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ABSTRACT The association of serum N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) with insulin resistance (IR), as measured by homeostasis model assessment of insulin resistance (HOMA‐IR), in the general population is unclear. Our study aimed to characterize its relationship in a large community‐based population. Subjects were recruited from the Danyang city between 2017 and 2019. Serum NT‐proBNP was measured using an enhanced chemiluminescence immunoassay. IR was defined by a HOMA‐IR in the highest sex‐specific quartile. Categorical and continuous analyses were performed with sex‐specific NT‐proBNP tertiles and naturally logarithmically transformed NT‐proBNP (lnNTproBNP), respectively. The 2945 participants (mean age 52.8 years) included 1728 (58.7%) women, 1167 (39.6%) hypertensive patients, 269 (9.1%) diabetic patients, and 736 (25.0%) patients with IR. In simple and multivariate‐adjusted regression analyses, serum lnNTproBNP were both negatively associated with HOMA‐IR (β = −0.19 to −0.25; p < 0.0001). Similar results were also obtained in multiple subgroup analyses. In multiple logistic regression analyses, elevated serum NT‐proBNP was associated with lower risks of IR (odds ratios: 0.68 and 0.39; 95% confidence intervals: 0.61–0.74 and 0.30–0.50 for lnNTproBNP and top vs. bottom tertiles, respectively; p < 0.0001). In conclusion, increased serum NT‐proBNP level was strongly associated with a lower risk of IR in Chinese.

Abstract The formation of human collagen requires the presence of Prolyl 3-hydroxylase 1 (P3H1), but the regulatory mechanism of P3H1 remained insufficiently understood. Our study aimed to identify the role of P3H1 in clear cell renal cell carcinoma (ccRCC). P3H1 expression in ccRCC was validated using multiple databases and in vitro experiments. We performed a correlation analysis of P3H1 with drug sensitivity, immune checkpoints, and immune cell infiltration using transcriptome and single-cell sequencing. Drawing upon the Encyclopedia of RNA Interactomes database, we selected P3H1 as the focal point of our investigation, meticulously uncovering the intricate network of microRNAs and lncRNAs that potentially orchestrate ceRNA mechanisms. This study employs a multidimensional approach integrating vitro assays and multi-omics bioinformatics analyses to investigate P3H1’s impact on ccRCC prognosis, immune modulation, immune checkpoints, ceRNA regulatory network, drug sensitivity, and therapeutic responses, aiming to uncover new insights into its therapeutic potential and inform future clinical strategies.

Abstract Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague–Dawley (SD) rat was employed to investigate the hydrogel’s wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel’s proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

Abstract In this work, a control strategy based on fuzzy sliding mode control (FSMC) is applied to effectively manage the large-amplitude chaotic vibrations exhibited by a simply supported beam. The analysis considers the nonlinear beam structure, which is subjected to an external load. Hamilton’s principle is employed, and the equations of motion are derived for the studied structure. The 3rd Galerkin discretization is employed to derive the ordinary differential governing equation of the structure. A control strategy is presented to decrease the response of the obtained multidimensional system. The vibration of a one-dimensional system is compared with that of the derived multidimensional system. As shown throughout the study, a multidimensional nonlinear system of the structure must be considered for accurate dynamic estimation. By using the recurrent neural network (RNN) model, we can accurately predict chaotic motion and effectively apply control strategies to suppress chaotic motion. The efficacy and suitability of the employed control strategy have been demonstrated by controlling chaos in the beam’s multidimensional system.

Abstract A new control approach based on fuzzy sliding mode control (FSMC) is proposed to regulate the chaotic vibration of an axial string. Hamilton’s principle is used to formulate the nonlinear equation of motion of the axial translation string, and the von Kármán equations are used to analyse the geometric nonlinearity. The governing equations are nondimensionalized as partial differential equations and transformed into a nonlinear 3-dimensional system via the third-order Galerkin approach. An active control technique based on the FSMC approach is suggested for the derived dynamic system. By using a recurrent neural network model, we can accurately predict and effectively apply a control strategy to suppress chaotic movements. The necessity of the suggested active control method in the regulation of the nonlinear axial translation string system is proven using different chaotic vibrations. The results show that the study of the chaotic vibrations of axially translating strings requires nonlinear multidimensional dynamic systems of axially moving strings; the validity of the proposed control strategy in controlling the chaotic vibration of axially moving strings in a multidimensional form is demonstrated.

Abstract Compared to traditional lower-limb prostheses (LLPs), intelligent LLPs are more versatile devices with emerging technologies, such as microcontrollers and user-controlled interfaces (UCIs). As emerging technologies allow a higher level of automation and more involvement from wearers in the LLP setting adjustments, the previous framework established to study human factors elements that affect wearer-LLP interaction may not be sufficient to understand the new elements (e.g., transparency) and dynamics in this interaction. In addition, the increased complexity of interaction amplifies the limitations of the traditional evaluation approaches of wearer-LLP interaction. Therefore, to ensure wearer acceptance and adoption, from a human factors perspective, we propose a new framework to introduce elements and usability requirements for the wearer-LLP interaction. This paper organizes human factors elements that appear with the development of intelligent LLP technologies into three aspects: wearer, device, and task by using a classic model of the human-machine systems. By adopting Nielsen’s five usability requirements, we introduce learnability, efficiency, memorability, use error, and satisfaction into the evaluation of wearer-LLP interaction. We identify two types of wearer-LLP interaction. The first type, direct interaction, occurs when the wearer continuously interacts with the intelligent LLP (primarily when the LLP is in action); the second type, indirect interaction, occurs when the wearer initiates communication with the LLP usually through a UCI to address the current or foreseeable challenges. For each type of interaction, we highlight new elements, such as device transparency and prior knowledge of the wearer with the UCI. In addition, we redefine the usability goals of two types of wearer-LLP interaction with Nelson’s five usability requirements and review methods to evaluate the interaction. Researchers and designers for intelligent LLPs should consider the new device elements that may additionally influence wearers’ acceptance and the need to interpret findings within the constraints of the specific wearer and task characteristics. The proposed framework can also be used to organize literature and identify gaps for future directions. By adopting the holistic usability requirements, findings across empirical studies can be more comparable. At the end of this paper, we discuss research trends and future directions in the human factors design of intelligent LLPs.

Abstract Covalent organic frameworks (COFs) have emerged as promising platforms for membrane separations, while remaining challenging for separating ions in a fast and selective way. Here, we propose a concept of COF membranes with vertically aligned nanorods for efficient separation of rare metal ions. A quaternary ammonium-functionalized monomer is rationally designed to synthesize COF layers on porous substrates via interfacial synthesis. The COF layers possess an asymmetric structure, in which the upper part displays vertically aligned nanorods, while the lower part exhibits an ultrathin dense layer. The vertically aligned nanorods enlarge contact areas to harvest water and monovalent ions, and the ultrathin dense layer enables both high permeability and selectivity. The resulting membranes exhibit exceptional separation performances, for instance, a Cs+ permeation rate of 0.33 mol m−2 h−1, close to the value in porous substrates, and selectivities with Cs+/La3+ up to 75.9 and 69.8 in single and binary systems, highlighting the great potentials in the separation of rare metal ions.

Abstract Small-caliber (≤ 6 mm) vascular grafts are commonly used to treat vascular diseases, yet intimal hyperplasia at the distal end-to-side anastomosis remains a significant complication with long-term use. Helical flow has been shown to reduce the risk of cardiovascular complications effectively. Integrating helical flow through an inbuilt helical ridge in vascular grafts is intended to improve hemodynamic performance and mitigate issues such as flow-induced thrombosis and intimal hyperplasia. However, inadequate helical flow strength may limit its effectiveness. This study proposes a novel design for an inbuilt helical ridge in small-caliber grafts to achieve enhanced helical flow. Two novel small-caliber vascular grafts with variable-pitch helical ridges, incorporating both decreasing and increasing pitches, were designed. Their effectiveness was assessed through numerical simulations and in vitro experiments to evaluate their performance in arterial graft applications. The small-caliber vascular grafts incorporating variable-pitch helical ridges significantly improved helical flow structure and distribution, optimized wall shear stress distribution, and reduced platelet adhesion compared to conventional and constant-pitch helical ridge grafts. Among the various new designs, the small-caliber vascular graft featuring decreasing variable-pitch helical ridges has demonstrated better performance. This design is well-suited for small-caliber bypass surgeries, as it is effective in improving hemodynamic performance by improving helical flow into asymmetric structures and increasing helical flow density distribution.

Abstract This article delves into a hybrid galloping energy harvester featuring a longitudinally aligned triangular-shaped bluff body. Numerically, it analyzes how the position of a lumped mass influences the average output power of the harvester under concurrent base excitation and galloping. In comparison with traditional hybrid energy harvesters, the impact of three factors—low airflow velocity, small base excitation amplitude, and low frequency—is examined for each case of lumped mass deployment. The findings reveal that optimal mass positioning markedly enhances the harvester’s average power output when there are low airflow velocities, small base excitation amplitudes, and low frequencies, constituting a novel contribution to the field. Through numerous numerical simulations, it is determined that the optimal position for deploying the lumped mass is approximately 60–70% along the length of the cantilever beam substrate.

Abstract Heat shock protein 70 (HSP70) is one kind of molecular chaperones which are widely found in organisms, and its members are highly conserved among each other, with important roles in plant growth and development. In this study, 56 HSP70 genes were identified from the apple genome database. Analysis of gene duplication events showed that tandem and segmental duplication events play an important role in promoting the amplification of the MdHSP70 gene family. Collinearity analysis showed that HSP70 family members of apple were more closely related to HSP70 family members of Arabidopsis, tomato and soybean. The promoter region of the apple HSP70 genes contains a large number of cis-acting elements in response to hormones and stress. Tissue-specific expression analysis showed that some of the genes were associated with various stages of the apple growth process. Codon preference analysis showed small differences between codon bases 1 and 3 in the apple HSP70 genome, and the codon base composition had a small effect on codon usage preference. The multiple expression patterns of the MdHSP70 gene suggested that MdHSP70 gene members play important roles in growth and development and in response to hormonal and abiotic stresses. The yeast two-hybrid (Y2H) demonstrated that MdHSP70-53 interacts with MdDVH24_032563. The qRT-PCR analysis showed that most MdHSP70 members’ hormonal and abiotic stresses (MdHSP70-6, MdHSP70-26 and MdHSP70-45) appeared to be highly expressed. To further elucidate the function of MdHSP70 (6, 26, 45), we introduced them into tobacco to confirm subcellular locations and noted that these genes are located in the cytoplasm and cell membrane. This study serves as a theoretical basis for further studies of the MdHSP70 gene and helps to further investigate the functional characterization of MdHSP70 gene.

Abstract Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.

ABSTRACT Introduction: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). Materials and Methods: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. Results: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). Conclusions: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

Abstract The relationship between smoking and testosterone levels in adult males remains a topic of ongoing debate. Serum cotinine is considered a reliable marker of both smoking intensity and exposure to tobacco smoke. Therefore, we aim to examine the association between serum cotinine levels and total testosterone concentrations in adult males using data from the U.S. National Health and Nutrition Examination Survey (NHANES) database. Our study assessed the relationship between serum cotinine and total testosterone using weighted linear regression models and subgroup analysis. A fully adjusted model with smooth curve fitting was employed to investigate the potential nonlinear association between serum cotinine and total testosterone. Threshold effects were analyzed to identify the inflection point between serum cotinine and total testosterone. Indeed, a total of 7797 participants were included in our study. After adjusting for potential confounding variables, the findings indicate a positive association between serum cotinine levels and total testosterone levels (β: 0.05, 95%CI: 0.02, 0.09). Furthermore, applying smoothed curve fitting analysis and threshold effects, an inflection point was detected at a serum cotinine level of 487 ng/ml. Above this threshold, total testosterone levels declined with increasing serum cotinine levels. In conclusion, the findings of our study suggest a positive association between elevated serum cotinine levels and total testosterone levels in adult men. However, it is essential to note that this association may be reversed at excessively high serum cotinine concentrations.

Fault slip rates are critical for understanding the evolution of active faults, earthquake recurrence, and crustal deformation. Yet variations in slip rate along the Haiyuan Fault Zone (HYFZ), a large-scale sinistral strike-slip fault in the northeastern margin of the Tibetan Plateau, remain disputed. Here, we investigate in detail late Quaternary and present-day fault slip rates for several segments across the HYFZ based on previously published geologic and geodetic (i.e. GNSS and InSAR) estimates. Our results reveal that the strike-slip rates increase from ~1.6±0.4–1.8±0.3 mm/a on the Halahu (HLH) fault to ~5.2±1.3–6.2±0.9 mm/a on the Lenglongling (LLL) and Jinqianghe (JQH) faults, then decrease to ~3.9±0.8–4.6±0.3 mm/a on the Maomaoshan (MMS) and Laohushan (LHS) faults, subsequently remain relatively constant (i.e. ~4.6±0.8–4.8±0.7 mm/a) on the Haiyuan (HY) fault (in narrow sense), and finally decrease to ~1.3±0.1–1.5±0.3 mm/a on the Liupanshan (LPS) fault, from west to east. These results indicate that the strike-slip rates on the LLL and JQH faults are highest and decrease toward fault tips along the HYFZ, approximating an asymmetrical bell-shaped distribution. Furthermore, geodetic (short-term) and geologic (long-term) slip rates are in general agreement, indicating that the slip rates were relatively constant in the recent geologic history. Despite the shallow creep on the LHS fault, the Tianzhu Seismic Gap, Tuolaishan (TLS), LLL, and LPS faults have a large locking depth, strain accumulation, and/or long seismic quiescence period, underscoring the substantial seismic hazard in these areas. Our study contributes to characterizing the total slip rate budget across the HYFZ and provides insight into further understanding of seismic hazard and regional crustal deformation.

Abstract This paper investigates the control problem of spacecraft rendezvous with obstacle constraint, considering the external disturbance forces caused by orbit perturbation. Firstly, the translational dynamic model of spacecraft rendezvous is given and then rewritten into a second‐order fully‐actuated system form. Then, by employing the prescribed performance control method, the performance function and error transformation are determined, pre‐defining the prescribed performance bounds. Moreover, the fully‐actuated system approach is used to linearize the original nonlinear system, which simplifies the processes of control law design and ensures model accuracy. After that, to ensure that the spacecraft could avoid the dangerous zone during its manoeuvre, the artificial potential function is introduced, based on which a sliding mode surface is designed. Finally, the prescribed performance control–artificial potential function‐based control law is derived, further adopting the neuro‐adaptive method to deal with external interferences. The stability of the close‐loop control system is analysed through the Lyapunov approach and the effectiveness of the proposed control scheme is verified by carrying out a numerical simulation.

Abstract Metavalent bonding is a unique bonding mechanism responsible for exceptional properties of materials used in thermoelectric, phase-change, and optoelectronic devices. For thermoelectrics, the desired performance of metavalently bonded materials can be tuned by doping foreign atoms. Incorporating dopants to form solid solutions or second phases is a crucial route to tailor the charge and phonon transport. Yet, it is difficult to predict if dopants will form a secondary phase or a solid solution, which hinders the tailoring of microstructures and material properties. Here, we propose that the solid solution is more easily formed between metavalently bonded solids, while precipitates prefer to exist in systems mixed by metavalently bonded and other bonding mechanisms. We demonstrate this in a metavalently bonded GeTe compound alloyed with different sulfides. We find that S can dissolve in the GeTe matrix when alloyed with metavalently bonded PbS. In contrast, S-rich second phases are omnipresent via alloying with covalently bonded GeS and SnS. Benefiting from the reduced phonon propagation and the optimized electrical transport properties upon doping PbS in GeTe, a high figure-of-merit ZT of 2.2 at 773 K in (Ge0.84Sb0.06Te0.9)(PbSe)0.05(PbS)0.05 is realized. This strategy can be applied to other metavalently bonded materials to design properties beyond thermoelectrics.

Abstract Combination of immunotherapy with radiotherapy is under active investigation. The PACIFIC trial firmly established the treatment paradigm of consolidation immunotherapy following definitive chemoradiotherapy, inspiring a series of similar or exploratory combination regimens. This summary highlighted six reports updated in the 2024 ASCO Annual Meeting.

Abstract Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.

The purpose of the present study was to assess the nutritional value of yeast culture (YC) and to explore the effect of YC on growth performance and health of piglets fed low-protein diets. In Exp. 1, 12 growing barrows were allocated into control diet and YC diet treatments to determine the available energy of YC. Results showed that the digestible energy and metabolizable energy of YC are 12.12 and 11.66 MJ/kg dry matter (DM), respectively. In Exp. 2, 12 growing barrows were surgically equipped with a T-cannula near the distal ileum and were assigned to 2 dietary treatments (nitrogen-free diet and YC diet), and the amino acid digestibility of YC was determined. In Exp. 3, a total of 96 weaned piglets were randomly divided into 4 treatments, including low-protein basal diet (Basal), Basal + 0.5% YC (0.5%YC), Basal + 1.0% YC (1.0%YC), and Basal + 1.5% YC (1.5%YC). The results were as follows: YC supplementation linearly improved the weight gain and feed intake ratio (P

ObjectivesThe hardness of silicon carbide is second only to those of diamond, cubic boron nitride, and boron carbide, making its processing very difficult. Compared with plastic metal materials, the brittle and hard nature of silicon carbide makes it prone to brittle fracture and edge fragmentation during processing, greatly affecting its superior performance. Therefore, it is crucial to carefully select appropriate cutting methods and establish reasonable cutting process conditions.MethodsThe finite element software Abaqus was used to establish a model of micro-cutting silicon carbide crystal with a diamond conical grain, and the selection range of micro-cutting depth and speed was determined by the pre-simulation model. Then, the main and secondary factors affecting the cutting force were analyzed, and the influence of a single cutting parameter on the cutting effect was studied. In addition, with the help of Hertzian contact stress, the influence of the loading force on the friction force, the morphology of the cutting edge, and the cutting depth was verified by the tip scratching experiment.Results(1) The cutting depth is a crucial factor that greatly impacts the quality of the cutting process. When the cutting depth is less than 1.50 μm, the removal of silicon carbide material primarily occurs through plastic removal. However, when the cutting depth exceeds 1.50 μm, cracks of varying lengths and pits of different sizes gradually form at the cutting edge of the workpiece. As the cutting depth increases, the length of cracks and the number of pits also increase. This type of removal is known as brittle removal. To ensure the integrity of the cutting edge and minimize damage to the silicon carbide workpiece, it is essential to control the cutting depth of the abrasive particles during stages I and III, keeping it below 1.50 μm. (2) Through variance and range analysis of the main cutting force, the relationship between the three factors and the magnitude of the main cutting force is V > W > U, meaning that cutting depth is the most important factor affecting cutting force. The optimal solution V1W1U2 and cutting parameters have been determined, namely a diamond abrasive cutting depth of 0.50 μm, a diamond abrasive cutting edge angle of 60°, and a cutting speed of 76 m/s. Cutting depth is the main factor affecting the magnitude of cutting force, while cutting speed and cutting edge angle are secondary factors. (3) As the cutting depth increases, the affected area surrounding the cut also expands, causing an increase in equivalent stress even in areas where the abrasive particles do not come into contact with the workpiece. This phenomenon is responsible for the development of cutting edge cracks and pits. Additionally, as the cutting depth increases, the main cutting force experiences greater fluctuations. To maintain cutting stability, it is important to control the cutting depth. In the high-speed cutting range of 60-106 m/s, the impact of cutting speed on cutting force is minimal. Therefore, increasing the cutting speed can be an effective method for improving cutting efficiency and ensuring high-quality cuts. For optimal results, a cutting depth of 0.50 μm and a cutting speed of 76 m/s are recommended. (4) The coefficient of friction is not only affected by the properties of the two materials in contact, but also by the depth of the diamond probe pressing into the workpiece. The greater the depth of pressing, the higher the coefficient of friction and the greater the frictional force. The surface of the microgrooves is clear and tidy, with relatively smooth edges. Under the same Hertz contact stress, the simulated depth values and experimental depth values show a consistent trend with the change in loading force.ConclusionsFinite element simulation has become a valuable tool for studying the interaction and removal of materials in the precision machining of crystal materials. The purpose of this article is to investigate the removal characteristics of silicon carbide and determine the optimal range of cutting parameters. The study analyzes cutting force, stress distribution, and removal mechanisms, and proposes effective methods for enhancing cutting efficiency. The findings of this research can contribute to improving the smoothness of the cutting edge and reducing subsurface damage to the workpiece. Furthermore, this research has significant implications for understanding the impact of process parameters on cutting accuracy and the removal mechanism of hard and brittle materials during cutting.

Abstract Purpose The causal relationship between life course adiposity with metabolic dysfunction-associated steatotic liver disease (MASLD) is ambiguous. We aimed to investigate whether there is an independent genetic causal relationship between body size at various life course and MASLD. Methods We performed univariable and multivariable Mendelian randomization (MR) to estimate the causal effect of body size at different life stages on MASLD (i.e., defined by the clinical comprehensive diagnosis from the electronic health record [HER] codes [ICD9/ICD10] or diagnostic phrases), including birthweight, childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP). Results In univariate analyses, higher genetically predicted lower birthweight (ORIVW = 0.61, 95%CI, 0.52 to 0.74), Childhood BMI ( ORIVW = 1.37, 95%CI, 1.12 to 1.64), and adult BMI (ORIVW = 1.41, 95%CI, 1.27 to 1.57) was significantly associated with subsequent risk of MASLD after Bonferroni correction. The MVMR analysis demonstrated compelling proof that birthweight and adult BMI had a direct causal relationship with MASLD. However, after adjusting for birthweight and adult BMI, the direct causal relationship between childhood BMI and MASLD disappeared. Conclusion For the first time, this MR elucidated new evidence for the effect of life course adiposity on MASLD risk, providing lower birthweight and duration of obesity are independent risk factors for MASLD. Our findings indicated that weight management during distinct time periods plays a significant role in the prevention and treatment of MASLD.

Abstract Smooth muscle cell (SMC) phenotypic modulation, primarily driven by PDGFRβ signaling, is implicated in occlusive cardiovascular diseases. However, the promotive and restrictive regulation mechanism of PDGFRβ and the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14) in neointimal hyperplasia remain unclear. Our study observes a marked upregulation of PTPN14 in SMCs during neointimal hyperplasia. PTPN14 overexpression exacerbates neointimal hyperplasia in a phosphatase activity-dependent manner, while SMC-specific deficiency of PTPN14 mitigates this process in mice. RNA-seq indicates that PTPN14 deficiency inhibits PDGFRβ signaling-induced SMC phenotypic modulation. Moreover, PTPN14 interacts with intracellular region of PDGFRβ and mediates its dephosphorylation on Y692 site. Phosphorylation of PDGFRβY692 negatively regulates PDGFRβ signaling activation. The levels of both PTPN14 and phospho-PDGFRβY692 are correlated with the degree of stenosis in human coronary arteries. Our findings suggest that PTPN14 serves as a critical modulator of SMCs, promoting neointimal hyperplasia. PDGFRβY692, dephosphorylated by PTPN14, acts as a self-inhibitory site for controlling PDGFRβ activation.

Abstract Diagnosing liver lesions is crucial for treatment choices and patient outcomes. This study develops an automatic diagnosis system for liver lesions using multiphase enhanced computed tomography (CT). A total of 4039 patients from six data centers are enrolled to develop Liver Lesion Network (LiLNet). LiLNet identifies focal liver lesions, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), metastatic tumors (MET), focal nodular hyperplasia (FNH), hemangioma (HEM), and cysts (CYST). Validated in four external centers and clinically verified in two hospitals, LiLNet achieves an accuracy (ACC) of 94.7% and an area under the curve (AUC) of 97.2% for benign and malignant tumors. For HCC, ICC, and MET, the ACC is 88.7% with an AUC of 95.6%. For FNH, HEM, and CYST, the ACC is 88.6% with an AUC of 95.9%. LiLNet can aid in clinical diagnosis, especially in regions with a shortage of radiologists.

Abstract Monoculture cultivation patterns in agro-ecosystems only provide less varied soil organic matter (SOM) molecules of plant origin. Whether and how the natural fallow stage between cultivation seasons facilitates the restoration of SOM molecular diversity and mitigates the adverse impacts of constant cropping pattern is elusive. Here, we utilized FT-ICR-MS, UHPLC-MS/MS, and high-throughput sequencing to investigate the biological change processes in SOM molecular composition under cultivation and fallow status in a long-farmed paddy field. Our study showed that SOM molecular diversity increased by 45.70%–85.36% in fallow stage compared to rice cultivation season. SOM molecular diversity was positively correlated with bacterial diversity and root exudate molecular diversity, and negatively correlated with fungal diversity. Notably, root exudate molecular diversity accounted for 48.48% of the variation in SOM molecular diversity. The increased SOM molecular diversity in fallow stage was attributed more to the diverse plant-produced molecules than the microbe-consumed molecules. Plant species turnover resulted in the conversion of root exudate components to Organoheterocyclic compounds and Organic acids/derivatives from rice planting stage to fallow stage. Recruited microbes were dominated by Basidiomycita, Ascomycota, Acidobacteria, Chloroflexi and Proteobacteria, resulting in the transformation from carbohydrates, lipid-like SOM molecules to lipid-like and lignin-like SOM molecules. Both field and microcosm experiments confirmed that root exudates are the main source of SOM molecules, and are influenced by the soil microbial community. This study provides solid evidence that fallow status in agro-ecosystems provides explosion of biodiversity and counteracts the negative effects of long-term monoculture cultivation on SOM diversity. Graphical Abstract

Abstract Dielectric capacitors are highly desired for electronic systems owing to their high-power density and ultrafast charge/discharge capability. However, the current dielectric capacitors suffer severely from the thermal instabilities, with sharp deterioration of energy storage performance at elevated temperatures. Here, guided by phase-field simulations, we conceived and fabricated the self-assembled metadielectric nanostructure with HfO2 as second-phase in BaHf0.17Ti0.83O3 relaxor ferroelectric matrix. The metadielectric structure can not only effectively increase breakdown strength, but also broaden the working temperature to 400 oC due to the enhanced relaxation behavior and substantially reduced conduction loss. The energy storage density of the metadielectric film capacitors can achieve to 85 joules per cubic centimeter with energy efficiency exceeding 81% in the temperature range from 25 °C to 400 °C. This work shows the fabrication of capacitors with potential applications in high-temperature electric power systems and provides a strategy for designing advanced electrostatic capacitors through a metadielectric strategy.

Abstract Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid–structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement.

Employing crystal facets to regulate the catalytic properties in electrocatalytic carbon dioxide reduction reaction (eCO2RR) has been well demonstrated on electrocatalysts containing single metals but rarely explored for bimetallic systems. Here, we synthesize ZnSn(OH)6 (ZSO) microcrystals (MCs) with distinct facets and investigate the facet effects in eCO2RR. Electrochemical studies and in situ Fourier Transform Infrared Spectroscopy (in situ-FTIR) reveal that ZSO MCs produce mainly C1 products of HCOOH and CO. The {111} facet of the ZSO MCS exhibits higher selectivity and faradaic efficiency (FE) than that of the {100} facet over a wide range of potentials (−0.9 V ∼ −1.3 V versus RHE). Density Functional Theory (DFT) calculations elucidate that the {111} facet is favorable to the adsorption/activation of CO2 molecules, the formation of intermediate in the rate-determining step, and the desorption of C1 products of CO and HCOOH molecules.

Abstract The low ionic conductivity of composite solid-state electrolytes due to the lack of free Li-ions and Li dendrite growth induced by the low transference number seriously hinder their application. Herein, we find that the giant dielectric ceramic of Li0.3Ti0.02Ni0.68O (LTNO) with ultra-high dielectric constant can greatly promote the dissociation of Li salt to generate abundant movable Li-ions and realize a high room-temperature ionic conductivity (4.09 × 10–4 S cm−1) as well as a low activation energy (0.16 eV). The oxygen vacancies on the surface of LTNO can effectively immobilize the anions to achieve a high Li transference number (0.61). Furthermore, the enhanced dielectric properties of the composite electrolyte induce homogenous Li plating/stripping to suppress the growth of Li dendrites. As a result, the Li||Li symmetric cells exhibit long lifespan of 2400 h and 1150 h at 0.1 mA cm−2 and 0.2 mA cm−2, respectively. The Li||LiNi0.8Co0.1Mn0.1O2 solid-state full cells show a high capacity retention of 83% after 430 cycles at 2C. This work highlights the critical role of high dielectric property and oxygen defects of fillers in composite solid-state electrolytes, and provides a demonstration for the application of giant dielectric materials in solid-state Li metal batteries.

Introduction: The purpose of this study was to investigate the association of central lean mass distribution with the risk of mortality. Methods: This cohort study included 40,283 UK Biobank participants. Cox proportional hazards regression models were used to estimate the association of central lean mass distribution, i.e., trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, with the risk of mortality. Results: The median age of the participants was 65 years, and 52% were women. During a median follow-up of 4.18 years, 674 participants died, of whom 366 were due to cancer and 126 were due to cardiovascular causes. Compared with the lowest tertile of a trunk-to-leg lean mass ratio, the multivariable-adjusted (age, sex, ethnicity, lifestyle, comorbidities, body mass index, and appendicular muscle mass index) hazards ratios of the highest tertile of trunk-to-leg lean mass ratio were 1.55 (95% CI: 1.23–1.94), 1.69 (95% CI: 1.26–2.26), and 1.14 (95% CI: 0.72–1.80) for all-cause, cancer, and cardiovascular mortality, respectively. Neutrophil-to-lymphocyte ratio mediated 9.3% (95% CI: 3.3%–40.4%) of the association of trunk-to-leg lean mass ratio with all-cause mortality. There was evidence for additive interactions of trunk-to-leg lean mass ratio with older age and poor diet quality for all-cause mortality. Conclusion: Trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, was positively associated with the risks of all-cause and cancer mortality, independent of general obesity and central obesity, in UK middle-aged and older adults. Central lean mass distribution may interact synergistically with aging and poor diet quality to further increase the risk of death.

Residual δ-ferrite is ubiquitous in M50NiL bearing steel and seriously deteriorates impact toughness. In the present work, the formation mechanism of δ-ferrite in M50NiL steel and the influence of element segregation on its formation process were investigated. The residual δ-ferrite was proved to form directly from the final liquid phase at the end of solidification due to serious segregation of Mo and V elements. Calculation results indicate that the segregation of Mo and V elements expanded the “L + δ'' two-phase region and stabilized δ-ferrite. Due to the high concentration of Mo and V, large-sized V-rich MC and Mo-rich M2C carbides would precipitate in δ-ferrite at 900–1200 °C if the cooling rate is slow. When kept at 1200 °C for no more than 30 min, Mo and V elements derived from the decomposition of large-sized carbides are preferentially diffused into δ-ferrite, enhancing the stability of δ-ferrite. To achieve the effective elimination of δ-ferrite in M50NiL steel, it is necessary to keep the ingot at 1200 °C for at least 20 h.

Abstract Background Patient safety is paramount for all healthcare agencies. Health professionals' lack of patient safety competencies threaten patients’ lives, and increase patients, families, hospitals, and social burdens. The new nurse-related patient safety issues have particularly attracted much attention. The aim of this study was to examine the impacts of practice environment and job stress on new nurses' patient safety attitudes by employing the job demands–resources model. Methods The study used a cross-sectional structural equation modeling (SEM). A convenience sample of 370 new nurses was recruited from seven tertiary hospitals in Anhui province, China, from April 2022 to August 2022. Data were collected using self-report questionnaires including the Chinese version of the Nurse Job Stressors Scale, the Practice Environment Scale, and the Safety Attitudes Questionnaire. Results New nurses' patient safety attitudes scores were moderate (126.99 ± 14.39). Practice environment had a significant direct effect on job stress (β = -0.337, t = 6.120), patient safety attitudes (β = 0.604, t = 13.766), practice environment had an indirect effect on patient safety attitudes through job stress (β = 0.066, t = 3.690), and the indirect effect accounted for 9.9% of the total effect. This model was able to explain 48.3% of patient safety attitudes with moderate prediction accuracy. Conclusions This study emphasizes the importance of improving new nurses' attitudes toward patient safety. Hospital administrators should develop policies and strategies to address job characteristics, and establish a favorable work environment to reduce new nurses' job stress as well as to improve patient safety.

Abstract The tumor microenvironment is a complex space comprised of normal, cancer and immune cells. The macrophages are considered as the most abundant immune cells in tumor microenvironment and their function in tumorigenesis is interesting. Macrophages can be present as M1 and M2 polarization that show anti-cancer and oncogenic activities, respectively. Tumor-associated macrophages (TAMs) mainly have M2 polarization and they increase tumorigenesis due to secretion of factors, cytokines and affecting molecular pathways. Hepatocellular carcinoma (HCC) is among predominant tumors of liver that in spite of understanding its pathogenesis, the role of tumor microenvironment in its progression still requires more attention. The presence of TAMs in HCC causes an increase in growth and invasion of HCC cells and one of the reasons is induction of glycolysis that such metabolic reprogramming makes HCC distinct from normal cells and promotes its malignancy. Since M2 polarization of TAMs stimulates tumorigenesis in HCC, molecular networks regulating M2 to M1 conversion have been highlighted and moreover, drugs and compounds with the ability of targeting TAMs and suppressing their M2 phenotypes or at least their tumorigenesis activity have been utilized. TAMs increase aggressive behavior and biological functions of HCC cells that can result in development of therapy resistance. Macrophages can provide cell–cell communication in HCC by secreting exosomes having various types of biomolecules that transfer among cells and change their activity. Finally, non-coding RNA transcripts can mainly affect polarization of TAMs in HCC.

Abstract Purpose To identify which non-invasive infection indicators could better predict post-cervical cerclage (CC) infections, and on which days after CC infection indicators should be closely monitored. Methods The retrospective, single-center study included 619 single-pregnancy patients from January 2021 to December 2022. Patients were categorized into infected and uninfected groups based on physicians’ judgments of post-CC infections. Registered information included patient characteristics, cervical insufficiency history, gestational age at CC, surgical method (McDonald/Shirodkar), purpose of CC, mid-pregnancy miscarriage/preterm birth, infection history or risk factors, and infection indices on days 1, 3, 5, and 7 after CC. Propensity score matching (PSM) was applied to reduce patient characteristic bias. Statistical analysis of C-reactive protein (CRP), white blood cell (WBC), neutrophil count (NEU), percentage of neutrophil count (NEU_P), interleukin-6 (IL-6), and procalcitonin (PCT) in the infected group compared with the uninfected group was performed using chi-square tests and t-tests. Receiver operating characteristic (ROC) curves were used to further assess the diagnostic value of CRP, PCT, and CRP-PCT in combination. Results Among the 619 included patients, 206 patients were matched using PSM and subsequently assessed. PCT values on day 1 and day 3 after CC exhibited significant differences between the two groups in two statistical ways (P

In this work, we demonstrate the feasibility of applying electric pulses to heal surface cracks on nickel-based alloy GH4169 under compressive load. There exists an incubation time for the onset of the healing of a crack, which is associated with local temperature at the crack tip. The crack size decreases with increasing the pulsing time at a constant healing rate prior to complete healing of the crack. Increasing compressive load accelerates the healing process. The electric pulsing leads to the formation of an influential zone surrounding the crack with the finest grain sizes in the healed crack and the coarsest grain sizes away from the influential zone. The indentation hardness increases with the increase the distance to the crack tip of the healed crack. A model of viscous flow in the crack channel is proposed for the crack healing. The resultant force on the crack faces due to the crack healing increases with the increase of the healing time and the decrease of the crack width.

Abstract Continuous cultivation of tobacco could cause serious soil health problems, which could cause bacterial soil to change to fungal soil. In order to study the diversity and richness of fungal community in tobacco-growing soil under different crop rotation, three treatments were set up in this study: CK (tobacco continuous cropping); B (barley-tobacco rotation cropping) and R (oilseed rape-tobacco rotation cropping). The results of this study showed that rotation with other crops significantly decreased the soil fungal OTUs, and also decreased the community richness, evenness, diversity and coverage of fungal communities. Among them, B decreased the most. In the analysis of the composition and structure of the fungal community, it was found that the proportion of plant pathogens Nectriaceae decreased from 19.67% in CK to 5.63% in B, which greatly reduced the possibility of soil-borne diseases. In the analysis of the correlation between soil environmental factors and fungal communities, it was found that Filobasidiaceae had a strong correlation with TP and AP, and Erysiphaceae had a strong correlation with TK and AK. NO3 −-N and NH4 +-N were the two environmental factors with the strongest correlation with fungal communities. The results of this study showed that rotation with other crops slowed down the process of soil fungi in tobacco-growing soil and changed the dominant species of soil fungi community. At the same time, crop rotation changed the diversity and richness of soil fungal community by changing the physical and chemical properties of soil.

Abstract. Background:. Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. Methods:. Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results:. A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. Conclusions:. PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Finger millet (Eleusine coracana (L.) Gaertn.) is a medicinal and food homologous cereal that is rich in nutrients. The nutritional ingredients of finger millet mainly include starch, minerals, amino acids, dietary fiber and polyphenols, which have effects of anti-oxidation, lowering blood sugar, improving intestinal health and lowering blood pressure. At present, finger millet is mainly used to make various traditional foods with replacing a small amount of flour or other grains. The product is single and the nutritional value of finger millet cannot been fully utilized. The functional properties of finger millet are gradually noticed and utilized with the pursuit of food nutrition and health function. However, the research on the functional ingredients contained in finger millet is only at the experimental stage, and few functional products are developed. This review summarizes the nutritional and functional ingredients, functional properties and product development status of finger millet in recent years, and aims to provide a theoretical basis for the in-depth study and applications of finger millet.

Abstract Cloud environment is a virtual, online, and distributed computing environment that provides users with large-scale services. And cloud monitoring plays an integral role in protecting infrastructures in the cloud environment. Cloud monitoring systems need to closely monitor various KPIs of cloud resources, to accurately detect anomalies. However, due to the complexity and highly dynamic nature of the cloud environment, anomaly detection for these KPIs with various patterns and data quality is a huge challenge, especially those massive unlabeled data. Besides, it’s also difficult to improve the accuracy of the existing anomaly detection methods. To solve these problems, we propose a novel Dynamic Graph Transformer based Parallel Framework (DGT-PF) for efficiently detect system anomalies in cloud infrastructures, which utilizes Transformer with anomaly attention mechanism and Graph Neural Network (GNN) to learn the spatio-temporal features of KPIs to improve the accuracy and timeliness of model anomaly detection. Specifically, we propose an effective dynamic relationship embedding strategy to dynamically learn spatio-temporal features and adaptively generate adjacency matrices, and soft cluster each GNN layer through Diffpooling module. In addition, we also use nonlinear neural network model and AR-MLP model in parallel to obtain better detection accuracy and improve detection performance. The experiment shows that the DGT-PF framework have achieved the highest F1-Score on 5 public datasets, with an average improvement of 21.6% compared to 11 anomaly detection models.

Abstract Background Body weight and its changes have been associated with cancer outcomes. However, the associations of short‐term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short‐term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. Methods This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height‐adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight‐related indicators and compared their prognostic performance using Harrell's C‐index, integrated discrimination improvement, continuous net reclassification improvement and time‐dependent C‐index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan–Meier analysis and multivariable‐adjusted Cox regression models. Results The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow‐up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C‐index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P 10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5–10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5–10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. Conclusions The prognostic performance of peridiagnosis RWC is superior to other weight‐related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change‐related premature deaths.

BackgroundRecently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.MethodsThis is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.DiscussionThis is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.Clinical trial registrationClinicalTrials.Gov, identifier NCT06266871.

Upon chemotherapy, excessive reactive oxygen species (ROS) often lead to the production of massive lipid peroxides in cancer cells and induce cell death, namely ferroptosis. The elimination of ROS is pivotal for tumor cells to escape from ferroptosis and acquire drug resistance. Nevertheless, the precise functions of long non-coding RNAs (lncRNAs) in ROS metabolism and tumor drug-resistance remain elusive. In this study, we identify LncRNA-HMG as a chemoresistance-related lncRNA in colorectal cancer (CRC) by high-throughput screening. Abnormally high expression of LncRNA-HMG predicts poorer prognosis in CRC patients. Concurrently, we found that LncRNA-HMG protects CRC cells from ferroptosis upon chemotherapy, thus enhancing drug resistance of CRC cells. LncRNA-HMG binds to p53 and facilitates MDM2-mediated degradation of p53. Decreased p53 induces upregulation of SLC7A11 and VKORC1L1, which contribute to increase the supply of reducing agents and eliminate excessive ROS. Consequently, CRC cells escape from ferroptosis and acquire chemoresistance. Importantly, inhibition of LncRNA-HMG by anti-sense oligo (ASO) dramatically sensitizes CRC cells to chemotherapy in patient-derived xenograft (PDX) model. LncRNA-HMG is also a transcriptional target of β-catenin/TCF and activated Wnt signals trigger the marked upregulation of LncRNA-HMG. Collectively, these findings demonstrate that LncRNA-HMG promotes CRC chemoresistance and might be a prognostic or therapeutic target for CRC.

Whey protein is an important food ingredient, but it is also considered a major food allergen. The aim of this study was to investigate the effect of ultrasound pretreatment on the structure, IgE binding capacity, functional properties and biological activity of whey protein isolate (WPI) hydrolysates (WPH), including WPI hydrolyzed by a combination of enzymes from Bromelain and ProteAXH (BA-WPI) and WPI hydrolyzed by a combination of enzymes from Papain W-40 and ProteAXH (PA-WPI). The IgE binding capacity of BA-WPI and PA-WPI was reduced to 40.28% and 30.17%, respectively, due to disruption/exposure/shielding of conformational and linear epitopes. The IgE binding capacity of sonicated WPI was increased, but ultrasound pretreatment further reduced the IgE binding capacity of the hydrolysates to 32.89% and 28.04%. This is due to the fact that ultrasound pretreatment leads to conformational changes including increased α-helix and β-sheet structure, exposure of aromatic amino acids, surface hydrophobicity, and increased sulfhydryl content, which increases the accessibility of allergenic epitopes to WPI by the enzyme. Multispectral and LC-MS/MS results further indicated that ultrasound pretreatment altered the conformational and primary structural changes of the hydrolysates. The thermograms showed that ultrasound pretreatment mainly altered the epitope spectra of β-lactoglobulin hydrolysates, while it had less effect on the epitope spectra of α-lactalbumin hydrolysates. Additionally, ultrasound pretreatment significantly improved the foaming properties, antioxidant activity, and α-glucosidase inhibition of the hydrolysates without impairing the solubility and emulsification properties of the hydrolysates. Therefore, ultrasound pretreatment is a feasible method to reduce the allergenicity of WPH and to improve their functional properties and bioactivity. Notably, ultrasonic pretreatment improved the effectiveness and efficiency of WPI hydrolysis, which is a feasible method to produce high-quality protein feedstock in a green, efficient, and economical way.

Background: This study aims to provide an estimated dataset of lens zonule balance tension (LZBT) measurements in cataractous lenses among Chinese patients and to conduct a statistical analysis of anterior segment parameters. Methods: This is a cross-sectional study. We included a total of 833 eyes from 833 Chinese participants aged 23–91 years who underwent cataract surgery. Anterior segment parameters were measured using swept-source anterior segment optical coherence tomography (SS-AS OCT) to calculate lens gravity (LG) and crystalline lens volume (VOL). Axial length (AL) was measured using IOL-Master 700. LZBT was calculated using force decomposition and synthesis methods. Results: The mean LZBT in the horizontal direction was 8.48E-05 ± 3.23E-05 N across all eyes. The LZBT in the subtemporal-supraspinal and supraspinal-temporal directions was 2 times greater than in the vertical direction. The balanced force on the suspensory ligament in the horizontal direction was twice as strong as in the vertical direction. Additionally, anterior segment parameters such as lens equivalent diameter (LE-dia), radius of the anterior lens surface curvature (RAL), radius of the posterior lens surface curvature (RPL), anterior chamber depth (ACD), iris area, iris volume, and iris thickness showed positive correlations with AL. Conclusions: Accounting for gravitational effects, we concluded that zonule force is asymmetrically distributed. Importantly, this study establishes the normal range of LZBT across different meridians using force synthesis and decomposition, offering new insights and feasibility for studying suspensory ligament biomechanics.

Reservoir computing (RC) possesses a simple architecture and high energy efficiency for time‐series data analysis through machine learning algorithms. To date, RC has evolved into several innovative variants. The next generation reservoir computing (NGRC) variant, founded on nonlinear vector autoregression (NVAR) distinguishes itself due to its fewer hyperparameters and independence from physical random connection matrices, while yielding comparable results. However, NGRC networks struggle with massive Kronecker product calculations and matrix‐vector multiplications within the read out layer, leading to substantial efficiency challenges for traditional von Neumann architectures. In this work, a hybrid digital‐analog hardware system tailored for NGRC is developed. The digital part is a Kronecker product calculation unit with data filtering, which realizes transformation of nonlinear vector of the input linear vector. For matrix‐vector multiplication, a computing‐in‐memory architecture based on resistive random access memory array offers an energy‐efficient hardware solution, which markedly reduces data transfer and greatly improve computational parallelism and energy efficiency. The predictive capabilities of this hybrid NGRC system are validated through the Lorenz63 model, achieving a normalized root mean square error (NRMSE) of 0.00098 and an energy efficiency of 19.42TOPS W−1.

Abstract Mortality rates due to lung cancer are high worldwide. Although PD‐1 and PD‐L1 immune checkpoint inhibitors boost the survival of patients with non‐small‐cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build‐up and potential lysine‐lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non‐histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi‐omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl‐APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti‐APOC2K70‐lac antibody that sensitized anti‐PD‐1 therapy in vivo is developed. This findings highlight the potential of anti lactyl‐APOC2‐K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

BackgroundOsteoarthritis (OA) is a degenerative disease with a high incidence worldwide. Most affected patients do not exhibit obvious discomfort symptoms or imaging findings until OA progresses, leading to irreversible destruction of articular cartilage and bone. Therefore, developing new diagnostic biomarkers that can reflect articular cartilage injury is crucial for the early diagnosis of OA. This study aims to explore biomarkers related to the immune microenvironment of OA, providing a new research direction for the early diagnosis and identification of risk factors for OA.MethodsWe screened and downloaded relevant data from the Gene Expression Omnibus (GEO) database, and the immune microenvironment-related genes (Imr-DEGs) were identified using the ImmPort data set by combining weighted coexpression analysis (WGCNA). Functional enrichment of GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to explore the correlation of Imr-DEGs. A random forest machine learning model was constructed to analyze the characteristic genes of OA, and the diagnostic significance was determined by the Receiver Operating Characteristic Curve (ROC) curve, with external datasets used to verify the diagnostic ability. Different immune subtypes of OA were identified by unsupervised clustering, and the function of these subtypes was analyzed by gene set enrichment analysis (GSVA). The Drug-Gene Interaction Database was used to explore the relationship between characteristic genes and drugs.ResultsSingle sample gene set enrichment analysis (ssGSEA) revealed that 16 of 28 immune cell subsets in the dataset significantly differed between OA and normal groups. There were 26 Imr-DEGs identified by WGCNA, showing that functional enrichment was related to immune response. Using the random forest machine learning model algorithm, nine characteristic genes were obtained: BLNK (AUC = 0.809), CCL18 (AUC = 0.692), CD74 (AUC = 0.794), CSF1R (AUC = 0.835), RAC2 (AUC = 0.792), INSR (AUC = 0.765), IL11 (AUC = 0.662), IL18 (AUC = 0.699), and TLR7 (AUC = 0.807). A nomogram was constructed to predict the occurrence and development of OA, and the calibration curve confirmed the accuracy of these 9 genes in OA diagnosis.ConclusionThis study identified characteristic genes related to the immune microenvironment in OA, providing new insight into the risk factors of OA.

IntroductionEpidemiological studies have assessed the correlation between daily dietary branch chain amino acid (BCAA) intakes and the risk of obesity, however, the findings from these studies were inconsistent and investigations among GDM women were few.ObjectiveThe present study was to investigate the associations of daily BCAA intakes with the risks of overweight and abdominal obesity among women with prior gestational diabetes mellitus (GDM) postpartum.MethodWe performed a cross-sectional study of 1,263 women with prior GDM at 1–5 years post-delivery. Logistic regression models were used to estimate the associations of daily dietary intakes of BCAAs with the risks of overweight and abdominal obesity.ResultsThe multivariable-adjusted odds ratios (ORs) across quartiles of daily BCAA intakes postpartum were 1.42 (95% confidence interval [CI] 1.02–1.97), 1.00 (reference), 1.21 (95% CI 0.88–1.68), and 1.31 (95% CI 0.95–1.81) for general overweight, and 1.38 (95% CI 0.99–1.90), 1.00, 1.19 (95% CI 0.86–1.64), and 1.43 (95% CI 1.04–1.98) for abdominal obesity, respectively. Women with the lowest quartile of daily BCAA intakes significantly increased the risks of general overweight (OR 1.49; 95 %CI 1.06–2.09) and abdominal obesity (OR 1.50; 95 %CI 1.08–2.11) compared with women at quartile 2 of daily BCAA intakes after further adjustment of daily energy intake.ConclusionThe present study indicated that daily lower BCAA intakes were associated with increased risks of general overweight and abdominal obesity among women with prior GDM.

Coupled grey and green infrastructure (CGGI) is increasingly recognized as a viable approach to sustainable urban stormwater management. This study evaluates CGGI and grey infrastructure (GREI)-only schemes with various degree of centralization of the layout (DCL) in addressing urban flood and drainage issues in a historical and cultural district (HCD) which typically consists of high impervious surfaces, dense urban structures, and fragile heritage buildings. Yongqing Fang Community in Guangzhou, China, was selected as a case study in which the performance of the Grey-only and CGGI schemes are evaluated and compared. The results obtained indicated that the CGGI scheme was more advantageous in terms of cost-effectiveness and scalability, yielding potential savings of $30,500 to $163,400. Moreover, the fully decentralized layout of the two schemes could result in cost savings of 29.0% and 29.6%, respectively, over the fully centralized layout. However, CGGI shows marginally lower adaptability in response to extreme rainfall events compared to that of GREI-only solutions. Technical resilience (Tech-R) of GREI-only scored higher by 0.1% to 0.8%, 0.5% to 3.5%, and 0.7% to 4.8% for 10-year, 50-year, and 100-year rainfall scenarios, respectively. Nonetheless, CGGI schemes demonstrated superior adaptability in structural failure scenarios, and reduced surface overflow by 22.6%, 19.0%, and 18.4% compared to GREI for the same scenarios. In both the CGGI and GREI-only schemes, decentralized layouts are likely to outperform centralized layouts in both extreme rainfall events and in failure scenarios. These findings underscore the importance of decentralized layout of the drainage infrastructure which could enhance the hydrological performance of integrated drainage infrastructures, offering insights for due considerations in designing multi-objective infrastructures for urban flood mitigation in HCDs.