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Indica and Japonica rice were selected as test materials to investigate the difference formation in textural perception, particle size, water content, leakage solid content and reducing sugar content of rice bolus during chewing process were analyzed by using in vivo oral masticatory properties as a reference and setting salivary addition amounts, chewing times in vitro. The results showed that the three types of rice were similar in composition, but their gelatinization characteristics and crystalline structures were different. Monitoring the dynamic textural perception of rice, it was found that the force worked on rice decreased from 44~66 N to 20~21 N, Daohuaxiang No.2 rice had a higher chewiness and adhesiveness, while Yexiangyoulisi rice had a lower adhesiveness and loose texture perception during in vitro chewing. Through analyzing the characteristics of rice bolus in simulated chewing process, results indicated that the moisture content of rice bolus of Yexiangyoulisi rice increased by 1.84%, significantly higher than the other Japonica rice (P

Picture fuzzy sets with four-dimensional features are widely used in decision-making as a mathematical tool because they can capture the uncertainty of data. However, the methods and techniques based on matrix theory are difficult to solve the decision problem involving high-dimensional data in a picture fuzzy setting. Therefore, operators that can identify high-dimensional data in a picture fuzzy environment are proposed to address this challenge. In this paper, firstly, by integrating the Frank operators into the picture fuzzy tensor, the generalized picture fuzzy Frank weighted arithmetic (GPFFWA) and generalized picture fuzzy Frank weighted geometric (GPFFWG) operators are defined. Their specific expressions are discussed, and the idempotency, order-preservation, boundedness, and commutativity of the proposed operators are also given. Then, combining the GPFFWA and GPFFWG operators, an algorithm is designed to solve the multi-criteria decision-making problem with high-dimensional data features in the picture fuzzy environment. Finally, a numerical example and related analysis demonstrate the effectiveness, superiority, and flexibility of the suggested technique. This work provides new theoretical and methodological support for developing and practicing the decision-making discipline.

Abstract In the evolution landscape of HIV, the coexistence of multiple subtypes has led to new, complex recombinants, posing public health challenges. CRF55_01B, first identified among MSM in Shenzhen, China, has spread rapidly across China. In this study, 47 plasma samples from newly diagnosed HIV-1 CRF55_01B patients in Shenzhen, of which the genotype was only identified by the routine HIV drug resistance test, were collected. Multiple gene regions were acquired using Sanger and next-generation sequencing methods, followed by the phylogenetic reconstruction, recombination breakpoint scanning, Bayesian molecular clock, and the prediction of coreceptors. From 47 samples, we found seven new unique recombinants formed by CRF55_01B and CRF07_BC, which shared similar breakpoints in certain gene regions and primarily utilized CCR5 receptors. All of the most recent common ancestors of subregions for these recombinants were estimated to be later than CRF55_01B and CRF07_BC, potentially suggesting they are the third-generation recombinants formed by CRF55_01B and CRF07_BC as parents. The continuous emergence of new recombinants highlights the increasing complexity of circulating strains in Shenzhen, and also suggests that subtype analysis using partial pol gene may lead to an overestimation of the major subtype strains and an underestimation of new complex HIV recombinants. Consequently, to effectively address and mitigate the complex HIV epidemic, there is an urgent need for expanded monitoring and the optimization of testing methodologies.

Abstract Silicon photonics enables the construction of chip-scale spectrometers, in which those using a single tunable interferometer provide a simple and cost-effective solution. Among various tuning mechanisms, electrostatic MEMS reconfiguration stands out as an ideal candidate, given its high tuning efficiency and ultra-low power consumption. Nonetheless, MEMS devices face significant noise challenges arising from their susceptible minuscule components, adversely impacting spectral resolution. Here, we propose a distinct paradigm of spectrometers through synergizing an easily-fabricated MEMS-reconfigurable low-loss waveguide coupler on a silicon photonic chip and a convolutional autoencoder denoising (CAED) mechanism. The spectrometer offers a 300 nm bandwidth and a reconstruction resolution of 0.3 nm in a noise-free condition. In a noisy environment with a signal-to-noise ratio as low as 30 dB, the reconstruction resolution of the interferograms processed by the CAED exhibits an enhancement from 1.2 to 0.4 nm, approaching the noise-free value. Our technology is envisaged to provide a powerful and cost-effective solution for applications requiring accurate, broadband, and energy-efficient spectral analysis.

The cladding layer of high entropy alloy (HEA), specifically AlCoCrFeNiMo, was fabricated using both continuous wave (CW) and pulse wave (PW) laser techniques, with pulse frequencies set at 0.5 Hz, 5 Hz, 50 Hz, 500 Hz, and 5000 Hz. The microstructure of the cladding layer was analyzed using X-ray diffraction, ultra-depth-of-field metallographic microscopy, and scanning electron microscopy. The wear resistance, corrosion resistance, and combined corrosion-wear resistance of the cladding layer were assessed using friction and wear tests, electrochemical corrosion tests, and corrosion-wear experiments. Additionally, the impact of pulse frequency on the microstructure and properties of HEA cladding layers was examined and compared with CW cladding layers. The research results indicate the presence of body-centered cubic (BCC), σ, and B2 phases in all cladding layers. Compared to the CW cladding layer, the PW cladding layer exhibits smaller grain sizes and a reduced proportion of the σ phase. With an increase in pulse frequency, there is a gradual increase in the proportion of the σ phase and a corresponding evolution in the grain sizes within the HEA cladding structure. Notably, at a specific pulse frequency of 50 Hz, the grain size reaches its minimum. PW cladding exhibited superior wear resistance, corrosion resistance, and corrosion-wear resistance compared to CW cladding, primarily due to the finer grain size observed in the former. The optimal performance of the cladding layer can be achieved when the pulse frequency was set at 50 Hz. The refinement of grain size, combined with an appropriate presence of the σ phase, synergistically contributes to enhancing cutting resistance during friction processes. This collaborative effect further hinders plastic deformation, consequently improving the wear resistance of HEA cladding. Furthermore, the grain refinement in PW cladding promotes the development of surface oxide films, which play a crucial role in reducing galvanic corrosion of alloying elements and minimizing oxygen atom diffusion rates during corrosion processes. Consequently, both corrosion resistance and corrosion wear resistance of PW cladding are significantly enhanced.

Abstract Tenebrio molitor, which is rich in various nutrients, and its polysaccharides, as significant bioactive substances, exhibit strong antioxidant effects. This study utilized defatted T. molitor as raw material and employed an ultrasound-assisted extraction method. The factors considered include extraction temperature, time, ultrasound power, and liquid-to-feed ratio, with the yield of T. molitor polysaccharides as the response value. Based on single-factor experiments and response surface methodology, the optimal extraction parameters for T. molitor polysaccharides were determined. Following purification, protein removal, and dialysis to eliminate impurities, the structure of the extracted polysaccharides was preliminarily investigated using infrared spectroscopy. Their antioxidant activities were explored by measuring their DPPH·, OH·, and ABTS+· radical scavenging abilities and Fe3+ reducing power. The results indicated that the optimal conditions for ultrasound-assisted extraction were an extraction temperature of 75 °C, an extraction time of 150 min, an ultrasound power of 270 W, and a liquid-to-feed ratio of 15:1 mL/g, yielding a polysaccharide extraction rate of 9.513%. Infrared spectroscopy analysis revealed the presence of pyranose sugars with main functional groups including C-O, C=O, and O-H. Antioxidant activity tests showed that within a certain concentration range, the higher the polysaccharide concentration, the stronger its radical scavenging abilities. Compared with Vitamin C(Vc), the polysaccharides had stronger scavenging abilities for DPPH· and OH·, some scavenging ability for ABTS+·, and Fe3+ reduction ability, and corresponding to IC50 values of 0.9625, 9.1909, and 235.69 mg/mL respectively. The Fe3+ reducing power reached a maximum absorbance of 0.38899 at a concentration of 1.6 mg/mL. T. molitor polysaccharides demonstrate promising antioxidant activity and potential as functional ingredients in food, health products, and pharmaceuticals, providing new technical references for the development and utilization of T. molitor resources.

Abstract Aluminium (Al)-tolerant beneficial bacteria confer resistance to Al toxicity to crops in widely distributed acidic soils. However, the mechanism by which microbial consortia maintain Al tolerance under acid and Al toxicity stress remains unknown. Here, we demonstrate that a soil bacterial consortium composed of Rhodococcus erythropolis and Pseudomonas aeruginosa exhibit greater Al tolerance than either bacterium alone. P. aeruginosa releases the quorum sensing molecule 2-heptyl-1H-quinolin-4-one (HHQ), which is efficiently degraded by R. erythropolis. This degradation reduces population density limitations and further enhances the metabolic activity of P. aeruginosa under Al stress. Moreover, R. erythropolis converts HHQ into tryptophan, promoting the synthesis of peptidoglycan, a key component for cell wall stability, thereby improving the Al tolerance of R. erythropolis. This study reveals a metabolic cross-feeding mechanism that maintains microbial Al tolerance, offering insights for designing synthetic microbial consortia to sustain food security and sustainable agriculture in acidic soil regions.

Abstract With the continuous development of deep oil and gas resources, the number of high‐temperature and high‐pressure wells is increasing, and the complexity of fracturing operations is becoming more pronounced. The safe conduct of fracturing operations is crucial for improving production efficiency. To investigate the strength and safety of fracturing strings in high‐temperature and high‐pressure wells, a transient calculation model of temperature‐pressure coupling was established for fracturing strings in high‐temperature and high‐pressure wells. The safety factor method and triaxial stress analysis were employed to evaluate the safety of fracturing strings in high‐temperature and high‐pressure wells. The method was used to assess the fracturing strings in high‐temperature and high‐pressure wells, and the effects of fracturing fluid injection rate and string size on the stress of the strings were analyzed. The results indicate that the axial force and equivalent stress at the wellhead of the fracturing string are the highest; as the fracturing time and injection rate of the fracturing fluid increase, the axial stress and equivalent stress at the wellhead of the fracturing string also increase. Small‐sized pipes are conducive to improving the safety factor of fracturing pipe string operations. The research findings can provide theoretical guidance for designing fracturing strings for high‐temperature and high‐pressure wells.

Facing the challenges of in-situ utilization of lunar regolith resources, applying an external electric field to manipulate lunar particles has become a promising method for space particle control, which mainly depends on the particle charging properties in the applied electric field. Using the surficial lunar regolith samples brought back from the Moon by the Chang’e-5 mission (CE5 LS), this work successively studied their charging properties, particle dynamics, and their collision damages to aerospace materials under the action of an external electric field in high-vacuum conditions. The results indicated that the charging process and electrostatic projection of lunar regolith particles under high-vacuum conditions were different from those under atmosphere conditions. The particle diameter range of CE5 LS used in the experiment is 27.7–139.0 μm. For electric field strength of 3–12 kV·cm−1, the charge obtained by CE5 LS is 4.8 × 10−15–4.7 × 10−13 C and the charge-to-mass ratio is 1.2 × 10−5–6.8 × 10−4 C·kg−1. The CE5 LS is easier to be negatively charged in an external electric field. Furthermore, significant damages were observed on the target impact surfaces, indicating severe influences of lunar regolith particles on aerospace materials. Our work contributes to a more comprehensive understanding of physical mechanisms controlling the lunar regolith shielding and utilization, and will inspire broad efforts to develop the lunar in-situ engineering solutions.

This paper systematically investigates the tensile deformation behavior of copper-aluminum laminated composites with nano single crystal Cu/Al2Cu/Al interface configuration. using molecular dynamics (MD) simulation. The influence of solid solubility and twin crystals on the deformation behavior of copper-aluminum laminated composites with nano single crystal Cu/Al2Cu/Al interface structures was analyzed in-depth. Four interface models are established:no solid solubility and twin crystals model (NN-model), solid solubility model (SN-model), twin crystals model (TN-model), and solid solubility and twin crystals model (ST-model). A comparative analysis revealed that dislocation slip serves as the primary deformation mechanism in the aluminum layer, while twinning dominates in the copper layer. Additionally, the Al2Cu layer contributes to synergistic deformation. Solid solubility minimally affects the Young's modulus of the material and diminishes both ultimate tensile strength and plasticity. Conversely, twin crystals substantially enhance Young's modulus and plasticity but also reduce the ultimate tensile strength. These effects result from the interactions among solid solubility, twin crystals, heterogeneous interfaces, and dislocations. Consequently, thoughtful regulation and design of solid solubility and twin crystals can facilitate the fabrication of copper-aluminum laminated composites with optimal strength-toughness synergy.

Abstract Background Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog (KRAS)‐driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen‐like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS‐mutated cancer. Methods The expression levels of FGL1 and SET1 histone methyltransferase (SET1A) in lung cancer were assessed using public databases and clinical samples. Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models. The effects of FGL1 and Yes‐associated protein (Yap) on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry. Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A‐directed transcriptional program. Results Upregulation of FGL1 expression in KRAS‐mutated cancer was inversely correlated with the infiltration of CD8+ T cells. Mechanistically, KRAS activated extracellular signal‐regulated kinase 1/2 (ERK1/2), which subsequently phosphorylated SET1A and increased its stability and nuclear localization. SET1A‐mediated methylation of Yap led to Yap sequestration in the nucleus, thereby promoting Yap‐induced transcription of FGL1 and immune evasion in KRAS‐driven LUAD. Notably, dual blockade of programmed cell death‐1 (PD‐1) and FGL1 further increased the therapeutic efficacy of anti‐PD‐1 immunotherapy in LUAD patients. Conclusion FGL1 could be used as a diagnostic biomarker of KRAS‐mutated lung cancer, and targeting the Yap‐FGL1 axis could increase the efficacy of anti‐PD‐1 immunotherapy.

Abstract Background Diminished ovarian reserve (DOR) is clinically characterized by a decrease in the number of available ovarian follicles and a decline in the quality of oocytes, accompanied by hormonal changes. Low quality of DOR oocyte leads to impaired embryo development, an increased risk of aneuploid pregnancies and miscarriages. However, the specific pathogenic mechanism remains unclear, posing a significant challenge for assisted reproductive technology. Methods For the first time, our study employed single-cell RNA sequencing to reveal the altered transcriptomic landscape of DOR oocytes at GV stage after ovarian stimulation. Differentially expressed genes analysis (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interactions network analysis were performed. Results We found 132 up-regulated genes and 466 down-regulated genes in DOR oocytes, with the down-regulated genes primarily enriched in mitochondrial function and translation. Hub genes, identified through integrated analysis of WGCNA and DEGs, were further validated in DOR and control oocytes using RT-qPCR. By utilizing hub genes and employing transcription factor enrichment tools, it had been predicted that pleomorphic adenoma gene 1 (PLAG1) played a crucial role as a transcriptional regulatory factor in DOR oocytes. Additionally, we conformed the PLAG1-IGF2 axis was dysregulated in DOR oocytes. Conclusions Transcriptome analysis revealed that DOR oocytes exhibited mitochondrial dysfunction and translational defects, and the PLAG1-IGF2 axis might be a potential contributor for the low quality of DOR oocytes.

Abstract Background Acetate is an important chemical feedstock widely applied in the food, chemical and textile industries. It is now mainly produced from petrochemical materials through chemical processes. Conversion of lignocellulose biomass to acetate by biotechnological pathways is both environmentally beneficial and cost-effective. However, acetate production from carbohydrate in lignocellulose hydrolysate via glycolytic pathways involving pyruvate decarboxylation often suffers from the carbon loss and results in low acetate yield. Results Escherichia coli BL21 (DE3) was confirmed to have high tolerance to acetate in this work. Thus, it was selected from seven laboratory E. coli strains for acetate production from lignocellulose hydrolysate. The byproduct-producing genes frdA, ldhA, and adhE in E. coli BL21 (DE3) were firstly knocked out to decrease the generation of succinate, lactate, and ethanol. Then, the genes pfkA and edd were also deleted and bifunctional phosphoketolase and fructose-1,6-bisphosphatase were overexpressed to construct an EP-bifido pathway in E. coli BL21 (DE3) to increase the generation of acetate from glucose. The obtained strain E. coli 5K/pFF can produce 22.89 g/L acetate from 37.5 g/L glucose with a yield of 0.61 g/g glucose. Finally, the ptsG gene in E. coli 5K/pFF was also deleted to make the engineered strain E. coli 6K/pFF to simultaneously utilize glucose and xylose in lignocellulosic hydrolysates. E. coli 6K/pFF can produce 20.09 g/L acetate from corn stover hydrolysate with a yield of 0.52 g/g sugar. Conclusion The results presented here provide a promising alternative for acetate production with low cost substrate. Besides acetate production, other biotechnological processes might also be developed for other acetyl-CoA derivatives production with lignocellulose hydrolysate through further metabolic engineering of E. coli 6K/pFF.

Abstract The role of circulating metabolome in cognitive impairment is inconclusive, and whether the associations are in the severity-dependent manner remains unclear. We aimed to identify plasma metabolites associated with cognitive impairment and evaluate the added predictive capacity of metabolite biomarkers on incident cognitive impairment beyond traditional risk factors. In the Rugao Longevity and Ageing Study (RuLAS), plasma metabolome was profiled by nuclear magnetic resonance spectroscopy. Participants were classified into the cognitively normal, moderately impaired, and severely impaired groups according to their performance in two objective cognitive tests. A two-step strategy of cross-sectional discovery followed by prospective validation was applied. In the discovery stage, we included 1643 participants (age: 78.9 ± 4.5 years) and conducted multinomial logistic regression. In the validation stage, we matched 68 incident cases of cognitive impairment (moderately-to-severely impaired) during the 2-year follow-up with 204 cognitively normal controls by age and sex at a 1:3 ratio, and conducted conditional logistic regression. We identified 28 out of 78 metabolites cross-sectionally related to severely impaired cognition, among which IDL particle number, ApoB in IDL, leucine, and valine were prospectively associated with 28%, 28%, 29%, and 33% lower risk of developing cognitive impairment, respectively. Incorporating 13 metabolite biomarkers selected through Lasso regression into the traditional risk factors-based prediction model substantially improved the ability to predict incident cognitive impairment (AUROC: 0.839 vs. 0.703, P

Abstract Background Pumpkin (Cucurbita moschata) is an important vegetable crop that often suffers from low-temperature stress during growth. However, the molecular mechanism involved in its response to chilling stress remains unknown. In this study, we comprehensively investigated the effect of chilling stress in pumpkin seedlings by conducting physiological, transcriptomic, and metabolomic analyses. Results Under chilling stress, there was an overall increase in relative electrical conductivity, along with malondialdehyde, soluble sugar, and soluble protein contents, but decreased superoxide dismutase and peroxidase activities and chlorophyll contents in seedling leaves compared with controls. Overall, 5,780 differentially expressed genes (DEGs) and 178 differentially expressed metabolites (DEMs) were identified under chilling stress. Most DEGs were involved in plant hormone signal transduction and the phenylpropanoid biosynthesis pathway, and ERF, bHLH, WRKY, MYB, and HSF transcription factors were induced. Metabolomic analysis revealed that the contents of salicylic acid (SA), phenylalanine, and tyrosine increased in response to chilling stress. The findings indicated that the SA signaling and phenylpropanoid biosynthesis pathways are key to regulating the responses to chilling stress in pumpkins. Conclusion Overall, our study provides valuable insights into the comprehensive response of C. moschata to chilling stress, enriching the theoretical basis of this mechanism and facilitating the development of molecular breeding strategies for pumpkin tolerance to chilling stress.

Abstract Background and aims Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM). Methods A total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed. Results Compared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%. Conclusion Elevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients.

Abstract This study compares the optical quality of zonal refractive multifocal and diffractive bifocal intraocular lenses (IOLs) and visual outcomes after implantation in 93 patients(93 eyes) with cataracts and high myopia. A retrospective analysis was conducted to measure visual acuity at far, intermediate, and near distances, defocus curves, wavefront aberrations, modulation transfer function (MTF), a Quality of Vision questionnaire (QoV) and visual quality self-evaluation were examined at 3 months. The results demonstrated the ZMB group showed better uncorrected near visual acuity (P

Abstract Background This study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression. Methods Pathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed. Results In GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis. Conclusion Specific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients.

Abstract Background Postoperative sore throat (POST) is a common complaint after general anaesthesia. The prevalence of POST caused by a neural integrity monitor electromyography endotracheal tube (NIM-EMG-ETT) is high. This study aimed to determine whether ultrasound-guided internal branch of superior laryngeal nerve block (iSLNB) could alleviate POST associated with a NIM-EMG-ETT. Methods This randomized controlled trial plans to enroll 182 patients scheduled to undergo general anaesthesia with a NIM-EMG-ETT. Patients will be randomly allocated into the iSLNB group or the control group according to randomized numbers generated by Excel. After induction, patients in the iSLNB group will undergo ultrasound-guided iSLNB with ropivacaine, and patients in the control group will undergo the same procedure with normal saline. The prevalence, severity, visual analogue scale score of POST, and postoperative acoustic analysis will be recorded. Discussion To the best of our knowledge, this is the first study to evaluate the effect of ultrasound-guided iSLNB with ropivacaine on the mitigation of POST induced by NIM-EMG-ETT. Our study will provide clinical answers to alleviate POST induced by NIM-EMG-ETT. The results of this study may provide a safe method to prevent POST caused by NIM-EMG-ETT. Trial registration Chinese Clinical Trial Registry, ChiCTR2300076393. Registered on October 24, 2023, http://www.chictr.org.cn/index.aspx .

Abstract Asthenoteratozoospermia is a major cause of male infertility. Thus far, the identified related genes can explain only a small share of asthenoteratozoospermia cases, suggesting the involvement of other genes. The transmembrane protein TMEM232 is highly expressed in mouse testes. In the present study, to determine its function of TMEM232 in testes, we constructed a Tmem232-null mouse model using CRISPR–Cas9 technology. Tmem232 knockout (KO) male mice was completely infertile, and their sperm were immotile, with morphological defects of the flagellum. Electron microscopy revealed an aberrant midpiece-principal junction and the loss of the fourth outer microtubule doublet in the sperm of Tmem232 −/− mice. Sperm cells presented an 8 + 2 conformation and an irregular arrangement of the mitochondrial sheath. Proteomic analysis revealed altered expression of proteins related to flagellar motility, sperm capacitation, the integrity and stability of sperm structure, especially an upregulated expression of multiple ribosome components in TMEM232-deficient spermatids. Additionally, TMEM232 was observed to be involved in autophagy by interacting with autophagy-related proteins, such as ATG14, to regulate ribosome homeostasis during spermiogenesis. These results suggest that TMEM232, as a potential scaffold protein involving in the correct assembly, distribution, and stability maintenance of certain functional complexes by recruiting key intracellular proteins, is essential for the formation of a highly structured flagellum and plays an important role in the autophagic elimination of cytosolic ribosomes to provide energy for sperm motility.

Background: RNA binding proteins (RBPs) play a role in sorting non-coding RNAs (ncRNAs) into exosomes. These ncRNAs, carried by exosomes, are involved in regulating various aspects of tumor progression, including metastasis, angiogenesis, control of the tumor microenvironment, and drug resistance. Recent studies have emphasized the importance of the RBP-ncRNA-exosome mechanism in tumor regulation. Aim of review: This comprehensive review aims to explore the RBP-ncRNA-exosome mechanism and its influence on tumor development. By understanding this intricate mechanism provides novel insights into tumor regulation and may lead to innovative treatment strategies in the future. Key scientific concepts of review: The review discusses the formation of exosomes and the complex relationships among RBPs, ncRNAs, and exosomes. The RBP-ncRNA-exosome mechanism is shown to affect various aspects of tumor biology, including metastasis, multidrug resistance, angiogenesis, the immunosuppressive microenvironment, and tumor progression. Tumor development relies on the transmission of information between cells, with RBPs selectively mediating sorting of ncRNAs into exosomes through various mechanisms, which in turn carry ncRNAs to regulate RBPs. The review also provides an overview of potential therapeutic strategies, such as targeted drug discovery and genetic engineering for modifying therapeutic exosomes, which hold great promise for improving cancer treatment.

Abstract Chickens are the most abundant agricultural animals globally, with controlling abdominal fat deposition being a key objective in poultry breeding. While GWAS can identify genetic variants associated with abdominal fat deposition, the precise roles and mechanisms of these variants remain largely unclear. Here, we use male chickens from two lines divergently selected for abdominal fat deposition as experimental models. Through the integration of genomic, epigenomic, 3D genomic, and transcriptomic data, we build a comprehensive chromatin 3D regulatory network map to identify the genetic regulatory mechanisms that influence abdominal fat deposition in chickens. Notably, we find that the rs734209466 variant functions as an allele-specific enhancer, remotely enhancing the transcription of IGFBP2 and IGFBP5 by the binding transcription factor IRF4. This interaction influences the differentiation and proliferation of preadipocytes, which ultimately affects phenotype. This work presents a detailed genetic regulatory map for chicken abdominal fat deposition, offering molecular targets for selective breeding.

Abstract Epidermal growth factor receptor wild type lung adenocarcinoma (EGFRWT LUAD) still has limited treatment options and unsatisfactory clinical outcomes. Ferroptosis, as a form of cell death, has been reported to play a dual role in regulating tumor cell survival. In this study, we constructed a 3-ferroptosis-gene signature, FeSig, and verified its accuracy and efficacy in predicting EGFRWT LUAD prognosis at both the RNA and protein levels. Patients with higher FeSig scores were found to have worse clinical outcomes. Additionally, we explored the relationship between FeSig and tumor microenvironment, revealing that enhanced interactions between fibroblasts and tumor cells in FeSighigh patients causing tumor resistance to ferroptosis. To address this challenge, we screened potential drugs from NCI-60 (The US National Cancer Institute 60 human tumour cell line anticancer drug screen) and Connectivity map database, ultimately identifying 6-mercatopurine (6-MP) as a promising candidate. Both in vitro and in vivo experiments demonstrated its efficacy in treating FeSighigh EGFRWT LUAD tumor models. In summary, we develop a novel FeSig for predicting prognosis and guiding drug application.

Abstract Acute lung injury (ALI) is a serious acute respiratory disease that can cause alveolar-capillary barrier disruption and pulmonary edema, respiratory failure and multiple organ dysfunction syndrome. However, there is no effective drugs in clinic until now. GSK3179106 has been reported can alleviate intestinal stress syndrome, but the protective effect of GSK3179106 on ALI has not been elucidated. The present study will evaluate the pharmacological activity of GSK3179106 on lipopolysaccharide (LPS)-induced inflammation and lung injury and clarify its underlying mechanism. We found that GSK3179106 significantly attenuated LPS-induced lung injury in vivo, accompanied by inhibited infiltration of inflammatory cells and reduced expression of inflammatory cytokines. Meanwhile, GSK3179106 dose-dependently reduced the LPS-induced IL-6 expression both in protein and gene levels in macrophages. Mechanistically, GSK3179106 could inhibited the phosphorylation of P38 MAPK induced by LPS. Importantly, results showed that there is a direct combination between GSK3179106 and P38 MAPK. Together, our findings not only clarified the anti-inflammatory activity of GSK3179106 but also discovered its new clinical indications. Therefore, compound GSK3179106 may be a potential candidate for the treatment of acute inflammatory diseases.

Abstract Background Knee osteoarthritis (OA) is a common and serious joint disease and patients mainly suffer from knee pain and dysfunction, significantly impacting their quality of life and daily activities. Non-pharmacological treatments and total knee arthroplasty (TKA) are the two major treatments for knee OA. TKA is the primary treatment for severe knee OA patients, however, the postoperative rehabilitation results are not entirely satisfactory. To enhance postoperative rehabilitation outcomes, preoperative lower-limb muscle strengthening has aroused attention and demonstrated significant results on functional recovery after TKA. Specifically, isokinetic muscle strengthening (IMS) has been highly anticipated as an efficient training method. Nevertheless, its effects in perioperative and long-term periods of TKA require further investigation. This study aims to evaluate the impact of preoperative lower-limb IMS during the 4 weeks before TKA on the perioperative and postoperative outcomes, with particular attention on knee function, pain, and inflammatory response. Methods In this study, 104 patients awaiting TKA will be randomized to 2 groups: the IMS and health education groups. All patients will be evaluated at baseline, post-intervention, discharge day, and postoperative day 14, with follow-up assessments at 6 weeks, 3, 6, and 12 months after discharge. The primary outcome will be the Knee Injury and Osteoarthritis Outcome Score 3 months after TKA and the medial-to-lateral knee contact force ratio. The secondary outcomes will be changes in lower-limb muscle strength, knee pain, inflammation response, active range of motion, performance-based function (5-times Sit-to-Stand Test, Time Up-and-Go Test, 3 m walking speed), Berg Balance Scale, and surgical need. Discussion Lower-limb IMS can improve muscle strength, pain, and function for early knee OA patients. However, the effects of different doses of IMS on perioperative and postoperative knee pain, inflammation response, and function after TKA are inconclusive. This study will provide high-quality evidence to assess the efficacy of IMS in end-stage patients who will undergo TKA. Understanding IMS in end-stage knee OA patients will help guide future surgical management for this population. Trial Registration Chinese Clinical Trial Registry ChiCTR2400088136.

Abstract Previous studies have indicated a potential association between the alanine aminotransferase to high-density lipoprotein cholesterol (ALT/HDL-C) ratio and the risk of Type 2 Diabetes Mellitus, but its relation with gestational diabetes mellitus (GDM) remains uncertain. This study aims to investigate the correlation between the ALT/HDL-C ratio in early pregnancy and the risk of GDM. This study is a secondary analysis based on an open-source cohort study. A total of 590 single pregnant women attending two hospitals in Korea up to 14 weeks gestation were included between November 2014 and July 2016. Logistic regression analysis, subgroup analysis, and smooth curve fitting were employed to explore the association between the ALT/HDL-C ratio and GDM risk. The predictive capability of the ALT/HDL-C ratio for GDM was assessed using ROC curve analysis. The average age of participants was 32.06 ± 3.80 years, with a GDM incidence rate of 6.27%. Multifactorial logistic regression analysis revealed that the serum ALT/HDL-C ratio is an independent influencing factor for GDM (OR = 1.08, 95% CI: 1.02–1.16). Furthermore, a non-linear relationship between the ALT/HDL-C ratio and GDM risk was observed, with a turning point at 5.51. The effect size (OR) on the left and right sides of the turning point were 0.75 (95% CI: 0.37–1.59) and 1.55 (95% CI: 1.18-2.00), respectively. Additionally, when combined with age, pre-pregnancy body mass index, parity, and insulin resistance index in a prediction model for GDM, the ALT/HDL-C ratio demonstrated improved sensitivity of prediction by reaching up to 67.6%, specificity of prediction by reaching up to 87.3%, and an area under curve value of 0.819 (95%CI: 0.743–0.894). In early pregnancy, the serum ALT/HDL-C ratio shows a positive correlation with maternal risk in a nonlinear manner. The combination of ALT/HDL-C ratio with maternal characteristics and metabolic indicators provides good predictive value for GDM. This study may facilitate optimization of GDM prevention in pregnant women and enable timely and effective intervention to enhance their prognosis.

New types of aerial robots (NTARs) have found extensive applications in the military, civilian contexts, scientific research, disaster management, and various other domains. Compared with traditional aerial robots, NTARs exhibit a broader range of morphological diversity, locomotion capabilities, and enhanced operational capacities. Therefore, this study defines aerial robots with the four characteristics of morphability, biomimicry, multi-modal locomotion, and manipulator attachment as NTARs. Subsequently, this paper discusses the latest research progress in the materials and manufacturing technology, actuation technology, and perception and control technology of NTARs. Thereafter, the research status of NTAR systems is summarized, focusing on the frontier development and application cases of flapping-wing micro-air vehicles, perching aerial robots, amphibious robots, and operational aerial robots. Finally, the main challenges presented by NTARs in terms of energy, materials, and perception are analyzed, and the future development trends of NTARs are summarized in terms of size and endurance, mechatronics, and complex scenarios, providing a reference direction for the follow-up exploration of NTARs.

To reveal the enrichment conditions and resource potential of coal-rock gas in the Ordos Basin, this paper presents a systematic research on the sedimentary environment, distribution, physical properties, reservoir characteristics, gas-bearing characteristics and gas accumulation play of deep coals. The results show that thick coals are widely distributed in the Carboniferous–Permian of the Ordos Basin. The main coal seams Carboniferous 5# and Permian 8# in the Carboniferous–Permian have strong hydrocarbon generation capacity and high thermal evolution degree, which provide abundant materials for the formation of coal-rock gas. Deep coal reservoirs have good physical properties, especially porosity and permeability. Coal seams Carboniferous 5# and Permian 8# exhibit the average porosity of 4.1% and 6.4%, and the average permeability of 8.7×10−3 μm2 and 15.7×10−3 μm2, respectively. Cleats and fissures are developed in the coals, and together with the micropores, constitute the main storage space. With the increase of evolution degree, the micropore volume tends to increase. The development degree of cleats and fissures has a great impact on permeability. The coal reservoirs and their industrial compositions exhibit significantly heterogeneous distribution in the vertical direction. The bright coal seam, which is in the middle and upper section, less affected by ash filling compared with the lower section, and contains well-developed pores and fissures, is a high-quality reservoir interval. The deep coals present good gas-bearing characteristics in Ordos Basin, with the gas content of 7.5–20.0 m3/t, and the proportion of free gas (greater than 10%, mostly 11.0%–55.1%) in coal-rock gas significantly higher than that in shallow coals. The enrichment degree of free gas in deep coals is controlled by the number of macropores and microfractures. The coal rock pressure testing shows that the coal-limestone and coal-mudstone combinations for gas accumulation have good sealing capacity, and the mudstone/limestone (roof)-coal-mudstone (floor) combination generally indicates high coal-rock gas values. The coal-rock gas resources in the Ordos Basin were preliminarily estimated by the volume method to be 22.38×1012 m3, and the main coal-rock gas prospects in the Ordos Basin were defined. In the central-east of the Ordos Basin, Wushenqi, Hengshan–Suide, Yan'an, Zichang, and Yichuan are coal-rock gas prospects for the coal seam #8 of the Benxi Formation, and Linxian West, Mizhi, Yichuan–Huangling, Yulin, and Wushenqi–Hengshan are coal-rock gas prospects for the coal seam #5 of the Shanxi Formation, which are expected to become new areas for increased gas reserves and production.

Abstract As oil production increasingly transitions from shallow to deep formation, the need for efficient PDC cutters to drill through deep hard rock becomes paramount. Currently, there is a lack of effective methods for optimizing cutter shapes and their cutting parameters. This study addresses this gap by developing a rock-breaking mechanism model for PDC cutters and proposing a Stability Index (SI) based on cutting force variations during the cutting process. Using the FDEM method, we simulated the rock-breaking processes of planar, stinger, and machete cutters under various cutting depths and angles. SI and Mechanical Specific Energy (MSE) were employed as evaluation metrics to analyze the rock-breaking characteristics and determine the optimal cutting parameters for each cutter type. The results indicate that at shallow cutting depths, cutting force changes are minimal, predominantly causing plastic damage to the rock, resulting in lower stress and reduced wear on the PDC cutters. Conversely, at greater cutting depths, significant fluctuations in cutting force occur, leading to brittle failure and the generation of large cuttings. This sudden increase in cutting force can accelerate rock breaking but also increases the risk of cutter wear. Our findings suggest that the planar cutter offers stable performance with high cutting force requirements, optimal at a cutting depth of 1.5 mm and an angle of less than 20°. The stinger cutter, requiring lower cutting forces, performs best at a cutting depth of 2 mm and an angle of 20°. The machete cutter exhibits characteristics similar to the stinger cutter at shallow depths and the planar cutter at deeper depths, making it suitable for drilling at a depth of 2 mm and an angle of less than 10°. By balancing SI and MSE, this study provides a comprehensive approach to optimizing PDC cutter performance, enhancing drilling efficiency while minimizing cutter wear.

Abstract Hypoxic-ischemic encephalopathy (HIE) is a diffuse brain tissue injury caused by acute ischemia and hypoxia, and it is most commonly found in newborn infants but can also occur in adults. Mesenchymal stem cell (MSC) therapies have showed improved outcomes for treating HIE-induced neuronal defects. However, many key issues associated with poor cell viability and tolerance of grafted MSCs after HIE remain to be resolved. Genetic engineering could endow MSCs with more robust regenerative capacities. Our research, along with that of other scientists, has found that the expression of intracellular erythropoietin (EPO) in human umbilical cord MSCs (hUC-MSCs) increases proportionally with the duration of hypoxia exposure. Furthermore, we observed that EPO, when introduced into the EPO gene-modified hUC-MSCs, can be secreted into the extracellular space. However, the underlying mechanisms that support the neuroprotective effects of EPO-MSCs remain unclear. EPO-MSCs, hUC-MSCs, and NC-MSCs were identified by flow cytometry, osteogenic, and adipogenic differentiation assays. The oxygen-glucose deprivation (OGD)-induced SH-SY5Y cell-line was established, and five groups were set up: control, 24-h ischemia-hypoxia, co-cultured with hUC-MSCs, NC-MSCs, and EPO-MSCs after hypoxia. LEGENDplex™ multi-factor flow cytometry was used to detect the secretion of inflammatory factors in cell supernatants and cerebrospinal fluid. Chromosome-targeted excision and tagging (CUT&Tag) sequencing was applied to detect genomic H3K4me2 modifications, and conjoint analysis with transcriptome sequencing (RNA-seq) was performed. Lentiviral vector infection was used to construct SH-SY5Y cells with stable knockdown of RE1-silencing transcription factor (REST), and flow cytometry was used to detect alterations in apoptosis. Finally, the molecular mechanism underlying the neuroprotective and anti-apoptotic effects of EPO-MSCs was investigated using RNA sequencing, qRT-PCR, and western blot assays. Our results suggest that EPO-MSCs are genetically engineered to secrete significantly more EPO. EPO-MSCs treatment has anti-apoptotic properties and offers neuronal protection during ischemic-hypoxic injury. Furthermore, RNA-seq results suggest that multiple inflammation-related genes were down-regulated after EPO-MSCs treatment. Application of RNA-seq and CUT&Tag combined analysis found that the expressions of REST were significantly up-regulated. Lentiviral vector infection to construct REST knockdown SH-SY5Y failed to rescue apoptosis after hypoxia and co-culture with EPO-MSCs, and SETD2-mediated H3K36me3 protein level expression was reduced. EPO-MSCs may promote neuronal survival by affecting H3K4me2 and thus activating the expression of REST and TET3. EPO-MSCs also upregulated the modification level of SETD2-mediated H3K36me3 and regulated the expression of inflammation-related genes such as PLCG2, as well as apoptosis genes BCL2A1. To investigate the neuroprotective effects of EPO-modified hUC-MSCs and the underlying epigenetic regulatory mechanisms, this study aims to provide a theoretical foundation for the potential application of EPO gene-modified hUC-MSCs in the treatment of HIE.

Abstract Materials capable of dynamic persistent luminescence (PersL) within the visible spectrum are highly sought after for applications in display, biosensing, and information security. However, PersL materials with eye-detectable and excitation-wavelength-dependent characteristics are rarely achieved. Herein, a nonstoichiometric compound CaGaxO4:Bi (x

Abstract Background Whey, which has high biochemical oxygen demand and chemical oxygen demand, is mass-produced as a major by-product of the dairying industry. Microbial fermentation using whey as the carbon source may convert this potential pollutant into value-added products. This study investigated the potential of using whey powder to produce α-ketoisovalerate, an important platform chemical. Results Klebsiella oxytoca VKO-9, an efficient L-valine producing strain belonging to Risk Group 1 organism, was selected for the production of α-ketoisovalerate. The leucine dehydrogenase and branched-chain α-keto acid dehydrogenase, which catalyzed the reductive amination and oxidative decarboxylation of α-ketoisovalerate, respectively, were inactivated to enhance the accumulation of α-ketoisovalerate. The production of α-ketoisovalerate was also improved through overexpressing α-acetolactate synthase responsible for pyruvate polymerization and mutant acetohydroxyacid isomeroreductase related to α-acetolactate reduction. The obtained strain K. oxytoca KIV-7 produced 37.3 g/L of α-ketoisovalerate from lactose, the major utilizable carbohydrate in whey. In addition, K. oxytoca KIV-7 also produced α-ketoisovalerate from whey powder with a concentration of 40.7 g/L and a yield of 0.418 g/g. Conclusion The process introduced in this study enabled efficient α-ketoisovalerate production from low-cost substrate whey powder. Since the key genes for α-ketoisovalerate generation were integrated in genome of K. oxytoca KIV-7 and constitutively expressed, this strain is promising in stable α-ketoisovalerate fermentation and can be used as a chassis strain for α-ketoisovalerate derivatives production.

Abstract. Background:. The causal relationship between visceral adipose tissue (VAT) and gout is still unclear. We aimed to examine the potential association between them using observational and Mendelian randomization (MR) analyses. Methods:. In the observational analyses, a total of 11,967 participants (aged 39.5 ± 11.5 years) were included from the National Health and Nutrition Examination Survey. Logistic regression models were used to investigate the association between VAT mass and the risk of gout. In two-sample MR analyses, 211 VAT mass-related independent genetic variants (derived from genome-wide association studies in 325,153 UK biobank participants) were used as instrumental variables. The random-effects inverse-variance weighted (IVW) method was used as the primary analysis. Additional sensitivity analyses were also performed to validate our results. Results:. Observational analyses found that an increase in VAT mass (per standard deviation) was associated with a higher risk of gout after controlling for confounding factors (odds ratio [OR] = 1.27, 95% confidence intervals [CI] = 1.11–1.45). The two-sample MR analyses demonstrated a causal relationship between increased VAT mass and the risk of gout in primary analyses (OR = 1.78, 95% CI = 1.57–2.03). Sensitivity analyses also showed similar findings, including MR-Egger, weighted median, simple mode, weighted mode, and leave-one-out analyses. Conclusions:. Observational analyses showed a robust association of VAT mass with the risk of gout. Meanwhile, MR analyses also provided evidence of a causal relationship between them. In summary, our findings suggested that targeted interventions for VAT mass may be beneficial to prevent gout.

In order to assessing the heterogeneity of Bacillus sp. isolates spoilage potential, six Bacillus sp. isolates isolated from spoiled low-temperature sausages were used to investigate the heterogeneity of their spoilage properties at 20 ℃ (room temperature) and 37 ℃ (optimum growth temperature). The growth curve, acid production capacity, gas production capacity, protease activity, lipase activity, and amylase activity of six strains of Bacillus sp. were measured in the experiment. The results revealed that Bacillus cereus (C) had the greatest capacity for producing acid and that after 48 hours at 37 ℃, the pH in the culture medium dropped by 0.71 relative to the blank control group. Following a 5-day culture at 37 ℃, Bacillus amyloliquefaciens (G) displayed the greatest protease and amylase activities, with a maximum protease activity of 7.17 U/mL and a decomposition circle area of starch agar of 16.53 cm2. Bacillus cereus (C) exhibited the least comprehensive spoiling ability, as evidenced by its protease activity of 2.63 U/mL and the decomposition circle area of starch agar of 7.55 cm2 after 5 days of culture at 37 ℃. Furthermore, it was discovered that the growth temperature significantly impacted the spoilage potential of the strains. In summary, there was great heterogeneity in the spoilage characteristics of Bacillus sp.. When examining its spoilage traits, it is important to consider this heterogeneity.

Introduction The purpose of this study was to examine the prevalence, clinical characteristics, and changing trends of non-smokers with lung cancer (LC) based on data from a population-wide cancer registry in northern China. Methods The study used LC incidence and follow-up data from 2010 to 2019 from the Cancer Registry System of Tianjin city, which included 82769 cases. Trends in the incidence and proportion of non-smokers with LC were examined by joinpoint regression analysis. Life table and Cox survival analyses were used to calculate the survival rates and compare the death hazard ratios (HRs) in different groups, respectively. Results Among the 82769 new diagnosis cases of LC during 2010 to 2019, there were 34589 (41.8%) current smokers, 14913 (18.0%) ex-smokers, 28123 (34.0%) non-smokers, and 5144 (6.2%) unknowns. The proportion of non-smokers changed slightly from 2010 (35.36%) to 2019 (36.87%) (annual percentage change, APC= -0.01%, p>0.05). This proportion declined in men (2010 vs 2019; 22.06% vs 20.66%) and increased in women (2010 vs 2019; 53.02% vs 62.35%), and in the 0–44 years age group it showed an upward trend from 2015 to 2019 (APC=4.82%, 95% CI: 1.8–7.9). Compared with smokers with LC, non-smokers with LC were predominantly females (64.15% vs 27.26%), had a predominantly adenocarcinoma histological subtypes (76.71% vs 42.22%), and had a 20% lower risk of death than smokers (HR=0.80; 95% CI: 0.78–0.81). Conclusions The proportion of non-smokers with LC was relatively high in northern China, with an increasing trend in the proportion of females and younger age groups. Non-smokers with LC had different epidemiological and clinical characteristics compared with smokers with LC.

Objective The clinical evidence on the management for congenital pseudoarthrosis of the tibia (CPT) in adults is limited. The aim of this study is to assess the functional and radiological outcomes of Ilizarov distraction for treating CPT in adults. Methods A retrospective analysis was conducted. Between 2013 and 2022, an Ilizarov distraction technique was performed on 14 adults (14 limbs) with CPT in our limb deformity center. There were seven females and seven males with a mean age of 33.7 (range, 18 ~ 53) years. The diagnosis of NF‐1 was confirmed in seven (50.0%) patients. Eight patients had a history of previous surgical failure. The pseudoarthrosis occurred in the middle and lower tibia in all limbs (six left and eight right). The CPT was classified by Crawford classification and Paley classification. The surgical procedures, external fixation time (EFT), and all outcomes and complications were recorded. The Kolmogorov–Smirnov test was performed to test the normality of the data. The American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hindfoot score at the preoperative and final follow‐up was compared by using the Wilcoxon's signed‐rank test. The limb‐length discrepancy (LLD) and a self‐made exercise capacity score at the preoperative and final follow‐up were compared by using the student's t‐test. The clinical and radiological outcomes were assessed by the Inan scale. Results The mean EFT of Ilizarov fixator was 19.5 months (range, 7.3 ~ 39.1). At a median follow‐up of 26.8 months (IQR, 20.2 ~ 34.3), bone union of the pseudarthrosis and consolidation of the distraction zone were achieved in all patients. The mean LLD was decreased from 11.3 cm (range, 3.4 ~ 17.3) preoperatively to 1.1 cm (range, 0.3 ~ 3.7) (p

Objective The management of femoral multiplanar deformity remains a great challenge for orthopaedic surgeons. The focal dome osteotomy (FDO) combined with Ilizarov technique is a theoretically ideal method for treating femoral multiplanar deformity, but the clinical evidence is limited. The aim of this study is to assess the clinical and radiological outcomes of this combined strategy for correcting femoral multiplanar deformities. Methods A retrospective analysis was conducted to analyze 20 patients (29 limbs) with femoral multiplanar deformities treated by FDO combined with Ilizarov external fixation in our limb deformity center between 2017 and 2022. Preoperative and postoperative radiographical parameters were measured, including lateral proximal femoral angle (LPFA), mechanical lateral distal femoral angle (mLDFA), middle diaphysis angle (MDA), anatomic posterior distal femoral angle (aPDFA), mechanical axis deviation (MAD), and limb length discrepancy (LLD). Clinical assessments included a self‐made questionnaire for exercise capacity score (ECS), visual analog scale (VAS), and the 36‐Item Short‐Form Health Survey (SF‐36) score. Results There were eight males and 12 females, with a mean age of 32.8 years (14–61 years). All patients completed follow‐up with a mean follow‐up duration of 41.5 (27–81) months. The mean EFT was 8.9 (1.4–20.2) months. At final follow‐up, significantly improvement was noted regarding mean LLD (from 1.8 to 0.4 cm, p 0.5 cm) was noted in four patients but without significant symptoms. No serious complications occurred. Conclusions The strategy of FDO combined with Ilizarov fixation could provide powerful ability and good flexibility for correcting femoral multiplanar deformities without significant complications.

Objective Midfoot osteotomy combined with Ilizarov methods of correction is a rarely reported treatment that is particularly well‐suited for severe rigid pes cavus. The study aimed to assess the radiological and clinical results of patients who had been treated for rigid pes cavus using this method. Methods The study retrospectively analyzed the clinical and radiological data of 15 pes cavus in 12 patients who were corrected by midfoot osteotomy with Ilizarov external frame in our department from March 2020 to September 2022. Radiologic outcomes were measured using the Meary angle (MA), talus‐first metatarsal angle (TM1A), calcaneal varus angle (CVA) and foot length with weight‐bearing radiographs. Functional assessments were evaluated in terms of pain, function, and quality of life by using the visual analogue scale (VAS), the American Orthopedic Foot and Ankle Society hindfoot scale score (AOFAS), and 36‐item Short Form Health Survey (SF‐36). Additionally, the postoperative satisfaction of patients was investigated by a questionnaire. The clinical and radiological results were evaluated by a paired t‐test. Results All patients received plantigrade feet and pain relief. The mean follow‐up was 33.1 ± 5.0 months (range from 25 to 41 months). The etiology included poliomyelitis (4), idiopathic (3), trauma (2), spina bifida (2) and tethered cord syndrome (1). The duration of gradual correction was 30.4 ± 10.6 days, and the external fixation time was 116.3 ± 33.3 days. The bony union rate was 100%. The VAS, AOFAS, and SF‐36 scores significantly improved (p

Abstract Radioactive safety in nuclear facilities is of utmost importance. Prior to workers entering these areas, a 3D radiation field is needed for accurately estimating their exposure. Due to the complex relationship between radiation measurements and radiation fields, implementing neural networks is a promising approach for reconstruction. However, research on direct 3D radiation field reconstruction using neural networks is limited, and there is no standardized open-source dataset for training and evaluation. To address these issues, we created a simplified model of a nuclear facility and utilized the Monte Carlo program MCShield to simulate 3D radiation parameters. MCShield, which is mainly used for shielding calculations, has been verified for accuracy through benchmark tests. In addition, this paper proves the correctness of the MCShield program and the effectiveness of the AIS variance reduction method through calculations on the WinFrith Iron benchmark experiment and the NUREG/CR-6115 benchmark. The results show that the MCShield program as well as the AIS method can be used for dataset calculations.

Abstract Visual working memory depends on both material-specific brain areas in the ventral visual stream (VVS) that support the maintenance of stimulus representations and on regions in the prefrontal cortex (PFC) that control these representations. How executive control prioritizes working memory contents and whether this affects their representational formats remains an open question, however. Here, we analyzed intracranial EEG (iEEG) recordings in epilepsy patients with electrodes in VVS and PFC who performed a multi-item working memory task involving a retro-cue. We employed Representational Similarity Analysis (RSA) with various Deep Neural Network (DNN) architectures to investigate the representational format of prioritized VWM content. While recurrent DNN representations matched PFC representations in the beta band (15–29 Hz) following the retro-cue, they corresponded to VVS representations in a lower frequency range (3–14 Hz) towards the end of the maintenance period. Our findings highlight the distinct coding schemes and representational formats of prioritized content in VVS and PFC.

Abstract Background While the significant association between leisure activities and frailty risk among older adults is well-established, the impact of integrated leisure activity scores and different categories of them on frailty trajectories over time remains unclear. Methods This study utilized longitudinal data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which enrolled participants aged 65 years and older between 2002 and 2018. Frailty trajectories were derived using group-based trajectory modelling, and based on these trajectories, subjects were classified into various categories. Leisure activity was measured by integrated scores as well as three distinct categories: physically, cognitively, and socially stimulating activity. The effect of leisure activity on frailty trajectories was examined using multinomial logistic regression. Results By analysing data from 2,299 older adults, three frailty trajectories were identified: non-frail, moderate progressive, and high progressive. The results indicated that an increase in the score of integrated leisure activity was associated with 11% (odds ratio [OR] 0.89; 95% Confidence Interval [CI] 0.85–0.93) and 14% (OR 0.86; 95% CI 0.80–0.91) decrease in the likelihood of being in the moderate and high progressive frailty trajectories, respectively. Engaging in physically stimulating activity lowered the odds of belonging to the moderate and high progressive trajectory by 43% (OR 0.57; 95% CI 0.40–0.81; OR 0.57; 95% CI 0.36–0.92, respectively). Participation in socially stimulating activity showed a lower odd of being in the moderate progressive trajectory (OR 0.68; 95% CI 0.49–0.93) and the high progressive trajectory (OR, 0.61; 95% CI, 0.39–0.95). The effects of leisure activities on frailty trajectories were observed not to vary by age, education level and retirement status. Conclusions This study suggests that older adults should be encouraged to increase both the amount and variety of their leisure activities. Physically stimulating activities should be considered the primary choice, followed by socially and cognitively stimulating activities.

Abstract T helper cells, particularly T follicular helper (TFH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from TFH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in TFH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of TFH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.

Abstract Background Human papillomavirus (HPV) infection significantly contributes to the global cancer burden. Understanding the factors influencing male clinical interns’ willingness to promote HPV vaccination is crucial for developing effective public health strategies in China. Methods This study employed a stratified random sampling method to select 1,980 male clinical interns from five provinces in China between January and March 2024. Data were collected on participants’ demographic characteristics, HPV-related clinical experience, and knowledge. The Theory of Planned Behavior framework, encompassing attitudes, subjective norms, and perceived behavioral control, was used to examine factors influencing the willingness to promote the HPV vaccine. Logistic regression analyses were conducted to identify factors associated with the willingness to promote the HPV vaccine. Results Among the respondents, 72.29% were willing to encourage others to receive the HPV vaccine. Significant factors influencing this willingness included older age (OR = 3.065, P ≤ 0.001), higher monthly household income (OR = 1.449, P = 0.025), participation in the diagnosis and treatment of HPV-related diseases (OR = 3.458, P ≤ 0.001), positive attitude towards the vaccine (OR = 13.503, P = 0.004), and strong perceived behavioral control (OR = 2.364, P = 0.006). Conclusion This study highlights the critical role of practical experience and targeted education in promoting HPV vaccination among male clinical interns in China. Enhancing the training and education of this group is essential for improving HPV vaccine advocacy and supporting public health efforts to reduce HPV-related diseases.

Abstract In this study, we successfully established a novel gallbladder cancer cell line, designated as GBC-X1, derived from a primary tumor of a gallbladder cancer patient. By comprehensively analyzing the cell line’s phenotype, molecular characteristics, biomarkers, and histological characteristics, we confirmed that GBC-X1 serves as a valuable model for investigating the pathogenesis of gallbladder cancer and developing therapeutic agents. GBC-X1 has been continuously cultured for one year, with over 60 stable passages. Morphologically, GBC-X1 exhibits typical features of epithelial tumors. The population doubling time of GBC-X1 is 32 h. STR analysis validated a high consistency between GBC-X1 and the patient’s primary tumor. Karyotype analysis revealed an abnormal hypertetraploid karyotype for GBC-X1, characterized by representative karyotypes of 98, XXXX del (4) p (12) del (5) p (21) der (10). Under suspension culture conditions, GBC-X1 efficiently forms tumor balls, while subcutaneous inoculation of GBC-X1 cells into NXG mice leads to xenograft formation with a rate of 80%. Drug sensitivity testing demonstrated that GBC-X1 is resistant to oxaliplatin and sensitive to 5-FU, gemcitabine, and paclitaxel. Immunohistochemistry revealed positive expression of CK7, CK19, E-cadherin, MMP-2, CD44, SOX2, and TP53 in GBC-X1 cells, weak positive expression of Vimentin, and a Ki67 positive rate of 35%. Our research highlights GBC-X1 as a novel gallbladder cancer cell line and emphasizes its potential as an effective experimental model for investigating the pathogenesis of gallbladder cancer and drug development.

Walnut kernels, selected as the raw material, underwent hydrolysis with protein-glutaminase (PG) following pulping. This process laid the foundation for producing set-type walnut yogurt, involving steps such as blending, homogenization, sterilization, and fermentation. The study investigated the impact of protein-glutaminase and five distinct starter cultures labeled I~V on the quality of walnut yogurt. This was evaluated by examining the yogurt's fermentation characteristics, physicochemical indicators, and microstructure. Furthermore, walnut yogurt developed under these optimal conditions was compared to traditional milk yogurt to assess its quality and characteristics. The findings revealed a significant improvement in the fermentation characteristics and textural parameters of yogurt fermented by walnut milk following enzymatic hydrolysis compared to non-enzymatic walnut milk. The optimal conditions were identified as 0.2% enzyme concentration and a 40-minute reaction time, with the pH, acidity, hardness, and consistency of walnut yogurt being 4.3, 55°T, 85.30 g, and 583.96 g·s, respectively. Walnut yogurt developed using starter culture I exhibited the highest acidity level, maintaining minimal fluctuation over a 21-day storage period. In contrast, yogurts prepared with alternative starter cultures demonstrated varying degrees of stratification and sedimentation. The yogurt fermented with culture I showed superior viscoelastic properties, presenting a denser gel network. Conversely, yogurts fermented with cultures IV and V displayed reduced apparent viscosity, lower values of G' (storage modulus), and G'' (loss modulus), along with a looser gel structure. Additionally, walnut yogurt produced with starter culture I maintained bacterial counts exceeding 106 CFU/mL throughout the storage duration. Despite walnut yogurt requiring further refinement in aspects such as consistency, water-holding capacity, and whey release rate compared to milk yogurt, the overall impact of PG was positive, enhancing the gelation quality of walnut yogurt. The yogurt prepared with starter culture I (Lactobacillus bulgaricus and Streptococcus thermophilus) was notably improved, receiving favorable overall assessments.

Abstract Mandarin Chinese is typologically unusual among the world’s languages in having flexible word order despite a near absence of inflectional morphology. These features of Mandarin challenge conventional linguistic notions such as subject and object and the divide between syntax and semantics. In the present study, we tested monolingual processing of argument structure in Mandarin verb-final sentences, where word order alone is not a reliable cue. We collected participants’ responses to a forced agent-assignment task while measuring their electroencephalography data to capture real-time processing throughout each sentence. We found that sentence interpretation was not informed by word order in the absence of other cues, and while the coverbs BA and BEI were strong signals for agent selection, comprehension was a result of multiple cues. These results challenge previous reports of a linear ranking of cue strength. Event-related potentials showed that BA and BEI impacted participants’ processing even before the verb was read and that role reversal anomalies elicited an N400 effect without a subsequent semantic P600. This study demonstrates that Mandarin sentence comprehension requires online interaction among cues in a language-specific manner, consistent with models that predict crosslinguistic differences in core sentence processing mechanisms.

Abstract Effectively controlling the selective conversion of CO2 photoreduction to C2 products presents a significant challenge. Here, we develop a heterojunction photocatalyst by controllably implanting Au nanoparticles and single atoms into unsaturated Mo atoms of edge-rich MoS2, denoted as Aun/Au1-CMS. Photoreduction of CO2 results in the production of CH3COOH with a selectivity of 86.4%, which represents a 6.4-fold increase compared to samples lacking single atoms, and the overall selectivity for C2 products is 95.1%. Furthermore, the yield of CH3COOH is 22.4 times higher compared to samples containing single atoms and without nanoparticles. Optical experiments demonstrate that the single atoms domains can effectively capture photoexcited electrons by the Au nanoparticles, or the local electric field generated by the nanoparticles promotes the transfer of photogenerated electrons in MoS2 to Au single atoms, prolonging the relaxation time of photogenerated electrons. Mechanistic investigations reveal that the orbital coupling of Au5d and Mo4d strengthens the oxygen affinity of Mo and carbon affinity of Au. The hybridized orbitals reduce energy splitting levels of CO molecular orbitals, aiding C–C coupling. Moreover, the Mo−Au dual-site stabilize the crucial oxygen-associated intermediate *CH2CO, thereby enhancing the selectivity towards CH3COOH. The cross-scale heterojunctions provide an effective strategy to simultaneously address the kinetical and thermodynamical limitations of CO2-to-CH3COOH conversion.