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Abstract Simultaneously improving the activity and stability of catalysts for anodic oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE) remains a notable challenge. Here, we report a chromium-doped ruthenium dioxide with oxygen vacancies, termed Cr0.2Ru0.8O2-x, that drives OER with an overpotential of 170 mV at 10 mA cm−2 and operates stably over 2000 h in acidic media. Experimental and theoretical studies show that the synergy of Cr dopant and oxygen vacancy induces an unconventional dopant-mediated hydroxyl spillover mechanism. Such dynamic hydroxyl spillover from Cr dopant to Ru active site changes the rate-determining step from OOH* formation to O2 formation and thus greatly improves the OER performance. Moreover, the Cr dopant and oxygen vacancy also play a crucial role in stabilizing surface Ru and lattice oxygen in the Ru-O-Cr structural motif. When assembled into the anode of a practical PEMWE device, Cr0.2Ru0.8O2-x enables long-term durability of over 200 h at an ampere-level current density and 60 degrees centigrade.

Abstract Background Idiopathic ventricular arrhythmias (IVAs) arising from different portions of the communicating vein of the left ventricular summit (summit-CV) are not a rare phenomenon. Whereas its electrocardiographic (ECG) and electrophysiological characteristics are not fully investigated. Objective This study aimed to identify distinct ECG and electrophysiological features of IVAs originating from different portions of summit-CV. Methods Nineteen patients confirmed arising from summit-CV were included in this study. Results The 19 patients were divided into proximal and distal portion groups based on their target sites in summit-CV. In the proximal portion group, 100% (11/11) VAs showed dominant negative (rs or QS) waves in lead I, while in the distal portion group, 87.5% (7/8) showed dominant positive waves (R, Rs or r) (p 4mV, SI3.5mV, RI/SI>0.83, and RV1/SV1< 2.6 indicated a distal portion of summit-CV with the predictive value of 0.909, 1.000, 0.653, 0.972, 0.903, 0.966, respectively. A more positive wave in lead I and a more negative wave in lead V1 indicated more distal origin in summit-CV. Target sites in proximal and distal summit-CV groups showed similar electrophysiological characteristics during mapping. Conclusions There were significant differences in ECG characteristics of VAs at different portions of summit-CV, which could aid pre-procedure planning and facilitate radiofrequency catheter ablation (RFCA) procedures.

Abstract Mechanochemistry studies the effect of mechanical force on chemical bonds, bringing opportunities for synthesizing alloys, ceramics, organics, polymers, and biomaterials. A vital issue of applying macro-scale mechanical force to manipulate crystal structures is finding ways to precisely adjust the force directions to break micro-scale target chemical bonds. Inspired by a common technique of driving a wedge into the wood to make wood chopping much easier, a wedging strategy of splitting three-dimensional structured crystalline frameworks and then converting them to nanosheets was proposed, where specific molecules were wedged into crystalline frameworks to drive the directional transmission of mechanical force to break chemical bonds. As a result, various crystalline framework nanosheets including metal−organic framework nanosheets, covalent organic framework nanosheets, and coordination polymer nanosheets were fabricated. This wedging crystal strategy exhibits advantages of operability, flexibility and designability, and furthermore, it is expected to expand mechanochemistry applications in material preparation.

Abstract Background A substantial proportion of patients with metastatic clear cell renal cell carcinoma (ccRCC) cannot derive benefit from immune checkpoint inhibitor (ICI) plus anti-angiogenic agent combination therapy, making identification of predictive biomarkers an urgent need. The members of pleckstrin homology-like domain family A (PHLDA) play critical roles in multiple cancers, whereas their roles in ccRCC remain unknown. Methods Transcriptomic, clinical, genetic alteration and DNA methylation data were obtained for integrated analyses from TCGA database. RNA sequencing was performed on 117 primary tumors and 79 normal kidney tissues from our center. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis were performed to explore transcriptomic features. Data from three randomized controlled trials (RCT), including CheckMate025, IMmotion151, JAVELIN101, were obtained for validation. Results Members of PHLDA family were dysregulated in pan-cancer. Elevated PHLDA2 expression was associated with adverse clinicopathologic parameters and worse prognosis in ccRCC. Aberrant DNA hypomethylation contributed to up-regulation of PHLDA2. An immunosuppressive microenvironment featured by high infiltrates of Tregs and cancer-associated fibroblasts, was observed in ccRCC with higher PHLDA2 expression. Utilizing data from three RCTs, the association of elevated PHLDA2 expression with poor therapeutic efficacy of ICI plus anti-angiogenic combination therapy was confirmed. Conclusions Our study revealed that elevated PHLDA2 expression regulated by DNA hypomethylation was correlated with poor prognosis and immunosuppressive microenvironment, and highlighted the role of PHLDA2 as a robust biomarker for predicting therapeutic efficacy of ICI plus anti-angiogenic agent combination therapy in ccRCC, which expand the dimension of precision medicine.

Factory recirculating aquaculture system (RAS) is facing in a stage of continuous research and technological innovation. Intelligent aquaculture is an important direction for the future development of aquaculture. However, the RAS nowdays still has poor self-learning and optimal decision-making capabilities, which leads to high aquaculture cost and low running efficiency. In this paper, a precise aeration strategy based on deep learning is designed for improving the healthy growth of breeding objects. Firstly, the situation perception driven by computer vision is used to detect the hypoxia behavior. Then combined with the biological energy model, it is constructed to calculate the breeding objects oxygen consumption. Finally, the optimal adaptive aeration strategy is generated according to hypoxia behavior judgement and biological energy model. Experimental results show that the energy consumption of proposed precise aeration strategy decreased by 26.3% compared with the manual control and 12.8% compared with the threshold control. Meanwhile, stable water quality conditions accelerated breeding objects growth, and the breeding cycle with the average weight of 400 g was shortened from 5 to 6 months to 3–4 months.

Full conversion of glucose and xylose from lignocellulosic hydrolysates is required for obtaining a high ethanol yield. However, glucose and xylose share flux in the pentose phosphate pathway (PPP) and glycolysis pathway (EMP), with glucose having a competitive advantage in the shared metabolic pathways. In this work, we knocked down ZWF1 to preclude glucose from entering the PPP. This reduced the [NADPH] level and disturbed growth on both glucose or xylose, confirming that the oxidative PPP, which begins with Zwf1p and ultimately leads to CO2 production, is the primary source of NADPH in both glucose and xylose. Upon glucose depletion, gluconeogenesis is necessary to generate glucose-6-phosphate, the substrate of Zwf1p. We re-established the NADPH regeneration pathway by replacing the endogenous NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene TDH3 with heterogenous NADP + -GAPDH genes GDH, gapB, and GDP1. Among the resulting strains, the strain BZP1 (zwf1Δ, tdh3::GDP1) exhibited a similar xylose consumption rate before glucose depletion, but a 1.6-fold increased xylose consumption rate following glucose depletion compared to the original strain BSGX001, and the ethanol yield for total consumed sugars of BZP1 was 13.5% higher than BSGX001. This suggested that using the EMP instead of PPP to generate NADPH reduces the wasteful metabolic cycle and excess CO2 release from oxidative PPP. Furthermore, we used a copper-repressing promoter to modulate the expression of ZWF1 and optimize the timing of turning off the ZWF1, therefore, to determine the competitive equilibrium between glucose-xylose co-metabolism. This strategy allowed fast growth in the early stage of fermentation and low waste in the following stages of fermentation.

Elastin-like polypeptides (ELPs) are popular biomaterials due to their reversible, temperature-dependent phase separation and their tunability, which is achievable by evolving procedures in recombinant technology. In particular, recursive direction ligation by plasmid reconstruction (PRe-RDL) is the predominant cloning technique used to generate ELPs of varying lengths. Pre-RDL provides precise control over the number of (VPGXG)n repeat units in an ELP due to the selection of type IIS restriction enzyme (REs) sites in the reconstructed pET expression plasmid, which is a low-to-medium copy number plasmid. While Pre-RDL can be used to seamlessly repeat essentially any gene sequence and overcome limitations of previous cloning practices, we modified the Pre-RDL technique, where a high copy number plasmid (pBluescript II SK(+)—using a new library of type IIS REs) was used instead of a pET plasmid. The modified technique successfully produced a diblock ELP gene of 240 pentapeptide repeats from 30 pentapeptide “monomers” composed of alanine, tyrosine, and leucine X residues. This study found that the large, GC-rich ELP gene compromised plasmid yields in pBluescript II SK(+) and favored higher plasmid yields in the pET19b expression plasmid. Additionally, the BL21 E. coli strain expression consistently provided a higher transformation efficiency and higher plasmid yield than the high cloning efficiency strain TOP10 E. coli. We hypothesize that the plasmid/high GC gene ratio may play a significant role in these observations, and not the total plasmid size or the total plasmid GC content. While expression of the final gene resulted in a diblock ELP with a phase separation temperature of 34.5 °C, future work will need to investigate RDL techniques in additional plasmids to understand the primary driving factors for improving yields of plasmids with large ELP-encoding genes.

Summary: Background: To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4 MP) for lung cancer risk assessment results in improved performance over a single time measurement. Methods: We conducted data analysis of the 4 MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history at each time point, was compared to a single-threshold (ST) method. Findings: Among ever-smoker participants, the PEB approach yielded an additional 4% improvement in the AUC compared to the ST approach (P-value: 0.009). When considering an ≥10 PY smoking history and at a fixing the specificity corresponding to 1% 6-year lung cancer risk, PEB resulted in significant improvement in the sensitivity (SenPEB:96.3% vs SenST:91.0%; P-value: 6.7e-3). The PEB algorithm identified 17 of the 35 cases that remained ST negative, at an average of 1.26 years before diagnosis. Ten case individuals who were positive based on ST at an average of 1.03 years prior to diagnosis were identified earlier by PEB, at an average of 2.70 years. Interpretation: An algorithm based on repeated measurements of the 4 MP improves sensitivity and results in an earlier detection of lung cancer compared to a single-threshold method. Funding: This study was supported by NIH Grant Nos. U01CA271888, U01CA194733, U01CA213285, NCI EDRN U01 CA200468, P30CA016672, and U24CA086368; the Cancer Prevention & Research Institute of Texas RP180505 and RP160693; the SPORE P50CA140388; the CCTS TR000371; and the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program and the Lyda Hill Foundation.

Solar-driven water splitting for photocatalytic hydrogen evolution is considered a highly promising and cost-effective solution to achieve a stable renewable energy supply. However, the sluggish kinetics of electron-hole pairs’ separation poses challenges in attaining satisfactory hydrogen production efficiency. Herein, we synthesized the exceptional performance of highly crystalline C3N5 (HC–C3N5) nanosheet as a photocatalyst, demonstrating a remarkable hydrogen evolution rate of 3.01 ​mmol ​h−1 ​g−1, which surpasses that of bulk C3N5 (B–C3N5) by a factor of 3.27. Experimental and theoretical analyses reveal that HC-C3N5 nanosheets exhibit intriguing macroscopic photoinduced color changes, effectively broadening the absorption spectrum and significantly enhancing the generation of excitons. Besides, the cyano groups in HC-C3N5 efficiently captures and converts photoexcited electrons into bound states, thereby prolonging their lifetimes and effectively separating electrons and holes into catalytically active regions. This research provides valuable insights into the establishment of bound electronic states for developing efficient photocatalysts.

Abstract In flight test engineering, the flight test duration (FTD) affects the aircraft’s delivery node and directly impacts costs. In the actual flight test process, the environmental status updates frequently, and various uncertain events are often encountered, which affect the flight test progress and project implementation. Therefore, when scheduling flight test tasks, rescheduling should be taken into account. This paper proposes a predictive-reactive strategy based on a deep reinforcement learning approach to solve the flight test task scheduling problem with consideration of aircraft grounding. In the predictive stage, a constructive heuristic algorithm is designed to generate an initial schedule. The rescheduling problem is solved by the appropriate rescheduling method that aims to optimize the FTD deviation, task reallocation, and workload cost simultaneously. The problem is modeled as a Markov decision process, including the well-designed state features, rewards, and actions based on different rescheduling methods. The policy is trained by the proximal policy optimization algorithm. At last, numerical results are provided to demonstrate the effectiveness and superiority of the proposed approach.

Abstract Understanding the intricate nanoscale architecture of neuronal myelin during central nervous system development is of utmost importance. However, current visualization methods heavily rely on electron microscopy or indirect fluorescent method, lacking direct and real-time imaging capabilities. Here, we introduce a breakthrough near-infrared emissive curcumin-BODIPY derivative (MyL-1) that enables direct visualization of myelin structure in brain tissues. The remarkable compatibility of MyL-1 with stimulated emission depletion nanoscopy allows for unprecedented super-resolution imaging of myelin ultrastructure. Through this innovative approach, we comprehensively characterize the nanoscale myelinogenesis in three dimensions over the course of brain development, spanning from infancy to adulthood in mouse models. Moreover, we investigate the correlation between myelin substances and Myelin Basic Protein (MBP), shedding light on the essential role of MBP in facilitating myelinogenesis during vertebral development. This novel material, MyL-1, opens up new avenues for studying and understanding the intricate process of myelinogenesis in a direct and non-invasive manner, paving the way for further advancements in the field of nanoscale neuroimaging. Graphical Abstract

Abstract Background Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD. Methods In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated. Results Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762–0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value. Conclusions Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.

This work attempts to understand how a customized bus (CB) operator decides to open or close a CB line. We look into the changes in the operation status of CB lines (i.e. reopening and closure) from one of the largest CB operators in Shanghai, China, with a 22-month consecutive observation ranging from January 2019 to October 2020. As all CB services were totally suspended at the beginning of 2020 due to the COVID-19 travel restriction and then gradually recovered in March 2020, we utilize this study period as a naturalistic observation experiment to investigate the changes in the operation status of each CB line before and after the travel restriction. Using the operation status at each month as the binary alternatives, the mixed logit models and the tree-based models with explainable machine learning techniques are respectively adopted to explore the factors that influence the decision-making process. The findings from both types of models are in general consistent. The results show that the characteristics of each CB line including the ridership, the length of the line, the closeness to charging stations, and the overlap of CB lines significantly impact the decisions. In addition, the land-use types around the CB stops and the market competition from alternative travel modes also play a key role in making the decisions.

To investigate the impact of bath composition and process conditions on Ni-W alloy coating, Ni-W alloy discs with low internal stress and high hardness were prepared for dynamic friction polishing of diamonds. The effects of complexing agent concentration, solution pH, and saccharin sodium concentration on the internal stress, tungsten content, hardness, and deposition rate of the coating were investigated by single experiments. Additionally, the effects of different additives on the surface leveling of the coating were also investigated. Finally, salicylaldehyde was selected as the leveling agent, and the reverse pulse current was applied to reduce the surface roughness of the coating. A Ni-W alloy disc with a hardness of HV 713 and a coating thickness of about 0.66 mm was prepared. Diamond dynamic friction polishing was carried out using these alloy discs to explore appropriate polishing process parameters. The best polishing effects were achieved at a disc speed of 8000 r/min and a pressure of 40 N, yielding a removal rate of 5.56 μm/min, a grinding ratio of 0.394, and a surface roughness (Ra) of 3.7 nm. Comparing wear parameters revealed that Ni-W alloy discs can achieve better polishing effects using traditional cast iron discs in friction chemical polishing of diamonds.

Abstract Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs with transcript lengths of >200 nucleotides. Mounting evidence suggests that lncRNAs are closely associated with tumorigenesis. LncRNA H19 (H19) was the first lncRNA to function as an oncogene in many malignant tumors. Apart from the established role of H19 in promoting cell growth, proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and metastasis, it has been recently discovered that H19 also inhibits programmed cell death (PCD) of cancer cells. In this review, we summarize the mechanisms by which H19 regulates PCD in cancer cells through various signaling pathways, molecular mechanisms, and epigenetic modifications. H19 regulates PCD through the Wnt/β-catenin pathway and the PI3K–Akt–mTOR pathway. It also acts as a competitive endogenous RNA (ceRNA) in PCD regulation. The interaction between H19 and RNA-binding proteins (RBP) regulates apoptosis in cancer. Moreover, epigenetic modifications, including DNA and RNA methylation and histone modifications, are also involved in H19-associated PCD regulation. In conclusion, we summarize the role of H19 signaling via PCD in cancer chemoresistance, highlighting the promising research significance of H19 as a therapeutic target. We hope that our study will contribute to a broader understanding of H19 in cancer development and treatment.

Dynamic multi-objective optimization problems have been popular because of its extensive application. The difficulty of solving the problem focuses on the moving PS as well as PF dynamically. A large number of efficient strategies have been put forward to deal with such problems by speeding up convergence and keeping diversity. Prediction strategy is a common method which is widely used in dynamic optimization environment. However, how to increase the efficiency of prediction is always a key but difficult issue. In this paper, a new prediction model is designed by using the rank sums of individuals, and the position difference of individuals in the previous two adjacent environments is defined to identify the present change type. The proposed prediction strategy depends on environment change types. In order to show the effectiveness of the proposed algorithm, the comparison is carried out with five state-of-the–art approaches on 20 benchmark instances of dynamic multi-objective problems. The experimental results indicate the proposed algorithm can get good convergence and distribution in dynamic environments.

ABSTRACTMyotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.

IntroductionThymic stromal lymphopoietin (TSLP) is integral to inducing innate and T helper two cell inflammation that leads to clinical symptoms of asthma. SHR-1905 is a humanized immunoglobulin G1 kappa monoclonal antibody that inhibits TSLP bioactivity, developed for the treatment of severe uncontrolled asthma. This phase 1, randomized, double-blind, placebo-controlled single ascending dose study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of subcutaneous SHR-1905 in healthy subjects.MethodsFive dose cohorts were planned (50, 100, 200, 400, and 600 mg) and subjects were randomized (8:2) in each cohort to receive SHR-1905 or placebo with a follow-up period up to Day 253.ResultsThe majority of treatment-emergent adverse events (TEAEs) were mild and the incidence of TEAEs was comparable between the SHR-1905 and the placebo groups. The maximum serum concentration was reached 7.0–17.6 days after injection. The serum concentration of SHR-1905 increased with increasing dose level, and SHR-1905 exposure exhibited in a slightly greater-than-dose-proportional manner from 50 to 600 mg. SHR-1905 had a prolonged serum half-life around 80 days supporting every 6-month dosing. In SHR-1905 treated subjects, 15% tested positive for anti-drug antibodies post-dose with no apparent effect on corresponding PK profiles or safety.ConclusionSHR-1905 demonstrated a good safety and tolerability profile with a long half-life in healthy subjects after a single administration in the dose range of 50–600 mg.Clinical Trial Registration:clinicaltrials.gov, identifier NCT04800263

IntroductionHuperzia serrata is a traditional Chinese herb that has gained much attention for its production of Huperzine A (HupA). HupA has shown promise on treating Alzheimer's disease (AD). However, the biosynthetic pathway and molecular mechanism of HupA in H. serrata are still not well understood.MethodsIntegrated transcriptome and metabolome analysis was performed to reveal the molecular mechanisms related to HupA biosynthesis and antioxidant activity in Huperzia serrata.ResultsHT (in vitro H. serrata thallus) exhibits higher antioxidant activity and lower cytotoxicity than WH (wild H. serrata). Through hierarchical clustering analysis and qRT-PCR verification, 7 important enzyme genes and 13 transcription factors (TFs) related to HupA biosynthesis were detected. Among them, the average |log2FC| value of CYP (Cytochrome P450) and CAO (Copper amine oxidase) was the largest. Metabolomic analysis identified 12 metabolites involved in the HupA biosynthesis and 29 metabolites related to antioxidant activity. KEGG co-enrichment analysis revealed that tropane, piperidine and pyridine alkaloid biosynthesis were involved in the HupA biosynthesis pathway. Furthermore, the phenylpropanoid, phenylalanine, and flavonoid biosynthesis pathway were found to regulate the antioxidant activity of H. serrata. The study also identified seven important genes related to the regulation of antioxidant activity, including PrAO (primary-amine oxidase). Based on the above joint analysis, the biosynthetic pathway of HupA and potential mechanisms of antioxidant in H. serrata was constructed.DiscussionThrough differential transcriptome and metabolome analysis, DEGs and DAMs involved in HupA biosynthesis and antioxidant-related were identified, and the potential metabolic pathway related to HupA biosynthesis and antioxidant in Huperzia serrata were constructed. This study would provide valuable insights into the HupA biosynthesis mechanism and the H. serrata thallus medicinal value.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. It is the second most common chronic progressive neurodegenerative disease. PD still lacks a known cure or prophylactic medication. Current treatments primarily address symptoms without halting the progression of PD, and the side effects of dopaminergic therapy become more apparent over time. In contrast, physical therapy, with its lower risk of side effects and potential cardiovascular benefits, may provide greater benefits to patients. The Anti-Gravity Treadmill is an emerging rehabilitation therapy device with high safety, which minimizes patients’ fear and allows them to focus more on a normal, correct gait, and has a promising clinical application. Based on this premise, this study aims to summarize and analyze the relevant studies on the application of the anti-gravity treadmill in PD patients, providing a reference for PD rehabilitation practice and establishing a theoretical basis for future research in this area.

Three methods are used for a numerical solution, the Monte Carlo method, diffusion approximation equation model, and beam broaden model based on Beer–Lambert’s law equation. The comparison between the first two methods is reported theoretically, and the latter is a better choice in the high-density tissue. However, the comparison between the third method and the first or the second method is rarely reported. Two classical theoretical models describing the interaction between the laser and the bio-tissue are analyzed and compared to determine which is more suitable for analyzing the interaction, the beam broaden model or diffusion approximation equation model. Intensity distribution is simulated and compared for the two models. Temperature distribution and thermal damage are investigated theoretically and experimentally for both models. The differences and the reasons are analyzed. The diffusion approximation equation model is more suitable for analyzing the mechanism between the laser and the bio-tissue based on the degree of fitting between the simulated and experimental data. Theoretical analyses for the two models are carried out in detail. The comparison between the two models is rarely reported, and it is reported in this article for the first time, theoretically and experimentally. This report provides a better choice for quickly analyzing the interaction mechanism between the laser and the bio-tissue.

The risk warning for steady-state power quality in the power grid is essential for its prevention and management. However, current risk warning methods fall short in predicting the power quality trend while accounting for potential risks. Consequently, this study introduces a novel steady-state power quality risk warning method utilizing VMD-LSTM and a fuzzy model. Firstly, a power quality index prediction method based on variational mode decomposition (VMD) and long short-term memory (LSTM) is proposed. This approach significantly enhances prediction accuracy. Secondly, a power quality risk warning method incorporating kernel density estimation (KDE) and a fuzzy model is proposed, which systematically addresses the uncertainty associated with power quality risks. To validate the effectiveness and practicality of the proposed method, experiments are conducted using field monitoring data from a residential load in southern China. The results affirm the reliability and applicability of the proposed method. The simulation results show that the median error of prediction of power quality indexes by the proposed method is 5.03 % during the evaluated time period, and the prediction accuracy is mostly maintained above 90 %.

The multi-point dynamic aggregation problem (MPDAP) that arises in practical applications is characterized by a group of robots that have to cooperate in executing a set of tasks distributed over multiple locations, in which the demand for each task grows over time. To minimize the completion time of all tasks, one needs to schedule the robots and plan the routes. Hence, the problem is essentially a combinatorial optimization problem. The manuscript presented a new MPDAP in which the priority of the task was considered that is to say, some tasks must be first completed before others begin to be executed. When the tasks were located at different priority levels, some additional constraints were added to express the priorities of tasks. Since route selection of robots depends on the priorities of tasks, these additional constraints caused the presented MPDAP to be more complex than ever. To efficiently solve this problem, an improved optimization algorithm, called the multi-strategy genetic algorithm (MSGA), was developed. First of all, a two-stage hybrid matrix coding scheme was proposed based on the priorities of tasks, then to generate more route combinations, a hybrid crossover operator based on 0-1 matrix operations was proposed. Furthermore, to improve the feasibility of individuals, a repair schedule was designed based on constraints. Meanwhile, a $ q $-tournament selection operator was adopted so that better individuals can be kept into the next generation. Finally, experimental results showed that the proposed algorithm is feasible and effective for solving the MPDAP.

[Objective] The current design calculation methods for platform width suffer from issues such as low passenger flow prediction accuracy, broad range of passenger flow density parameter values, unclear selection criteria, and a lack of quantifiable basis for design margins. Improvement is needed targeting the situation, parameter values for platform width design is calibrated based on stimulation tests. [Method] Based on the standards outlined in the Code for Design of Metro, a grading standard for platform service levels is established, and a single-side platform width design method based on platform service level is proposed. Through simulation tests, key parameters are calibrated, and a conversion coefficient between theoretical and actual values of passenger flow density is obtained by fitting the relationship curve of passenger volume and single-side platform peak density using least squares method. Considering the factors influencing platform width, passenger flow conversion calculations are performed for passenger dwell proportion and passengers carrying large items proportion through simulation test, providing platform width calculation methods under corresponding conditions. For computing scenarios that consider the influence of multiple factors, an orthogonal test is designed to adjust parameters and obtain the final calculation method for single-side platform width. [Result & Conclusion] The single-side platform actual peak density is approximately 0.9 times the theoretical value. The impact of passenger dwell and passengers carrying large items on single-side platform peak density is approximately equivalent to 1.19 and 1.75 times the impact of regular boarding and alighting passengers. When both the above factors simultaneously act on the single-side platform, the resulting impact exceeds the cumulated effects of single factor.

Abstract Past studies have shown that the Gelsolin-like actin-capping protein (CAPG) regulates cell migration and proliferation and is strongly associated with tumor progression. We present the first study of the mechanism of action of CAPG in early gastric cancer (EGC). We demonstrate that CAPG expression is upregulated in gastric cancer (GC) especially EGC. CAPG promotes GC proliferation, migration, invasion, and metastasis in vivo and in vitro. More importantly, CAPG plays a role in GC by involving the Wnt/β-catenin signaling pathway. Our findings suggest that CAPG may function as a novel biomarker for EGC.

Abstract Malignant pleural effusion (MPE), which is a complex microenvironment that contains numerous immune and tumour signals, is common in lung cancer. Gene alterations, such as driver gene mutations, are believed to affect the components of tumour immunity in the microenvironment (TIME) of non-small-cell lung cancer. In this study, we have shown that pleural CD39 + CD8 + T cells are selectively elevated in lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFRwt) compared to those with newly diagnosed mutant EGFR (EGFRmu). Furthermore, these CD39 + CD8 + T cells are more prevalent in MPE with acquired resistance to EGFR-tyrosine kinase inhibitors (AR-EGFR-TKIs). Our analysis reveals that pleural CD39 + CD8 + T cells exhibit an exhausted phenotype while still retaining cytolytic function. Additionally, they have a higher T cell receptor (TCR) repertoire clonality compared to CD39-CD8 + T cells, which is a unique characteristic of LUAD-related MPE. Further investigation has shown that TCR-Vβ clonality tends to be more enhanced in pleural CD39 + CD8 + T cells from MPE with AR-EGFR-TKIs. In summary, we have identified a subset of CD8 + T cells expressing CD39 in MPE, which may potentially be tumour-reactive CD8 + T cells. This study provides new insights into the dynamic immune composition of the EGFRmu tumour microenvironment.

Abstract Background Diseases caused by Toxoplasma gondii (T. gondii) have introduced serious threats to public health. There is an urgent need to develop a rapid detection method for T. gondii infection in cats, which are definitive hosts. Recombinant apical membrane antigen 1 (rAMA1) was produced in a prokaryotic expression system and used as the detection antigen. The aim of this study was to evaluate and optimize a reliable indirect enzyme-linked immunosorbent assay (iELISA) method based on rAMA1 for the detection of antibodies against T. gondii in cats. Results The rAMA1-iELISA method was developed and optimized by the chessboard titration method. There were no cross-reactions between T. gondii-positive cat serum and positive serum for other pathogens, indicating that rAMA1-iELISA could only detect T. gondii in most cases. The lowest detection limit of rAMA1-iELISA was 1:3200 (dilution of positive serum), and the CV of repeated tests within batches and between batches were confirmed to be less than 10%. The results of 247 cat serum samples detected by rAMA1-iELISA (kappa value = 0.622, p

The typical single-event characteristics of a voltage dip include residual voltage, duration, dip type, point-on-wave and phase-angle jump, which may influence the operation of the sensitive equipment under voltage dip. This operation is the foundation on which the single-event characteristics of a voltage dip can be accurately calculated to mitigate the voltage dip. The challenge of existing studies is that no unified and systematic method to calculate multiple single-event characteristics. This study proposes a robust adaptive method based on Goodness-of-Fit (GoF) test to calculate the characteristics of a voltage dip. First, a calculation method for the transition segment of voltage dip is proposed based on the GoF test. Then, four methods are presented for calculating four different characteristics of the dip based on the detected transition segment. The proposed method is subsequently unified and thus reduces the computation of monitor devices. Moreover, this method can adaptively adjust the critical value according to the sampling rate, avoiding the influence of noise. Finally, this study applies 516 sets of measured voltage dips to verify the performance of the proposed method, comparing the results with that of the existing methods.

In recent years, the phenomenon of black–odorous water has occurred frequently, and constructed wetlands have been widely used as an effective means of treating black–odorous water. In order to achieve the goal of low-carbon and high-efficiency long-term clean-up of black–odorous water, the modular constructed wetland system was optimized in this study. The optimized modular constructed wetland consisted of aeration, denitrification, and phosphorus removal, of which the denitrification module was a sulfur–iron autotrophic denitrification unit and the phosphorus removal module was a polyaluminum chloride composite filler phosphorus-removal unit. Experimental findings indicated that modular systems with layout ratios of 1:3:1 (A) and 1:2:2 (B) exhibit outstanding performance in remediating contaminants from black–odorous water. Notably, system B demonstrated superior treatment efficiency. Under conditions of high pollution loading, system B consistently achieved stable removal rates for COD (95.79%), TN (91.74%), NH4+-N (95.17%), and TP (82.21%). The combination of along-track changes and high-throughput sequencing results showed that the synergies among the units did not produce negative effects during the purification process, and each unit realized its predefined function. Changes in the substrate and internal environment of the wetland units caused changes in the microbial populations, and the unique microbial community structure of the units ensured that they were effective in removing different pollutants.

This paper addresses the fuzzy resilient control of DC microgrids with constant power loads. The DC microgrid is subject to abrupt parameter changes which are described by the Markov jump model. Due to the constant power loads, the DC microgrid exhibits nonlinear dynamics which are characterized by a T-S fuzzy model. According to the parallel distributed compensation principle, mode-dependent fuzzy resilient controllers are designed to stabilize the resultant T-S fuzzy Markov jump DC microgrid. The “resilient” means the controller could cope with the uncertainty caused by the inaccurate execution of the control laws. This uncertainty is governed by a Bernoulli distributed random variable and thus may not occur. Then, the mean square exponential stability is analyzed for the closed-loop system by using the mode-dependent Lyapunov function. Since the stability conditions are not convex, a design algorithm is further derived to calculate the fuzzy resilient controller gains. Finally, simulations are provided to test the effectiveness of the proposed results.

In order to establish a proper geometry of an Unmanned Underwater Vehicle (UUV) for stable motion control and energy usage reduction, this paper analyzes the hydrodynamic performance of a complex shape underwater vehicle and develops a systematic Computational Fluid Dynamics (CFD) simulation method to solve the hydrodynamic parameters of the system. Based on the simulation method and their results, the streamlines and pressure distributions of the water flow around the underwater vehicle are analyzed, and the geometric model design is improved based on the drag characteristics. Also, a comparison scheme is designed to evaluate the vehicle model before and after the geometry improvement. Simulation result shows that the design schemes brings 18% drag reductions in surge direction and 32% in heave direction. Moreover, by establishing the physical and mathematical models of the UUV on a physical simulation platform, a complete model of the underwater vehicle is constructed, laying the foundation for further simulations and experiments.

The formula of food for special medical purpose has a direct impact on physicochemical stability, especially in hot climes and high temperature transport storage environments. An accelerated test (50 °C for 7 weeks) was used to analyze the mechanism of the physicochemical instability of formula A with lactose and maltodextrin, and formula B with maltodextrin. Deep dents and wrinkles were observed on the surface of the formula B, and more fat globules covered the surface of formula A particles after storage for a long time. Significantly higher amounts of furosine and Nε-carboxymethl-l-lysine (CML) were formed and the loss of available lysine was greater in formula A than in formula B. No significant difference was observed in lipid oxidation indicators between the two formulas. The results of this research demonstrated lactose was more active than maltodextrin and led to physicochemical instability.

Background: With our growing insight into the molecular heterogeneity and biological characteristics of breast cancer, individualized treatment is the future of cancer treatment. In this prospective Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series study – neoadjuvant therapy (FASCINATE-N) trial, we classify breast cancer patients using multiomic characteristics into different subtypes to evaluate the efficacy of precision-based targeted therapies compared to standard neoadjuvant chemotherapy. Methods and design: The FASCINATE-N trial is a prospective, randomized, precision-based umbrella trial that plans to enroll 716 women with early breast cancer. After enrollment, patients will first be divided into three groups: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HER2+, and HR−/HER2−. The HR+/HER2− patients are further stratified using fusion and clustering of similarity network fusion (SNF) algorithm into four subtypes; HER2+ patients are divided into HR+/HER2+ and HR−/HER2+ subtypes; and HR−/HER2− patients are stratified using the Fudan University Shanghai Cancer Center classification. For the assignment of drugs to patients, Bayesian methods of adaptive randomization will be used. The primary endpoint is pathological complete response rate; secondary endpoints include 3-year invasive disease-free survival, overall response rate, and toxicities according to common terminology criteria for adverse events (CTCAE) scale version 4.0 and the ratio of patients with complete cell cycle arrest (Ki67 < 2.7%) in HR+/HER2+ breast cancer. Discussion: The goal of our trial is to test the efficacy of our subtyping-based treatment in a neoadjuvant setting and to conduct a pilot study into the efficacy of targeted therapies within each precision-based subtype. The precision-based treatment arm can be updated with the refinement of our subtyping method, the discovery of new targets, and the development of novel targeted drugs. Our trial offers a unique opportunity to provide patients with individualized neoadjuvant therapy and test promising novel treatments that may further benefit patients. Trial registration: ClinicalTrials.gov identifier: NCT05582499 ( https://classic.clinicaltrials.gov/ct2/show/NCT05582499 ).

Abstract Land surface phenology (LSP) products are currently of large uncertainties due to cloud contaminations and other impacts in temporal satellite observations and they have been poorly validated because of the lack of spatially comparable ground measurements. This study provided a reference dataset of gap-free time series and phenological dates by fusing the Harmonized Landsat 8 and Sentinel-2 (HLS) observations with near-surface PhenoCam time series for 78 regions of 10 × 10 km2 across ecosystems in North America during 2019 and 2020. The HLS-PhenoCam LSP (HP-LSP) reference dataset at 30 m pixels is composed of: (1) 3-day synthetic gap-free EVI2 (two-band Enhanced Vegetation Index) time series that are physically meaningful to monitor the vegetation development across heterogeneous levels, train models (e.g., machine learning) for land surface mapping, and extract phenometrics from various methods; and (2) four key phenological dates (accuracy ≤5 days) that are spatially continuous and scalable, which are applicable to validate various satellite-based phenology products (e.g., global MODIS/VIIRS LSP), develop phenological models, and analyze climate impacts on terrestrial ecosystems.

Abstract Hydrogen spillover is the migration of activated hydrogen atoms from a metal particle onto the surface of catalyst support, which has made significant progress in heterogeneous catalysis. The phenomenon has been well researched on oxide supports, yet its occurrence, detection method and mechanism on non-oxide supports such as metal–organic frameworks (MOFs) remain controversial. Herein, we develop a facile strategy for efficiency enhancement of hydrogen spillover on various MOFs with the aid of water molecules. By encapsulating platinum (Pt) nanoparticles in MOF-801 for activating hydrogen and hydrogenation of C=C in the MOF ligand as activated hydrogen detector, a research platform is built with Pt@MOF-801 to measure the hydrogenation region for quantifying the efficiency and spatial extent of hydrogen spillover. A water-assisted hydrogen spillover path is found with lower migration energy barrier than the traditional spillover path via ligand. The synergy of the two paths explains a significant boost of hydrogen spillover in MOF-801 from imperceptible existence to spanning at least 100-nm-diameter region. Moreover, such strategy shows universality in different MOF and covalent organic framework materials for efficiency promotion of hydrogen spillover and improvement of catalytic activity and antitoxicity, opening up new horizons for catalyst design in porous crystalline materials.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of kidney cancer. Dysregulation of long-chain acyl-CoA synthetase 1 (ACSL1) is strongly implicated in undesirable results in varieties of cancers. Nevertheless, the dysregulation and associated multi-omics characteristics of ACSL1 in ccRCC remain elusive. Methods We probed the mRNA and protein profiles of ACSL1 in RCC using data from the Cancer Genome Atlas, Gene Expression Omnibus, the Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort and RCC cell lines. Correlations between ACSL1 expression and clinicopathological features, epigenetic modification and immune microenvironment characteristics were analyzed to reveal the multi-omics profile associated with ACSL1. Results ACSL1 was down-regulated in ccRCC tissues compared to adjacent normal tissues. Lower expression of ACSL1 was linked to unfavorable pathological parameters and prognosis. The dysregulation of ACSL1 was greatly ascribed to CpG island-associated methylation modification. The ACSL1 high-expression subgroup had enriched fatty acid metabolism-related pathways and high expression of ferroptosis-related genes. In contrast, the ACSL1 low-expression subgroup exhibited higher immune and microenvironment scores, elevated expression of immune checkpoints PDCD1, CTLA4, LAG3, and TIGIT, and higher TIDE scores. Using data from the GDSC database, we corroborated that down-regulation of ACSL1 was associated with higher sensitivity towards Erlotinib, Pazopanib, and PI3K-Akt-mTOR-targeted therapeutic strategies. Conclusion Taken together, our findings point to ACSL1 as a biomarker for prognostic prediction of ccRCC, identifying the tumor microenvironment (TME) phenotype, and even contributing to treatment decision-making in ccRCC patients.

Abstract Prognostic models in cancer use patient demographic and tumor characteristics to predict survival and dynamic disease prognosis. Past work in breast cancer has shown that cancer detection method, screen-detected or symptom-detected, has prognostic significance. We investigate this phenomenon in the lung component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial. Patients were randomized to intervention, receiving four annual chest x-rays (CXRs), or to control, receiving usual care. Patients were followed for a total of approximately 13 years. In PLCO, lung cancer detection method has independent prognostic value exceeding that of variables commonly used in lung cancer prognostic models, including sex, histology, and age. Results are robust to cohort selection and type of predictive model. These results imply that detection method should be considered when developing prognostic models in lung cancer studies, and cancer registries should routinely collect cancer detection method.

Abstract A comorbidity of chronic pain is sleep disturbance. Here, we identify a dual-functional ensemble that regulates both pain-like behaviour induced by chronic constrictive injury or complete Freund’s adjuvant, and sleep wakefulness, in the nucleus accumbens (NAc) in mice. Specifically, a select population of NAc neurons exhibits increased activity either upon nociceptive stimulation or during wakefulness. Experimental activation of the ensemble neurons exacerbates pain-like (nociceptive) responses and reduces NREM sleep, while inactivation of these neurons produces the opposite effects. Furthermore, NAc ensemble primarily consists of D1 neurons and projects divergently to the ventral tegmental area (VTA) and preoptic area (POA). Silencing an ensemble innervating VTA neurons selectively increases nociceptive responses without affecting sleep, whereas inhibiting ensemble-innervating POA neurons decreases NREM sleep without affecting nociception. These results suggest a common NAc ensemble that encodes chronic pain and controls sleep, and achieves the modality specificity through its divergent downstream circuit targets.

Polysaccharides have been assessed as a potential natural active component in Chinese herbal medicine with anti-inflammatory properties. However, the complex and indefinite structures of polysaccharides limit their applications. This study explains the structures and anti-inflammatory potentials of three neutral polysaccharides, RIP-A1 (Mw 1.8 × 104 Da), RIP-B1 (Mw 7.4 × 104 Da) and RIP-B2 (Mw 9.3 × 104 Da), which were isolated from the roots of Isatis indigotica Fort. with sequenced ultrafiltration membrane columns, DEAE-52 and Sephadex G-100. The planar structures and microstructures of RIP-A1, RIP-B1 and RIP-B2 were further determined by HPGPC, GC–MS, methylation analysis, FT-IR, SEM and AFM, in which the structure of RIP-A1 was elucidated in detail using 1D/2D NMR. The Raw 264.7 cells were used for the anti-inflammatory activity in vitro. The results showed that RIP-A1, RIP-B1 and RIP-B2 are all neutral polysaccharides, with RIP-A1 having the smallest Mw and the simplest monosaccharide composition of the three. RIP-A1 is mainly composed of Ara and Gal, except for a small quantity of Rha. Its main structure is covered with glycosidic linkages of T-α-Araf, 1,2-α-Rhap, 1,5-α-Araf, T-β-Galp, 1,2,4-α-Rhap, 1,3,5-α-Araf and 1,6-β-Galp with 0.33:0.12:1.02:0.09:0.45:11.41:10.23. RIP-A1 significantly inhibited pro-inflammatory cytokines (NO, TNF-α, IL-6 and IL-1β) and increased anti-inflammatory cytokines (IL-4) in LPS-stimulated RAW 264.7 cells. Moreover, RIP-A1 could significantly inhibit the mRNA expression of TNF-α, IL-6 and L-1β. It could also activate IKK, p65 and IκBα (the components of the NF-κB signaling pathway). In conclusion, the above results show the structural characterization and anti-inflammatory potentials of RIP-A1 as an effective natural anti-inflammatory drug.

A theoretical model, based on the classical Pennes’ bioheat theory, incorporating various boundary conditions, was established and compared to analyze the influence of the latent heat of vaporization via simulation. The aim was to elucidate the extent of its influence. The thermal damage rate, governed by the vaporization heat of biological tissue, is introduced as a key factor. Functional relationships between temperature and incident laser power, spatial position, and time are derived from the classical Pennes’ bioheat equation. According to the theoretical model, numerical simulations and experimental validations are conducted using Comsol Multiphysics 6.0, considering the tissue latent heat of vaporization. The model incorporating the latent heat of vaporization proved more suitable for analyzing the interactions between laser and biological tissue, evident from the degree of fit between simulated and experimental data. The minimum deviations between theoretical and experimental observations were determined to be 2.43% and 5.11% in temperature and thermal damage, respectively. Furthermore, this model can be extended to facilitate the theoretical analysis of the impact of vaporization heat from different primary tissue components on laser-tissue interaction.

Abstract Background Neonatal calf diarrhea (NCD) is typically treated with antibiotics, while long-term application of antibiotics induces drug resistance and antibiotic residues, ultimately decreasing feed efficiency. Pueraria polysaccharide (PPL) is a versatile antimicrobial, immunomodulatory, and antioxidative compound. This study aimed to compare the therapeutic efficacy of different doses of PPL (0.2, 0.4, 0.8 g/kg body weight (BW)) and explore the effect of plasma metabolites in diarrheal calves by the best dose of PPL. Results PPL could effectively improve the daily weight gain, fecal score, and dehydration score, and the dosage of 0.4 g/kg BW could reach curative efficacy against calf diarrhea (with effective rates 100.00%). Metabolomic analysis suggested that diarrhea mainly affect the levels of taurocholate, DL-lactate, LysoPCs, and intestinal flora-related metabolites, trimethylamine N-oxide; however, PPL improved liver function and intestinal barrier integrity by modulating the levels of DL-lactate, LysoPC (18:0/0:0) and bilirubin, which eventually attenuated neonatal calf diarrhea. It also suggested that the therapeutic effect of PPL is related to those differential metabolites in diarrheal calves. Conclusions The results showed that 0.4 g/kg BW PPL could restore the clinical score of diarrhea calves by improving the blood indexes, biochemical indexes, and blood metabolites. And it is a potential medicine for the treatment of calf diarrhea.

Milk is rich in many nutrients, including protein, lipids, carbohydrates, etc. Every 100 g of milk contains 3 g of protein, including mainly whey protein and casein. β-casein accounts for 24%~28% of total milk protein, and it mainly consists of two genotypes: A1 and A2. A1β-casein produces β-casein-7 after digestion, which can cause digestive disorders, cardiovascular diseases, and other adverse effects in humans. A2β-casein produces less or no β-casein-7 and has beneficial effects in gastrointestinal digestion, improving antioxidant function and lowering cholesterol concentration. This paper reviews the effects of β-casein genotypes after digestion in humans and discusses the probiotic functions of A2β-casein and its effects on human health. Moreover, the research progress of A2β-casein dairy products is described from the application of β-casein genotypes in dairy products to provide guidance for future research on the function of A2β-casein in dairy products.

The multi-point dynamic aggregation problem (MPDAP) comes mainly from real-world applications, which is characterized by dynamic task assignation and routing optimization with limited resources. Due to the dynamic allocation of tasks, more than one optimization objective, limited resources, and other factors involved, the computational complexity of both route programming and resource allocation optimization is a growing problem. In this manuscript, a task scheduling problem of fire-fighting robots is investigated and solved, and serves as a representative multi-point dynamic aggregation problem. First, in terms of two optimized objectives, the cost and completion time, a new bilevel programming model is presented, in which the task cost is taken as the leader's objective. In addition, in order to effectively solve the bilevel model, a differential evolution is developed based on a new matrix coding scheme. Moreover, some percentage of high-quality solutions are applied in mutation and selection operations, which helps to generate potentially better solutions and keep them into the next generation of population. Finally, the experimental results show that the proposed algorithm is feasible and effective in dealing with the multi-point dynamic aggregation problem.

Abstract Background For patients with low- and intermediate-risk stage II/III rectal cancer, current studies have reached a consensus that preoperative radiotherapy may be dispensed with, and neoadjuvant chemotherapy (NCT) alone might achieve an accepted local control. Our previous phase II study has evidenced that the morphological response of NCT could be better judged at a relatively early stage. Low- and intermediate-risk stage II/III rectal cancer patients could achieve a high rate of tumor shrinkage and downgrade after only 4 cycles of NCT and obvious tumor morphological changes could be observed after 2 cycles of NCT. However, there is still a lack of more detailed stratification and evidence for pathological criteria. The aim of the present study (comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks, COPEC trial) is to determine the pathological tumor regression grade (pTRG) rate of 2 or 4 cycles of NCT in low- and intermediate-risk stage II/III rectal cancer and verify the feasibility of early identification of chemotherapy-insensitive population. Methods/design This is a multicenter, prospective, non-inferior, randomized controlled trial (RCT) initiated by West China Hospital of Sichuan University and designed to be conducted in fourteen hospitals around China. Eligible patients will be centrally randomized into 2 or 4 cycles of CAPOX in a 1:1 ratio using the central automated randomization system offered by the O-trial online system ( https://plus.o-trial.com/ ) and accept total mesorectal excision after 2 or 4 cycles of CAPOX (oxaliplatin 130 mg/m2, once daily on day 1, every 21 days and capecitabine 1000 mg/m2, twice daily on days 1 to 14, every 21 days). The primary endpoint is the proportion of patients with pathological no-tumor regression (pTRG 3), which is determined postoperatively by each sub-center and verified by the primary center. Discussion COPEC trial is designed to verify that the preoperative CAPOX chemotherapy for low- and intermediate-risk stage II/III rectal cancer could achieve a good response judgment after 2 cycles and obtain the tumor pathological response rate after 2 cycles of CAPOX. We hope the COPEC trial could help in establishing a consensus standard of low- and intermediate-risk rectal cancer and the early identification of stage II/III rectal patients with low- and intermediate-risk who are poorly responding to NCT. Trial registration Clinicaltrial.gov NCT04922853. Registered on June 4, 2021.

Abstract Background Toxoplasma gondii is an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis. It is essential to develop an effective anti-T. gondii vaccine for the control of toxoplasmosis, and this study is to explore the immunoprotective effects of a live attenuated vaccine in mice and cats. Methods First, the ompdc and uprt genes of T. gondii were deleted through the CRISPR-Cas9 system. Then, the intracellular proliferation and virulence of this mutant strain were evaluated. Subsequently, the immune responses induced by this mutant in mice and cats were detected, including antibody titers, cytokine levels, and subsets of T lymphocytes. Finally, the immunoprotective effects were evaluated by challenge with tachyzoites of different strains in mice or cysts of the ME49 strain in cats. Furthermore, to discover the effective immune element against toxoplasmosis, passive immunizations were carried out. GraphPad Prism software was used to conduct the log-rank (Mantel–Cox) test, Student’s t test and one-way ANOVA. Results The RHΔompdcΔuprt were constructed by the CRISPR-Cas9 system. Compared with the wild-type strain, the mutant notably reduced proliferation (P

Abstract In recent years, the birth rate in China has rapidly declined. While much research has been done on the penalties in earnings that women incur when they fall behind men in the labor market due to childbirth, there has been little to no research on the mental health effects. This study addresses the gap in current literature by examining the mental health penalties that women experience after having a child in comparison to men. We applied econometric modeling to data collected from China Family Panel Studies (CFPS) and found that women experienced a significant, immediate, and long-run decline (4.3%) in life satisfaction after their first child, while men were unaffected. We also found that women experienced a significant increase in depression after their first child. This suggests mental health penalties since the mental health risk proxied by these two measurements is only significant for women. This is likely related to child penalties in labor market performance and childbirth-related physical health issues. When countries adopt multiple tools to stimulate the birth rate for economic growth, they must consider the implicit burden on women—especially the long-term negative effects on mental health.

As a migratory ungulate species, the chiru (Pantholops hodgsonii) primarily inhabits the Qinghai–Xizang Plateau. The population of the chiru has experienced a steady increase in recent years due to the implementation of rigorous conservation measures, including the establishment of nature reserves and legislation prohibiting hunting and killing. However, the study of chiru population ecology remains poorly understood duo to the unique and harsh natural conditions, as well as the seasonal migration and breeding patterns. In our study, we observed a higher overall population of the chiru (with average daily observations of 352 in 2012–2013 and 453 in 2023) and a demographic shift toward younger age groups (with juvenile percentage at 17.23% in 2023 and 15.85% in 2012–2013), implying the effectiveness of conservation efforts. But the marked increase in mortality rates among chiru warrants serious attention, particularly with regard to juvenile fatalities (from 1 death in 2012–2013 to 51 deaths in 2023). During past conservation efforts, the chiru population has gradually recovered; however, it is imperative to acknowledge the potential future risks due to accelerated climate change and intensification of human activity.

Alpine marginal ecosystems above the natural tree line are considered to be the most vulnerable habitats for maintaining local biodiversity. The soil microbial community is crucial for ecosystem stability and function. However, our comprehension of the overall soil microbial community in alpine marginal ecosystems remains limited, particularly regarding environmental stress. We selected the Baima Mountain National Nature Reserve (BMNNR) in the northwest Yunnan provinces as our study area and collected soil samples from three different depth layers, in alpine marginal ecosystems. The phospholipid fatty acid (PLFA) analysis method was utilized to evaluate alterations in soil microbial communities. The results showed that: (1) the PLFA content gradually decreased with increasing soil depth; (2) on the whole, the variations in PLFA across alpine marginal ecosystems were obviously, the highest in alpine meadow (AM) and the lowest in alpine screes (AS); (3) the site effect exerted a greater direct influence than microhabitat effect and elevation (0–5 cm, 32 %, 16 % and 9 %, respectively; 20–40 cm, 46 %, 29 % and 0 %, respectively), with the direct impact of elevation decreasing as soil depth increased (0–5 cm, 5–20 cm and20-40 cm, 9 %, 1 % and 0 %, respectively); and (4) the ratio of cyclopropyl to precursors (Cy:Pre) in all communities was > 0.1, indicating that the soil microbial community was under environmental stress. This study demonstrates the potential of PLFA analysis to profile soil microbial communities and their stress status under field conditions and also provides a better understanding of the correlation between soil microbial communities and the function and health of alpine marginal ecosystems.

With the modernization and intelligent development of agriculture, the energy demand in rural areas continues to increase, which leads to an increased operational burden on the existing rural distribution network. Integrated energy stations (IESs), in rural areas, use renewable energy sources such as biogas, wind power, and photovoltaic as energy inputs, which can fully improve energy efficiency and help reduce the operating load and peak valley difference of rural distribution networks. In this paper, a multistage planning model is proposed for rural distribution networks with IESs based on the robust optimization method. Firstly, a rural distribution network operation framework with IESs is proposed, and a mathematical model of rural IESs is built based on the energy hub (EH). Then, the multistage robust planning model of rural distribution net-works with IESs is developed and typical scenarios of stochastic source and load are generated based on improved k-means. An iterative solution method for a two-stage robust optimization method is proposed based on the nested column constraint generation (NC&CG) algorithm. Finally, the effectiveness of the presented model and solution approach is assessed through case studies on a modified IEEE 33-node distribution network and a real 152-node distribution network.

Abstract The integration of liposomes into hydrogels through direct soaking presents advantages such as facile formulation, enhanced drug stability, and controlled release kinetics. However, the feasibility of this approach is impeded by the difficulty of developing matching porous structures within hydrogels and achieving appropriate affinity with liposomes. To address these challenges, an alternative method is proposed for synthesizing macroporous hydrogels using thiolated hyaluronic acid and hyperbranched polyethylene glycol macromonomers in combination with a freezing‐induced secondary crosslinking process. This approach allows the locking of macropores formed by ice crystals during freezing and enables easy modification of the hydrogels with cholesterol groups to promote liposome association. Furthermore, these macroporous hydrogels can be crushed into granular hydrogels, which offer numerous benefits such as high loading capacity, injectability, self‐healing properties, and convenience in storage, dosing, and administration. Therefore, a liposome‐in‐hydrogel system can be formulated without any gelation or pre‐treatment, providing valuable insights for the further development of liposome‐based formulations for medical and cosmetic applications.