongoing or prior medical illnesses was recruited at the start of an early singleton pregnancy. Expression levels of the magnesium transporters—SLC41A1, CNNM2, MAGT1, TRPM6, and TRPM7—were assessed in the peripheral leukocytes, while total calcium and magnesium were assessed in the serum between 10 and 13 weeks gestation. Glucose parameters were assessed between 24 and 28 weeks gestation using the 75 g oral glucose tolerance test. Results: A total of 208 patients were included in the study. The expressions of the magnesium transports were generally unrelated to age, body mass index (BMI), or serum levels of calcium and magnesium. The magnesium transporters were correlated with each other at baseline (correlation coefficients: 0.31 to 0.51). BMI was a strong predictor of fasting glucose levels, while both BMI and age were strong predictors of post-load glucose levels. The expression of TRPM7 was found to be predictive of 1-h post-load blood glucose after accounting for the effects of age and BMI (β = −0.196, p = 0.020). Conclusion: The increased maternal expression of the magnesium transporter TRPM7 may be associated with decreased glucose tolerance in pregnant women. In particular, the association between TRPM7 and 1-h post-load glucose levels was found to be independent of the effects of age and BMI. Future studies are needed to determine whether a mechanistic relationship can be demonstrated between TRPM7 and glucose metabolism.

Background/Purpose: Various microRNAs (miRs) have been found to be associated with the development of the precancerous condition of the oral cavity, oral submucous fibrosis (OSF). The expression of miR-29c is dysregulated in oral cancer, but its role in OSF has not been investigated. The purpose of the study is to investigate the functional role of miR-29c and its target in OSF. Methods: The expression levels of miR-29c in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were assessed using next-generation sequencing and real-time Polymerase Chain Reaction (PCR) analysis. MiR-29c mimic and inhibitors were employed to examine its functional role of myofibroblast transdifferentiation. In addition, several myofibroblast phenotypes, such as collagen gel contraction and migration were tested, and a luciferase reporter assay was conducted to confirm the relationship between miR-29c and its predicted target, tropomyosin-1 (TPM1). Results: We observed that miR-29c expression was downregulated in fBMFs. fBMFs transfected with miR-29c mimics exhibited reduced migration ability and collagen gel contractility, whereas inhibition of miR-29c in normal BMFs induced the myofibroblast phenotypes. Results from the luciferase reporter assay showed that TPM1 was a direct target of miR-29c and the expression of TPM1 was suppressed in the fBMFs transfected with miR-29c mimics. Besides, we confirmed that the expression of miR-29c was indeed downregulated in OSF specimens. Conclusion: MiR-29c seems to exert an inhibitory effect on myofibroblast activation, such as collagen gel contractility and migration ability, via suppressing TPM1. These results suggested that approaches to upregulate miR-29c may be able to ameliorate the progression of OSF.

To build a synchronization error prediction model for the machine tool efficiently, a robust whale optimization algorithm (RWOA) method proposed in this study is applied to the hyperparameter optimization of its model. The proposed RWOA method integrated a non-linear time-invariant inertia weighting (NTIW) method and a Taguchi-based adaptive parameter exploration (ATPE) to improve the performance of WOA and promote robustness. The NTIW method can improve the performance of other algorithms, so this study used the NTIW method in the WOA. In addition, the Taguchi method can get an excellent combination of variables with optimal values and stable performance, making the WOA robust. First, to verify the validity of the proposed RWOA method, 13 benchmark functions were used in this study. The results of the benchmark function tests include the mean, standard deviation, and p -value of the t -distribution test. The results show that 11 of the 13 functions differ significantly. In other non-significant difference functions, the means and standard deviations obtained by the proposed RWOA are considerably better than those obtained by WOA. Since the product cost of machine tools is higher, if a prediction model can be built effectively, it can reduce the cost. Therefore, in this study, the proposed RWOA was used to explore the best hyperparameter combination for the model. From the results, the model’s average MAPE (mean absolute percentage error) was 7.2604% for training data and 9.2603% for the testing data under 30 modeling runs. For the best one in 30 models, the MAPE was 6.8384% for the training data and 6.7372% for the testing data. This model was also introduced into the actual machine in this study, and the experimental results showed the MAPE 6.3447%. The proposed RWOA method effectively explores a suitable synchronization error model for the tool machine.

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]

Single-stranded DNA-binding proteins (SSBs) play a crucial role in DNA metabolism by binding and stabilizing single-stranded DNA (ssDNA) intermediates. Through their multifaceted roles in DNA replication, recombination, repair, replication restart, and other cellular processes, SSB emerges as a central player in maintaining genomic integrity. These attributes collectively position SSBs as essential guardians of genomic integrity, establishing interactions with an array of distinct proteins. Unlike Escherichia coli, which contains only one type of SSB, some bacteria have two paralogous SSBs, referred to as SsbA and SsbB. In this study, we identified Staphylococcus aureus SsbA (SaSsbA) as a fresh addition to the roster of the anticancer drug 5-fluorouracil (5-FU) binding proteins, thereby expanding the ambit of the 5-FU interactome to encompass this DNA replication protein. To investigate the binding mode, we solved the complexed crystal structure with 5-FU at 2.3 Å (PDB ID 7YM1). The structure of glycerol-bound SaSsbA was also determined at 1.8 Å (PDB ID 8GW5). The interaction between 5-FU and SaSsbA was found to involve R18, P21, V52, F54, Q78, R80, E94, and V96. Based on the collective results from mutational and structural analyses, it became evident that SaSsbA’s mode of binding with 5-FU diverges from that of SaSsbB. This complexed structure also holds the potential to furnish valuable comprehension regarding how 5-FU might bind to and impede analogous proteins in humans, particularly within cancer-related signaling pathways. Leveraging the information furnished by the glycerol and 5-FU binding sites, the complexed structures of SaSsbA bring to the forefront the potential viability of several interactive residues as potential targets for therapeutic interventions aimed at curtailing SaSsbA activity. Acknowledging the capacity of microbiota to influence the host’s response to 5-FU, there emerges a pressing need for further research to revisit the roles that bacterial and human SSBs play in the realm of anticancer therapy.

In this study, robust composite solid electrolytes were developed and employed to enhance the performance of Li-metal batteries significantly. The robust composite solid electrolytes are composed of a soft polymer, poly(ethylene oxide), a Li salt, bis(trifluoromethanesulfonyl)imide (LiTFSI), and super ionic conductive ceramic fillers such as Li1.5Al0.5Ti1.5(PO4)3 (LATP), and Li6.4La3Zr1.4Ta0.6O12 (LLZTO). The main goal of this study is to enhance the electrochemical stability and ionic conductivity. The ionic conductivities of the composite solid electrolytes were found to be 2.08 × 10−4 and 1.64 × 10−4 S cm−1 with the introduction of LATP and LLZTO fillers, respectively. The results prove that the fabricated solid electrolyte was electrochemical stable at voltage exceeding 4.25 V vs. Li/Li+. The internal resistance of the solid electrolyte significantly reduced compared to gel electrolyte. This reduction can be attributed to the alleviation of bulk electrolyte, charge-transfer, and interfacial electrolyte/electrode impedance. When LiFePO4 cathode sheets are coated with a composite solid electrolyte containing LATP powders, the resulting Li-metal battery displays high capacity at 5 C (with a capacity retention of 65.2% compared to the original capacity at 0.2 C) as well as superior cyclic stability and excellent Coulombic efficiency (>99.5%, 200 cycles). These results confirm that the composite solid electrolyte acts as a protective layer which has the ability to prevent the growth of Li dendrites. Consequently, the fabricated electrolyte configuration can be engineered to enable high energy/power density and electrochemical stable cyclability in Li-metal batteries.

An electrochemical zinc oxide (ZnO) pH sensor is proposed and prototyped using a flexible printed circuit board (FPCB). The device is resistant to acidic and alkaline solutions and exhibits excellent electrical conductivity. The sensing film was deposited by radio-frequency sputtering, providing a dense ZnO layer, and (3-aminopropyl)triethoxysilane (APTES) was used to enhance the chemical stability of the ZnO in acidic solutions. The proposed pH sensor has an average sensitivity of 37.52 mV/pH, linearity of 0.995, and a repeatable RSD value of 2.4%. Testing was conducted with Carmody’s buffer pH 2–10 and a voltage-time measurement system. The stability of the prototype was determined by the measurement of the drift and hysteresis effects.

As customer satisfaction explicitly leads to repurchase behavior, the level of customer satisfaction affects both sales performance and enterprise growth. Traditionally, measuring satisfaction requires customers spending extra time to fill out a post-purchase questionnaire survey. Recently, ASR (Automatic Speech Recognition) is utilized to extract spoken words from conversation to measure customer satisfaction. However, as oriental people tend to use vague words to express emotion, the approach has its limitation. To solve the problem, this study strived to complete following tasks: devising a process to collect customer voice expressing satisfaction and corresponding verifiable ground truth; a dataset of 150 customer voices speaking in Mandarin was collected; MFCCs were extracted from the voice data as features; as the size of dataset was limited, Auto Encoder was utilized to further reduce the features of voices; models based on Long Short-Term Memory (LSTM) Recurrent Neural Networks (RNNs) and Support Vector Machine (SVM) were constructed to predict satisfaction. With nested cross validation, the average accuracy of LSTM and SVM could reach 71.95% and 73.97%, respectively.

The advantage of the dye-sensitized solar cell (DSSC) is utilized indoor fluorescent light illumination, but the output power of DSSC is not high enough. In this study, we provided a structure for DSSCs, and characterized the photovoltaic performances under air mass 1.5 global and indoor fluorescent light illumination. The photoanode of DSSC is based on titanium dioxide (TiO2) – magnet beads (MBs) – reduced graphene oxide (rGO) composited photoanode (TMGP), which was fabricated by hydrothermal method, spin coating, and doctor blade. According to the experimental results, adding MBs and rGO to DSSCs can enhance the charge transfer ability, reducing the occurrence of charge recombination, thereby improving the photovoltaic performance. DSSCs with TMGP photoanode can maintain a photovoltaic conversion efficiency of around 14 % under indoor light.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age. Although its essential clinical manifestation includes a plethora of symptoms and signs, which largely reflects the underlying hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, PCOS may also be associated with many metabolic derangements. These metabolic derangements happen to overlap with many of the core constituents of the metabolic syndrome (MBS)—increased insulin resistance, central obesity, and dyslipidemia. The two disorders also display similarly increased risks for certain metabolic and vascular diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Due to the many similarities between metabolic syndrome and PCOS, this review aims to examine the evidence concerning the overlapping features, the risks for comorbidities, possible shared mechanisms, and treatment strategies in patients with coexisting PCOS and MBS.

This study investigated the impacts of enteral cholecalciferol and/or intravenous calcitriol administration on the balance of cluster of differentiation 4-positive T cell subsets, the renin-angiotensin system (RAS), and the severity of acute lung injury (ALI) in obese mice with sepsis. Mice were fed a high-fat diet and then cecal ligation and puncture (CLP) was performed. Obese mice were divided into four sepsis groups: without vitamin D (VD) (S), with oral cholecalciferol 1 d before CLP (G), with intravenous calcitriol 1 h after CLP (V), and with both cholecalciferol before and intravenous calcitriol after CLP (GV). Mice were euthanized after CLP. The V and GV groups showed higher blood T helper (Th)1/Th2 and lower Th17/T regulatory (Treg) ratios than did the S and G groups. In the lungs, The V group had the lowest nuclear factor-κB and interleukin-1β gene expressions among all groups 24 h post-CLP. In parallel, gene expressions of angiotensin type 2 receptor (AT2R), angiotensin-converting enzyme 2 (ACE2), and Mas receptor (MasR) were highest in the V group compared to other groups. The protein levels of MasR in the GV group and the AT2R/AT1R ratio in the V group were higher than those in the G and/or S groups. All of the VD-treated groups had lower injury scores than the S group. These findings suggest that calcitriol administration had more-pronounced impacts on regulating the homeostasis of Th/Treg cells and is prone to RAS-associated anti-inflammatory pathway in the lungs. However, both forms of VD attenuated sepsis-induced ALI in obese animals.

Abstract Background The prevalence of chronic disease is growing in aging societies, and artificial-intelligence–assisted interpretation of macular degeneration images is a topic that merits research. This study proposes a residual neural network (ResNet) model constructed using uniform design. The ResNet model is an artificial intelligence model that classifies macular degeneration images and can assist medical professionals in related tests and classification tasks, enhance confidence in making diagnoses, and reassure patients. However, the various hyperparameters in a ResNet lead to the problem of hyperparameter optimization in the model. This study employed uniform design—a systematic, scientific experimental design—to optimize the hyperparameters of the ResNet and establish a ResNet with optimal robustness. Results An open dataset of macular degeneration images ( https://data.mendeley.com/datasets/rscbjbr9sj/3 ) was divided into training, validation, and test datasets. According to accuracy, false negative rate, and signal-to-noise ratio, this study used uniform design to determine the optimal combination of ResNet hyperparameters. The ResNet model was tested and the results compared with results obtained in a previous study using the same dataset. The ResNet model achieved higher optimal accuracy (0.9907), higher mean accuracy (0.9848), and a lower mean false negative rate (0.015) than did the model previously reported. The optimal ResNet hyperparameter combination identified using the uniform design method exhibited excellent performance. Conclusion The high stability of the ResNet model established using uniform design is attributable to the study’s strict focus on achieving both high accuracy and low standard deviation. This study optimized the hyperparameters of the ResNet model by using uniform design because the design features uniform distribution of experimental points and facilitates effective determination of the representative parameter combination, reducing the time required for parameter design and fulfilling the requirements of a systematic parameter design process.

Abstract Background Heart sound measurement is crucial for analyzing and diagnosing patients with heart diseases. This study employed phonocardiogram signals as the input signal for heart disease analysis due to the accessibility of the respective method. This study referenced preprocessing techniques proposed by other researchers for the conversion of phonocardiogram signals into characteristic images composed using frequency subband. Image recognition was then conducted through the use of convolutional neural networks (CNNs), in order to classify the predicted of phonocardiogram signals as normal or abnormal. However, CNN requires the tuning of multiple hyperparameters, which entails an optimization problem for the hyperparameters in the model. To maximize CNN robustness, the uniform experiment design method and a science-based methodical experiment design were used to optimize CNN hyperparameters in this study. Results An artificial intelligence prediction model was constructed using CNN, and the uniform experiment design method was proposed to acquire hyperparameters for optimal CNN robustness. The results indicate Filters ( $${X}_{1}$$ X 1 ), Stride ( $${X}_{3}$$ X 3 ), Activation functions ( $${X}_{6}$$ X 6 ), and Dropout ( $${X}_{7}$$ X 7 ) to be significant factors considerably influencing the ability of CNN to distinguish among heart sound states. Finally, the confirmation experiment was conducted, and the hyperparameter combination for optimal model robustness was Filters ( $${X}_{1}$$ X 1 ) = 32, Kernel Size ( $${X}_{2})$$ X 2 ) = 3 × 3, Stride ( $${X}_{3}$$ X 3 ) = (1,1), Padding ( $${X}_{4})$$ X 4 ) as same, Optimizer ( $${X}_{5})$$ X 5 ) as the stochastic gradient descent, Activation functions ( $${X}_{6}$$ X 6 ) as relu, and Dropout ( $${X}_{7}$$ X 7 ) = 0.544. With this combination of parameters, the model had an average prediction accuracy rate of 0.787 and standard deviation of 0. Conclusion In this study, phonocardiogram signals were used for the early prediction of heart diseases. The science-based and methodical uniform experiment design was used for the optimization of CNN hyperparameters to construct a CNN with optimal robustness. The results revealed that the constructed model exhibited robustness and an acceptable accuracy rate. Other literature has failed to address hyperparameter optimization problems in CNN; a method is subsequently proposed for robust CNN optimization, thereby solving this problem.

Water pollution has emerged as a major global environmental crisis due to the massive contamination of water resources by the textile dyeing industry, organic waste, and agricultural residue. Since water is fundamental to life, this grave disregard puts lives at risk, making the protection of water resources a serious issue today. Recent research has shown great interest in improving the photocatalytic performance of graphitic carbon nitride (g-C3N4) for wastewater treatment. However, the photocatalytic removal activity of pure g-C3N4 is poor, owing to its minimal surface area, fast recombination of photo-generated electron–hole pairs, and poor light absorption. Recently, titanate perovskites (TNPs) have attracted significant attention in both environmental remediation and energy conversion due to their exceptional structural, optical, physiochemical, electrical, and thermal properties. Accordingly, TNPs can initiate a variety of surface catalytic reactions and are regarded as an emerging category of photocatalysts for sustainability and energy-related industries when exposed to illumination. Therefore, in this review article, we critically discuss the recent developments of extensively developed g-C3N4/TNPs that demonstrate photocatalytic applications for wastewater treatment. The different synthetic approaches and the chemical composition of g-C3N4/TNP composites are presented. Additionally, this review highlights the global research trends related to these materials. Furthermore, this review provides insight into the various photocatalytic mechanisms, including their potential impact and significance. Also, the challenges faced by such materials and their future scope are discussed.