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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 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.

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.

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 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.

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 The increasing incidence of hyperlipidemia is a serious threat to public health. The development of effective and safe lipid‐lowering drugs with few side effects is necessary. The purpose of this study was to assess the lipid‐lowering activity of Sanghuangporus vaninii extract (SVE) in rat experiments and reveal the molecular mechanism by transcriptome analysis. Hyperlipidemia was induced in the animals using a high‐fat diet for 4 weeks. At the end of the 4th week, hyperlipidemic rats were assigned into two control groups (model and positive simvastatin control) and three treatment groups that received SVE at 200, 400, or 800 mg kg−1 day−1 for another 4 weeks. A last control group comprised normal chow‐fed rats. At the end of the 8th week, rats were sacrificed and lipid serum levels, histopathology, and liver transcriptome profiles were determined. SVE was demonstrated to relieve the lipid disorder and improve histopathological liver changes in a dose‐dependent manner. The transcriptomic analysis identified changes in hepatocyte gene activity for major pathways including steroid biosynthesis, bile secretion, cholesterol metabolism, AMPK signaling, thyroid hormone signaling, and glucagon signaling. The changed expression of crucial genes in the different groups was confirmed by qPCR. Collectively, this study revealed that SVE could relieve hyperlipidemia in rats, the molecular mechanism might be to promote the metabolism of lipids and the excretion of cholesterol, inhibit the biosynthesis of cholesterol by activating the AMPK signaling pathway, the thyroid hormone signaling pathway, and the glucagon signaling pathway.

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.

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.

Abstract Background During the pandemic, a notable increase in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), conditions that warrant emergent management, was reported. We aimed to investigate the trend of DKA‐ and HHS‐related mortality and excess deaths during the pandemic. Methods Annual age‐standardized mortality rates related to DKA and HHS between 2006 and 2021 were estimated using a nationwide database. Forecast analyses based on prepandemic data were conducted to predict the mortality rates during the pandemic. Excess mortality rates were calculated by comparing the observed versus predicted mortality rates. Subgroup analyses of demographic factors were performed. Results There were 71 575 DKA‐related deaths and 8618 HHS‐related deaths documented during 2006–2021. DKA, which showed a steady increase before the pandemic, demonstrated a pronounced excess mortality during the pandemic (36.91% in 2020 and 46.58% in 2021) with an annual percentage change (APC) of 29.4% (95% CI: 16.0%–44.0%). Although HHS incurred a downward trend during 2006–2019, the excess deaths in 2020 (40.60%) and 2021 (56.64%) were profound. Pediatric decedents exhibited the highest excess mortality. More than half of the excess deaths due to DKA were coronavirus disease 2019 (COVID‐19) related (51.3% in 2020 and 63.4% in 2021), whereas only less than a quarter of excess deaths due to HHS were COVID‐19 related. A widened racial/ethnic disparity was observed, and females exhibited higher excess mortality than males. Conclusions The DKA‐ and HHS‐related excess mortality during the pandemic and relevant disparities emphasize the urgent need for targeted strategies to mitigate the escalated risk in these populations during public health crises.

Background: In-stent neoatherosclerosis (ISNA) is identified as the primary cause of in-stent restenosis (ISR). The systemic immune inflammation index (SII), shows promise for predicting post-percutaneous coronary intervention (PCI) adverse cardiovascular events and is associated with coronary stenosis severity; however, its specific relationship with ISNA remains unclear. This study aimed to investigate the association between the SII and ISNA after drug-eluting stent (DES) implantation. Methods: This cross-sectional study included 195 participants with 195 ISR lesions who underwent optical coherence tomography (OCT)-guided PCI between August 2018 and October 2022. Participants were categorized based on the SII levels into Tertile 1 (SII 751.94, n = 65). Baseline Clinical, angiographic, and OCT characteristics were analyzed. The association of the SII with ISNA and thin-fibroatheroma (TCFA) was investigated using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of the SII in detecting ISNA and TCFA. Results: Patients in Tertile 3 had a significantly higher incidences of ISNA and TCFA than did those in Tertile 1. Logistic regression analysis revealed the SII is an independent indicator of ISNA and TCFA in ISR lesions (P = 0.045 and P = 0.002, respectively). The areas under the ROC curves for ISNA and TCFA were 0.611 and 0.671, respectively. Conclusion: The SII is associated with ISNA and TCFA and may serve as an independent indicator in patients with ISR.

Background: The role of interleukins in sarcopenia development has been acknowledged, yet the specifics of their involvement remain to be fully understood. This study aimed to explore alterations in interleukin levels among sarcopenia patients. Methods: Searches were conducted in Embase, Medline, and the Cochrane Library for literature published up to May 2023. Eligible observational studies with a diagnosis of sarcopenia were included. The Newcastle–Ottawa Scale was utilized for quality assessment. For data synthesis, a random-effects model was used, and the Mantel–Haenszel method was used for pooled estimates. Results: Of the 7685 articles screened, 37 met the inclusion criteria. Statistically significant differences in the levels of IL-1β, IL-6 and IL-10 were detected in sarcopenia patients. Specifically, IL-1β (95 % CI: 0.33 [0.12, 0.54], P

The response of preferential flow to the soil − root − rock fragment systems is essential for understanding the eco-hydrological processes in karst rocky desertification (KRD) areas. In this study, we investigated the soil properties, root, and rock fragment distribution characteristics and preferential flow in this system. Results show that there are differences in the development of preferential flow under five grades of rocky desertification: light rocky desertification (LRD) > potential rocky desertification (PRD) > non-rocky desertification (NRD) > moderate rocky desertification (MRD) > severe rocky desertification (SRD). Different degrees of rocky desertification have facilitating or inhibiting effects on preferential flow. LRD and PRD promote preferential flow with ratio of 6.6 %–9.6 %, while MRD and SRD inhibit preferential flow with ratio of 4.2 %–6.7 %. The preferential flow is simultaneously influenced by the components of soil − root − rock fragment systems. Root system indicators (i.e., root biomass, root bulk density, and root length density) generally decrease as grades of rocky desertification increase. The surface outcrops density, rock fragment density, and volume fraction tend to increase with grades of rocky desertification. A principal components analysis found that preferential flow of MRD and SRD is highly influenced by rock fragments, while LRD is more driven by root systems and soil properties. PRD is averagely influenced by the combination. These findings suggest that appropriate plant and rock fragment ratios can effectively avoid water loss in the form of preferential flow and more attention should be paid to the ecological problems of LRD and PRD areas.

Abstract Bioinspired micropillar adhesives have shown broad application prospects in space capture and docking, due to their strong adhesion, good environmental adaptability, and reusability. However, when performing space missions, unavoidable contact collision with target objects may cause large deformation of the micropillars, resulting in the loss of adhesion ability. This study reports a novel micropillar adhesive through the in‐plane combination of micropillars (IPCM) with different aspect ratios, consisting of small pillars for retaining strong adhesion and large ones for resisting overload‐induced adhesion failure. It is demonstrated that the IPCM array can still maintain 85% of the adhesion peak after static large deformation compared to a general micropillar array composed of the same pillars. The impact of element size and layout of the IPCM, as well as detachment velocity on adhesion performance under high preload is discussed. Furthermore, finite element contact analysis qualitatively reproduces the experimentally observed micropillar deformations and attributes the overload‐induced adhesion failure to the redistribution of surface normal stress. Finally, the potential application of the IPCM in dynamic capture is demonstrated on different objects. The proposed IPCM opens up new design concepts for practical applications of bioinspired adhesives in space capture and docking.

Abstract Since the origin of life, temperatures on earth have fluctuated both on short and long time scales. How such changes affect the rate at which Darwinian evolution can bring forth new phenotypes remains unclear. On the one hand, high temperature may accelerate phenotypic evolution because it accelerates most biological processes. On the other hand, it may slow phenotypic evolution, because proteins are usually less stable at high temperatures and therefore less evolvable. Here, to test these hypotheses experimentally, we evolved a green fluorescent protein in E. coli towards the new phenotype of yellow fluorescence at different temperatures. Yellow fluorescence evolved most slowly at high temperature and most rapidly at low temperature, in contradiction to the first hypothesis. Using high-throughput population sequencing, protein engineering, and biochemical assays, we determined that this is due to the protein-destabilizing effect of neofunctionalizing mutations. Destabilization is highly detrimental at high temperature, where neofunctionalizing mutations cannot be tolerated. Their detrimental effects can be mitigated through excess stability at low temperature, leading to accelerated adaptive evolution. By modifying protein folding stability, temperature alters the accessibility of mutational paths towards high-fitness genotypes. Our observations have broad implications for our understanding of how temperature changes affect evolutionary adaptations and innovations.

Abstract Physical factors in the cellular microenvironment have critical effects on stem cell differentiation. The utilization of physical factors to promote the osteogenic differentiation of stem cells has been established as a new strategy for developing bone tissue engineering scaffolds. In this context, scaffolds with multiscale anisotropy are considered to possess biomimetic properties, which are advantageous for their biological performance. In the present study, a novel magnetic anisotropic hydrogel (MAH) with magnetic and topographic anisotropy was designed by combining static magnetic field-induced magnetic nanomaterials and a hydrogel. In in vitro studies, the MAH exhibited excellent biocompatibility and osteogenic bioactivity. The alkaline phosphatase activity and the expression of osteogenic-related genes and proteins induced by the MAH were greater than those induced by the pure PEGDA–GelMA hydrogel (PGH) and the magnetic isotropic hydrogel (MIH). In addition, the present study revealed that the dual anisotropic properties of the MAH activated the NOTCH1/2 pathway by upregulating SNHG5 and downstream SIRT6, which modulates the level of NOTCH1/2 by antagonizing DNMT1 protein stability, ultimately inducing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, the MAH, MIH, and PGH were tested for in vivo bone regeneration in rabbits with femur defects, and the results demonstrated that the MAH effectively stimulated bone regeneration. Taken together, these findings suggest that this magnetically and topographically anisotropic biomimetic hydrogel might be a promising candidate for application in the field of bone tissue regeneration.

For the first time, the underwater wet wire and arc directed energy deposition (UW-WADED) multi-tracks deposition layers with favorable morphology were obtained. The forming characteristics of single-track UW-WADED were determined through response surface methodology. It was found that the power function curve provided the best fit for the profile of single-track UW-WADED owing to its changing plumpness value. Subsequently, the formation characteristics of multi-track UW-WADED with varying intervals were investigated. The deposition layer exhibited the flattest surface and the least root-mean-square deviation, measuring 321.79 μm when the interval was 8 mm. The dynamic process of UW-WADED was unveiled through X-ray high-speed images, leading to the formulation of UW-WADED droplet force model. As the arc bubble expanded, the horizontal component of the air drag force pointed to the opposite side of the molten pool and was the principal factor for the droplets to become spatters in UW-WADED. The mechanism of the defect formation was also revealed. The accumulation of the molten pool on the previous deposition layer coupled with the downflow of the molten slag were the inducers of slag inclusion defect while the exorbitant molten pool increased the likelihood of molten pool explosion and subsequent spatter formation.