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Phosphorus is a limiting factor in agriculture due to restricted availability in soil and low utilization efficiency of crops. The identification of superior haplotypes of key genes responsible for low-phosphate (Pi) tolerance and their natural variation is important for molecular breeding. In this study, we conducted genome-wide association studies on low-phosphate tolerance coefficients using 152 maize inbred lines, and identified a significant association between SNPs on chromosome 7 and a low-phosphate tolerance coefficient. ZmGRF10 was identified as a candidate gene involved in adaptation of maize to Pi starvation. Expression of ZmGRF10 is induced by Pi starvation. A mutation in ZmGRF10 alleviated Pi starvation stress. RNA-seq analyses revealed significant upregulation of genes encoding various phosphatases in the zmgrf10-1 mutant, suggesting that ZmGRF10 negatively regulates expression of these genes, thereby affecting low-Pi tolerance by suppressing phosphorus remobilization. A superior haplotype with variations in the promoter region exhibited lower transcription activity of ZmGRF10. Our study unveiled a novel gene contributing to tolerance to low-Pi availability with potential to benefit molecular breeding for high Pi utilization.

Objectives: Diamond tools are widely used in fields such as oil drilling, geological exploration, and stone processing, among which sintered metal bond diamond tools have become the most representative due to their wide applicability and strong durability. Cobalt (Co) has become the preferred material for preparing diamond tools due to its excellent physical properties, but its price is relatively expensive. As market competition gradually intensifies, the application range of Co is becoming limited. It has been found that Fe-based pre-alloy powder has similar properties to Co and can be used as an important way to reduce costs. However, Fe-based diamond tools face problems such as high sintering temperature, narrow controllable process range, easy erosion of diamond, weak holding force, and the tendency for the matrix to burn during production. Additionally, the Sn element is prone to segregation and loss during long-term sintering in the furnace, resulting in unstable performance of diamond tools. This article describes the preparation of FeCuNi-Cu/Sn/Bi alloy powder using a multi-layer coating process to improve the densification of diamond matrix sintering and reduce component segregation. Methods: Co powder, Cu powder, Fe powder, Sn powder, Ni powder, and FeCuNi alloy powder were selected, and Cu, Sn, and Bi were respectively plated onto the surface of FeCuNi alloy powder by chemical methods, forming a uniform coating on the surface. Metal powder and diamond were mixed using a three-dimensional mixer for 2 hours. After mixing, the required weight of uniform powder was weighed, and sample blocks with dimensions of 4 mm × 8 mm × 40 mm were prepared using a hot press sintering machine. The mold material was graphite, and 4 sample blocks were prepared for each group. The experiment was repeated twice. For the tested materials, Rockwell hardness was measured, as well as the three-point bending strength. The microstructure and energy spectrum were analyzed using an electron microscope, and the changes in composition, structure, and mechanical properties of the tire body with fewer joints under different processes were compared and analyzed. Four formulations of sintered diamond tool bodies were designed, and their physical properties were tested. Eight samples were prepared for each formulation. After removing the maximum and minimum values, the average value of the data was calculated for analysis. Results: The hardness of the coated alloy powder formulation body decreased from 110 HRB to 106 HRB, but the decrease was less than 4%, indicating that the hardness remained similar. After adding the coated alloy powder, the flexural strength of the tire body increased by more than 10%. Specifically, for the formulation containing FeCuNi-Bi powder, the flexural strength increased from 945 MPa to 1,120 MPa, an increase of nearly 20%. The improvement was due to the even distribution of low-melting point elements coated on the surface of the alloy powder, which reduced the porosity of the matrix during the sintering process, thereby improving the bending strength of the matrix. Analysis of the microstructure of the four sintered tire bodies revealed that Sn in the original formula reacted with metal elements such as Cu in the tire body, gradually forming CuSn alloy. The distribution of Sn was uneven, and segregation was severe. As the sintering temperature increased, some CuSn alloys with higher Sn content began to melt. However, the wettability between the liquid CuSn alloy and Co or Fe particles was poor, and the distribution in the tire body was discontinuous. The vast majority of the CuSn liquid phase could not penetrate the Co and Fe skeleton phases to form a network connection. Under the interaction of sintering temperature and pressure, a strong and dense bond could not be formed, resulting in an uneven microstructure of the tire body and negatively affecting the performance and application of diamond tools. After adding FeCuNi-Cu/Sn/Bi alloy powder to the formula, the distribution of the coated alloy powder was relatively uniform. During sintering, Sn and Bi on the surface of FeCuNi alloy powder particles melted first, reacting with Cu to form liquid phases such as Cu-Sn and Cu-Bi. These phases gradually diffused along the FeCuNi alloy powder particles from the outside to the inside, entering the gaps between Fe, Ni, FeCuNi and other particles. Ultimately, Cu-Sn and Cu-Bi alloys formed a continuous network structure, encapsulating and bonding particles such as FeCuNi, Fe, and Ni, making the composition and microstructure distribution of the diamond tool bodies more uniform and dense, thus avoiding component segregation. Conclusions: FeCuNi-Cu/Sn/Bi alloy powder was prepared by chemically plating Cu, Sn, and Bi onto the surface of FeCuNi alloy powder. After adding the metal-coated alloy powder to the formula, the microstructure of the matrix was refined, and both hardness and strength were improved. The FeCuNi-Cu/Sn/Bi alloy powder, using coating technology, was sintered to obtain a denser matrix with higher diamond holding force and better mechanical properties.

ObjectiveTo elucidate the bidirectional causal relationship between lipid profiles and colorectal cancer (CRC) by using the two-sample and two-step Mendelian randomization (MR) methods, and to explore the mediating role and proportion of immune cells as intermediary factors. MethodsThe pooled statistical data related to the study were screened, and 179 lipids and CRC were analyzed using two-sample and two-step MR with the inverse variance weighted method. Simultaneously, the causal effect was verified via Bayesian weighted MR. Two-step MR analysis was conducted to determine whether a mediated effect was exerted on immune cell traits. Sensitivity, heterogeneity, and pleiotropy analyses were performed to verify the reliability of the study results. ResultsThe causal relationship between nine lipid traits and CRC was preliminarily identified, and no reverse causal effect was found (P>0.05). The validity of the results was verified via Bayesian weighted MR (P

Abstract Background To establish a three-dimensional finite element model of the lumbar spine and investigate the impact of different fixation techniques on the biomechanical characteristics of oblique lumbar interbody fusion (OLIF). Methods The study aimed to establish and validate a comprehensive three-dimensional model of the lower lumbar spine (L3-S1) using the finite element method. L4-L5 was selected as the surgical segment, and four distinct OLIF surgical models were constructed: Stand-alone (SA), unilateral cortical bone trajectory screw (UCBT), bilateral cortical bone trajectory screw (BCBT), and bilateral pedicle screw (BPS). The models were underwent a pure moment of 10N·m to simulate lumbar extension, flexion, left bending, right bending, left and right rotation movements. Subsequently, the range of motion (ROM), cage stress, and fixation stress were calculated. Results In the L3-L5 segment, the BCBT group showed the most limited range of motion (ROM) under exercise load, indicating superior stability within this group. The ROM and cage stress values were found to be highest in the SA group. In contrast, the cage and internal fixation stress in the BPS group were observed to be lowest (9.91 ~ 53.83MPa, 44.93 ~ 84.85 MPa). With the exception of right bending and right rotation, the UCBT group demonstrated higher levels of internal fixation stress (102.20 ~ 164.62 MPa). Conclusions The study found that OLIF-assisted internal fixation improved segmental stability and reduced cage stress. The BPS group had advantages over the CBT group in preventing endplate damage and reducing the risk of cage subsidence. However, BCBT group has distinct merits in maintaining surgical segment stability, distributing stress load on the spinal motor unit, and reducing the likelihood of adjacent segment degeneration (ASD).

Abstract Alzheimer’s Disease (AD) is a neurodegenerative disorder, and various molecules associated with PANoptosis are involved in neuroinflammation and neurodegenerative diseases. This work aims to identify key genes, and characterize PANoptosis-related molecular subtypes in AD. Moreover, we establish a scoring system for distinguishing PANoptosis molecular subtypes and constructing diagnostic models for AD differentiation. A total of 5 hippocampal datasets were obtained from the Gene Expression Omnibus (GEO) database. In total, 1324 protein-encoding genes associated with PANoptosis (1313 apoptosis genes, 11 necroptosis genes, and 31 pyroptosis genes) were extracted from the GeneCards database. The Limma package was used to identify differentially expressed genes. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify gene modules significantly associated with AD. The ConsensusClusterPlus algorithm was used to identify AD subtypes. Gene Set Variation Analysis (GSVA) was used to assess functional and pathway differences among the subtypes. The Boruta, Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithms were used to select the three PANoptosis-related Key AD genes (PKADg). A scoring model was constructed based on the Boruta algorithm. PANoptosis diagnostic models were developed using the RF, SVM-RFE, and Logistic Regression (LR) algorithms. The ROC curves were used to assess the model performance. A total of 48 important genes were identified by intersecting 725 differentially expressed genes and 2127 highly correlated module genes from WGCNA with 1324 protein-encoding genes related to PANoptosis. Machine learning algorithms identified 3 key AD genes related to PANoptosis, including ANGPT1, STEAP3, and TNFRSF11B. These genes had strong discriminatory capacities among samples, with Receiver Operating Characteristic Curve (ROC) analysis indicating Area Under the Curve (AUC) values of 0.839, 0.8, and 0.868, respectively. Using the 48 important genes, the ConsensusClusterPlus algorithm identified 2 PANoptosis subtypes among AD patients, i.e., apoptosis subtype and mild subtype. Apoptosis subtype patients displayed evident cellular apoptosis and severe functionality damage in the hippocampal tissue. Meanwhile, mild subtype patients showed milder functionality damage. These two subtypes had significant differences in apoptosis and necroptosis; however, there was no apparent variation in pyroptosis functionality. The scoring model achieved an AUC of 100% for sample differentiation. The RF PANoptosis diagnostic model demonstrated an AUC of 100% in the training set and 85.85% in the validation set for distinguishing AD. This study identified two PANoptosis-related hippocampal molecular subtypes of AD, identified key genes, and established machine learning models for subtype differentiation and discrimination of AD. We found that in the context of AD, PANoptosis may influence disease progression through the modulation of apoptosis and necrotic apoptosis.

Objective Chemical oxidation and infiltration technology has become a mature method for shale gas exploitation. This study aims to investigate the influence of geochemical factors on the exploitation process. Methods In this study, the Doushantuo Formation shale in Yichang, Hubei Province, which exhibits significant potential for shale gas exploitation and contains a high organic matter content along with pyrite, was selected as the research object. Two commonly used oxidants, 15% H2O2 and 0.5 mol/L Na2S2O8, were selected for oxidation corrosion experiments conducted at normal temperature and pressure. Post-reaction measurements included cation concentration, pH, Eh, mass loss and XRD analysis. Results The results show that Na2S2O8 outperforms H2O2, and the advanced oxidation process driven by pyrite and the erosion effect of carbonate under acid production make the acidic environment more suitable for the dissolution of carbonate-rich shale. An increase in temperature enhances the thermal decomposition of Na2S2O8 and H2O2. The thermal decomposition of H2O2 produces O2, and Na2S2O8 produces H2SO4, O2 and SO4- with strong oxidation. Thus, the temperature's enhancement effect on Na2S2O8 is greater than that on H2O2. Sodium ions (chloride) can promote the release of Ca2+ and Mg2+ during Na2S2O8 and H2O2 oxidation, indicating that a high concentration of NaCl in groundwater plays a positive role in the oxidation and dissolution of shale. Both calcium ions and sulfate ions can cause gypsum precipitation by influencing the interactions between the reactions, thus affecting the oxidative dissolution of shale. Low concentrations of exogenous calcium ions reduce the buffering effect of carbonate and promote its dissolution, while high concentrations of exogenous calcium ions cause secondary mineral precipitation, block shale pores and hinder the oxidation and dissolution of shale. However, the effect of sulfate ions on the oxidative corrosion of shale differs from that of calcium ions. A low concentration of exogenous sulfate ions inhibits the oxidative corrosion of shale by generating secondary ore and impeding the oxidation of pyrite. Conclusion Therefore, in the future process of shale gas oxidative fracturing for extraction, it is necessary to preassess the water chemical parameters of the exploitation formation in advance and select the oxidation liquid and mining modes based on the temperature, pH and cationions.

Abstract Background The commercial utilization of genetically modified soybeans has yielded substantial economic advantages. Nevertheless, the genetic drift towards wild soybeans is one of the main ecological risks that needs to be addressed. Previous experiments demonstrated the absence of fitness cost or florescence overlap in hybrid offspring resulting from the crossbreeding of transgenic soybean GTS40-3-2 and Zhengzhou wild soybeans. In this study, hybrid progeny was systematically crossed with wild soybeans to establish a backcross progeny system. This system was employed to evaluate the ecological risk associated with the backcross progeny of transgenic and wild soybeans. Results The findings indicated that the offspring from the backcross exhibited glyphosate tolerance. Furthermore, the expression of foreign proteins in the backcross offspring was notably lower than in the transgenic soybean, and there was no significant difference when compared to the hybrid progeny. Parameters such as germination rate, aboveground biomass, pods per plant, full seeds per plant, and 100-grain weight exhibited no significant differences between the negative and positive lines of the backcross progenies, and no fitness cost was identified in comparison to wild soybeans. These results underscore the potential for foreign genes to propagate within other wild soybeans, which requires continuous attention. Conclusions The widespread adoption of genetically modified soybeans has undeniably led to substantial economic gains. However, the research findings emphasize the critical importance of addressing the ecological risks posed by genetic drift towards wild soybeans. The backcross progeny system established in this study indicates that the potential for foreign gene dissemination to wild soybean populations warrants continued attention and mitigation strategies.

Objectives: The objective of the present study was to investigate whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes pathways were involved in an experimental model of fibroblast activation named nemosis, which was used to mimic circumstances without bacteria stimulation. Methods: Nemosis of human dental pulp fibroblast (DPFs) was induced by three-dimensional culture in U-shaped 96-well plates and investigated by scanning electron microscopy (SEM). DPFs monolayers were used as control. Annexin V-FITC/7-AAD apoptosis assay was performed on the DPFs spheroids by flowcytometry. Caspase-1 activity detection assay was conducted on the DPFs spheroids. Quantitative real-time polymerase chain reaction (qRT-PCR), cytokine measurements, Western blot and the effect of COX-2 inhibitor on spheroids was studied. Results: SEM study observed human dental pulp fibroblast clusters and cell membranes damage on the surface of DPFs spheroids. The percentages of necrotic cells from DPFs spheroids gradually increased as the incubation time increased. A statistically significant increase in caspase-1 activity was observed after DPFs spheroids formation. DPFs spheroids displayed significant amounts of NLRP3, AIM2 mRNA and protein expression, caspase-1 mRNA expression and cleaved Caspase-1 protein expression and high IL-1β concentrations (P

Objectives: Diamond tools are crucial in stone processing, and their performance is directly related to processing quality and cost. With the rise of stone and labor costs, the performance requirements on diamond tools are also increasing, including sharpness, self sharpening, tool life, and cutting efficiency. To improve efficiency and reduce costs, users often increase the cutting machine power and speed, which further requires diamond tools to have higher sharpness and strength at the risk of breakage. A practical method method is to increase the content of tin (Sn) in the segment to enhance its brittleness without changing the diamond concentration and particle size. However, an increase in Sn content will reduce the strength of the segment and may lead to a decrease in the holding force between CuSn alloy and diamond. For example, the commonly used CuSn10 and CuSn15 pre alloy powders in industry have low strength and weak holding force on diamond. Therefore, it is necessary to improve the powder properties and processing technology. Methods: Adding Zn element to CuSn10 alloy powder can improve powder strength and holding force. CuSnZn-x alloy powder (mass fraction of Zn, x=10.00%, 15.00%, 20.00%, 25.00%, 30.00%) was prepared by atomization process. The hot pressing sintering temperatures were 610 ℃, 615 ℃, 630 ℃, 645 ℃, 655 ℃, and the sintering pressure was 21 MPa. The melting temperature of CuSnZn alloy powder was tested using a differential thermal analyzer. The density of the sintered segment was tested using Archimedes drainage method. The bending strength of the sintered segment was tested using mechanical performance testing equipment. The Rockwell hardness of the sintered segment was measured using a Rockwell hardness tester. The microstructure morphology of the sintered segment and its fracture were analyzed using scanning electron microscopy. Other performances of samples with different Zn contents were analyzed and compared as well, namely theoretical density, Rockwell hardness, and flexural strength, to study the influence of Zn content on sample microstructure. Results: With the increase of Zn content, the rate of decrease in melting temperature of CuSnZn alloy powder first increases and then decreases. When the Zn mass fraction is 30%, the melting temperature decreases to 848 ℃, which is 164 ℃ lower than that of CuSn10. As the Zn content increases, the brass in the sintered segment gradually transforms from the α phase to the α+β phase and then the α+β+β´ phase, resulting in a significant increase in the Rockwell hardness of the segment. The bending strength of the sintered segment first increases and then decreases, reaching a maximum value of 542 MPa when the Zn mass fraction is 20.00%. When the mass fraction of Zn is 10.00% and 15.00%, obvious toughness dimples are observed on the fracture surface of the sintered segment, and particle peeling is observed on the fracture surface. The peeling surface is smooth and flat, indicating grain boundary peeling fracture of the phase structure. When the mass fraction of Zn is 20.00% and 25.00%, a large number of cleavage fracture surfaces are observed on the fracture surface of the sintered segment, and a small amount of smooth concave transgranular fracture is observed, which is partially intergranular fracture and partially transgranular fracture. When the mass fraction of Zn is 30.00%, the fracture surface of the sintered segment is flat and smooth, and the crack passes through the phase interface and grain along the hard and brittle structure, which is transgranular fracture. Conclusions: Adding Zn element can effectively reduce the melting point of alloy powder, and with the increase of Zn content, the hardness of sintered samples increases while the toughness decreases. When the Zn content is 30.00%, the melting temperature of CuSnZn alloy powder reaches its minimum value. When the Zn content exceeds 25.00%, the strength of the sintered samples will gradually decrease. Therefore, in actual production, the appropriate amount of Zn addition and sintering process should be selected based on comprehensive consideration of demand.

Purpose: To investigate the efficacy and safety of a modified dual-incision ophthalmic viscosurgical device-free (OVD-free) method for implantable collamer lens (ICL) implantation in high myopic eyes. Methods: A total of 68 participants were enrolled in this prospective randomized clinical trial, including 33 in the OVD-free group and 35 in the standard group. Operation time and intraocular pressure (IOP) at 2 hours postoperatively were recorded. Visual acuity, refractive power, IOP, corneal endothelium parameters, and anterior segment parameters were assessed at 1 day, 1 week, 1 month, 3 months, and 6 months postoperatively. Postoperative subjective visual quality at 3 months was recorded through a Quality of Vision (QoV) questionnaire. Results: No significant differences in visual acuity, refractive outcomes, and corneal endothelial parameters were found, while the operation time was significantly shorter in the OVD-free group. Both groups showed a significant increase in IOP at 2 hours after surgery, but the increase in the OVD-free group was significantly smaller than that in the standard group. In addition, the frequency of ring-shaped dysphotopsia in the OVD-free group (15.15%) was significantly lower than that in the standard group (40%), and the severity and annoyance of this symptom were also significantly lower in the OVD-free group. Conclusion: The modified OVD-free ICL implantation is a safe, effective, and predictable method for myopia correction, which could be a better choice for short surgery time, better subjective visual perception, and low occurrence of IOP elevation.

Abstract Background Asthma’s complexity, marked by airway inflammation and remodeling, is influenced by hypoxic conditions. This study focuses on the role of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and P53 ubiquitination in asthma exacerbation. Methods High-throughput sequencing and bioinformatics were used to identify genes associated with asthma progression, with an emphasis on GO and KEGG pathway analyses. An asthma mouse model was developed, and airway smooth muscle cells (ASMCs) were isolated to create an in vitro hypoxia model. Cell viability, proliferation, migration, and apoptosis were assessed, along with ELISA and Hematoxylin and Eosin (H&E) staining. Results A notable increase in HIF-1α was observed in both in vivo and in vitro asthma models. HIF-1α upregulation enhanced ASMCs’ viability, proliferation, and migration, while reducing apoptosis, primarily via the promotion of P53 ubiquitination through MDM2. In vivo studies showed increased inflammatory cell infiltration and airway structural changes, which were mitigated by the inhibitor IDF-11,774. Conclusion The study highlights the critical role of the HIF-1α-MDM2-P53 axis in asthma, suggesting its potential as a target for therapeutic interventions. The findings indicate that modulating this pathway could offer new avenues for treating the complex respiratory disorder of asthma.

Abstract As a typical failure phenomenon in transformers, sulfur corrosion has garnered significant attention in the field of high‐voltage engineering. Grain boundary character distribution (GBCD) copper windings have been introduced to enhance sulfur corrosion resistance by slowing down intergranular corrosion. In this study, the sulfur corrosion behaviour and mechanisms of the GBCD copper windings under various temperatures were experimentally and theoretically studied. Results show that GBCD can enhance the corrosion resistance of copper in liquid environments. With the increase in temperatures, the insulating properties of oil and papers in traditional copper windings experience notable degradation, while GBCD copper windings show more stable insulating behaviours. In addition, modelling of grain boundary energy indicates that the grain boundary structure of GBCD copper windings has a lower average interface energy of 0.170 eV/Å2. Calculations of reaction thermodynamics show that GBCD copper windings possess a higher failure temperature (135.2°C) and inhibition degree (activation energy) of the sulfur corrosion (32,557.62 J/mol), revealing the stability and enhanced sulfur corrosion resistance at elevated temperatures.

Abstract Objectives To assess the influence of loneliness on the healthy life expectancy of older adults in China and its gender disparities across different health indicators, in order to provide insights for enhancing the health status and subjective well-being of the older population. Method We conducted a cohort analysis using four waves of weighted samples (2008, 2011, 2014, and 2018) from the Chinese Longitudinal Healthy Longevity Survey, encompassing 15,507 respondents aged 65–99. Physical and subjective health were assessed through activity of daily living (ADL) and self-rated health (SRH), respectively. Utilizing loneliness status as a time-variant variable, we employed the multi-state interpolated Markov Chain to explore the associations between loneliness and age-specific life expectancy (LE), healthy life expectancy (HLE), and the proportion of healthy life expectancy in life expectancy (HLE/LE). Results Compared to the non-lonely population, both LE and HLE were lower among lonely individuals. Regarding gender differences, the HLE/LE for females in the lonely population was consistently lower than that for males. The impact of loneliness on the health of older adults varied by measurement indicators and gender. Specifically, based on ADL results, the decline in HLE/LE was greater for females, with a decline of 53.6% for lonely females compared to 51.7% for non-lonely females between the ages of 65 and 99. For males, the decline was 51.4% for lonely males and 51.5% for non-lonely males. According to SRH, the gender difference in the decline of HLE/LE due to loneliness was less apparent. For males, the change in HLE/LE for non-lonely individuals was 3.4%, compared to 4.2% for lonely individuals, whereas for females, the change was 3.7% for non-lonely individuals and 4.4% for lonely individuals. Conclusion Loneliness exerts varied effects on health across different measurement indicators and gender demographics. Targeted health promotion interventions are imperative to mitigate these negative impacts, particularly emphasizing the enhancement of subjective well-being and physical functioning, especially among older adult females.

Bacterium-like particles (BLPs) have gained significant attention in vaccine development due to their potential as effective immune enhancers and antigen delivery systems. BLPs are generated by boiling lactic acid bacteria in an acidic solution and are devoid of proteins and nucleic acids, offering advantages in terms of ease of preparation, high safety, and good stability. Furthermore, by employing protein anchor (PA), heterogeneous antigens can be efficiently displayed on the surface of BLPs, resulting in enhanced delivery effectiveness. Despite these benefits, most BLP-based vaccines are currently administered via injection or intranasal delivery, with oral delivery remaining limited. This limitation is primarily due to the harsh environment of the gastrointestinal tract, which degrades the antigens displayed on the surface of these particles. To enhance the efficacy of oral immunization with subunit vaccines, we developed a simple and rapid method for self-assembling a lipid membrane onto the surface of BLPs vaccines, achieving an encapsulation efficiency of up to 99%, and the combination has good biosafety. The novel oral delivery system not only preserves the adjuvant activity of BLPs but also efficiently protects antigens from adverse gastrointestinal environments, increasing the absorption of the vaccine in intestinal Peyer’s patches (PPs). Oral immunization was required only once, and protection after the challenge was up to 100%. Furthermore, we observed rapid immunity and cross-protection. Transcriptome analysis of the small intestine suggested that immune enhancement probably be exerted by promoting the absorption and transport of antigens. Therefore, we posit that the design of this new oral delivery system presents a novel approach to advancing the development of oral subunit vaccines.

BackgroundThe gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.Methods16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.ResultsThe composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.ConclusionSex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.

IntroductionIn patients with rheumatoid arthritis (RA), the increased risk of concomitant type 2 diabetes mellitus (T2D) is an important contributor to increased mortality and decreased quality of life; however, the mechanisms and pathogenetic factors remain unknown. MethodsIn this study, we aimed to assess the risk factors for T2D in patients with RA. We recruited 206 healthy controls and 488 patients with RA, 160 of whom had comorbid T2D. General clinical information, disease characteristics, and circulating lymphocyte levels detected using modified flow cytometry were collected from all participants. Logistic regression models adjusted for confounders were fitted to estimate the risk factors of T2D in patients with RA.ResultsThe incidence of RA in patients with T2D was 15.6%. Patients with RA and T2D had a longer disease duration, higher BMI, and a higher incidence of hypertension and a family history of diabetes than those with RA but no T2D. The absolute numbers of T helper 2 cell (Th2) and Regulatory T cells (Treg) decreased in patients with RA and T2D, which led to an increase in the ratios of Th1/Th2 and Th17/Treg cells. Multivariate logistic regression analysis showed that a family history of diabetes, a higher incidence of hypertension, higher neutrophil-lymphocyte ratio (NLR) levels, lower platelet-lymphocyte ratio (PLR) levels, and fewer circulating Th2 and Treg cells were associated with an increased risk of T2D in patients with RA.DiscussionThe levels of peripheral lymphocytes, especially Th2 and Treg cells, are closely related to the occurrence of T2D in patients with RA; however, the influence of body mass index (BMI), family history of diabetes, and systemic inflammation should not be ignored.

Wild soybeans retain many substances significantly reduced or lost in cultivars during domestication. This study utilized LC-MS to analyze metabolites in the seed coats and embryos of wild and cultivated soybeans. 866 and 815 metabolites were identified in the seed extracts of both soybean types, with 35 and 10 significantly differing metabolites in the seed coat and embryos, respectively. The upregulated metabolites in wild soybeans are linked to plant defense, stress responses, and nitrogen cycling. MALDI-MSI results further elucidated the distribution of these differential metabolites in the cotyledons, hypocotyls, and radicles. In addition to their role in physiological processes like growth and response to environmental stimuli, the prevalent terpenoids, lipids, and flavonoids present in wild soybeans exhibit beneficial bioactivities, including anti-inflammatory, antibacterial, anticancer, and cardiovascular disease prevention properties. These findings underscore the potential of wild soybeans as a valuable resource for enhancing the nutritional and ecological adaptability of cultivated soybeans.

Objective: To develop machine learning-based prediction models for all-cause and premature mortality among the middle-aged and elderly population in China. Method: Adults aged 45 years or older at baseline of 2011 from the China Health and Retirement Longitudinal Study (CHARLS) were included. The stacked ensemble model was built utilizing five selected machine learning algorithms. These models underwent training and testing using the CHARLS 2011–2015 cohort (derivation cohort) and subsequently underwent external validation using the CHARLS 2015–2018 cohort (validation cohort). SHapley Additive exPlanations (SHAP) was introduced to quantify the importance of risk factors and explain machine learning algorithms. Result: In derivation cohort, a total of 10,677 subjects were included, 478 died during the follow-up. The stacked ensemble model demonstrated the highest efficacy in terms of its discrimination capability for predicting all-cause mortality and premature death, with an AUC[95 % CI] of 0.826[0.792–0.859] and 0.773[0.725–0.821], respectively. In validation cohort, the corresponding AUC[95 % CI] were 0.803[0.743–0.864] and 0.791[0.719–0.863], respectively. Risk factors including age, sex, self-reported health, activities of daily living, cognitive function, ever smoker, levels of systolic blood pressure, Cystatin C and low density lipoprotein were strong predictors for both all-cause mortality and premature death. Conclusion: Stacked ensemble models performed well in predicting all-cause and premature death in this Chinese cohort. Interpretable techniques can aid in identifying significant risk factors and non-linear relationships between predictors and mortality.

Human exposure to plastic particles has raised great concern among all relevant stakeholders involved in the protection of human health due to the contamination of the food chain, surface waters, and even drinking water as well as due to their persistence and bioaccumulation. Now more than ever, it is critical that we understand the biological fate of plastics and their interaction with different biological systems. Because of the ubiquity of plastic materials in the environment and their toxic potential, it is imperative to gain reliable, regulatory-relevant, science-based data on the effects of plastic micro- and nanoparticles (PMNPs) on human health in order to implement reliable risk assessment and management strategies in the circular economy of plastics. This review presents current knowledge of human-relevant PMNP exposure doses, pathways, and toxic effects. It addresses difficulties in properly assessing plastic exposure and current knowledge gaps and proposes steps that can be taken to underpin health risk perception, assessment, and mitigation through rigorous science-based evidence. Based on the existing scientific data on PMNP adverse health effects, this review brings recommendations on the development of PMNP-specific adverse outcome pathways (AOPs) following the AOP Users’ Handbook of the Organisation for Economic Cooperation and Development (OECD).

Abstract The blood urea nitrogen to albumin ratio (BAR) has been demonstrated as a prognostic factor in sepsis and respiratory diseases, yet its role in severe coronary heart disease (CHD) remains unexplored. This retrospective study, utilizing data from the Medical Information Mart for Intensive Care-IV database, included 4254 CHD patients, predominantly male (63.54%), with a median age of 74 years (IQR 64–83). Primary outcomes included in-hospital, 28-day and 1-year all-cause mortality after ICU admission. The Kaplan–Meier curves, Cox regression analysis, multivariable restricted cubic spline regression were employed to assess association between BAR index and mortality. In-hospital, within 28-day and 1-year mortality rates were 16.93%, 20.76% and 38.11%, respectively. Multivariable Cox proportional hazards analysis revealed associations between the increased BAR index and higher in-hospital mortality (HR 1.11, 95% CI 1.02–1.21), 28-day mortality (HR 1.17, 95% CI 1.08–1.27) and 1-year mortality (HR 1.23, 95% CI 1.16–1.31). Non-linear relationships were observed for 28-day and 1-year mortality with increasing BAR index (both P for non-linearity

Background: Although still the significance of the lung-gut axis for COPD is increasingly highlighted, it’s urgent to ulteriorly comprehend the sophisticated disturbance of the core material system along the lung-gut axis, which is of great importance for the accurate precaution and prognosis of COPD efficiently. Aim of the study: The purpose of this study was to analyze the information connections of the lung-gut axis, thus supporting the effective treatment of COPD. Materials and methods: An integrated multi-omics approach was applied to explore the lung-gut axis in COPD rats. Firstly, based on transcriptomics, the ssGSEA algorithm was used to evaluate changes in pulmonary inflammatory cells. Then, the disturbances of metabolic pathways in lung and feces were revealed by the Lilikoi algorithm using LC-MS and 1H NMR metabolomics. Next, the composition and function of microbial communities in lung and feces were analyzed by 16 s rRNA sequencing. Finally, the association analysis was employed to explore the possible crosstalk between the lung and gut. Furthermore, the core material system in the lung-gut axis was described based on network topology analysis. Result: Firstly, 1652 differential expression genes (involving in immune response-regulating signaling pathway, etc.) and 15 types of inflammatory cells (including neutrophil, etc.) were identified related to COPD. 135 pulmonary differential metabolites (involving in arachidonic acid metabolism, etc.) and 105 fecal differential metabolites (involving in alanine metabolism, etc.) were revealed by metabolomics. The f_Pasteurellaceae, etc. and g_Ruminococcus_2, etc. were identified associated with COPD in lung and gut. Finally, disturbances of the core material system, composed of macrophage, neutrophil, activated dendritic cell, myeloid derived suppressor cell, arachidonic acid metabolism, alpha linolenic acid & linoleic acid metabolism, g_Psychrobacter in lung and bile secretion, p_Proteobacteria in gut, were obtained to analyze the possible information flow of the lung-gut axis. Conclusion: The core material system for the lung-gut axis have been revealed, which might contribute to the illustration of the pathogenesis of COPD. In the future, more researches are required on the impact of the core material system in the lung-gut axis on the onset and recovery process of COPD, suggesting more precise identifying effective treatments for the disease.

Background Nontuberculous mycobacteria pulmonary disease (NTM-PD) exhibits clinical and radiological characteristics similar to those of pulmonary tuberculosis (PTB). This study aimed to develop a novel hematological score (HS) and its related nomogram model to identify NTM-PD in patients with suspected multidrug-resistant pulmonary tuberculosis (SMDR-PTB) due to lack of response to first-line anti-TB treatment (ATT).Methods We retrospectively recruited patients with SMDR-PTB from Wuhan Jinyintan Hospital between January 2014 and January 2022. These patients were divided into NTM-PD and MDR-PTB groups based on pathogen test results. Participants were randomly allocated to training and validation set in a 7:3 ratio. The ROC and LASSO regression were employed to select variables. Multivariate logistic analysis was conducted on the training set to develop the HS and its related nomogram models, followed by internal validation on the validation set.Results The HS was constructed and developed on CKMB, ADA, GGT, LDL, and UHR, demonstrating good predictive value with AUCs of 0.900 and 0.867 in the training and validation sets, respectively. The HS-based nomogram model consists of Age, Gender, DM, HIV infection, ILD and HS, and exhibited strong discriminative ability, accuracy, and clinical utility in two sets. The AUCs were 0.930 and 0.948 in the training set and validation set, respectively.Conclusion HS may be a useful biomarker for identifying NTM-PD in patients with SMDR-PTB. The HS-based nomogram model serves as a convenient and efficient tool for guiding the treatment of SMDR-PTB patients.

Recycled aggregate concrete is a promising low carbon material, which need further analysis on the durability. To investigate the influence of sulfate erosion on recycled concrete made with high-belite sulfoaluminate cement (HBCSA), this study utilized compressive strength and microhardness test to evaluate the effect of sulfate on ITZ. Then by using backscattered electron imaging, scanning electron microscope and energy spectrometry, the mechanism for the microstructural changes that occurred before and after sulfate erosion is revealed. Results showed that after 60 days of sulfate erosion, both aggregate-new mortar and new–old mortar interfaces display reduced microhardness and widened transition zones. Specifically, in the C30 group post-erosion, the microhardness values for the aggregate-new mortar interface ranged from 50.3 to 66.9 MPa, while the new–old mortar interface exhibited a range of 47–77 MPa. Besides, the new–old mortar interface exhibit marginally superior sulfate resistance to the aggregate–new mortar interface at the same concrete strength grade. Moreover, sulfate resistance improvs across all interfaces with increasing strength class. For instance, in the aggregate-new mortar interface, the maximum microhardness post-erosion for C40 showed a 51.6 % increase compared to C30. Through microstructure analysis, it is found that after sulfate erosion, the aggregate–new mortar and new–old mortar interfaces of HBCSA recycled concrete are both enriched with abundant ettringite and gypsum, which causes considerable swelling erosive product formation and even cracking. The less formed cracks in new–old mortar interfaces results in the better sulfate resistance. The finding is helpful for the future research on the high sulfate resistant recycled aggregate concrete.

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

This study explores the combined effects of coal fly ash (FA) and CO2 curing on the flexural strength, compressive strength, and water resistance of magnesium potassium phosphate cement (MKPC). Additionally, the hydration products and microstructure of MKPC and MKPC-FA blends are examined using X-ray diffraction (XRD), thermogravimetric analysis (TGA), mercury injection porosity (MIP), and scanning electron microscopy (SEM). The results demonstrate that carbonation curing effectively improves the mechanical strength and water resistance of MKPC-FA blends by refining the pore structure and reducing porosity. Incorporating fly ash into magnesium phosphate cement leads to a longer setting time and appropriate enhancement in the water resistance of MKPC-FA blends. It should be mentioned that the mechanical strength of MKPC-FA blends declines with increasing fly ash content, and carbonation curing can partially ameliorate these negative effects. Therefore, both incorporating fly ash and storing carbon dioxide have positive effects on the durability and environmental sustainability aspects associated with MKPC preparation.

The field of emergency risk management in chemical parks has been characterized by a lack of fast, precise and dynamic prediction methods. The application of computational fluid dynamics (CFD) models, which offer the potential for dynamic and precise prediction, has been hindered by high computational costs. Therefore, taking liquid benzene as a case study, this paper combined machine learning (ML) algorithms with a CFD-based precise prediction model, to develop an ML model for fast dynamic prediction of heavy gas leakage consequences in chemical parks. Employing the CFD data as the input, the prediction models were developed using ML algorithms, refined with Bayesian optimization for parameter tuning. This study utilized PHOENICS software to establish a dynamic prediction model for the diffusion of liquid benzene leakage, validated by Burro nine experiment data. Comparative analyses of models based on five ML algorithms were conducted to evaluate the reliability of their predictions using both CFD standard and noisy data. The results indicated that temperature had the most significant effect on the consequences of the leakage accidents among four key factors (wind speed, temperature, leakage aperture and atmospheric stability), followed by wind speed. These factors served as input variables for ML model training. Among the models evaluated, the eXtreme Gradient Boosting (XGBoost) model showed superior performance, irrespective of the presence of noise in the data. An XGBoost-based fast prediction model was ultimately developed for predicting the consequences of liquid benzene leakage. A case analysis was conducted to validate the feasibility of the model prediction. The relative errors between the predicted and actual values of the model for acute exposure guideline level-1 (AEGL-1), AEGL-2, and AEGL-3 distances were 2.70%, 2.58%, and 0.23%, respectively. Furthermore, the XGBoost model completed the prediction in only 0.218 s, a stark contrast to the hours necessitated by the CFD model, thus offering substantial computational time savings while maintaining high accuracy levels. This paper introduces an ML model for fast dynamic prediction of heavy gas leakage, enabling chemical parks to make more timely and accurate decisions in emergency risk management.

Central nervous system (CNS) damage is usually irreversible owing to the limited regenerative capability of neurons. Following CNS injury, astrocytes are reactively activated and are the key cells involved in post-injury repair mechanisms. Consequently, research on the reprogramming of reactive astrocytes into neurons could provide new directions for the restoration of neural function after CNS injury and in the promotion of recovery in various neurodegenerative diseases. This review aims to provide an overview of the means through which reactive astrocytes around lesions can be reprogrammed into neurons, to elucidate the intrinsic connection between the two cell types from a neurogenesis perspective, and to summarize what is known about the neurotranscription factors, small-molecule compounds and MicroRNA that play major roles in astrocyte reprogramming. As the malignant proliferation of astrocytes promotes the development of glioblastoma multiforme (GBM), this review also examines the research advances on and the theoretical basis for the reprogramming of GBM cells into neurons and discusses the advantages of such approaches over traditional treatment modalities. This comprehensive review provides new insights into the field of GBM therapy and theoretical insights into the mechanisms of neurological recovery following neurological injury and in GBM treatment.

Ab initio molecular dynamics (AIMD) simulations have become an important tool used in the construction of equations of state (EOS) tables for warm dense matter. Due to computational costs, only a limited number of system state conditions can be simulated, and the remaining EOS surface must be interpolated for use in radiation-hydrodynamic simulations of experiments. In this work, we develop a thermodynamically consistent EOS model that utilizes a physics-informed machine learning approach to implicitly learn the underlying Helmholtz free-energy from AIMD generated energies and pressures. The model, referred to as PIML-EOS, was trained and tested on warm dense polystyrene producing a fit within a 1% relative error for both energy and pressure and is shown to satisfy both the Maxwell and Gibbs–Duhem relations. In addition, we provide a path toward obtaining thermodynamic quantities, such as the total entropy and chemical potential (containing both ionic and electronic contributions), which are not available from current AIMD simulations.

Introduction: An increasing number of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been reported during clinical treatment. We aimed to explore the clinical characteristics of patients with ICIs-induced ITP under different therapeutic strategies based on the FAERS database and explore the potential biological mechanisms in combination with TCGA pan-cancer data.Methods: Data from FAERS were collected for ICIs adverse reactions between January 2012 and December 2022. Disproportionality analysis identified ICIs-induced ITP in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PRP), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker algorithms (MGPS). The potential biological mechanisms underlying ITP induced by ICIs were examined using TCGA transcriptome data on cancers.Results: In the FAERS, 345 ICIs-induced ITP reports were retrieved, wherein 290 (84.06%) and 55 (15.94%) were reported as monotherapy and combination therapy, respectively. The median age of the reported patients with ICIs-induced ITP was 69 years (IQR 60-76), of which 62 (18%) died and 47 (13.6%) had a life-threatening outcome. The majority of reported indications were lung, skin, and bladder cancers, and the median time to ITP after dosing was 42 days (IQR 17-135), with 64 patients (43.5%) experiencing ITP within 30 days of dosing and 88 patients experiencing ITP in less than 2 months (59.9%). The occurrence of ICIs-induced ITP may be associated with ICIs-induced dysregulation of the mTORC1 signaling pathway and megakaryocyte dysfunction.Conclusion: There were significant reporting signals for ITP with nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab/ipilimumab, and pembrolizumab/ipilimumab. Patients treated with anti-PD-1 in combination with anti-CTLA-4 are more likely to have an increased risk of ICIs-induced ITP. Patients with melanoma are at a higher risk of developing ITP when treated with ICI and should be closely monitored for this risk within 60 days of treatment. The potential biological mechanism of ICIs-induced ITP may be related to the dysfunction of megakaryocyte autophagy through the overactivation of the mTOR-related signaling pathway. This study provides a comprehensive understanding of ICIs-induced ITP. Clinicians should pay attention to this potentially fatal adverse reaction.

Abstract Cellular automata (CA) are computational systems that exhibit complex global behavior arising from simple local rules, making them a fascinating candidate for various research areas. However, challenges such as limited flexibility and efficiency on conventional hardware platforms still exist. In this study, we propose a memristor-based circuit for implementing elementary cellular automata (ECA) by extending the stateful three-memristor logic operations derived from material implication (IMP) logic gates. By leveraging the inherent physical properties of memristors, this approach offers simplicity, minimal operational steps, and high flexibility in implementing ECA rules by adjusting the circuit parameters. The mathematical principles governing circuit parameters are analyzed, and the evolution of multiple ECA rules is successfully demonstrated, showcasing the robustness in handling the stochastic nature of memristors. This approach provides a hardware solution for ECA implementation and opens up new research opportunities in the hardware implementation of CA.

Cardiovascular surgery has a high risk of neurological complications, which can increase the burden of disease. Perioperative real⁃time monitoring of neurological function in cardiovascular surgery can assist clinicians to detect neurological abnormalities as early as possible, intervene and reduce the risk of neurological complications in time. The main monitoring indicators include cerebral oxygen saturation (ScO2), EEG, cerebral blood flow (CBF), etc. In this paper, the common perioperative neuromonitoring techniques and their research advances in cardiovascular surgery are reviewed to provide theoretical basis for reducing neurological complications and improve the prognosis of patients.

Following publication, concerns were raised regarding the peer-review process related to the publication of this article [...]

Neofusicoccum laricinum is the causal agent of larch shoot blight, a fungal disease affecting several species of larch. It causes severe damage, including stunting and mortality. This study aims to address the severe impact of larch shoot blight by evaluating the effect of farrerol on the inhibition of Neofusicoccum laricinum in Larix olgensis. We used LC-MS/MS and weighted gene co-expression network analysis to investigate farrerol’s effects on Neofusicoccum laricinum and identify associated genes in resistant and susceptible larch. Our study identified significant differences in metabolite profiles between resistant and susceptible cultivars, with higher concentrations of farrerol showing complete inhibition of N. laricinum. Additionally, specific genes associated with farrerol content were up-regulated in resistant larch. Farrerol at higher concentrations completely inhibited N. laricinum, showing a strong correlation with increased disease resistance. This research suggests that farrerol enhances disease resistance in larch and provides a foundation for developing disease-resistant larch varieties based on antifungal metabolite traits.

A plentiful number of facial expressions is the basis of natural human–robot interaction for high-fidelity humanoid robots. The facial expression imitation of humanoid robots involves the transmission of human facial expression data to servos situated within the robot’s head. These data drive the servos to manipulate the skin, thereby enabling the robot to exhibit various facial expressions. However, since the mechanical transmission rate cannot keep up with the data processing rate, humanoid robots often suffer from jitters in the imitation. We conducted a thorough analysis of the transmitted facial expression sequence data and discovered that they are extremely redundant. Therefore, we designed a two-stage strategy for humanoid robots based on facial keyframe detection and facial keypoint detection to achieve more natural and smooth expression imitation. We first built a facial keyframe detection model based on ResNet-50, combined with optical flow estimation, which can identify key expression frames in the sequence. Then, a facial keypoint detection model is used on the keyframes to obtain the facial keypoint coordinates. Based on the coordinates, the cubic spline interpolation method is used to obtain the motion trajectory parameters of the servos, thus realizing the robust control of the humanoid robot’s facial expression. Experiments show that, unlike before where the robot’s imitation would stutter at frame rates above 25 fps, our strategy allows the robot to maintain good facial expression imitation similarity (cosine similarity of 0.7226), even at higher frame rates.

CsPbIBr2, with its suitable bandgap, shows great potential as the top cell in tandem solar cells. Nonetheless, its further development is hindered by a high defect density, severe carrier recombination, and poor stability. In this study, CsPbI1.5Br1.5 quantum dots were utilized as an additive in the ethyl acetate anti-solvent, while a layer of CsPbBr3 QDs was introduced between the ETL and the CsPbIBr2 light-harvester film. The combined effect of these two QDs enhanced the nucleation, crystallization, and growth of CsPbIBr2 perovskite, yielding high-quality films characterized by an enlarged crystal size, reduced grain boundaries, and smooth surfaces. And a wider absorption range and better energy band alignment were achieved owing to the nano-size effect of QDs. These improvements led to a decreased defect density and the suppression of non-radiative recombination. Additionally, the presence of long-chain organic molecules in the QD solution promoted the formation of a hydrophobic surface, significantly enhancing the long-term stability of CsPbIBr2 PSCs. Consequently, the devices achieved a PCE of 9.20% and maintained an initial efficiency of 85% after 60 days of storage in air. Thus, this strategy proves to be an effective approach for the preparation of efficient and stable CsPbIBr2 PSCs.

Given the increasing environmental concerns and energy consumption, the transformation of the new energy vehicle industry is a key link in the innovation of the energy structure. The shift from traditional fossil fuels to clean energy encompasses various dimensions such as technological innovation, policy support, infrastructure development, and changes in consumer preferences. Predicting the future ownership of electric vehicles (EVs) and then estimating the energy demand for transportation is a pressing issue in the field of new energy. This study starts from dimensions such as cost, technology, environment, and consumer preferences, deeply explores the influencing factors on the ownership of EVs, analyzes the mechanisms of various factors on the development of EVs, establishes a predictive model for the ownership of motor vehicles considering the penetration of electric vehicles based on system dynamics, and then simulates the future annual trends in EV and conventional vehicle (CV) ownership under different scenarios based on the intensity of government funding. Using energy consumption formulas under different power modes, this study quantifies the electrification energy demand for transportation flows as fleet structure changes. The results indicate that under current policy implementation, the domestic ownership of EVs and CVs is projected to grow to 172.437 million and 433.362 million, respectively, by 2035, with the proportion of EV ownership in vehicles and energy consumption per thousand vehicles at 28.46% and 566,781 J·km−1, respectively. By increasing the technical and environmental factors by 40% and extending the preferential policies for purchasing new energy vehicles, domestic EV ownership is expected to increase to 201.276 million by 2035. This study provides data support for the government to formulate promotional policies and can also offer data support for the development of basic charging infrastructure.

Background: C1q/tumor necrosis factor-related protein-9 (CTRP9) is critically involved in the pathophysiology of metabolic and cardiovascular disorders. This investigation aimed to clarify the mechanism underlying the role of CTRP9 in atherosclerosis in apolipoprotein E (ApoE) knockout (KO) mice. Methods: ApoE KO mice were fed a Western diet and injected with a virus which resulted in CTRP9 overexpression or knockdown for 12 weeks. The plasma lipid levels and atherosclerotic plaque areas were measured after the mice were euthanized. Aortas were isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, plasma oxidative stress factors were measured to demonstrate the reliability of the RNA sequencing results. Results: The plasma lipid levels in the CTRP9 overexpression group did not significantly differ from those in the green fluorescence protein (GFP) group. Markablely, CTRP9 overexpression inhibited atherosclerotic plaque formation in ApoE KO mice, whereas CTRP9 knockdown promoted plaque formation. RNA sequencing analysis identified 3485 differentially expressed genes that were prominently enriched across 55 signaling pathways. Additionally, plasma oxidative stress factors were significantly reduced after CTRP9 overexpression, whereas these factors were increased after CTRP9 knockdown, which was consistent with the results of the RNA sequencing analysis. Conclusions: These findings demonstrated that CTRP9 alleviated inflammation and cholesterol metabolism, which reduced oxidative stress in an atherosclerotic animal model. These beneficial effects may mediate the suppression of lesion development in the aorta.

Objective We aimed to assess long-term safety and tolerability of fezolinetant, a nonhormonal neurokinin 3 receptor antagonist, among Chinese women with vasomotor symptoms associated with menopause participating in the MOONLIGHT 3 trial. Methods In this phase 3 open-label study, women in menopause aged 40–65 years received fezolinetant 30 mg once daily for 52 weeks. The primary endpoint was frequency and severity of treatment-emergent adverse events (TEAEs), assessed at every visit through week 52 and one follow-up visit at week 55. Results Overall, 150 women were enrolled (mean age, 54 years) and 105 completed treatment. The frequency of TEAEs was 88.7%. Most TEAEs were mild (63.3%) or moderate (22.7%). The most common TEAE was upper respiratory tract infection (16.0%), followed by dizziness, headache, and protein urine present (10.7% each). There was no clinically relevant change (mean ± standard deviation) in endometrial thickness (baseline, 2.95 ± 1.11 mm; week 52, 2.94 ± 1.18 mm). Alanine aminotransferase and/or aspartate aminotransferase levels >3 times the upper limit of normal were reported in 1.4% of women; no Hy’s Law cases occurred. Conclusions Fezolinetant 30 mg once daily was generally safe and well tolerated over a 52-week period among women in China with vasomotor symptoms associated with menopause. ClinicalTrials.gov Identifier: NCT04451226

Objective To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. Methods In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1–12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13–24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. Results Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was −0.65 (−1.41 to 0.12) at week 4 and −0.55 (−1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were −0.06 (−0.14 to 0.03) and −0.13 (−0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. Conclusions Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study. ClinicalTrials.Gov Identifier: NCT04234204

IntroductionIn many parts of Asia Pacific (APAC), insufficient intake of micronutrients that are important for conception and pregnancy remains a prevalent issue among women of reproductive age. It is crucial to gain insights into women's nutritional awareness and nutrition-related behaviors, as well as how these relate to their health literacy (HL). This understanding can help identify gaps and guide the development of appropriate intervention strategies. However, there appears to be limited relevant data available for the APAC region. We therefore examined nutritional awareness and behaviors among preconception and pregnant women in three APAC countries, and explored how these were related to women's HL.MethodsCross-sectional online surveys were conducted among preconception (i.e., planning to conceive within the next 12 months or currently trying to conceive) and pregnant women in Australia (N = 624), China (N = 600), and Vietnam (N = 300). The survey questionnaire included a validated tool for HL (Newest Vital Sign) and questions to examine awareness and behaviors relating to healthy eating and prenatal supplementation during preconception and pregnancy.ResultsDespite recommendations for a quality diet complemented by appropriate supplementation during preconception and pregnancy, many respondents in each country were not aware of the specific impact of adequate nutrition during these stages. While many respondents reported changes in their diet to eat more healthily during preconception and pregnancy, a substantial proportion were not taking prenatal supplements. Higher HL was related to greater nutritional awareness and higher use of prenatal supplements.DiscussionOur findings suggest that there are gaps in nutritional awareness and practices of many preconception or pregnant women in the three countries. Interventions to improve HL would be valuable to complement conventional knowledge-centric nutrition education, and enhance understanding and empower women to adopt appropriate nutritional practices throughout their preconception/pregnancy journey.

Background: Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality. Methods: We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors. Results: Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend

BackgroundNeural tube defects (NTDs) is the most common birth defect of the central nervous system (CNS) which causes the death of almost 88,000 people every year around the world. Much efforts have been made to investigate the reasons that contribute to NTD and explore new ways to for prevention. We trawl the past decade (2013–2022) published records in order to get a worldwide view about NTDs research field.Methods7,437 records about NTDs were retrieved from the Web of Science (WOS) database. Tools such as shell scripts, VOSviewer, SCImago Graphica, CiteSpace and PubTator were used for data analysis and visualization.ResultsOver the past decade, the number of publications has maintained an upward trend, except for 2022. The United States is the country with the highest number of publications and also with the closest collaboration with other countries. Baylor College of Medicine has the closest collaboration with other institutions worldwide and also was the most prolific institution. In the field of NTDs, research focuses on molecular mechanisms such as genes and signaling pathways related to folate metabolism, neurogenic diseases caused by neural tube closure disorders such as myelomeningocele and spina bifida, and prevention and treatment such as folate supplementation and surgical procedures. Most NTDs related genes are related to development, cell projection parts, and molecular binding. These genes are mainly concentrated in cancer, Wnt, MAPK, PI3K-Akt and other signaling pathways. The distribution of NTDs related SNPs on chromosomes 1, 3, 5, 11, 14, and 17 are relatively concentrated, which may be associated with high-risk of NTDs.ConclusionBibliometric analysis of the literature on NTDs field provided the current status, hotspots and future directions to some extant. Further bioinformatics analysis expanded our understanding of NTDs-related genes function and revealed some important SNP clusters and loci. This study provided some guidance for further studies. More extensive cooperation and further research are needed to overcome the ongoing challenge in pathogenesis, prevention and treatment of NTDs.

After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E2 supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E2 supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E2 treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.

This study first demonstrates that the random distributed feedback fiber laser (RDFL) can be implemented for sensing detection by using the self-mixing effect as a sensing mechanism. By constructing a compact self-mixing velocimeter based on Er-doped RDFL with the integration of a laser, sensing element, and transmission platform, we successfully measured the minimum detectable feedback intensity of 38.65 fW for the velocity signal, corresponding to 0.55 photons per Doppler cycle, exhibiting ultra-high sensitivity dynamics characteristics. In addition, the velocity measurement of a non-cooperative target at a single-channel distance of 100 km is accomplished because of the natural feature of long-distance transmission for the random distributed feedback fiber lasers, which greatly improves the ultra-long detection range in the field of self-mixing sensing. The proposed sensing scheme not only unveils a fresh perspective on the exploration of random fiber laser sensing but also showcases its diverse and wide-ranging applications within the realm of remote sensing measurements.

Introduction:Rana dybowskii Guenther (RDG), as a traditional Chinese medicine, has been shown to have antioxidant effects. However, studies on the anti-aging effect of RDG are still limited.Methods: In this study, we prepared polysaccharides from the skin of RDG (RDGP) by hot water extraction, alcohol precipitation, ion-exchange chromatography and gel chromatography. The proteins were removed using the Sevage method in combination with an enzymatic method. The structural features were analyzed using high-performance gel permeation chromatography, β-elimination reaction and Fourier transform infrared spectra. The anti-aging effect of RDGP was investigated by using D-Gal to establish an aging model in mice, and pathological changes in the hippocampus were observed under a microscope.Results: We obtained the crude polysaccharide DGP from the skin of RDG, with a yield of 61.8%. The free protein was then removed by the Sevage method to obtain DGPI and deproteinated by enzymatic hydrolysis combined with the Sevage method to further remove the bound protein to obtain the high-purity polysaccharide DGPII. Then, DGPIa (1.03 × 105 Da) and DGPIIa (8.42 × 104 Da) were obtained by gel chromatography, monosaccharide composition analysis showed that they were composed of Man, GlcA, GalNAc, Glc, Gal, Fuc with molar ratios of 1: 4.22 : 1.55: 0.18 : 8.05: 0.83 and 0.74 : 1.78: 1: 0.28: 5.37 : 0.36, respectively. The results of the β-elimination reaction indicated the presence of O-glycopeptide bonds in DGPIa. The Morris water maze test indicated that mice treated with DGPIIa exhibited a significantly shorter escape latency and increased time spent in the target quadrant as well as an increase in the number of times they traversed the platform. Pathologic damage to the hippocampus was alleviated in brain tissue stained with hematoxylin-eosin. In addition, DGPIIa enhanced the activities of SOD, CAT, and GSH-Px and inhibited the level of MDA in the serum and brain tissues of aging mice.Discussion: These results suggest that RDGP has potential as a natural antioxidant and provide useful scientific information for anti-aging research.

Abstract Background Postoperative pain is one of the most common complications after surgery. In order to detect early and intervene in time for moderate to severe postoperative pain, it is necessary to identify risk factors and construct clinical prediction models. This study aimed to identify significant risk factors and establish a better-performing model to predict moderate to severe acute postoperative pain after orthopedic surgery under general anesthesia. Methods Patients who underwent orthopedic surgery under general anesthesia were divided into patients with moderate to severe pain group (group P) and patients without moderate to severe pain group (group N) based on VAS scores. The features selected by Lasso regression were processed by the random forest and multivariate logistic regression models to predict pain outcomes. The classification performance of the two models was evaluated through the testing set. The area under the curves (AUC), the accuracy of the classifiers, and the classification error rate for both classifiers were calculated, the better-performing model was used to predict moderate to severe acute postoperative pain after orthopedic surgery under general anesthesia. Results A total of 327 patients were enrolled in this study (228 in the training set and 99 in the testing set). The incidence of moderate to severe postoperative pain was 41.3%. The random forest model revealed a classification error rate of 25.2% and an AUC of 0.810 in the testing set. The multivariate logistic regression model revealed a classification error rate of 31.3% and an AUC of 0.764 in the testing set. The random forest model was chosen for predicting clinical outcomes in this study. The risk factors with the greatest and second contribution were immobilization and duration of surgery, respectively. Conclusions The random forest model can be used to predict moderate to severe acute postoperative pain after orthopedic surgery under general anesthesia, which is of potential clinical application value.

Abstract Background Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. Methods We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis. Conclusion This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary.

Abstract Background This meta-analysis compares the efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) to conventional interbody fusion in lumbar degenerative diseases (LDD). Methods An extensive literature search was conducted in PubMed, Web of Science, and the Cochrane Library. Research related to UBE-TLIF published up to November 2022 was reviewed. The relevant articles were selected based on inclusion and exclusion criteria, as well as an evaluation of the quality of the data extraction literature. Meta-analysis was performed using Review Manager 5.3 software. Results This meta-analysis included six high-quality case–control trials (CCTs) involving 621 subjects. The clinical outcomes assessment showed no statistical differences in complication rates, fusion rates, leg pain VAS scores, or ODI scores. After UBE-TLIF, low back pain VAS scores were significantly improved with less intraoperative blood loss and a shorter hospital stay. A longer time was required for UBE-TLIF, however. Conclusion Despite the lack of sufficient high quality randomized controlled trials (RCTs) in this study, the results of this meta-analysis suggest that UBE-TLIF is more effective than open surgery in terms of length of stay, blood loss reduction during surgery, and improved low back pain after surgery. Nevertheless, the evidence will be supplemented in the future by more and better quality multicenter randomized controlled trials.