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Nematode parasites enter their definitive host at the developmentally arrested infectious larval stage (iL3), and the ligand-dependent nuclear receptor DAF-12 contributes to trigger their development to adulthood. Here, we characterized DAF-12 from the filarial nematodes Brugia malayi and Dirofilaria immitis and compared them with DAF-12 from the non-filarial nematodes Haemonchus contortus and Caenorhabditis elegans. Interestingly, Dim and BmaDAF-12 exhibit high sequence identity and share a striking higher sensitivity than Hco and CelDAF-12 to the natural ligands Δ4- and Δ7-dafachronic acids (DA). Moreover, sera from different mammalian species activated specifically Dim and BmaDAF-12 while the hormone-depleted sera failed to activate the filarial DAF-12. Accordingly, hormone-depleted serum delayed the commencement of development of D. immitis iL3 in vitro. Consistent with these observations, we show that spiking mouse charcoal stripped-serum with Δ4-DA at the concentration measured in normal mouse serum restores its capacity to activate DimDAF-12. This indicates that DA present in mammalian serum participate in filarial DAF-12 activation. Finally, analysis of publicly available RNA sequencing data from B. malayi showed that, at the time of infection, putative gene homologs of the DA synthesis pathways are coincidently downregulated. Altogether, our data suggest that filarial DAF-12 have evolved to specifically sense and survive in a host environment, which provides favorable conditions to quickly resume larval development. This work sheds new light on the regulation of filarial nematodes development while entering their definitive mammalian host and may open the route to novel therapies to treat filarial infections.

Abstract Background During electricity generation of nuclear power plant, heat energy cannot be completely converted into electrical energy, and a part of it is lost in the form of thermal discharge into the environment. The thermal discharge is harmful to flora and fauna leading to environmental deterioration, biological diversity decline, and even biological extinction. Results The present study investigated the influence of thermal discharge from a nuclear power plant on the growth and development of Pacific oyster Crassostrea gigas which is widely used as bio indicator to monitor environmental changes. The growth of soft part and the gonad development of oysters were inhibited due to thermal discharge. During winter season, temperature elevation caused by thermal discharge promoted the growth of oyster shells. During summer season, the growth rate of oysters in thermal discharge area was significantly lower than that of the natural sea area. Conclusions The results of this study provided a better understanding of assessing the impact of thermal discharge on the marine ecological environment and mariculture industry. It also provided a scientific basis for defining a safe zone for aquaculture in the vicinity of nuclear power plants.

Dirofilaria immitis is a filarial nematode causing infection and heartworm disease in dogs and other canids, cats, and occasionally in humans. Prevention with macrocyclic lactones (ML) is recommended during the mosquito transmission season. Recently, ML resistance has been reported. ABC-B transporter genes are thought to be involved in the mechanism of ML resistance in other nematodes. This study aimed to identify all the ABC-B transporter genes in D. immitis using as a reference the nDi.2.2 D. immitis whole genome, which is not completely annotated. Using bioinformatic tools and PCR amplification on pooled D. immitis genomic DNA and on pooled cDNA, nine ABC transporter genes including one pseudogene were characterized. Bioinformatic and phylogenetic analyses allowed identification of three P-glycoproteins (Pgps) (Dim-pgp-3 Dim-pgp-10, Dim-pgp-11), of two ABC-B half transporter genes (one ortholog of Cel-haf-4 and Cel-haf-9; and one ortholog of Cel-haf-1 and Cel-haf-3), of one ABC half transporter gene (ortholog of Cel-haf-5) that contained an ABC-C motif, and of one additional half transporter that would require functional study for characterization. The number of ABC-B transporter genes identified was lower than in Caenorhabditis elegans and Haemonchus contortus. Further studies are needed to understand their possible role in ML resistance in D. immitis. These ABC transporters constitute a base for ML resistance investigation in D. immitis and advance our understanding of the molecular biology of this parasite.

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations.

Eosinophils are one of the major mammalian effector cells encountered by helminths during infection. In the present study, we investigated the effects of eosinophil granule exposure on the sheep parasitic nematode Haemonchus contortus as a model. H. contortus eggs exposed to eosinophil granule products showed increased rhodamine 123 efflux and this effect was not due to loss of egg integrity. Rh123 is known to be a specific P-glycoprotein (Pgp) substrate and led to the hypothesis that in addition to their critical role in xenobiotic resistance, helminth ABC transporters such as Pgp may also be involved in the detoxification of host cytotoxic products. We showed by quantitative RT-PCR that, among nine different H. contortus Pgp genes, Hco-pgp-3, Hco-pgp-9.2, Hco-pgp-11 and, Hco-pgp-16 were specifically up-regulated in parasitic life stages suggesting a potential involvement of these Pgps in the detoxification of eosinophil granule products. Using exsheathed L3 larvae that mimic the first life stage in contact with the host, we demonstrated that eosinophil granules induced a dose dependent overexpression of Hco-pgp-3 and the closely related Hco-pgp-16. Taken together, our results provide the first evidence that a subset of helminth Pgps interact with, and could be involved in the detoxification of, host products. This opens the way for further studies aiming to explore the role of helminth Pgps in the host-parasite interaction, including evasion of the host immune response.

Abstract Combined with the advanced drilling of the central return air shaft in Kekegai Coal Mine, the distribution law of slag discharge flow field by drilling method and the influencing factors of slag discharge effect are studied. Firstly, the numerical model of gas–liquid–solid coupling slag discharge is established by CFD-DEM (computational fluid dynamics coupled discrete element method). Then, the flow field distribution law of the site slag outlet layout model and the optimization model is compared and analyzed. Finally, the influence of drilling parameters on slag discharge effect is studied. The results show that the best arrangement of slag suction ports is: the number is two, the length-diameter ratio is 0.4, the area ratio is 1, and the total area ratio is 1.94%. The fluid movement at the bottom of the well is mainly tangential flow, while the fluid in the slag discharge pipe is mainly axial flow. The construction parameters of efficient slag discharge are put forward: bit rotation speed is 8.7 r/min, gas injection rate is 4200 m3/h, air duct sinking ratio is 0.84, and mud viscosity is 165 MPa·s. The research results can provide useful theoretical reference for large-scale sinking construction in deep wells.

Abstract A model for studying displacement damage in irradiated HfO2 ferroelectric thin films was developed using deep learning and a repulsive table, combining the accuracy of density functional theory with the efficiency of molecular dynamics. This model accurately predicts the properties of various HfO2 phases, such as PO (Pca21), T (P42/nmc), AO (Pbca), and M (P21/c), and describes the atom collision-separation process during irradiation. The displacement threshold energies for the Hf atoms, three-coordinated O atoms, and four-coordinated O atoms are 57.72, 41.93, and 32.89 eV, respectively. The defect formation probabilities (DFPs) for the O primary knock-on atoms (PKAs) and Hf PKAs increase with energy, reaching 1. Below 80.27 eV, the O PKAs are more likely to form point defects than the Hf PKAs. Above this energy, the Hf PKAs have a higher DFP because the O PKAs form replacement loops more easily, inhibiting the generation of point defects. This study provides a comprehensive understanding of defect formation, which is crucial for increasing the reliability of HfO2 ferroelectric devices under irradiation.

Abstract The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLpro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLpro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discover a series of novel potent non-covalent PLpro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLpro with lead compounds reveal that the residues D164 and Q269 around the S2 site are critical for improving the inhibitor’s potency. The lead compound GZNL-P36 not only inhibits SARS-CoV-2 and its variants at the cellular level with EC50 ranging from 58.2 nM to 306.2 nM, but also inhibits HCoV-NL63 and HCoV-229E with EC50 of 81.6 nM and 2.66 μM, respectively. Oral administration of the GZNL-P36 results in significantly improved survival and notable reductions in lung viral loads and lesions in SARS-CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLpro inhibitors represent a promising SARS-CoV-2 therapy.

Abstract With the continuous advancement of industrial automation, the performance requirements for metallurgical industrial robots, especially in teleoperation systems, are increasingly demanding. This paper presents an adaptive force/position control algorithm based on Fuzzy CMAC (Cerebellar Model Articulation Controller) for an asymmetric teleoperation system. The system consists of a novel 6-degree-of-freedom master robot and a Baxter slave robot. Our design focuses on addressing tracking and transparency issues in asymmetric systems. Experimental results demonstrate that the proposed control algorithm significantly outperforms the adaptive fuzzy PID control algorithm in terms of control performance, meeting the requirements for stability, tracking, and transparency in asymmetric teleoperation systems. The innovation of this study lies in the development of a new 6-DOF haptic device and its successful application in an asymmetric teleoperation system, enhancing control precision and user experience. The results of this research not only hold application potential in the metallurgical field but also provide new technical pathways for the future development of teleoperation systems.

Abstract Background A lower dietary sodium intake has been associated with a reduced risk of cardiovascular disease (CVD) mortality in the general population. However, the evidence is less clear in diabetic patients. The study aims to investigate whether the usage of table salt is associated with all-cause and CVD mortality among individuals with diabetes. Methods In this prospective cohort study, participants with diabetes from the U.S. National Health and Nutritional Examination Survey (NHANES) 2003–2018 were included. Weighted linear regression models were employed to assess the association between the usage of table salt and dietary sodium intake. Weighted Cox proportional hazards regression models were used to assess the association between the usage of table salt and all-cause and CVD mortality. Results This cohort study included data from 6,258 participants in analysis. During 44,035 person-years of follow-up, 1,504 deaths from all-causes and 427 from CVD were documented. Not using table salt was significantly associated with lower dietary sodium intake, with a β of -192.60 (95% CI, -297.01 to -88.18) mg. A higher risk of all-cause and CVD mortality was observed in the group of participants not using table salt among patients with diabetes. Compared with participants using table salt, the hazard ratios for all-cause mortality were 1.18 (95% CI, 1.03 to 1.35), and for CVD were 1.48 (95 CI, 1.16 to 1.90) for participants not using table salt. The subgroup analysis revealed a significantly stronger link between the usage of table salt and all-cause mortality in participants with CVD (P for interaction = 0.004). Conclusions This study indicated that not using table salt was associated with a lower dietary sodium intake, and an increased risk of all-cause and CVD mortality among individuals with diabetes. Interventional studies are needed to determine more beneficial relevant approaches to dietary management in diabetes care.

Abstract To reveal the velocity distribution law of a gas lift reverse circulation well washing flow field in drilling shaft sinking, a velocity mathematical model of well washing flow field is established. The theoretical analytical solutions and velocity distribution laws in the drill pipe and bottom hole were provided and validated through numerical simulations and similar model tests. Furthermore, this study explores the impacts of mud circulation, wind pressure, rock debris, and mud properties on the flow field distribution, presenting the sensitivity order of the factors. This study indicated the following findings. (1) The velocity theoretical model of well washing flow field was validated through numerical simulation and similar model tests, and the relative error ranged from 4.2 to 18.5%, demonstrating the high consistency. (2) The rock debris and mud experienced slight and consistent deceleration within the drill pipe. Upon reaching the gas input end, the axial upward return of the multiphase flow resulted in a “jumping” sharp increase. (3) The mud circulation, wind pressure, and void fraction positively correlated with the multiphase fluid velocity in the drill pipe, but negatively correlated with the mud density and slag content. The axial upward velocity of the rock debris decreased with increasing particle size and density. (4) The sensitivity of each factor to the discharge speed of rock debris was summarized as follows: air content > mud circulation > wind pressure > mud density > rock debris density > rock debris particle size > slag content. These findings could offer a theoretical basis for selecting well washing parameters and enhancing drilling and washing efficiency.

AIM: To observe the changes in corneal subepithelial nerve fibers (CNFs) and Langerhans cells (LCs) in patients with type 2 diabetes using corneal laser confocal microscopy (CLCM). METHODS: A total of 60 patients (64 eyes), including 40 patients with type 2 diabetes (DM group) and 20 subjects without diabetes (control group) were included with CLCM. Neuron J plugin of Image J software were used for quantitative analysis of CNF length (CNFL), CNF density (CNFD), corneal nerve branch fiber density (CNBD), main branch length density, branch length density, corneal nerve fiber tortuosity (NT) score, and LCs density. An independent samples t-test to analyze the variability between the two groups was performed, and Pearson correlation analysis was used to analyze the relationships between CNF and multiple biochemical indicators in the DM group. The predictive power of CNF for type 2 diabetes was assessed using the receiver operating characteristic (ROC) curve. RESULTS: There were significant differences in the CNFL, CNFD, and main branch length density between two groups. The results of Pearson correlation analysis showed a significant negative correlation between CNFD and the duration of diabetes as well as triglyceride levels and total cholesterol, and a significant positive correlation between CNFD and serum albumin. In addition, the NT score showed a positive correlation and urea nitrogen, similar to the positive correlation observed between LC density and glycosylated hemoglobin (HbA1c) levels. CNFD showed the highest area under the curve (AUC of ROC) value, followed by main branch length density and CNFL. The AUC of the ROC curve under the logistic regression model also demonstrated good predictive values. The cut-off values of CNFD, CNFL, and main branch length density for diabetes showed 31.25, 18.85, and 12.56, respectively. CONCLUSION: In patients with type 2 diabetes, there is a notable reduction in both CNFL and CNFD. These measurements can be influenced by various blood biochemical factors. However, the compromised nerve fibers can serve as valuable indicators for predicting the onset of type 2 diabetes and also as biomarkers for detecting diabetic neuropathy and its related complications.

Abstract TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet’s disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD.

Abstract Existing deep foundation pit support structures are commonly composed of external earth-retaining structures, internal horizontal bracings, and vertical columns. A closed bracing system, often formed by a horizontal support through a bracket board, frequently impedes vertical excavation and soil removal operations in the foundation pit, and the processes of assembly and dismantling are complex and time-consuming. This study presents a combined support system and construction method consisting of cast-in-place piles and diagonal steel lattice braces. For sloped excavation, diagonal braces were constructed by slotting through the reserved soil, allowing the use of a single layer of support within the excavation depth. This approach significantly optimizes the construction process, reducing both project duration and overall cost. The field monitoring results indicated that the support method effectively controlled the lateral displacement of the pile bodies. Field monitoring results demonstrated that the proposed support system effectively controlled the lateral displacement of the pile bodies. The adoption of a support-first, excavation-second approach significantly controlled the settlement of the ground surface around the foundation pit, thereby preventing excessive increments in the axial force of the supports due to the large longitudinal depth excavation. The calculation results of the three-dimensional finite element model for foundation pit excavation and support indicate that the proposed support method results in a decreasing ratio of the maximum lateral deformation depth of the pile body, denoted as δ h-m , to the excavation depth H e as the excavation depth increases. This implied that the displacement of the pile body was strictly controlled. When the depth of the foundation pit excavation exceeded 10 m, the maximum lateral deformation occurred below 10 m along the pile shaft. The diagonal steel lattice braces transferred the load to the top of the cast-in-place piles at the bottom of the pit, where the stress concentration occurred. During construction, special attention must be paid to the strength of the connection between the pile top and the connecting beams.

Abstract Over the past few decades, metasurfaces have revolutionized conventional bulky optics by providing an effective approach to manipulate optical waves at the subwavelength scale. This advancement holds great potential for compact, multifunctional, and reconfigurable optical devices. Notably, metasurfaces constructed with anisotropic nanostructures have exhibited remarkable capability in manipulating the polarization state of optical waves. Furthermore, they can be employed to achieve independent control of the amplitude and phase of optical waves in different polarization channels. This capability has garnered significant attention from the photonics community due to its unprecedented potential for polarization-selective and -multiplexed optical wave manipulation, offering versatile applications in optical imaging, communication, and detection. This paper reviews the design principles, representative works, and recent advancements in anisotropic nanostructures for optical polarization manipulation, detection, as well as polarization-selective and -multiplexed optical wave manipulation. Personal insights into further developments in this research area are provided.

Tunnel Boring Machines (TBMs) have been successfully applied in the excavation of deep shaft roadways in coal mines, yielding substantial socio-economic benefits. However, technical bottlenecks remain that hinder their further promotion and application. In response to the challenge of current support structures and techniques failing to simultaneously meet the requirements of support efficiency, strength, and construction costs, which impedes the full utilization of TBM speed advantages, a research team has developed a novel steel pipe segment assembly support structure. Large-scale model tests of the new prefabricated support structure were conducted to ascertain the deformation and failure patterns under loaded conditions, and the support structure was optimized based on the test results. Numerical simulations were performed to evaluate the reliability of the new support structure under TBM tunneling conditions. Industrial trials were subsequently conducted to field-test the feasibility of the new steel pipe segment support structure for TBM-excavated roadways in coal mines. The test results indicate that the maximum tensile strain of the surrounding rock is 803 με, and the deformation of the steel pipe support structure is less than 1 mm. The new support structure can be installed quickly, with the installation of one ring of segments (1.5 m) completed within 90 minutes, significantly enhancing the support strength in TBM-excavated roadways and the adaptability to strata conditions. This research provides a technical reference for further increasing the tunneling speed of coal mine roadways and ensuring the continuity of coal mining operations.

Abstract Background Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. Methods This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. Results The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P

Abstract Objective To explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs). Methods The Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution. Results TAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups. Conclusions Discrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established.

Abstract Background To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini‐pigs were observed dynamically. Methods An AS model in Bama miniature pigs was established by a high‐cholesterol and high‐fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini‐pigs to AS. The metabolomics was detected using a high‐resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility. Results Based on pathological analysis, mini‐pigs were divided into two groups: a susceptible group (n = 3) and a non‐susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism. Conclusions During the progression of AS in mini‐pigs induced by high‐cholesterol/high‐fat diet, the alterations in serum metabolic profile exhibited a time‐dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS.

Abstract Regioselective C–H functionalization of pyridines remains a persistent challenge due to their inherent electronically deficient properties. In this report, we present a strategy for the selective pyridine C3-H thiolation, selenylation, and fluorination under mild conditions via classic N−2,4-dinitrophenyl Zincke imine intermediates. Radical inhibition and trapping experiments, as well as DFT theoretical calculations, indicated that the thiolation and selenylation proceeds through a radical addition-elimination pathway, whereas fluorination via a two-electron electrophilic substitution pathway. The pre-installed electron-deficient activating N-DNP group plays a crucial and positive role, with the additional benefit of recyclability. The practicability of this protocol was demonstrated in the gram-scale synthesis and the late-stage modification of pharmaceutically relevant pyridines.

Abstract Background Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. Methods We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan–Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. Results The TSR cutoff was identified to be − 6.6%. Median PFS and OS were longer in the group with a TSR − 6.6%. Brain metastasis-free survival was better in the group with a TSR

Objectives Cervical alignment and range of motion (ROM) changes after cervical spine surgery are related to cervical biomechanical and functions. Few studies compared these parameters between posterior laminoplasty and anterior 3‐level hybrid surgery incorporating anterior cervical discectomy and fusion (ACDF) with cervical disc replacement (CDR). This study is aimed to detect the differences of cervical alignment and ROM changes of the two surgeries in a matched‐cohort study. Methods From January 2018 and May 2020, 51 patients who underwent 3‐level hybrid surgery incorporating ACDF with ACDR were included. A 1:1 match of the patients who underwent cervical laminoplasty based on age, gender, duration of symptoms, body mass index, and cervical alignment type was utilized as control group. General data (operative time, blood loss, etc.), Japanese Orthopaedic Association (JOA) score, VAS (Visual Analog Score), NDI (The Neck Disability Index), cervical sagittal alignment, and cervical range of motion (ROM) were recorded and compared. Results Both groups gained significant improvement in JOA, VAS, NDI scores postoperatively (p

Objective As osteoporosis progresses, the primary compressive trabeculae (PCT) in the proximal femur remains preserved and is deemed the principal load‐bearing structure that links the femoral head with the femoral neck. This study aims to elucidate the distribution patterns of PCT within the proximal femur in the elderly population, and to assess its implications for the development and optimization of internal fixation devices used in hip fracture surgeries. Methods This is a retrospective cohort study conducted from March 2022 to April 2023. A total of 125 patients who underwent bilateral hip joint CT scans in our hospital were enrolled. CT data of the unaffected side of the hip were analyzed. Key parameters regarding the PCT distribution in the proximal femur were measured, including the femoral head's radius (R), the neck‐shaft angle (NSA), the angle between the PCT‐axis and the head–neck axis (α), the distance from the femoral head center to the PCT‐axis (δ), and the lengths of the PCT's bottom and top boundaries (L‐bottom and L‐top respectively). The impact of gender differences on PCT distribution patterns was also investigated. Student's t‐test or Mann–Whitney U test were used to compare continuous variables between genders. The relationship between various variables was investigated through Pearson's correlation analysis. Results PCT was the most prominent bone structure within the femoral head. The average NSA, α, and δ were 126.85 ± 5.85°, 37.33 ± 4.23°, and 0.39 ± 1.22 mm, respectively, showing no significant gender differences (p > 0.05). Pearson's correlation analysis revealed strong correlations between α and NSA (r = −0.689, p

IntroductionBlended learning combines the strengths of online and offline teaching and has become a popular approach in higher education. Despite its advantages, maintaining and enhancing students’ continuous learning motivation in this mode remains a significant challenge.MethodsThis study utilizes questionnaire surveys and structural equation modeling to examine the role of AI performance assessment in influencing students’ continuous learning motivation in a blended learning environment.ResultsThe results indicate that AI performance assessment positively influences students’ continuous learning motivation indirectly through expectation confirmation, perceived usefulness, and learning satisfaction. However, AI performance assessment alone does not have a direct impact on continuous learning motivation.DiscussionTo address these findings, this study suggests measures to improve the effectiveness of AI performance assessment systems in blended learning. These include providing diverse evaluation metrics, recommending personalized learning paths, offering timely and detailed feedback, fostering teacher-student interactions, improving system quality and usability, and visualizing learning behaviors for better tracking.

In recent years, formal verification has emerged as a crucial method for assessing security against Side-Channel attacks of masked implementations, owing to its remarkable versatility and high degree of automation. However, formal verification still faces technical bottlenecks in balancing accuracy and efficiency, thereby limiting its scalability. Former tools like maskVerif and CocoAlma are very efficient but they face accuracy issues when verifying schemes that utilize properties of Boolean functions. Later, SILVER addressed the accuracy issue, albeit at the cost of significantly reduced speed and scalability compared to maskVerif. Consequently, there is a pressing need to develop formal verification tools that are both efficient and accurate for designing secure schemes and evaluating implementations. This paper’s primary contribution lies in proposing several approaches to develop a more efficient and scalable formal verification tool called Prover, which is built upon SILVER. Firstly, inspired by the auxiliary data structures proposed by Eldib et al. and optimistic sampling rule of maskVerif, we introduce two reduction rules aimed at diminishing the size of observable sets and secret sets in statistical independence checks. These rules substantially decrease, or even eliminate, the need for repeated computation of probability distributions using Reduced Ordered Binary Decision Diagrams (ROBDDs), a time-intensive procedure in verification. Subsequently, we integrate one of these reduction rules into the uniformity check to mitigate its complexity. Secondly, we identify that variable ordering significantly impacts efficiency and optimize it for constructing ROBDDs, resulting in much smaller representations of investigated functions. Lastly, we present the algorithm of Prover, which efficiently verifies the security and uniformity of masked implementations in probing model with or without the presence of glitches. Experimental results demonstrate that our proposed tool Prover offers a better balance between efficiency and accuracy compared to other state-of-the-art tools (IronMask, CocoAlma, maskVerif, and SILVER). In our experiments, we also found an S-box that can only be verified by Prover, as IronMask cannot verify S-boxes, and both CocoAlma and maskVerif suffer from false positive issues. Additionally, SILVER runs out of time during verification.

Abstract The safety and efficacy of the lipid nanoparticle (LNP) delivery system are crucial for the successful development of messenger RNA vaccines. We designed and synthesized a series of ketal ester lipids (KELs), featuring a biodegradable ketal moiety in the linker and ester segments in the tail. Through iterative optimization of the head and tail groups of KELs, we tuned the pKa and molecular shapes, and identified (4S)‐KEL12 as a safe and efficient ionizable lipid for mRNA delivery. (4S)‐KEL12 LNP showed significantly higher delivery efficacy and lower toxicity than the DLin‐MC3‐DMA LNP. In comparison to SM‐102 LNP, (4S)‐KEL12 LNP exhibited better spleen tropism, reduced liver tropism, and hepatotoxicity. Additionally, (4S)‐KEL12 demonstrated good biodegradability following intramuscular or intravenous injection. Notably, (4S)‐KEL12 LNP encapsulated with a therapeutic mRNA cancer vaccine elicited robust cellular immune responses leading to substantial tumor regression along with prolonged survival in tumor‐bearing mice. Our results suggest that (4S)‐KEL12 LNP holds great promise for mRNA vaccine delivery. The comprehensive analysis of the structure‐activity relationship, toxicity, biodegradability, distribution, expression, efficacy, and stereochemistry of these LNPs will greatly contribute to the rational design and discovery of novel lipid‐based delivery systems.

Transmembrane transport remains a significant challenge for nucleic acid vaccine vectors. Promoting the ability of immune cells, such as macrophages, to capture foreign stimuli is also an effective approach to improving cross-presentation. In addition, polyethyleneimine (PEI) has gained attention in the field of nucleic acid vaccine carriers due to its excellent gene transfection efficiency and unique proton buffering effect. However, although high molecular weight PEI exhibits high efficiency, its high-density positive charges make it highly toxic, which limits its application. In this study, mannose/stearyl chloride functionalized polyethylenimine (SA-Man-PEI) was prepared by functionalizing PEI (molecular weight of 25 kDa) with mannose with immunomodulatory and phagocyte targeting effects, and an alkyl hydrophobic chain segment, which could easily promote cell uptake. Moreover, the functionalized-PEI retains a strong proton buffering effect, which helps the carrier escape from the lysosome. The particle sizes of the composite particles formed by SA-Man-PEI and ovalbumin (OVA) were below 200 nm, with good storage stability at both 4 °C and 37 °C. At a drug concentration of 2 μg/mL, the cell survival rate of functionalized-PEI was 19.2% higher than that of unfunctionalized PEI. In vitro macrophage endocytosis experiments showed that SA-Man-PEI could significantly enhance the macrophage uptake of composite particles, compared to unfunctionalized PEI or single-functionalized PEI. This study offers a new approach for developing PEI as a nucleic acid vaccine carrier, which could simultaneously enhance cell targeting and promote cell uptake.

Purpose Infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality.Methods This retrospective cohort study included patients with pneumonia caused by CRKP between January 1, 2020 and December 31, 2022. The primary outcomes were 7-day bacterial eradication rate and 14- and 28-day all-cause mortality. The secondary outcome was incidence of acute kidney injury.Results Seventy-three patients were included in this study, 29 in the polymyxin B-based combination therapy group and 44 in tigecycline-based combination therapy group. There were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p = 0.409), the 14-day all-cause mortality (37.93% vs 22.73%, p = 0.160), and the incidence of acute kidney injury (14.29% vs 6.82%, p = 0.526). The 28-day all-cause mortality in the polymyxin B-based therapy group was higher than in the tigecycline-based group (75.86% vs 45.45%, p = 0.010). Binary logistic regression analysis revealed that male and previous use of carbapenems were independent factors associated with 28-day all-cause mortality for patients treated with polymyxin B (p

Model-Free Adaptive Control (MFAC) is a control strategy that eliminates the need for prior knowledge of the system model by leveraging online data to learn the system dynamics and design controllers. This paper offers a comprehensive exploration of the significance of control theory in unmanned surface vessels (USVs), with a particular focus on data-driven approaches. It provides a comprehensive overview of various MFAC algorithms proposed for USVs in diverse scenarios, including neural network-based MFAC, reinforcement learning-based MFAC, and fuzzy logic-based MFAC. The objective of this review is to provide a profound understanding of the latest advancements in MFAC technologies and serve as a guiding resource for further developments in the field.

Head pose estimation plays a crucial role in various applications, including human–machine interaction, autonomous driving systems, and 3D reconstruction. Current methods address the problem primarily from a 2D perspective, which limits the efficient utilization of 3D information. Herein, a novel approach, called pose orientation‐aware network (POANet), which leverages normal maps for orientation information embedding, providing abundant and robust head pose information, is introduced. POANet incorporates the axial signal perception module and the rotation matrix perception module, these lightweight modules make the approach achieve state‐of‐the‐art (SOTA) performance with few computational costs. This method can directly analyze various topological 3D data without extensive preprocessing. For depth images, POANet outperforms existing methods on the Biwi Kinect head pose dataset, reducing the mean absolute error (MAE) by ≈30% compared to the SOTA methods. POANet is the first method to perform rigid head registration in a landmark‐free manner. It also incorporates few‐shot learning capabilities and achieves an MAE of about 1° on the Headspace dataset. These features make POANet a superior alternative to traditional generalized Procrustes analysis for mesh data processing, offering enhanced convenience for human phenotype studies.

BackgroundRadial deviation of the interphalangeal (IP) joint is a common complication of treating Wassel type IV-D preaxial polydactyly. Long-term radial deviation can place excessive tension on the radial skin and cause overabundance of the ulnar skin. To overcome this problem, we aimed to utilize a fascial flap for ulnar reconstruction of a defect in the radial skin.MethodsWe used a fascial flap for ulnar reconstruction of a defect in the radial skin, eight patients (average: 12 years, range: 5–33 years) who underwent reconstructive surgery at our department for radial deviation of the interphalangeal (IP) joint after the initial operation were included between August 2017 and August 2021. An incision was made on the radial side of the thumb. An olive-shaped flap was designed on the ulnar eminence of the IP joint. The skin and fascia in the other three quadrants were incised. While the flap was protected, children with epiphyseal plates underwent wedge osteotomy at the maximum ulnar deviation of the proximal phalanx, and adults underwent direct fusion of the distal IP joint. Absorbable sutures were used to suture the flap. The Tada functional and visual analog scale (VAS) scores were recorded before and after the operation.ResultsAll flaps survived without infection or necrosis. The preoperative and postoperative Tada scores were 1 and 5, respectively, and the preoperative and postoperative VAS scores were 3 and 9, respectively. The postoperative scores showed a statistically significant degree of improvement.ConclusionsAn ulnar fascial flap is an effective and feasible option for repair of radial deviation following surgery for preaxial polydactyly.

In early 2021, China introduced the “30–60” objective of “Carbon Neutral and Carbon Peak,” establishing low-carbon and high-quality development as a pivotal direction for China’s economic and social progress. China’s textile industry assumes a vital role in achieving low-carbon and high-quality development. Technological innovation emerges as a means to meet environmental regulations, facilitating an advantageous synergy between economic prosperity and environmental protection. The purpose of this study is to investigate the relationship between direct environmental regulation (DER) and enterprise innovation in the context of the Chinese textile industry. To achieve it, the study utilizes data collected from publicly listed textile companies in China, covering the period from 2004 to 2018, to construct a moderation-mediation model that explores the complex interplay between DER and enterprise innovation. The study’s novelty lies in comparing the impact of environmental regulation on innovation quality through substantive innovation and green innovation, as well as conducting stratified classification analyses by incorporating heterogeneous factors such as DER intensity, region, and sub-industry. The results demonstrate that DER significantly promotes both the input and output quality of innovation in Chinese textile enterprises, exhibiting a complex pattern of mediating and moderating effects. Specifically, DER exerts a substantial influence on the capital investment in innovation by Chinese textile enterprises, with high-intensity DER yielding more pronounced effects. The impact of DER on enterprise innovation quality is also contingent upon enterprise heterogeneity. Additionally, innovation capital investment serves as a pivotal mediating factor that links DER to the innovation quality of Chinese textile enterprises. The enterprise scale exhibits a moderating effect between DER and enterprise innovation quality. In summary, the mediation of innovation input and the moderation of enterprise scale collectively contribute to a comprehensive moderation-mediation effect on the relationship between DER and innovation quality in Chinese textile enterprises. Based on these findings, this study provides novel empirical support for the narrow “Porter Hypothesis” and offers targeted recommendations for enterprise management and policymakers in future applications.

BackgroundCell death plays an essential role in carcinogenesis, but its function in the recurrence and postoperative prognosis of head and neck cancer (HNC), which ranks as the 7th most common malignancy globally, remains unclear.MethodsData from five main subtypes of HNC related single-cell RNA sequencing (scRNA-seq) were recruited to establish a single-cell atlas, and the distribution of cell death models (CDMs) across different tissues as well as cell subtypes were analyzed. Bulk RNA-seq from the Cancer Genome Atlas Program (TCGA) dataset was subjected to a machine learning-based integrative procedure for constructing a consensus cell death-related signature risk score (CDRscore) model and validated by external data. The biofunctions including different expression analysis, immune cell infiltration, genomic mutations, enrichment analysis as well as cellchat analysis were compared between the high- and low- risk score groups categorized by this CDRscore model. Finally, samples from laryngeal squamous cell cancer (LSCC) were conducted by spatial transcriptomics (ST) to further validate the results of CDRscore model.ResultsT cells from HNC patients manifested the highest levels of cell death while HPV infection attenuates malignant cell death based on single-cell atlas. CDMs are positively correlated with the tumor-cell stemness, immune-related score and T cells are infiltrated. A CDRscore model was established based on the transcription of ten cell death prognostic genes (MRPL10, DDX19A, NDFIP1, PCMT1, HPRT1, SLC2A3, EFNB2, HK1, BTG3 and MAP2K7). It functions as an independent prognostic factor for overall survival in HNC and displays stable and powerful performance validated by GSE41613 and GSE65858 datasets. Patients in high CDRscore manifested worse overall survival, more active of epithelial mesenchymal transition, TGF-β-related pathways and hypoxia, higher transcription of T cell exhausted markers, and stronger TP53 mutation. ST from LSCC showed that spots with high-risk scores were colocalized with TGF-β and the proliferating malignant cells, additionally, the risk scores have a negative correlation with TCR signaling but positive association with LAG3 transcription.ConclusionThe CDRscore model could be utilized as a powerful prognostic indicator for HNC.

Energy theft poses a significant threat to the power industry, causing financial losses and grid instability. Existing detection methods often struggle with limited labeled data and the emergence of new, unobserved theft patterns. To address these challenges, we propose a novel method for energy theft detection that effectively leverages both partially observed anomalies and unlabeled data. Our approach integrates Discrete Wavelet Transform (DWT) for feature extraction, Fuzzy C-Means clustering for anomaly grouping, and weighted multi-class logistic regression for ensemble learning. Extensive experiments on a realistic dataset demonstrate that our method achieves high detection accuracy, outperforming several state-of-the-art methods, including deep learning models, while maintaining significantly lower computational cost. This robust and efficient approach enables effective detection of unobserved anomaly classes and reduces false positives, making it a valuable tool for developing reliable energy theft detection systems. We further conduct a feature importance analysis to identify influential features for optimizing detection accuracy and efficiency.

Abstract The tomb of Marquis Yi of Zeng was unearthed in 1978 at Leiguudun in Suizhou City, Hubei Province, China. This is the largest wooden coffin in rock pit and vertical cave in the Warring States period in China. The large wooden coffin components provide reliable material data for the study of the feudal burial system in the pre-Qin period and have high value. In this paper, the wooden coffin excavated from the tomb of Marquis Yi of Zeng was studied. By understanding the composition of wood, studying the weight gain rate, shrinkage rate, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compression resistance, the wood reinforced by rosin and epoxy resin was compared, and the reinforcement effect and principle of the two reinforcement methods were discussed. The study found that the wood properties of rosin reinforced group were better than those of epoxy reinforced group in the aspects of compressive strength, weight gain rate and volume shrinkage rate, and the mechanical properties of wood were significantly improved. In addition, methanol or ethanol can be used to dissolve the rosin shellac in this strengthening process, which can achieve reversible strengthening treatment. The results provide valuable examples and research ideas for the selection of different conservation techniques of large wooden cultural relics unearthed in the middle and lower reaches of the Yangtze River during the Warring States Period.

Introduction: Sepsis and septic shock are significant contributors to the development of acute kidney injury (AKI) in critically ill patients. This study aimed to elucidate the role and mechanism of microRNA-223-3p in sepsis-associated AKI (SA-AKI). Methods: Bioinformatics methods were used to analyze the expression of microRNA-223-3p in sepsis patients, its correlation with inflammatory cytokines, and to predict the binding site of microRNA-223-3p with SGK1. The binding relationship between microRNA-223-3p and SGK1 was validated using a dual-luciferase reporter gene assay. The expression of microRNA-223-3p was assayed using qPCR in patient serum or lipopolysaccharide (LPS)-treated HK-2 cells. Cell apoptosis; expression of Bax, Bcl-2, cleaved caspase-3; and levels of TNF-α, IL-1β, and IL-6 were measured using TUNEL assay, Western blot (WB), and ELISA, respectively. SGK1 expression of HK-2 cells with different treatments was detected using qPCR and WB. Results: The expression of microRNA-223-3p was found to be upregulated in sepsis patients and HK-2 cells treated with LPS. Furthermore, microRNA-223-3p promoted apoptosis and inflammation in LPS-induced HK-2 cells. This promotion was mediated by the negative regulation of SGK1 by microRNA-223-3p. Conclusion: The microRNA-223-3p was found to regulate SGK1 and promote apoptosis and inflammation in LPS-induced HK-2 cells. Our study has elucidated the mechanism of microRNA-223-3p in SA-AKI, providing a potential target for sepsis treatment.

Abstract Recent demonstrations of moiré magnetism, featuring exotic phases with noncollinear spin order in the twisted van der Waals (vdW) magnet chromium triiodide CrI3, have highlighted the potential of twist engineering of magnetic (vdW) materials. However, the local magnetic interactions, spin dynamics, and magnetic phase transitions within and across individual moiré supercells remain elusive. Taking advantage of a scanning single-spin magnetometry platform, here we report observation of two distinct magnetic phase transitions with separate critical temperatures within a moiré supercell of small-angle twisted double trilayer CrI3. By measuring temperature-dependent spin fluctuations at the coexisting ferromagnetic and antiferromagnetic regions in twisted CrI3, we explicitly show that the Curie temperature of the ferromagnetic state is higher than the Néel temperature of the antiferromagnetic one by ~10 K. Our mean-field calculations attribute such a spatial and thermodynamic phase separation to the stacking order modulated interlayer exchange coupling at the twisted interface of moiré superlattices.

Abstract Objective To explore the relationship between the timing of non-emergency surgery in mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infected individuals and the quality of postoperative recovery from the time of confirmed infection to the day of surgery. Methods We retrospectively reviewed the medical records of 300 cases of mild or asymptomatic SARS-CoV-2 infected patients undergoing elective general anaesthesia surgery at Yijishan Hospital between January 9, 2023, and February 17, 2023. Based on the time from confirmed SARS-CoV-2 infection to the day of surgery, patients were divided into four groups: ≤2 weeks (Group A), 2–4 weeks (Group B), 4–6 weeks (Group C), and 6–8 weeks (Group D). The primary outcome measures included the Quality of Recovery-15 (QoR-15) scale scores at 3 days, 3 months, and 6 months postoperatively. Secondary outcome measures included postoperative mortality, ICU admission, pulmonary complications, postoperative length of hospital stay, extubation time, and time to leave the PACU. Results Concerning the primary outcome measures, the QoR-15 scores at 3 days postoperatively in Group A were significantly lower compared to the other three groups (P 0.05). The QoR-15 scores at 3 and 6 months postoperatively showed no statistically significant differences among the four groups (P > 0.05). In terms of secondary outcome measures, Group A had a significantly prolonged hospital stay compared to the other three groups (P 0.05). Conclusion The timing of surgery in mild or asymptomatic SARS-CoV-2 infected patients does not affect long-term recovery quality but does impact short-term recovery quality, especially for elective general anaesthesia surgeries within 2 weeks of confirmed infection. Therefore, it is recommended to wait for a surgical timing of at least greater than 2 weeks to improve short-term recovery quality and enhance patient prognosis.

The coal mine drilling shaft wall is a single-layer structure, and water leakage in the deep alluvium will seriously threaten mine safety. If there are construction defects in the stubble part of the well wall at the construction stage, it will lead to groundwater corrosion and rust through the metal and the weld seam of the stubble part, resulting in water leakage from well wall, which, if not treated promptly, is prone to lead to a sudden water-sand inrush and flooding accidents. In order to explore an effective treatment technology, a research on the control technology of water leakage from the wall of coal mine drilling wells was carried out with the background of water leakage control of wall of sub-well of the Xutong Coal Mine. Firstly, the causes of water leakage from the single-layer well wall of the drilling method were analyzed with the information of hydrogeological characteristics of mine. It was found that the main reason of water leakage at the sub-well wall of Xutong Mine was that the high-pressure groundwater recharged from the aquifers flowed into the well through the gravel packing layer with great pore connectivity, after the corrosive effects of groundwater jointly penetrated the stubs of well walls. Then, the feasibility and safety of using post-wall grouting and ground drilling grouting for water leakage control in the wall of sub-well wall in Xutong Coal Mine were compared and analyzed. Post-wall grouting of reinforced concrete single-layer well walls constructed using the drilling method in fluvial sand layer was found to pose a high safety risk, affecting the normal lifting of wellbore and risking the reoccurrence of water leakage. Ground directional drilling grouting technology had a large grouting volume, and the pores in the gravel filling layer behind the wall can be fully filled by cement slurry, improving the leakage prevention and bearing capacity of the wellbore, and the construction personnel operated on the ground, which was safe and did not affect the normal lifting of the wellbore. Finally, the ground directional drilling grouting technology for water leakage control of coal mine wall in deep alluvium was proposed and demonstrated. A total of 130.9 m3 of cement slurry was injected into the two boreholes, which completely filled the pores space between the gravel of the filling layer behind the wall of the layer from 94.00-131.40 m, and successfully blocked the water outlet point at 94 m downhole. No further water leakage from this section of the well wall had been observed on site over a long period of time. The research results shown that, the ground directional drilling grouting technology had good control effect and high safety for the water leakage of coal mine drilling well wall in deep alluvium. The research results can provide a certain reference for the water leakage control of coal mine drilling well wall in deep alluvium.