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Yan-Lin Huang,1,2,* Gang Ning,1,* Lu-Biao Chen,1,* Yi-Fan Lian,2 Yu-Rong Gu,1,2 Jia-Liang Wang,2 Dong-Mei Chen,2 Huan Wei,2 Yue-Hua Huang1,2 1Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; 2Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background: A growing body of evidence suggests that E2Fs, by regulating gene expression related to cell cycle progression and other cellular processes, play a pivotal role in human cancer. However, the distinct roles of each E2F in the development and treatment of hepatocellular carcinoma (HCC) remain unknown. In the present study, the mRNA expression and prognostic value of different E2Fs in HCC are analyzed.Materials and methods: Transcriptional and survival data related to E2F expression in patients with HCC were obtained through ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The sequence alteration data for E2Fs were obtained from The Cancer Genome Atlas and c-BioPortal. Gene functional enrichment analyses were performed in Database for Annotation, Visualization and Integrated Discovery.Results: The mRNA expression levels of E2F1–E2F8 were all significantly upregulated in HCC patients, and high expression of each E2F was obviously related to poor prognosis. Similarly, the expression of E2Fs showed prognostic prediction value in HCC patients with different cancer stages and pathological grades. Moreover, the mutation rate of E2Fs was relatively high in HCC patients, and the DNA sequence alterations primarily occurred in E2F5, E2F3, and E2F6, which were associated with worse overall survival and disease-free survival in HCC patients. Network analysis confirmed that the expression levels of cell cycle-related genes were mostly affected by E2F mutations.Conclusion: High expression of individual E2Fs was associated with poor prognosis in all liver cancer patients. E2Fs may be exploited as good prognostic targets for comprehensive management of HCC patients, but this notion should be further evaluated in clinical studies. Keywords: HCC, E2F, prognosis, ONCOMINE, Kaplan–Meier plotter

Jing-Hui Zheng, Gui-Lan Ning, Wen-Hua Xu, Xin-Cheng Wu, Xiao-Cong Ma Department of Cardiology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, China Background: In recent years, there has been substantial research evaluating the relationship between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) polymorphisms and ischemic stroke (IS). The objective of this study was to systematically review and analyze the existing evidence.Methods: A comprehensive search of major electronic databases for studies published between 1990 and 2018 was carried out. Data were synthesized as OR and 95% CI using fixed-effects and random-effects models.Results: A total of 30 studies were available for analysis. The aggregate sample size across all studies was 32,782 (16,294 cases and 16,488 controls). We found no association of the ALOX5AP rs10507391 (OR=1.03 for A allele vs T allele; 95% CI: 0.93–1.14; P=0.557), rs4769874 (OR=1.13 for A allele vs G allele; 95% CI: 1.00–1.28; P=0.050), rs9551963 (OR=1.03 for A allele vs C allele; 95% CI: 0.96–1.11; P=0.372), rs17222814 (OR=1.09 for A allele vs G allele; 95% CI: 0.96–1.24; P=0.195), rs17222919 (OR=0.89 for G allele vs T allele; 95% CI: 0.75–1.06; P=0.175), and rs4073259 (OR=1.20 for A allele vs G allele; 95% CI: 1.00–1.45; P=0.056) polymorphisms with IS risk. Haplotype analysis also did not yield significant findings for the HapA (rs17222814G–rs10507391T–rs4769874G–rs9551963A; OR=1.20; 95% CI: 0.91–1.56; P=0.192) and HapB (rs17216473A–rs10507391A–rs9315050A–rs17222842G; OR=1.11; 95% CI: 0.90–1.38; P=0.339) haplotypes.Conclusion: Current evidence does not support an association of rs10507391, rs4769874, rs9551963, rs17222814, rs17222919, rs4073259, and HapA and HapB with IS risk. Keywords: ischemic stroke, ALOX5AP, genetic polymorphism, haplotype

Jiaxiao Shi,1,2,* Yulin Li,1,2,* Cong Xing,1,2,* Peng Peng,1,2 Hongyu Shi,1,2 Han Ding,1,2 Pengyuan Zheng,1,2 Guangzhi Ning,1,2 Shiqing Feng1,2 1Department of Orthopaedics, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, PR China; 2Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Heping District, Tianjin 300052, PR China *These authors contributed equally to this work Objectives: The application of urapidil for treating hypertensive patients with acute heart failure in the emergency department remains controversial. Our objective was to organize the relevant articles and assess the clinical indexes between urapidil and nitroglycerin. Materials and methods: PubMed, EMBASE, the Cochrane Library and China National Knowledge Infrastructure were searched for randomized studies that compared urapidil treatment with nitroglycerin treatment for hypertensive patients with acute heart failure. The risk ratio, with 95% CI, was calculated by using a corresponding effects model, according to the value of I2. Results: Seven randomized controlled trials were identified, in order to compare the clinical indexes. On comparing the clinical indexes, the urapidil group was found to be better than the nitroglycerin group in regard to left ventricular ejection fraction, systolic blood pressure, N-terminal prohormone of brain natriuretic peptide, left ventricular end-diastolic volume, cardiac index, ALT, AST and health complications (P0.05). Conclusion: Based on the current evidence, urapidil treatment had better clinical safety features than the traditional pharmaceutical treatment with nitroglycerin. For those indicators with a small amount of data, a greater number of randomized, high-quality controlled trials should be conducted in order to further verify the findings, which could give researchers a more comprehensive evaluation of urapidil treatment. Keywords: urapidil, nitroglycerin, acute heart failure, meta-analysis

Abstract To discuss the application value of Case-based Learning (CBL) combined with Bridge-In, Objective, Pre-assessment, Participatory Learning, Post-assessment, and Summary (BOPPPS) model into master students’ program of oral and maxillofacial surgery. 38 master’s students in oral and maxillofacial surgery at Y2 and Y3 from January 2022 to December 2022 are selected as the research objects. They are randomly assigned into two learning groups, namely the traditional LBL (Learn-based Learning) (19 participants) and CBL combined with BOPPPS mode (19 participants). Their theoretical knowledge was assessed after training and the modified Mini-Clinical Evaluation Exercise (Mini-CEX) scale was used to score their clinical thinking. At the same time, the Personal Teaching Efficiency and the Teachers’ Sense of Teaching Efficiency (TSTE) were evaluated, and students’ satisfaction with teaching outcomes was investigated. The basic theoretical knowledge, clinical case analysis and total scores of the experimental group were better than those of the control group, with statistically significant difference (P 0.05), the other four items and total scores in the experimental group were better than those in the control group, with statistically significant difference (P 0.05). CBL combined with BOPPPS teaching method can improve students’ clinical critical thinking ability and help them adapt to the clinical rhythm. It is an effective measure to ensure teaching quality and is worthy of promotion. It is worthwhile to promote the application of CBL combined with BOPPPS mode into master’s course of oral and maxillofacial surgery, which not only improve the basic theoretical knowledge and speculative thinking ability of master’s students, but also improve the teaching efficiency.

14C, a radionuclide, which is widely used in all works of life, such as medical research and determination of PM2.5, has been realized autonomous production in China. It relied on imports, which was expensive and unstable supply in the past time. At present, Qinshan Nuclear Power has started 14C production to completely solve the problem of the serious shortage of 14C independent supply in China. Aluminum nitride powder is the main raw material for the preparation of 14C, whose elemental aluminum directly affects the safety and quality of 14C isotopic targets in nuclear reactors. Aluminum nitride is very stable in an inert high temperature environment. But a lot of elemental aluminum will react with water producing hydrogen in a high temperature environment which can result in the expansion of component rods or it will react with cladding tubes producing hydrogen embrittling effect, and these can affect the quality of 14C isotopic target. According to the characteristic of aluminum nitride insoluble in acid, this study researched different dissolution effect of elemental aluminum in aluminum nitride nano-powder by nitric acid, hydrochloric acid and sulfuric acid. It was found that the above mentioned acid can only dissolve a small amount of aluminum nitride powder, and there was a small amount of aluminum nitride powder suspending in solution, which would seriously interfere the determination of elemental aluminum. At present, microwave digestion, laser ablation, X-ray fluorescence and other methods are used to dissolve or determinate aluminum nitride, but they are not suitable for the determination of elemental aluminum. The determination of elemental aluminum is generally used in pharmaceutical, soil, tea and other samples, but most of the aluminum in the above samples exists as an impurity element, or aluminum is combined with organic matter, which is easy to separate from elemental aluminum. However, it is difficult to achieve complete separation of elemental aluminum(unbound elemental aluminum) and the aluminum nitride matrix in the aluminum nitride powder. This study used replacement reaction to selectively dissolve elemental aluminum. Then the suspended aluminum nitride powder was separated by filter membrane filter. By this method, it could solve the determination interference to elemental aluminum. This study established the determination of elemental aluminum in aluminum nitride nanoparticles by inductively coupled plasma mass spectrometer(ICP-MS), which has the advantages of low determination limit, high accuracy, fast determination speed and small matrix effect. This method’s linear range is 10-100 μg/g and the relative standard deviation is 3.8%(n=6). Using high purity alumina powder to verify the established determination method, the dissolution efficiency can reach 96%-98%.

Due to anthropogenic and long-term geological factors, radionuclide leakage may occur in deep geological repositories of radioactive waste when groundwater infiltrates a failed waste canister. The released radionuclides can migrate to near and far field regions through groundwater, posing a serious threat to the ecological environment and human health. As a consequence, knowledge of radionuclide speciation in groundwater is essential for understanding their transport behavior. Uranium is one of the key elements of significant concern for deep geological disposal of high-level radioactive waste. In this study, the uranium species in groundwater from boreholes BS03(pH=9.43) and BS05(pH=7.51) located at the Beishan area(Gansu province) were calculated by the hydrogeochemical software PHREEQC(version 3). The effects of pH, temperature, and initial uranium concentrations on ternary uranyl species are presented. The results indicate that UO2CO3(aq) and (UO2)2CO3(OH)\begin{document}$_3^- $\end{document} are the dominant species in a mildly acidic condition, while CaUO2(CO3)\begin{document}$_3^{2-} $\end{document} and Ca2UO2(CO3)3(aq) are the major species in neutral and weakly alkaline conditions. In BS05 groundwater, the concentration of Ca2+(5.11 mmol/L) is about three times higher than that of Mg2+(1.58 mmol/L). However, the concentration of calcium uranyl carbonate is estimated to be about 250 times higher than that of magnesium uranyl carbonate(MgUO2(CO3)\begin{document}$ _3^{2-}$\end{document}). With an increase of temperature, Ca2UO2(CO3)3(aq), CaUO2(CO3)\begin{document}$_3^{2-} $\end{document} and UO2(CO3)\begin{document}$_3^{4-} $\end{document} concentrations progressively diminish. At uranium concentrations between 4×10−4 and 1×10−1 mmol/L (25 ℃), the dominant uranium species, in order of decreasing concentration are: Ca2UO2(CO3)3(aq)(x＞62%)＞CaUO2(CO3)\begin{document}$_3^{2-} $\end{document}(x≈35%)＞MgUO2(CO3)\begin{document}$_3^{2-} $\end{document}/UO2(CO3)\begin{document}$_3^{4-} $\end{document}(x≈1%), irrespective of the concentrations of Ca2+, Mg2+, and Na+. In the near-neutral and slightly alkaline conditions, the results suggest that the formation of neutral Ca2UO2(CO3)3(aq) and anionic CaUO2(CO3)\begin{document}$_3^{2-} $\end{document} in Beishan groundwater reduces the distribution coefficient between uranium and environmental geo-medium, thereby enhancing the mobility and migration potential of uranium. The research findings contribute to understanding the transport and release mechanisms of uranium, as well as interactions between uranium species and engineered and natural barriers.

Abstract Background Creatinine-to-cystatin C ratio (CCR) has been associated with multiple adverse outcomes. However, little is known about its relationship with frailty. We aimed to explore the association between CCR and frailty among older adults. Methods A total of 2599 participants aged ≥ 60 years (mean age 67.9 ± 6.0 years, 50.4% males) were included from the China Health and Retirement Longitudinal Study (2011–2015). Baseline CCR was calculated as plasma creatinine (mg/dL) / cystatin C (mg/L) × 10 and was grouped by quartiles. Frailty was evaluated by the validated physical frailty phenotype (PFP) scale and was defined as PFP score ≥ 3. The generalized estimating equations model was used to explore the relationship between CCR and frailty. Results The frailty risk decreased gradually with increasing CCR in the quartiles (P for trend = 0.002), and the fourth CCR quartile was associated with a significantly lower risk of frailty compared with the lowest quartile (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19–0.70). When modeling as a continuous variable, per 1-unit increase in CCR was related to 17% decreased odds of frailty (OR 0.83, 95% CI 0.74–0.93). The association was consistent in male and female participants (P for interaction = 0.41). Poisson models revealed that frailty score was negatively associated with CCR (β= -0.11, 95% CI= -0.19 to -0.04), and sex did not significantly moderate the associations (P for interaction = 0.22). The results were not affected by further adjusting for high-sensitivity C-reactive protein. Similar results were observed by analyses with multiple imputation technique and analyses excluding participants with baseline frailty. Conclusions Higher CCR was associated with a lower frailty risk. CCR may be a simple marker for predicting frailty in older adults.

Abstract Background Calcium-dependent protein kinase (CDPK) plays a key role in cotton tolerance to abiotic stress. However, its role in cotton heat stress tolerance is not well understood. Here, we characterize the GhCDPK gene family and their expression profiles with the aim of identifying CDPK genes associated with heat stress tolerance. Results This study revealed 48 GhCDPK members in the cotton genome, distributed on 18 chromosomes. Tree phylogenetic analysis showed three main clustering groups of the GhCDPKs. Cis-elements revealed many abiotic stress and phytohormone pathways conserved promoter regions. Similarly, analysis of the transcription factor binding sites (TFBDS) in the GhCDPK genes showed many stress and hormone related sites. The expression analysis based on qRT-PCR showed that GhCDPK16 was highly responsive to high-temperature stress. Subsequent protein-protein interactions of GhCDPK16 revealed predictable interaction with ROS generating, calcium binding, and ABA signaling proteins. Overexpression of GhCDPK16 in cotton and Arabidopsis improved thermotolerance by lowering ROS compound buildup. Under heat stress, GhCDPK16 transgenic lines upregulated heat-inducible genes GhHSP70, GHSP17.3, and GhGR1, as demonstrated by qRT-PCR analysis. Contrarily, GhCDPK16 knockout lines in cotton exhibited an increase in ROS accumulation. Furthermore, antioxidant enzyme activity was dramatically boosted in the GhCDPK16-ox transgenic lines. Conclusions The collective findings demonstrated that GhCDPK16 could be a viable gene to enhance thermotolerance in cotton and, therefore, a potential candidate gene for improving heat tolerance in cotton.

Background/Objectives: Glomerular hyperfiltration has been considered an early marker of kidney injury in prediabetes and prehypertension. Heavy alcohol consumption remains highly prevalent and is considered a major public health problem worldwide. The degree of glomerular hyperfiltration associated with alcohol consumption remains unclear. Subjects/Methods: This study was conducted in three communities in China. A total of 15 390 participants (5396 males and 9994 females) aged 40-65 years were included in the study. Glomerular hyperfiltration was defined as estimated glomerular filtration rate >97.5th percentile value of the total population. Results: Current drinkers had a 1.51 times higher risk for developing renal hyperfiltration (RHF) as compared with never drinkers, adjusted for age, body mass index, smoking status, systolic and diastolic blood pressure, physical activity and the levels of fasting glucose, triglyceride, total cholesterol, low-density lipoprotein and high-density lipoprotein. Furthermore, heavy alcohol consumption of >210 g per week was associated with an elevated risk for RHF in a dose-dependent manner among male current drinkers. Conclusions: In middle-aged Chinese men, heavy alcohol intake was associated with an elevated risk for RHF. On the other hand, former drinkers or light-moderate alcohol intake did not show any increased risks for these conditions., Author(s): M Lin [sup.1] , Q Su [sup.2] , H Huang [sup.3] , Y Zheng [sup.3] , J Wen [sup.3] , J Yao [sup.3] , J Liang [sup.3] , L [...]

Abstract The introduction of antiferroelectric filler AgNbO3 into the polyvinylidene fluoride (PVDF) polymer matrix enhances its energy storage properties of PVDF. However, AgNbO3 and PVDF matrix are incompatible due to their distinct physical and chemical properties, resulting in poor compatibility between the two phases. Surface modification enhances the large difference in physical and chemical properties between the filler and the polymer matrix, and improves the compatibility between the two phases. Silane coupling agents (KH550, KH560), dopamine (DA), and grafted poly(methyl methacrylate) (PMMA) were used to modify the surface of AgNbO3 particles, and the effects of different surface modification methods on the energy storage performance of the composites were studied. The PVDF matrix was introduced with 0.3 wt% AgNbO3 particle filler. The results showed that the amino group in KH550 had the strongest binding with PVDF. The ester group in PMMA has a strong binding with PVDF. The epoxy group in KH560 has a weak binding with PVDF, while the amino group in DA has the worst binding with PVDF. The compatibility of the two phases in AgNbO3@KH550/PVDF composites is the best, and the charge distribution on the surface of the filler is uniform. Under an electric field of 350 kV/mm, the energy storage density is 8.48 J/cm3.

Abstract The authors investigate the effects of nanofillers with varying band‐gap energies on the space charge properties, breakdown field strength, and bulk resistivity of epoxy (EP)‐based composites. Additionally, the molecular orbital distribution of both the epoxy resin and nanofillers were examined through density functional theory. Experimental results indicate that the space charge accumulation within silicon dioxide/EP and germanium oxide/EP is reduced, leading to a more uniformly distributed electric field intensity within the specimen when compared to epoxy. As a result, both materials exhibit improved AC breakdown field strength and volume resistivity. Conversely, the amount of charge accumulated within tin dioxide/EP is higher, resulting in lower breakdown field strength than epoxy. The lowest unoccupied molecular orbital and the highest occupied molecular orbital energy level differences between epoxy and nanofillers introduce electron traps and hole traps at the interface, forming interfacial traps that affect the space charge distribution within the specimen, as well as the trap energy levels within the material. From the experimental results, shallow traps promote space charge accumulation and reduce the breakdown field strength, while deep traps have the opposite effect.

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer. Herein, a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell. The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation, self-renewal, migration, and invasion of lung cancer cell lines at low micromolar concentrations. The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays. In the H460R231Q OE cell-derived xenograft (CDX) model, 37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks (TGI = 54.38%), without obvious toxicities. A pharmacokinetic study revealed that 37 possessed tolerable properties (t1/2 = 1.93 ± 0.91 h, F = 97.2%) after intraperitoneal administration in rats. Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway. Moreover, analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the “Induced-fit” allosteric model in favor to the discovery of potent DOT1L candidates.

Abstract Background Conventional single-energy CT can only provide a raw estimation of electron density (ED) for dose calculation by developing a calibration curve that simply maps the HU values to ED values through their correlations. Spectral CT, also known as dual-energy CT (DECT) or multi-energy CT, can generate a series of quantitative maps, such as ED maps. Using spectral CT for radiotherapy simulations can directly acquire ED information without developing specific calibration curves. The purpose of this study is to assess the feasibility of utilizing electron density (ED) maps generated by a novel dual-layer detector spectral CT simulator for dose calculation in radiotherapy treatment plans. Methods 30 patients from head&neck, chest, and pelvic treatment sites were selected retrospectively, and all of them underwent spectral CT simulation. Treatment plans based on conventional CT images were transplanted to ED maps with the same structure set, including planning target volume (PTV) and organs at risk (OARs), and the dose distributions were then recalculated. The differences in dose and volume histogram (DVH) parameters of the PTV and OARs between the two types of plans were analyzed and compared. Besides, gamma analysis between these plans was performed by using MEPHYSTO Navigator software. Results In terms of PTV, the homogeneity index (HI), gradient index (GI), D2%, D98%, and Dmean showed no significant difference between conventional plans and ED plans. For OARs, statistically significant differences were observed in parotids D50%, brainstem in head&neck plans, spinal cord in chest plans and rectum D50% in pelvic plans, whereas the variance remained minor. For the rest, the DVH parameters exhibited no significant difference between conventional plans and ED plans. All of the mean gamma passing rates (GPRs) of gamma analysis were higher than 90%. Conclusion Compared to conventional treatment plans relying on CT images, plans utilizing ED maps demonstrated similar dosimetric quality. However, the latter approach enables direct utilization in dose calculation without the requirements of establishing and selecting a specific Hounsfield unit (HU) to ED calibration curve, providing an advantage in clinical applications.

The underwater 10CrNi3MoV high-strength low-alloy steel thin-walled part with forming quality up to in-air laser deposition quality was successfully manufactured for the first time. The influencing mechanisms of complicated thermal history and water environment on microstructure evolution and mechanical properties of thin-walled part were researched. Due to austenitization and interlocking effect, the microstructure in the bottom, middle and top (below the 56th layer) areas of underwater sample and the middle area of in-air sample were composed of fine grain ferrite and granular bainite. With the increase of building height, the heat accumulation effect of underwater sample enhanced, resulting in small grain size (GS), high dislocation density, strong solution strengthening effect and low maximum texture strength at the bottom area, while the high proportion of high-angle grain boundaries (HAGBs) at the top area. These resulted in the greatest tensile strength (714 MPa) and microhardness (232 HV) at the bottom area and the highest elongation (11%) at the top area. Due to the cooling effect of water environment, the proportion of HAGBs reduced and there were oxides in fracture. As a result, the horizontal elongation of underwater sample was about 90.9% of in-air sample. Additionally, the GS reduced, and the dislocation density and solution strengthening effect increased, so the microhardness of underwater sample was slightly higher than that of in-air sample. However, due to some microscopic defects, the horizontal and vertical tensile strength of underwater sample were about 97.6% and 90.7% of in-air sample.

Abstract Objectives The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. Methods Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. Results The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. Conclusions The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

Abstract Steering on the intrinsic active site of an electrode material is essential for efficient electrochemical biomass upgrading to valuable chemicals with high selectivity. Herein, we show that an in-situ surface reconstruction of a two-dimensional layered CdPS 3 nanosheet electrocatalyst, triggered by electrolyte, facilitates efficient 5-hydroxymethylfurfural (HMF) hydrogenation to 2,5-bis(hydroxymethyl)furan (BHMF) under ambient condition. The in-situ Raman spectroscopy and comprehensive post-mortem catalyst characterizations evidence the construction of a surface-bounded CdS layer on CdPS3 to form CdPS 3 /CdS heterostructure. This electrocatalyst demonstrates promising catalytic activity, achieving a Faradaic efficiency for BHMF reaching 91.3 ± 2.3 % and a yield of 4.96 ± 0.16 mg/h at − 0.7 V versus reversible hydrogen electrode. Density functional theory calculations reveal that the in-situ generated CdPS 3 /CdS interface plays a pivotal role in optimizing the adsorption of HMF* and H* intermediate, thus facilitating the HMF hydrogenation process. Furthermore, the reconstructed CdPS 3 /CdS heterostructure cathode, when coupled with MnCo 2 O 4.5 anode, enables simultaneous BHMF and formate synthesis from HMF and glycerol substrates with high efficiency.

The therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) in myocardial infarction (MI) is hindered by poor cell survival. This study explored the role of N6-methyladenosine (m6A) regulation, specifically YTHDC1, in improving BMSC transplantation for MI. By screening m6A-related regulators in hypoxia and serum deprivation (HSD)-induced BMSC apoptosis, YTHDC1 was found to be downregulated. Overexpression of Ythdc1 in BMSCs reduced apoptosis markers, reactive oxygen species (ROS) release, and improved cell survival under HSD conditions. Conversely, Ythdc1 knockdown enhanced apoptosis. In rat MI models, transplantation of Ythdc1-overexpressing BMSCs improved cardiac function and reduced myocardial fibrosis. Mechanistically, YTHDC1 interacts with nuclear factor kappa B (NF-κB) inhibitor-alpha mRNA, suggesting its involvement in BMSC survival pathways. This study identifies YTHDC1 as a potential target to enhance BMSC efficacy in MI therapy.

Incorporating authentic tactile interactions into virtual environments presents a notable challenge for the emerging development of soft robotic metamaterials. In this study, a vision‐based approach is introduced to learning proprioceptive interactions by simultaneously reconstructing the shape and touch of a soft robotic metamaterial (SRM) during physical engagements. The SRM design is optimized to the size of a finger with enhanced adaptability in 3D interactions while incorporating a see‐through viewing field inside, which can be visually captured by a miniature camera underneath to provide a rich set of image features for touch digitization. Employing constrained geometric optimization, the proprioceptive process with aggregated multi‐handles is modeled. This approach facilitates real‐time, precise, and realistic estimations of the finger's mesh deformation within a virtual environment. Herein, a data‐driven learning model is also proposed to estimate touch positions, achieving reliable results with impressive R2 scores of 0.9681, 0.9415, and 0.9541 along the x, y, and z axes. Furthermore, the robust performance of the proposed methods in touch‐based human–cybernetic interfaces and human–robot collaborative grasping is demonstrated. In this study, the door is opened to future applications in touch‐based digital twin interactions through vision‐based soft proprioception.

Background Long‐QT syndrome is a primary cardiac ion channelopathy predisposing a patient to ventricular arrhythmia through delayed repolarization on the resting ECG. We aimed to establish a patient‐specific, human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes model of long‐QT syndrome type 3 (LQT3) using clustered regularly interspaced palindromic repeats (CRISPR/Cas9), for disease modeling and drug challenge. Methods and Results HiPSCs were generated from a patient with LQT3 harboring an SCN5A pathogenic variant (c.1231G>A; p.Val411Met), and an unrelated healthy control. The same SCN5A pathogenic variant was engineered into the background healthy control hiPSCs via CRISPR/Cas9 gene editing to generate a second disease model of LQT3 for comparison with an isogenic control. All 3 hiPSC lines were differentiated into cardiomyocytes. Both the patient‐derived LQT3 (SCN5A+/−) and genetically engineered LQT3 (SCN5A+/−) hiPSC‐derived cardiomyocytes showed significantly prolonged cardiomyocyte repolarization compared with the healthy control. Mexiletine, a cardiac voltage‐gated sodium channel (NaV1.5) blocker, shortened repolarization in both patient‐derived LQT3 and genetically engineered LQT3 hiPSC‐derived cardiomyocytes, but had no effect in the control. Notably, calcium channel blockers nifedipine and verapamil showed a dose‐dependent shortening of repolarization, rescuing the phenotype. Additionally, therapeutic drugs known to prolong the corrected QT in humans (ondansetron, clarithromycin, and sotalol) demonstrated this effect in vitro, but the LQT3 clones were not more disproportionately affected compared with the control. Conclusions We demonstrated that patient‐derived and genetically engineered LQT3 hiPSC‐derived cardiomyocytes faithfully recapitulate pathologic characteristics of LQT3. The clinical significance of such an in vitro model is in the exploration of novel therapeutic strategies, stratifying drug adverse reaction risk and potentially facilitating a more targeted, patient‐specific approach in high‐risk patients with LQT3.

ObjectiveInvestigating the causal connection that exists between inflammatory bowel disease (IBD) and hypertension (HT). To gain a deeper insight into the correlation among IBD, gut microbiota, and HT, we conducted a two-step, two-sample Mendelian randomization study.MethodsAn investigation of genome-wide association study (GWAS) summary-level data was utilized to conduct a two-sample Mendelian randomization (MR) analysis of genetically predicted inflammatory bowel disease: (12,882cases, 21,770controls) on Systolic/Diastolic blood pressure (N = 2,564). Subsequently, two-step MR analyses revealed that the relationship between IBD and SBP was partly mediated by Faecalicatena glycyrrhizinilyticum. The robustness of the findings was confirmed through several sensitivity assessments.ResultsThis MR study showed that increase in genetically predicted IBD was associated with higher risk of genetically predicted SBP (OR: 1.08, 95% CI: 1.01–1.16, P

Background: Plantar fasciitis (PF) is one of the most common causes of plantar heel pain, and previous studies found that acupuncture is effective for relieving pain in patients with PF. Nevertheless, the impact of different sessions of electroacupuncture on PF has not been investigated through randomized, controlled trials. Methods/design: This is a two parallel-group, assessor-blinded, randomized controlled trial, consisting of a four-week treatment phase followed by a 12-week follow-up. Eighty patients with chronic PF will be recruited and randomly allocated to receive 12 (three sessions per week; the multiple electroacupuncture weekly treatment group (group M)) or four (one session per week; single electroacupuncture weekly treatment group (group S)) sessions of electroacupuncture treatment in a 1:1 ratio. The primary outcome to be studied is the response rate, defined as a minimum of 50 % improvement in most severe pain intensity with first steps in the morning, compared with baseline. We will perform all analyses based on the intention-to-treat principle, with differences considered significant when the P value

Abstract Cistrome‐wide association studies (CWAS) are pivotal for identifying genetic determinants of diseases by correlating genetically regulated cistrome states with phenotypes. Traditional CWAS typically develops a model based on cistrome and genotype data to associate predicted cistrome states with phenotypes. The random effect cistrome‐wide association study (RECWAS), reevaluates the necessity of cistrome state prediction in CWAS. RECWAS utilizes either a linear model or marginal effect for initial feature selection, followed by kernel‐based feature aggregation for association testing is introduced. Through simulations and analysis of prostate cancer data, a thorough evaluation of CWAS and RECWAS is conducted. The results suggest that RECWAS offers improved power compared to traditional CWAS, identifying additional genomic regions associated with prostate cancer. CWAS identified 102 significant regions, while RECWAS found 50 additional significant regions compared to CWAS, many of which are validated. Validation encompassed a range of biological evidence, including risk signals from the GWAS catalog, susceptibility genes from the DisGeNET database, and enhancer‐domain scores. RECWAS consistently demonstrated improved performance over traditional CWAS in identifying genomic regions associated with prostate cancer. These findings demonstrate the benefits of incorporating kernel methods into CWAS and provide new insights for genetic discovery in complex diseases.

IntroductionThis double-blind, placebo-controlled, randomized (1:1) clinical trial was conducted at the West China Hospital, Sichuan University, from March to September 2017.MethodsEligible participants included adults aged 18 years and older, living in the community, diagnosed with type 2 Diabetes Mellitus according to ADA guidelines, capable of self-managing their diabetes, and able to visit the study site for follow-up. The intervention group received 25 ml of a probiotic beverage containing with over 10^8 CFU/mL of Lactobacillus, administered four times daily. An equal volume of inactivated Lactobacillus was administered to the control group and the control group was administered the same volume of inactivated Lactobacillus. This study aimed to evaluate the effectiveness of probiotics on glycemic control and other diabetes-related outcomes in patients with type 2 diabetes patients. The primary outcomes were changes in HbA1c and FBG levels post-intervention. Investigators, participants, and study site personnel were blinded to the treatment allocation until the conclusion of the study. This double-blind, randomized, placebo-controlled clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR-POR-17010850).ResultsOf the 490 participants screened, 213 were randomized to either the probiotics group (n = 103) or the placebo group (n = 110). After 16 weeks of follow-up, the probiotic group showed reductions in HbA1c [-0.44 (-0.66 to -0.22)] and FBG [-0.97 (-1.49 to 0.46)] post-intervention, similar to the placebo group with reductions in HbA1c [-0.33 (-0.52 to -0.15)] and FBG [-0.90 (-1.32 to -0.47)], but these changes were not statistically significant in PP and ITT analyses (P>0.05). Adverse events were similarly distributed among groups, indicating comparable safety profiles.DiscussionOverall, 16-week probiotic supplementation showed no beneficial effects on glycemic control, lipid profiles, or weight.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=18421, identifier ChiCTR-POR-17010850.

The transient receptor potential vanilloid 1 (TRPV1) channel plays a dual role in peripheral neuropathic pain (NeuP) by acting as a “pain switch” through its sensitization and desensitization. Hyperalgesia, commonly resulting from tissue injury or inflammation, involves the sensitization of TRPV1 channels, which modulates sensory transmission from primary afferent nociceptors to spinal dorsal horn neurons. In chemotherapy-induced peripheral neuropathy (CIPN), TRPV1 is implicated in neuropathic pain mechanisms due to its interaction with ion channels, neurotransmitter signaling, and oxidative stress. Sensitization of TRPV1 in dorsal root ganglion neurons contributes to CIPN development, and inhibition of TRPV1 channels can reduce chemotherapy-induced mechanical hypersensitivity. In diabetic peripheral neuropathy (DPN), TRPV1 is involved in pain modulation through pathways including reactive oxygen species and cytokine production. TRPV1’s interaction with TRPA1 channels further influences chronic pain onset and progression. Therapeutically, capsaicin, a TRPV1 agonist, can induce analgesia through receptor desensitization, while TRPV1 antagonists and siRNA targeting TRPV1 show promise in preclinical studies. Cannabinoid modulation of TRPV1 provides another potential pathway for alleviating neuropathic pain. This review summarizes recent preclinical research on TRPV1 in association with peripheral NeuP.

Summary: The traditional parameter adjustment design makes it difficult to effectively regulate the acoustic insulation performance of periodic sandwich structures while meeting the lightweight and mechanical stiffness requirements. A dynamic three-field floating projection topology optimization (FPTO) method for periodic structures is proposed to meet the optimization requirements of low-noise and high-stiffness performance of lightweight periodic sandwich structures. The sound transmission loss is taken as the optimization objective, and the lightweight volume and mechanical stiffness performance are taken as the multiple constraints. The results show that a smooth topology configuration with superior sound insulation performance, high stiffness, and a freely customizable number of periodic cores can be obtained via the proposed method. The accuracy and effectiveness of the presented method are verified via 3D printing technology and impedance tube sound insulation experiments, providing an important reference for the optimal design of lightweight composite structures for vibration and noise reduction in transportation equipment.

IntroductionFruit color significantly influences the quality of horticultural crops, which affects phytochemical diversity and consumer preferences. Despite its importance, the genetic basis of the white-colored fruit in tomatoes remains poorly understood.MethodsIn this study, we demonstrate that white-fleshed tomato varieties accumulate fewer carotenoids than yellow-fleshed varieties. We developed various segregating populations by hybridizing red, yellow, and white fruit tomato cultivars.ResultsGenetic analysis revealed that the white fruit color trait is controlled by a single gene that dominates both red and yellow fruits. Bulk segregant RNA sequencing provided a preliminary map of a 3.17 Mb region on chromosome 3 associated with the white color trait. Based on kompetitive allele-specific PCR (KASP) markers, we narrowed the candidate gene region to 819 kb. Within this region, we identified a 4906-bp sequence absence variation near Phytoene Synthase 1 (SlPSY1) specific to white-colored tomatoes. Genotyping of the progeny and natural populations using a single nucleotide polymorphism adjacent to this absence of variation confirmed its key role in white fruit formation.DiscussionCollectively, our findings provide insights into white fruit trait formation in tomatoes, enabling tomato breeders to precisely introduce white fruit traits for commercial exploitation.

Positive interspecific interactions in resource capture and soil property modification benefit the establishment of mixed plantations, contingent on environmental conditions. However, primary species frequently reject companion tree species frequently arises in forest management practices. To understand this contradiction, we investigated the effects of five planting patterns involving two local companion tree species (Phoebe chekiangensis and Torreya grandis) and Phyllostachys edulis on the soil nitrogen (N) and phosphorus (P) content, enzyme activities, net N mineralization rates, microbial composition, fungal functional groups, and the AMO gene abundance under both shade and full light conditions using a pot experiment. Under the full light condition, altered soil properties were predominantly influenced by interspecific interaction compared to intraspecific interactions, leading to an overall enhancement in nutrient availability and enzymatic activities. Under the shade condition, mixing with P. edulis similarly facilitated increased NH4+-N content, ammonification rate, and urease activity. However, P. edulis significantly decreased ammonia monooxygenase and its encoding gene, as evidence by the unbalanced ratio of net ammonification to net nitrification (2.2-fold) under the shade condition, resulting in high NH4+-N/NO3–-N ratios. Additionally, the shade condition induced soil microbial communities in the mixture to resemble those of monocultured dominant species (P. edulis). Our findings also indicated that specific plant-fungal associations in companion species were disrupted when intercropped with P. edulis. Therefore, this study highlights how the performance of companion species, linked to soil NH4+-N/NO3–-N ratios and plant-fungal associations, leads to their suppression by P. edulis under shade conditions.

This study aims to experimentally and numerically explore the bearing capacity of windshield glass for rail vehicles under projectile impact by gravel along the railway. The gravel particle sizes, ranging from 0.5 to 10 mm, were divided into 7 levels, and two conditions were chosen based on loading angles: 90° vertical impact and 45° oblique impact. Multiple gravel impacts were conducted based on the conversion of wind-blown sand flow intensity, analysing the difference in fracture velocity of windshield glass compared with single gravel impact. Finally, a stable 4 kPa wind pressure was applied to the windshield glass, and simultaneous gravel impact was performed. By comparing the impact test results without wind pressure, the weakening effect of wind pressure load on the impact resistance of windshield glass was analysed. Lastly, the dynamic process of projectile penetration and fracture of windshield glass was numerically simulated. This involved studying the crack propagation process and analysing the fracture velocity of windshield glass under projectiles made of different materials. By comparing the simulation and experimental results, the accuracy and reliability of this study were verified. The research results show that the larger the gravel particle size, the lower the chip and fracture velocities of the windshield glass. The chip velocity and fracture velocity of windshield glass under single gravel oblique impact at 45° are higher than those under vertical impact conditions, approximately 1.2 times and 1.13 times higher, respectively. Moreover, the fracture velocities under 3 and 6 gravel impacts are approximately 12 % and 20 % lower, respectively, compared to single gravel impact condition. Additionally, stress oscillations were observed to occur due to the cyclic process of stress accumulation, energy release through crack propagation, stress decline, and further stress accumulation. This was observed by tracking the stress state near the crack tip of the windshield glass.

Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500 μM, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5 % ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5 % ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.

The significant progress in additive manufacturing has resulted in the development of well-engineered microstructures with innovative topological configurations, showcasing exceptional performance across diverse fields. Topology optimization is widely recognized as an advanced design tool that provides engineers with new insights for creating lightweight structures. As integration devices continue to trend towards miniaturization, the size effect in small-scale structures remains a persistent challenge. The absence of characteristic parameters to describe this size effect hinders proper explanation through traditional multiscale topology optimization based on classical mechanics. Therefore, we propose a size-dependent topology optimization framework for concurrent multiscale design involving multiple-phase materials. The modified couple stress theory is proposed to account for the size effect in small-scale structures. The numerical findings suggest that the size effect is significantly influenced by the ratio of elastic modulus, volume fraction, and width-to-length ratio of the representative volume element as its characteristic size approaches the length of the material. These results highlight the importance of considering size-dependent effects in topology optimization for multiscale design and provide valuable insights for engineers and researchers in this field.

To explain the moisture adsorption properties and improve the package material of polydextrose product, the adsorption and desorption isotherms of five domestic samples with initial moisture content (IMC) of 1.01%~4.89% were determined in this study in the range of 20~35 ℃ and ERH10%~90% using a dynamic water sorption analyzer. The adsorption and desorption isotherms were sigmoidal-shaped curves, and there was a hysteresis between desorption isotherm and the adsorption isotherm when ERH was less than 80%. Because polydextrose is an amorphous phase powder, we assumed that the water adsorption process of polydextrose was an equilibrium that existed among the vapor phase, the liquid phase (polylayer adsorption) and the solid solution (monolayer adsorption), and the adsorptive and desorptive sigmoidal-shaped isotherms can be de-convolved into a monolayer (Mh) and a polylayer component (Md) in accordance with Hailwood- Horrobin (HH) model. The polylayer water content of adsorption and desorption showed a sigmoidal increase with increasing ERH. The monolayer water content of desorption remained constant with increasing ERH, while that of the adsorption increased slowly for samples a1 to a4 with IMC 4.87% to 2.35% and decreased almost linearly for sample a5 with IMC 1.01%. As the IMCs of the samples decreased, the molecular weight of the polymer at the sorption site was maximum for sample a1 and minimum for sample a5. Although the FTIR showed the smallest intensity of hydroxyl group (3 416 cm–1) and amorphous structural functional group (1 027 cm–1) for a5 sample, a5 sample had the largest moisture absorption rate. These results suggested that, for the lower moisture content of polydextrose samples processed by different processes, their adsorptive monolayer water content seemed to decrease almost linearly with an increase of ERH. However their adsorptive polylayer water content sigmoidally increased with an increase of ERH, and their moisture absorption rate and hygroscopic capacity increased.

Abstract Background The objective of this research is to investigate the dynamic developmental trends between Age-Friendly Environments (AFE) and healthy aging in the Chinese population. Methods This study focused on a sample of 11,770 participants from the CHARLS and utilized the ATHLOS Healthy Aging Index to assess the level of healthy aging among the Chinese population. Linear mixed model (LMM) was used to explore the relationship between AFE and healthy aging. Furthermore, a cross-lagged panel model (CLPM) and a random-intercept cross-lagged panel model (RI-CLPM) were used to examine the dynamic developmental trends of healthy aging, taking into account both Between-Person effects and Within-Person effects. Results The results from LMM showed a positive correlation between AFE and healthy aging (β = 0.087, p

Abstract Background Parkinson’s disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD. Methods This protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded. Discussion This study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting. Trial registration Chinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.

Abstract Purpose The corneal cap thickness is a vital parameter designed in small incision lenticule extraction (SMILE). The purpose was to investigate the changes in corneal subbasal nerve plexus (SNP) and stromal cells with different cap thicknesses and evaluate the optimized design for the surgery. Methods In this prospective, comparative, non-randomized study, a total of 108 eyes of 54 patients who underwent SMILE were allocated into three groups with different corneal cap thicknesses (110 μm, 120 μm or 130 μm group). The SNP and stromal cell morphological changes obtained from in vivo corneal confocal microscopy (IVCCM) along with their refractive outcomes were collected at 1 week, 1 month, 3 months and 6 months postoperatively. One-way analysis of variance (ANOVA) was used to compare the parameters among the three groups. Results The SNPs in the three groups all decreased after surgery and revealed a gradual increasing trend during the 6-month follow-up. The values of the quantitative nerve metrics were significantly lower in the 110 μm group than in the 120 μm and 130 μm groups, especially at 1 week postoperatively. No difference was detected between the 120 μm and 130 μm groups at any time point. Both Langerhans cells and keratocytes were activated after surgery, and the activation was alleviated during the follow-up. Conclusions The SMILE surgeries with 110 μm, 120 μm or 130 μm cap thickness design achieved good efficacy, safety, accuracy and stability for moderate to high myopic correction while the thicker corneal cap was more beneficial for corneal nerve regeneration.