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Abstract The exploration of traumatic spinal fractures (TSFs) within the senior demographic has not been thoroughly scrutinized, particularly with respect to variations across genders, age groups, seasonal periods, and causative factors. This retrospective analysis aimed to dissect differences in the prevalence and characteristics of TSFs among the elderly, factoring in gender, age, seasonal timing, and causation. A retrospective analysis was conducted on the medical and imaging records of 1,415 patients, all aged 60 years or older, who were diagnosed with TSFs from 2013 to 2019. This study categorized the data by gender, age groups (60–70, 70–80, and 80 years or older), seasons, and the cause of injuries, including road traffic crashes (RTCs), falls from low heights (LHF), falls from high heights (HHF), and injuries incurred during everyday activities and agricultural labor (DFI). Male patients exhibited notably higher incidences of RTCs, high-height falls (HHFs), outdoor incidents, comas post-injury, fractures of the lower limbs (LLFs), pelvic fractures (PFs), rib fractures (RFs), intra-thoracic injuries (ITIs), intra-abdominal injuries (IAIs), cervical fractures, and spinal cord injuries (SCIs). With advancing age, there was a marked decline in occurrences of RTCs, HHFs, outdoor incidents, RFs, craniocerebral injuries (CCIs), ITIs, cervical fractures, and SCIs, while the incidences of DFIs, indoor incidents, and thoracic and lumbar (T + L) fractures notably increased. During autumn, LLF occurrences were significantly reduced, whereas the winter season saw an increase in thoracic fractures. Spring time was associated with a higher frequency of lumbar fractures and noncontiguous spinal fractures (NSFs). Significant distinctions were observed in the age distribution, injury circumstances, associated injuries, and SCIs between high-energy impacts (RTCs and HHFs) and low-energy traumas (LHFs and DFIs). In the elderly demographic, TSFs exhibited discernible distinctions based on gender, age, seasonal variations, and etiological factors, impacting the nature and circumstances of injuries, associated traumas, complications, fracture sites, and the occurrence of SCIs.

In order to study the seismic performance of bottom-frame masonry structures under complex three-dimensional vibration characteristics, six types of ground shaking records with complex characteristics were selected from the ground shaking database of the Pacific Earthquake Engineering Research Center (PEERC) and inputted into the numerical models of bottom-frame masonry structures and their seismic isolation structures with two different storeys, and the seismic response parameters were calculated under the dynamical-elastic-plastic time course to evaluate their seismic performance under complex ground shaking. The results show that the impulse-type earthquake can cause more intense seismic response for the base frame masonry structure, and the soft soil impulse-type earthquake can cause more seismic response for the base frame masonry isolation structure. Analyzed from the point of view of velocity impulse effect, velocity impulse effect reduces the damping rate of base frame masonry isolation structures at all storeys. Foundation isolation has a certain effect on improving the seismic performance of the bottom frame masonry structure, considering the seismic performance and economic rationality, the foundation isolation design is not recommended for the low bottom frame masonry structure, while for the higher bottom frame masonry structure, the foundation isolation can effectively reduce the tensile damage of the brick masonry on the upper part of the structure.

Abstract Background Approximately 40–70% of older adults who have experienced falls develop fear of falling (FOF), with the incidence rate in nursing home residents reaching as high as 79.4%. An increasing number of studies have focused on the effect of the Otago Exercise Programme (OEP) on reducing FOF among older adults, yet comprehensive analysis is lacking due to regional and demographic variations. Therefore, this study integrates the relevant literature to provide evidence supporting interventions aimed at alleviating FOF among older adults. Objective To evaluate the impact of OEP on FOF in older adults through meta-analysis. Methods We searched ten databases using computer systems, covering all records up to May 1, 2024. Two researchers independently conducted the literature screening, bias risk assessment, and data extraction. We performed data analysis using RevMan 5.3 and Stata 15.0 software, assessed result stability through sensitivity analysis, and examined publication bias with funnel plots and Egger’s test. Results Sixteen RCTs were included. Meta-analysis revealed that the OEP significantly reduced FOF among older adults [SMD = 0.96, 95%CI (0.68, 1.23), P

The accurate identification and positioning of the anchor position of the coal mine tunneling roadway is the key technology that the drilling anchor robot urgently needs to break through to achieve intelligent permanent support. An intelligent identification and positioning method for roadway anchor hole position based on visual image and laser point cloud fusion is proposed, which includes three steps: image target recognition, point cloud image feature fusion, and positioning coordinate extraction: ① In order to solve the problem of blurred image of anchor hole contour caused by environmental factors such as low illumination, water mist and dust in coal mines, the IA (Image-Adaptive)-SimAM-YOLOv7-tiny network was used to visually identify the position of the anchor hole to be anchored in the roadway, which can adaptively enhance the image brightness and contrast, recover the high-frequency information at the edge of the anchor hole, and make the model focus on the characteristics of the anchor hole, so as to improve the success rate of anchor hole detection; ② The Region of Interest (ROI) of image detection is generated by perspective projection relationship to generate a cone-shaped area of interest to obtain the corresponding target point cloud cluster; ③ The point cloud processing algorithm is used to extract the anchor hole boundary point cloud, obtain the central coordinates of the hole position and its normal vector, and judge the correctness of the anchor hole recognition by comparing the coordinate depth difference. In this paper, a drilling and positioning system for bolting trolley manipulator is built to verify the accuracy and accuracy of the algorithm's autonomous positioning, and the experimental results show that the mean average precision (mAP) of the IA-SimAM-YOLOv7-tiny model is 87.3%, which is 4.6% higher than that of the YOLOv7-tiny model. Compared with the single vision method, the fusion algorithm proposed in this paper has a positioning error of 3 mm, and the average recognition time of the system in the case of a single anchor hole is 0.77 s, compared with the single vision method, the fusion of laser and visual multi-source can not only reduce the influence of environment and small sample training on positioning performance, but also obtain the normal vector of the anchor hole position, which provides a basis for the manipulator to adjust the drilling posture to achieve accurate anchoring.

Introduction: In this study, we aim to describe the radiological characteristics of degenerative cervical kyphosis (DCK) with cervical spondylotic myelopathy (CSM) and discuss the relationship between DCK and the pathogenesis of spinal cord dysfunction. Methods: In total, 90 patients with CSM hospitalized in our center from September 2017 to August 2022 were retrospectively examined in this study; they were then divided into the kyphosis group and the nonkyphosis group. The patients' demographics, clinical features, and radiological data were obtained, including gender, age, duration of illness, cervical Japanese Orthopaedic Association (JOA) score, cervical lordosis (CL), height of intervertebral space, degree of wedging vertebral body, degree of osteophyte formation, degree of disc herniation, degree of spinal cord compression, and anteroposterior diameter of the spinal cord. In the kyphosis group, kyphotic segments, apex of kyphosis, and segmental kyphosis angle were recorded. Radiological characteristics between the two groups were also compared. Correlation analysis was performed for different spinal cord compression types. Results: As per our findings, the patients in the kyphosis group showed more remarkable wedging of the vertebral body, more severe anterior compression of the spinal cord, and a higher degree of disc herniation, while the posterior compression of the spinal cord was relatively mild when compared with the nonkyphosis group. CL was related to the type of spinal cord compression, as cervical kyphosis is an independent risk factor for anterior spinal cord compression. Conclusions: DCK might play a vital role in the pathogenesis of spinal cord dysfunction. In patients with DCK, it was determined that the anterior column is less supported, and more severe anterior spinal cord compression is present. The anterior approach is supposed to be preferred for CSM patients with DCK.

Abstract Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Abstract Background The significance of A-to-I RNA editing in nervous system development is widely recognized; however, its influence on retina development remains to be thoroughly understood. Results In this study, we performed RNA sequencing and ribosome profiling experiments on developing mouse retinas to characterize the temporal landscape of A-to-I editing. Our findings revealed temporal changes in A-to-I editing, with distinct editing patterns observed across different developmental stages. Further analysis showed the interplay between A-to-I editing and alternative splicing, with A-to-I editing influencing splicing efficiency and the quantity of splicing events. A-to-I editing held the potential to enhance translation diversity, but this came at the expense of reduced translational efficiency. When coupled with splicing, it could produce a coordinated effect on gene translation. Conclusions Overall, this study presents a temporally resolved atlas of A-to-I editing, connecting its changes with the impact on alternative splicing and gene translation in retina development.

The hydraulic support is the core of the stability of the ‘surrounding rock and equipm ent’ system in the pitching oblique working face of steeply dipping coal seam. The existing hydraulic support structure can not meet the requirements of spatial stability of pitching oblique mining, which seriously affects the safe and efficient mining of working face under such conditions. Taking the pitching oblique working face of steeply dipping coal seam as the research background, the comprehensive research methods of engineering analogy, structural kinematics analysis and numerical simulation are used to analyze the stability characteristics of ‘support-surrounding rock’ in the pitching oblique working face of steeply dipping coal seam. Based on ZY7000/22/45 hydraulic support, a new parallelogram hydraulic support is invented, the structural rationality design is carried out, and the kinematic response characteristics of key components are analyzed.The research shows that the non-uniform filling of the caving gangue and the crushing, pressing and pushing effect of the gangue on the support are the key factors affecting the stability of the support. The parallelogram top beam and the base are more suitable for the pitching oblique working face. The arrangement of the top beam, base and column of the parallelogram support is parallelogram. The special-shaped shield beam, the rear connecting rod, the oil cylinder connecting rod and the base constitute a flexible four-link structure. The column of the parallelogram support is the main bearing structure, and the cylinder connecting rod is the main motion mechanism. The main influencing factors of its motion characteristics are the distance between the upper and lower column sockets and the distance between the front and rear connecting rods and the hinged position of the shield beam. The shield beam and the rear connecting rod are the key to the position and posture control of the support, and there is no double torsion line during the movement of the support. The research results provide a type selection for the support of this kind of working face, which ensures the safe production of this kind of coal seam to a certain extent.

The construction of intelligent fully mechanized mining faces in China’s coal mines is in its early stages, and the automation technology of hydraulic support electro-hydraulic control has been widely applied. However, at present, the automation control logic of a single solidification of hydraulic supports is difficult to adapt to complex, ever-changing, and dynamic production scenarios. The actual control process in mine face still mostly adopts a collaborative approach of automation and manual intervention. In response to the demand for human-machine interaction and cooperation tasks in the complex scenarios of fully mechanized mining faces, a theoretical method and technical principle of a multimodal human-machine collaborative control system for hydraulic supports following the shearer in the middle range mining face (hereinafter referred to as hydraulic supports following) was proposed. Firstly, four human-machine collaborative modes, namely manual, division of labor, approval, and veto, were designed. Based on the factors such as coal seam geology, gas and dust, shearer speed, hydraulic support intelligence level, system status, job technical level, and task load, an AND-OR graph model for hydraulic support human-machine collaborative mode selection was constructed, which achieved a modal selection with manual or machine preferences. Then, a human-machine collaborative control decision-making mechanism for hydraulic supports following was designed. On this basis, an AI inference technology for the secondary control strategy of hydraulic supports following was proposed. Specifically, using on-site data to learn manual operation experience, a decision tree classification model for whether the hydraulic support should be secondary controlled and a Bayesian regression model for estimating the secondary control time of pulling hydraulic support were constructed. Based on the above model, a human-machine collaborative control decision-making program for the hydraulic support following was developed, which achieved human-machine collaborative control of hydraulic supports following based on AND/OR inference for modal selection and AI inference for secondary control strategy. Finally, using cloud edge end architecture software and hardware technology, a multimodal human-machine collaborative control system for hydraulic supports following was developed, which achieved the control functions such as model evolution, operational reasoning, and program execution. The system has undergone industrial trial operation on the 3404 mining face of Shaqu No.2 Mine. The result shows the efficiency of the hydraulic support following has increased by an average of 2% compared to that before. This paper forms an efficient and safe human-machine interactive decision-making mechanism for the comprehensive mining equipment group, which will provide practical theoretical methods and feasible technical paths for the development of intelligent comprehensive mining working faces.

Objective The CBTC (communication-based train control) system on urban rail transit lines has certain limitations in specific scenarios: when there are multiple protection sections along a route, the interlocking system cannot flexibly select protection sections based on the train forward direction, causing inability to meet the requirements of flexible and automatic route arrangement establishment. Therefore, there is a need to optimize the protection section trigger strategy. Method The basic principles of route triggering and protection section setup in CBTC system are briefly introduced, highlighting two typical problem scenarios under existing protection section control schemes. An optimization scheme for the protection section trigger strategy is proposed, where ATS (automatic train supervision) automatically selects the protection section direction and delegates it to the interlocking system. Taking scenario I (train skip-stop and turn-back to depot) as example, according to train dynamics characteristics, the train skip-stop performance before and after optimization is compared and analyzed. Result & Conclusion The case analysis results of train skip-stop and turn-back to depot scenario show that after optimizing the protection section control strategy, the time performance of train skip-stop is greatly improved. The proposed optimization method is feasible and can significantly enhance the flexibility of protection section handling, improving the efficiency of train skip-stop.

Abstract Background To compare the outcomes of hypospadias repair using tubularized incised plate (TIP) urethroplasty and modified TIP with lateral skin to widen the urethral plate (WTIP). Materials and methods Data were obtained from pre-pubertal boys who underwent primary hypospadias repair between May 2018 and July 2023. The cases were divided into two groups; one group underwent TIP with urethral plate ≥ 6 mm width and the other group with urethral plate width

Abstract Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value

The structure and stress environment of the surrounding rock at the longwall mining area in the steeply dipping coal seam are alienated, and the composition factors and disaster modes of the ”support and surrounding rock” system in the working face are affected. This leads to some frequent safety accidents in the working face, low coal extraction rate, and high roadway excavation rate. This paper analyzes the mining mechanics behavior of surrounding rock of in the steeply dipping coal seam and proposes a technological concept of partial backfill non-pillar mining in the longwall faces of steeply dipping coal seam. During the process of advancing the working face, partial backfill is carried out along the inclined direction in the lower part of the goaf. The filling body not only forms a gob-side roadway with the support effect of the roadway side, but also eliminates the protection coal pillar, achieving a non-pillar mining. At the same time, the length of the filling and compaction area at the lower dip of the working face is increased, enhancing the stability of the ”support and surrounding rock” system of the working face. Based on the characteristics of the longwall mining area in the steeply dipping coal seam, the partial backfill process of the steeply dipping coal seam paste was optimized and determined. And the partial backfill recovery system and mining and filling process in the steeply dipping coal seam were designed. By using a combination of theoretical analysis, simulation experiments, and numerical calculations, the regulatory mechanism of partial backfill on the mechanical behavior of surrounding rock at the longwall mining area in the steeply dipping coal seam was analyzed. The results show that the filling body affects the deformation and failure of the main roof rock beam, as well as the bearing characteristics of the coal and rock mass on the lower side of the mining area. The deformation of the main roof and the roof of the head entry, as well as the constraints on the coal and rock mass on the lower side of the head entry, all decrease with the increase of filling length. In order to prevent the hanging roof disaster in the unfilled area of the goaf, the filling length should not exceed 1/3 of the working face length. The partial backfill body restricts the fracture of the roof in the lower area of the working face, reduces the formation layer of the critical zone of the overlying rock, forms a stable roadway, and reduces the deformation of the surrounding rock gob-side roadway retained. At the same time, the length of the filling area at the lower part of the working face increases, and the length of the unstable area of the middle and upper surrounding rock structures decreases, improving the stability of the ”support and surrounding rock” system. The filling body changes the stress transmission path of the surrounding rock in the mining area, bearing part of the overlying rock load. The side abutment pressure on the lower side of the working face and the front advanced pressure both decrease with the increase of filling length, and the front support pressure in the lower filling area of the working face has the greatest decrease. The stress state of the gob-side roadway and the working face is improved. Technology of partial backfill non-pillar mining in the longwall faces of steeply dipping coal seam has the advantages of effectively improving resource recovery rate, reducing the roadway drivage ratio, alleviating the tension of mining and replacement, and strengthening the stability of the ”support and surrounding rock” system in the working face. It is of great scientific significance for guiding the green, safe, and efficient mining in the steeply dipping coal seam.

Abstract Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P

[Objective] In order to strengthen the passive safety design ability of urban rail transit trains during operation, it is necessary to study the effects of train crash dynamics parameters on climbing behavior. [Method] Based on the vehicle-track coupling crash dynamics model, Hertz contact theory and rigid nonlinear connection model, a three-dimensional train crash dynamics simulation platform is built. Speed, acceleration and maximum wheelset lift are selected as comparison parameters, and the finite element model of train crash is used to verify the precision of the three-dimensional dynamic model of train crash. Based on the established simulation platform, some important parameters of the train structure are selected to study their effects on the wheelset lift. Five relatively more sensitive parameters, including the vertical distance from the installation points of the devices such as energy absorbing anti-climbing device, head car coupler, middle car coupler to the barycenter of the car body, the mass of the car body, the height of the barycenter of the car body, the vertical stiffness of the secondary suspension device and the vertical stiffness of the primary suspension device, are screened out to analyze the sensitivity of the above parameters to the train crash dynamics. [Result & Conclusion] Based on the finite element model of train crash, the precision of the three-dimensional dynamic model of train crash meeting the requirements is verified. The sensitivity analysis shows that when the parameter ratio varies within the range of 0.8~1.0, the five sensitive parameters of sensitivity is in the sequence of the vertical stiffness of the secondary suspension device, the mass of the car body, the height of the barycenter of the car body, the vertical distance from the installation point to the barycenter of the car body, and the vertical stiffness of the primary suspension device. When the parameter ratio varies within the range of 1.0 to 1.2, the above parameters of sensitivity is in the sequence of the vertical stiffness of the primary suspension device, the vertical distance from the installation point to the barycenter of the car body, the height of the barycenter of the car body, the mass of the car body, and the vertical stiffness of the secondary suspension device.

Abstract “Golden Hook” beans turn purple to different degrees due to the different compositions and contents of flavonoids during storage. At the same time, quality losses due to softening or pathogen invasion, and the deteriorations of flavor associated with carbohydrate metabolism occur. To reveal the effect of nitric oxide (NO) generated from sodium nitroprusside (SNP) on the postharvest quality of “Golden Hook” beans, we used metabolome, transcriptome, and assay for transposase‐accessible chromatin with high‐throughput sequencing approaches to compare beans at the time of treatment with untreated and SNP‐treated beans stored at 8°C for 12 days. The results showed that NO induced the expression of CERK1, FLS2, JAZ, and MYC2, stimulated the expression of polyphenol oxidase, CAT, and l‐ascorbate oxidase, the accumulation of flavonoids, and the synthesis of lignin in the antioxidant system, improving the ability of beans to resist stress while maintaining the balance of reactive oxygen species. High expressions of F3′H, FLS, INV, SUS, BCAT, and the accumulation of 6‐C‐methylquercetin‐3‐O‐rutinoside were associated with the maintenance of the fresh purplish red appearance of the beans in the SNP‐12d group, without loss of flavor. SNP treatment downregulated the transcription factors blimp‐1, OBP1, COG1, and AT1G6957 associated with bean senescence. These results provide insight into the postharvest quality control of “Golden Hook” beans.

Abstract To solve the problem that the macroscopic deformation and failure of coal–rock medium under external loads are easy to be observed while the internal stress transfer mode and path are unclear. Based on the discrete element idea, the numerical models for pure coal or rock samples and coal–rock combination samples with different lithologies and combination methods under concentrated force are established by PFC2D software. Then the influence of coal or rock strength and combination methods on the internal stress transfer law and distribution evolution characteristics of coal–rock medium are discussed from the perspectives of macroscopic stress and mesoscopic force chain, respectively. The results showed that under concentrated load, the macroscopic stress transfer paths within pure coal or rock samples and coal–rock combination samples are primarily in the form of ‘point source radiation’. However, when transferring between coal–rock interfaces, there is a certain interface effect. For pure coal or rock samples, differences in lithology does not change the transfer rules and macro distribution patterns of internal stress, but it can cause changes in internal unit transfer stress value and local area transfer direction. For coal–rock combination samples, the greater the difference in lithology between the two sides of the interface, the more likely the interface effect will occur. In addition, the internal stress transfer is also influenced by the relative stratigraphic relationships of coal and rock. When the stress is transferred from a higher-strength rock to a lower-strength coal mass, the interface effect will be more significant. However, regardless of the combination pattern, the locations where significant stress surges occur are always within the higher strength rock mass near the interface. The findings are helpful to understand the mechanical properties and failure mechanism of mining coal and rock mass, and provide a theoretical basis for the study of the mining-induced mechanical behavior of the floor under the action of the coal pillar.

Background: Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized.Methods: We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated.Results: A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases.Conclusions: AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

Objective: Chronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. Patients and methods: This was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. Results: We found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p

Platelet-derived growth factor receptor β (PDGFRβ) plays a crucial role in murine haematopoiesis. Baicalein (BAI), a naturally occurring flavonoid, can alleviate disease damage through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms. However, whether BAI attenuates oxidative damage in murine haematopoietic cells by PDGFRβ remains unexplored. In this study, we utilized a tert-butyl hydroperoxide (TBHP)-induced BaF3 cell injury model and an ionising radiation (IR)-induced mice injury model to investigate the impact of the presence or absence of PDGFRβ on the pharmacological effects of BAI. In addition, the BAI-PDGFRβ interaction was characterized by molecular docking and dynamics simulations. The results show that a specific concentration of BAI led to increased cell viability, reduced reactive oxygen species (ROS) content, upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression, and its downstream target genes heme oxygenase 1 (HO-1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), and activated protein kinase B (AKT) pathway in cells expressing PDGFRβ plasmid and experiencing damage. Similarly, BAI elevated lineage−Sca1+cKIT+ (LSK) cell proportion, promoted haematopoietic restoration, enhanced NRF2-mediated antioxidant response in PDGFRβ+/+ mice. However, despite BAI usage, PDGFRβ knockout mice (PDGFRβ−/−) showed lower LSK proportion and less antioxidant capacity than the total body irradiation (TBI) group. Furthermore, we demonstrated an interaction between BAI and PDGFRβ at the molecular level. Collectively, our results indicate that BAI attenuates oxidative stress injury and helps promote haematopoietic cell recovery through regulation of PDGFRβ.

The ecological sustainability of arid and semi-arid areas is under increasing threat due to global climate change, and well-established ecological networks are essential for improving landscape connectivity and conserving biodiversity. This study takes the Tacheng-Emin Basin in China as an example. Based on the “source-resistance-corridor” research paradigm and sustainable development theory, the “contribution-organization-vitality-resilience” and circuit theory of the ecosystem are incorporated into the construction of the ecological networks. The results show that (1) the ecosystem service value of the Tacheng-Emin basin is 5.85 × 1010 Yuan, the ecosystem of the basin is of medium health level, and the ecological security hierarchy has low level and uncoordinated problems. (2) The total integrated resistance surface in the basin is of medium level, dominated by natural resistance, and characterized by evident fragmentation. (3) 25 ecological sources, 58 ecological corridors, 32 ecological stepping stones, 39 obstacle points, and 46 ecological fracture points were extracted at the threshold of 10,000 in the circuit model. (4) The reconstruction cost of the ecological network is 1,007.41 × 104 Yuan, and the reconstructed ecological network have increased 2 ecological sources, 1 stepping stone, and reduced 3 obstacle points, while the closure of the ecological networks structure has been significantly improved and the ecological networks has developed toward a stable multi-grid structure. (5) The ecological zoning protection and restoration scheme of “one ring, one belt, one sink, multiple zones, and multiple corridors” is conducive to the sustainable ecological development of the basin. The results of this study can serve as a reference for ecological management and sustainable development in arid and semi-arid regions of Central Asia.

Genetic mutations in TP53 contribute to human malignancies through various means. To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. This review focuses on the functions of TP53 and discusses the aberrant roles of mutant p53 in various types of cancer. Recombinant human p53 adenovirus, trademarked as Gendicine, which is the first anti-tumor gene therapy drug, has made tremendous progress in cancer gene therapy. We herein discuss the biological mechanisms by which Gendicine exerts its effects and describe the clinical responses reported in clinical trials. Notably, the clinical studies suggest that the combination of Gendicine with chemotherapy and/or radiotherapy may produce more pronounced efficacy in slowing tumor growth and progression than gene therapy/chemotherapy alone. Finally, we summarize the methods of administration of recombinant human p53 adenovirus for different cancer types to provide a reference for future clinical trials.

The dynamic properties of concrete structures after being exposed to high temperatures play a crucial role in post-disaster repair and accident prevention measures. This study examined three different mixture ratios of Steel Fiber Reinforced Concrete (SFRC) with matrix strength of C60 and steel fiber contents of 0%, 1%, and 2%. A Split Hopkinson Pressure Bar (SHPB) with a diameter of 75 mm, along with a heating furnace, was employed to comprehensively investigate the dynamic compression behavior of materials. The specimens were exposed to temperatures ranging from 200 °C to 600 °C. In addition to evaluating the extent of mechanical degradation in SFRC after cooling, auxiliary impact experiments were also carried out at ambient temperature. The experimental data revealed that the dynamic peak stress and peak strain initially increased but eventually decreased as the loading rates continued to rise. The degree of strengthening, toughening, and energy absorption capacity of concrete materials progressively decreased as the escalation of strain rate after the cooling process. Moreover, the inclusion of steel fibers proved effective in preventing cracking and damage to the concrete, preserving the integrity of specimens even at higher temperatures. Simultaneously, the residual stress and deformation capacity of SFRC showed considerable enhancement after exposure to elevated temperatures.

BackgroundPrevious studies reported that variations in dietary intake patterns substantially impact human health, specifically tumorigenesis. However, confounding factors in previous cohort studies have obscured the relationship between dietary differences and the risk of oral cancer (OC).Materials and methodsWe developed an outcome dataset from genome-wide association studies (GWAS) data on three OCs within the GAME-ON project, using GWAS-META merging. We extracted 21 dietary exposures, including 10 dietary patterns, 6 vitamins, and 5 micronutrients, from the UK Biobank database, using the inverse variance weighting method as the primary statistical method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. Serum metabolite concentrations were adjusted using multivariate Mendelian randomization.ResultsOf the 10 analyzed dietary patterns, 8 showed no significant association with the risk of developing OC. Consumption of dark chocolate (inverse variance weighted [IVW]: Odds ratio (OR) = 0.786, 95% confidence interval [CI]: 0.622–0.993, p = 0.044) and sweet pepper exhibited an inverse relationship with OC risk (IVW: OR = 0.757, 95% CI: 0.574–0.997, p = 0.048). Reverse MR analysis revealed no reverse causality. Furthermore, no significant correlation was observed between the intake of 6 vitamins and 5 micronutrients and the risk of developing OC. After using multivariable MR to adjust for serum caffeine, linoleate, theophylline, and theobromine metabolism levels, consuming dark chocolate was unrelated to a decreased risk of OC. After adjusting each serum metabolite individually, the observed p-values deviated from the original values to varying degrees, indicating that the components of dark chocolate could have different effects. Among these components, theophylline demonstrated the most significant inhibitory effect.ConclusionThis study demonstrated a causal relationship between the intake of dark chocolate and sweet peppers and a lower risk of OC. The components of dark chocolate could have different effects.

This study evaluates the effectiveness of GN (Graphene Nanoplatelets) salt inhibitor-treated concrete in inhibiting chloride ion diffusion and corrosion compared to untreated concrete under various erosion conditions. Through an accelerated indoor chloride erosion test lasting 180 days, we examined the temporal changes in internal chloride ion concentration with and without the GN salt inhibitor. Quantitative assessment of the inhibitor's impact was achieved by introducing reduction factors for surface chloride concentration and diffusion coefficient. Our findings reveal a significant reduction of 31.3 % in chloride ion diffusion coefficient and 22.67 % in surface chloride concentration in concrete treated with GN salt inhibitor. This indicates the inhibitor's potential to extend the service life of gearbox and substation foundations exposed to chloride ion erosion environments.

Study Design Retrospective clinical trial. Purpose To establish a morphological classification of the cervical spinal canal using its parameters. Overview of Literature Cervical spine computed tomography (CT) data of 200 healthy volunteers in 2 years were analyzed. The morphology of the spinal cord was also analyzed. Methods The median sagittal diameter and transverse diameter of the spinal canal from C2 to C7 were measured on CT images. The ratio of the median sagittal diameter to the transverse diameter was calculated. Accordingly, the spinal canal shape of each segment was classified into four, and the specific criteria of lunar phase classification were determined through linear discriminant analysis based on the ratio of the median sagittal diameter to the transverse diameter. The inter-rater reliability of the classification was explored using Kappa coefficients. Finally, the morphology of the different segments of the cervical spinal canal in healthy volunteers was revised and compared. Results According to the ratio of the median sagittal diameter and the transverse diameter of the cervical spinal canal, the lunar phase classification of the cervical bony spinal canal was determined as follows: full-moon >0.65, 0.55< convex-moon ≤0.65, 0.46≤ quarter-moon ≤0.55, and residual-moon 0.05). The frequency of the spinal canal of the residual-moon type was the highest, and the full-moon (6.5%) and residual-moon (7.5%) types of C7 were rare. Conclusions The morphological classification of the cervical spinal canal was established to present anatomical variations. The classification showed good inter-rater reliability.

Abstract Anisotropic planar polaritons - hybrid electromagnetic modes mediated by phonons, plasmons, or excitons - in biaxial two-dimensional (2D) van der Waals crystals have attracted significant attention due to their fundamental physics and potential nanophotonic applications. In this Perspective, we review the properties of planar hyperbolic polaritons and the variety of methods that can be used to experimentally tune them. We argue that such natural, planar hyperbolic media should be fairly common in biaxial and uniaxial 2D and 1D van der Waals crystals, and identify the untapped opportunities they could enable for functional (i.e. ferromagnetic, ferroelectric, and piezoelectric) polaritons. Lastly, we provide our perspectives on the technological applications of such planar hyperbolic polaritons.

The steeply dipping coal seam is one of the main forms of coal storage in China. It is widely and regionally distributed. According to incomplete statistics, twenty-six provinces, autonomous regions and municipalities directly under the central government are involved in the mining of such coal seams, with abundant reserves, large production and high production concentration in the central and western regions. It shows diversity and complexity in terms of the conditions of existence, with different regions having different coal formation periods and different tectonic control processes, forming diverse and complex mining conditions and giving rise to different mining technology requirements. The mining of steeply dipping coal seam is technically difficult. The asymmetry of the movement and damage of the peripheral rock in the mining area affected by the inclination angle of the coal seam is obvious, and the difficulty of the stability control of the support system and equipment, the matching and coordination of the “three machines”, the layout and support of the mining roadway, and the safety guarantee of the “human-machine” environment at the working face has increased significantly, which seriously restricts the safe and efficient mining of the mine. This has seriously restricted the improvement of safe and efficient mining. The regional economic demand for the mining of steeply dipping coal seam is strong. This kind of coal seams and the production of more concentrated areas are mostly seen in the coal industry-based resource cities, the economic structure is relatively single, the safe and efficient development and utilization of coal resources for the regional energy supply, people’s livelihood, economic stability has the role of the bottom of the pocket, the demand is urgent. For a long time, mining technologies for the steeply dipping coal seam changes focus on solving the “difficult” and “need” contradiction. In the coal mining methods and techniques, strata control theory and technology, complete sets of equipment development and application of the three aspects of continuous improvement, innovation, development, to achieve the transformation from non-mechanized to fully-mechanized mining, the level of safety and production efficiency has increased dramatically, the personnel labor intensity has decreased dramatically, and the operating environment has improved significantly. In the mid-1990s, Lvshuidong Coal Mine of Sichuan Coal Industry Group Limited Liability Company successfully realized longwall fully-mechanized mining in steeply dipping coal seam with medium mining height for the first time, breaking through the "forbidden zone" in this filed. Under this demonstration, the three pioneering engineering practices of longwall fully-mechanical mining of steeply dipping coal seam with thick mining height, steeply dipping coal seam with large mining height, and longwall fully-mechanical mining of steeply dipping coal seam with thin mining height in pseudo-inclination have been successful successively, which innovated the non-linear limiting arrangement of the working face and the way of adjusting the slanting, established a multi-dimensional interactive control mode of the system stability of the “bracket-surrounding rock”, and researched and developed the “support and stability and heavy weight, high-strength and light-weight, safe and reliable, and matching synergistic” complete set of equipment of the working face, which has achieved good results, and the scope of application of the comprehensive mechanized mining technology has further been widened. At the same time, there are still many key scientific problems and technical bottlenecks that need to be broken through in the mining of steeply dipping coal seams, resulting in a large gap between the intelligence level and that of the flat/gently inclined coal seams. Research on the mining dynamics of coal and rock bodies in inclined bedded coal beds, revealing their control mechanisms on the disaster of the surrounding rocks in the mining field, and realizing quantitative characterization need to be further strengthened. It is necessary to further clarify the multi-dimensional dynamic process and law between the system of “rock-bearing structure - mining equipment group”, improve the theoretical and technological basis of “multi-dimensional dynamic multi-objective synergistic control of equipment and surrounding rock”, and realize the transformation and application of the technology. On the basis of breakthroughs in scientific issues, we will carry out systematic technological innovation and research and development of coal mining methods, mining techniques, rock formation control, and complete sets of equipment, so as to crack the bottleneck of the constraints on the double enhancement of “safety and efficiency” in the mining of steeply dipping coal seams, and make the upper limit of the inclination of the steeply dipping coal seams for comprehensive mechanized mining extend upward under the prerequisite of reliable technological safeguards, so as to lay the foundation for the realization of automated and intelligent mining.

Abstract Background Sleep disordered breathing (SDB) is broadly recognized to be associated with neurobehavioral deficits, which have significant impacts on developing-aged children and adolescents. Therefore, our study aimed to quantify the proportion of neurobehavioral impairments attributed to SDB in general children and adolescents by population attributable fraction (PAF). Methods The study was registered at PROSPERO (ID: CRD42023388143). We collected two types of literature on the prevalence of SDB and the risk of SDB-related neurobehavioral deficits from ten electronic databases and registers, respectively. The pooled effect sizes (Pe, Pc, RR) by random-effects meta-analysis were separately substituted into Levin’s formula and Miettinen’s formula to calculate PAFs. Results Three prevalence literature and 2 risk literature, all with moderate/high quality, were included in the quantitative analysis individually. The prevalence of SDB was 11% (95%CI 2%-20%) in children and adolescents (Pe), while the SDB prevalence was 25% (95%CI 7%-42%) in neurobehavioral patients (Pc). SDB diagnosis at baseline was probably associated with about threefold subsequent incidence of neurobehavioral deficits (pooled RR 3.24, 95%CI 1.25–8.41), after multi-adjustment for key confounders. Up to 19.8% or 17.3% of neurobehavioral consequences may be attributed to SDB from Levin’s formula and Miettinen’s formula, respectively. Conclusions A certain number of neurobehavioral consequences may be attributable to SDB. It is essential for clinicians to identify and treat SDB timely, as well as screen for SDB in patients with neurobehavioral impairments. More longitudinal studies of SDB and neurobehavioral deficits are needed in the future to further certify the association between them.

Wnt signaling plays a major role in regulating cell proliferation and differentiation. The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either through β-catenin in the canonical pathway or through a series of other proteins in the noncanonical pathway. Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body, establishing the complex interplay between Wnt signaling and other signaling pathways. This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes. Dysregulation of this system has been implicated in many diseases affecting a wide array of organ systems, including cancer and embryological defects, and can even cause embryonic lethality. The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments. However, both stimulatory and inhibitory treatments come with potential risks that need to be addressed. This review synthesized much of the current knowledge on the Wnt signaling pathway, beginning with the history of Wnt signaling. It thoroughly described the different variants of Wnt signaling, including canonical, noncanonical Wnt/PCP, and the noncanonical Wnt/Ca2+ pathway. Further description involved each of its components and their involvement in other cellular processes. Finally, this review explained the various other pathways and processes that crosstalk with Wnt signaling.

Cancer cachexia is a multifactorial syndrome characterized by progressive weight loss and a disease process that nutritional support cannot reverse. Although progress has been made in preclinical research, there is still a long way to go in translating research findings into clinical practice. One of the main reasons for this is that existing preclinical models do not fully replicate the conditions seen in clinical patients. Therefore, it is important to understand the characteristics of existing preclinical models of cancer cachexia and pay close attention to the latest developments in preclinical models. The main models of cancer cachexia used in current research are allogeneic and xenograft models, genetically engineered mouse models, chemotherapy drug-induced models, Chinese medicine spleen deficiency models, zebrafish and Drosophila models, and cellular models. This review aims to revisit and summarize the commonly used animal models of cancer cachexia by evaluating existing preclinical models, to provide tools and support for translational medicine research.

Recombinant adenovirus (rAdV) is a commonly used vector system for gene transfer. Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive, possibly attributable to rAdV infection-associated oxidative stress and reactive oxygen species (ROS) production. Here, we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells, and expedites adenovirus production. By stably overexpressing GAPDH in HEK293 (293G) and 293pTP (293GP) cells, respectively, we demonstrated that rAdV-induced ROS production and cell apoptosis were significantly suppressed in 293G and 293GP cells. Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells. Similarly, Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells. We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells. 293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells, indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production. These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production. Therefore, the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.

In Northeast China, permafrost is controlled by a combination of biotic, climatic, physiographic, and anthropogenic factors. Due to the complexity of these governing or influencing factors, it is challenging to exactly describe the features of the Xing’an permafrost in Northeast China. By integrating remote sensing (RS) and geographic information system (GIS) technologies, we have quantified these influencing factors of permafrost changes as an important approach to understanding the nature of latitudinal and mountain permafrost in Northeast China at the mid-latitudes in the Northern Hemisphere. In this study, we combine Geographical Detector (Geodetector) model, trend analysis, and multi-source RS data to quantify the controlling or influencing factors of permafrost thermal state and of permafrost changes, and explain the interactions among permafrost, environment, and climate. The results indicate that, at the regional scale, changes in the thermal state of permafrost are primarily governed or influenced by mean annual land surface temperature (MALST), precipitation, and snow cover duration (SCD). Topographic factors also affect the spatial patterns of permafrost development. Additionally, in the context of climate warming, the insulation effect of snow cover on the permafrost is weakened, or has been weakening. Moreover, the interactive effects among various factors significantly enhance their explanatory power for changes in the thermal state of permafrost. The study emphasizes the complexity of the interactions among permafrost, climate, and the environment, and highlights the significance of understanding these interactions for regional socio-economic development, ecological management, carbon pool stabilization, and research on future climate change in Northeast China.

The study of spatial conflicts of land use (SCLU) is an important breakthrough to reveal the evolution mechanism of regional human-land relationship. Accurate identification of SCLU and scientific exploration of its spatio-temporal characteristics of their driving factors are pivotal for regional sustainable development. However, the basic theoretical system of SCLU still needs to be improved, and the spatio-temporal characteristics of SCLU at different spatial scales and landforms as well as the spatio-temporal correlation effects of its driving factors need to be further studied. This study utilizes theoretical models for the identification of SCLU. Employing a comprehensive index approach involving ArcGIS, FRAGSTATS landscape pattern analysis, and the multi-scale geographically weighted regression model, the spatio-temporal characteristics of SCLU are analyzed across different administrative scales and Macro-landforms. The investigation unveils the intrinsic mechanisms of spatio-temporal differentiation driven by various factors from 2000 to 2020 in the arid and semiarid region of Xinjiang, China. Results indicated that: (1) SCLU is a sensitive indicator of human-land interaction, measurable using conflict risk and effect; (2) The SCLU in Xinjiang presents a spatial pattern of “severe conflict around the three mountains and mild conflict around the two basins” and the SCLU transitioned from an outbreak to a relief stage over the past two decades; (3) SCLU varies significantly among landform types, with conflict intensity in Plain > Mountains > Platform > Hill areas; (4) Elevation and slope in natural environmental factors, human footprint and distance of patches from water, from roads, and from railroads in social activity factors have inhibitory effects on SCLU, and GDP, population density, and human impact index in economic development factors have positive effects on SCLU, and focusing on controlling potentially high-conflict risk areas and enhancing the upgrading of ecological quality are key to mitigating SCLU. The results validate the proposed theoretical framework and provide theoretical and practical references for accurately identifying SCLU and optimizing national territory spatial patterns.

The standardization of river system structures has reduced hydrological connectivity, exerting significant pressure on both river ecology and urban development. The precise diagnosis and proposal of optimization strategies remain key challenges. This study utilizes graph theory to delineate the river network topology in Chengdu city and establishes an evaluation index system (α, β, and γ) for hydrological connectivity. Spatiotemporal changes in Chengdu's hydrological connectivity from 2000 to 2020 are analyzed, alongside a validated optimization scheme focusing on “pressure dispersion” among river network nodes. The findings reveal a simplification of Chengdu's river network structure over the past two decades, marked by a reduction of 72 nodes and 81 river segments. Particularly in the city center (region II), these changes have significantly diminished overall connectivity. Following the implementation of the “pressure dispersion” optimization method, the distribution of critical nodes in Region II has been more equitably, enhancing resilience against disasters like floods by diversifying the burden on key nodes. Furthermore, the hydrological connectivity indices in Region II showed improvements post-optimization, with the α, β, and γ indices rising by 75%, 7.26%, and 7.26%, respectively, thereby validating the efficacy of the approach. Analyzing variations in hydrological connectivity parameters across river systems identifies vulnerable links and fundamental issues, laying groundwork for future improvements. The proposed optimization methodology offers insights applicable to cities worldwide grappling with similar connectivity challenges.

Epigallocatechin gallate (EGCG), an active constituent of tea, is recognized for its anticancer and anti-inflammatory properties. However, the specific mechanism by which EGCG protects osteoblasts from cadmium-induced damage remains incompletely understood. Here, the action of EGCG was investigated by exposing MC3T3-E1 osteoblasts to EGCG and CdCl2 and examining their growth, apoptosis, and differentiation. It was found that EGCG promoted the viability of cadmium-exposed MC3T3-E1 cells, mitigated apoptosis, and promoted both maturation and mineralization. Additionally, CdCl2 has been reported to inhibit both the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) signaling pathways. EGCG treatment attenuated cadmium-induced apoptosis in osteoblasts and restored their function by upregulating both signaling pathways. The findings provide compelling evidence for EGCG’s role in attenuating cadmium-induced osteoblast apoptosis and dysfunction through activating the PI3K/AKT/mTOR and Nrf2/HO-1 pathways. This suggests the potential of using EGCG for treating cadmium-induced osteoblast dysfunction.

BackgroundTrimethylamine-N-oxide (TMAO) is produced by hepatic flavin-containing monooxygenase 3 (FMO3) from trimethylamine (TMA). High TMAO level is a biomarker of cardiovascular diseases and metabolic disorders, and it also affects periodontitis through interactions with the gastrointestinal microbiome. While recent findings indicate that periodontitis may alter systemic TMAO levels, the specific mechanisms linking these changes and particular oral pathogens require further clarification.MethodsIn this study, we established a C57BL/6J male mouse model by orally administering Porphyromonas gingivalis (P. gingivalis, Pg), Fusobacterium nucleatum (F. nucleatum, Fn), Streptococcus mutans (S. mutans, Sm) and PBS was used as a control. We conducted LC-MS/MS analysis to quantify the concentrations of TMAO and its precursors in the plasma and cecal contents of mice. The diversity and composition of the gut microbiome were analyzed using 16S rRNA sequencing. TMAO-related lipid metabolism and enzymes in the intestines and liver were assessed by qPCR and ELISA methods. We further explored the effect of Pg on FMO3 expression and lipid molecules in HepG2 cells by stimulating the cells with Pg-LPS in vitro.ResultsThe three oral pathogenic bacteria were orally administered to the mice for 5 weeks. The Pg group showed a marked increase in plasma TMAO, betaine, and creatinine levels, whereas no significant differences were observed in the gut TMAO level among the four groups. Further analysis showed similar diversity and composition in the gut microbiomes of both the Pg and Fn groups, which were different from the Sm and control groups. The profiles of TMA-TMAO pathway-related genera and gut enzymes were not significantly different among all groups. The Pg group showed significantly higher liver FMO3 levels and elevated lipid factors (IL-6, TG, TC, and NEFA) in contrast to the other groups. In vitro experiments confirmed that stimulation of HepG2 cells with Pg-LPS upregulated the expression of FMO3 and increased the lipid factors TC, TG, and IL-6.ConclusionThis study conclusively demonstrates that Pg, compared to Fn and Sm, plays a critical role in elevating plasma TMAO levels and significantly influences the TMA-TMAO pathway, primarily by modulating the expression of hepatic FMO3 and directly impacting hepatic lipid metabolism.

Silicosis is a progressive pulmonary fibrosis disease caused by long-term inhalation of silica. The early diagnosis and timely implementation of intervention measures are crucial in preventing silicosis deterioration further. However, the lack of screening and diagnostic measures for early-stage silicosis remains a significant challenge. In this study, silicosis models of varying severity were established through a single exposure to silica with different doses (2.5mg/mice or 5mg/mice) and durations (4 weeks or 12 weeks). The diagnostic performance of computed tomography (CT) quantitative analysis was assessed using lung density biomarkers and the lung density distribution histogram, with a particular focus on non-aerated lung volume. Subsequently, we developed and evaluated a stacking learning model for early diagnosis of silicosis after extracting and selecting features from CT images. The CT quantitative analysis reveals that while the lung densitometric biomarkers and lung density distribution histogram, as traditional indicators, effectively differentiate severe fibrosis models, they are unable to distinguish early-stage silicosis. Furthermore, these findings remained consistent even when employing non-aerated areas, which is a more sensitive indicator. By establishing a radiomics stacking learning model based on non-aerated areas, we can achieve remarkable diagnostic performance to distinguish early-stage silicosis, which can provide a valuable tool for clinical assistant diagnosis. This study reveals the potential of using non-aerated lung areas as a region of interest in stacking learning for early diagnosis of silicosis, providing new insights into early detection of this disease.

Protection of the structural and functional integrity of the blood-brain barrier (BBB) is crucial for treating ischemic stroke (IS). Hydroxysafflor yellow A (HSYA) and quercetin (Quer), two main active components in the edible and medicinal plant Carthamus tinctorius L., have been reported to exhibit neuroprotective effects. We investigated the anti-IS and BBB-protective properties of HSYA and Quer and the underlying mechanisms. They decreased neurological deficits in middle cerebral artery occlusion (MCAO) mice, while their combination showed better effects. Importantly, HSYA and Quer ameliorated BBB permeability. Their effects on reduction of both EB leakage and infarct volume were similar, which may contribute to improved locomotor activities. Moreover, HSYA and Quer showed protective effects for hCMEC/D3 monolayer against oxygen-glucose deprivation. Src, p-Src, MMP-9, and P-gp were associated with ingredients treatments. Furthermore, molecular docking and molecular dynamics simulations revealed stable and tight binding modes of ingredients with Src and P-gp. The current study supports the potential role of HSYA, Quer, and their combination in the treatment of IS by regulating BBB integrity.

BackgroundGreen tea intake has been reported to improve the clinical outcomes of patients with cardiovascular diseases or cancer. It may have a certain role in the development of venous thromboembolism (VTE) among cancer patients. The current study aimed to address this issue, which has been understudied.MethodsWe carried out a retrospective study to explore the role of green tea intake in cancer patients. Patients with and without green tea intake were enrolled in a 1:1 ratio by using propensity scoring matching. The primary and secondary outcomes were VTE development and mortality 1 year after cancer diagnosis, respectively.ResultsThe cancer patients with green tea intake (n = 425) had less VTE development (10 [2.4%] vs. 23 [5.4%], p = 0.021), VTE-related death (7 [1.6%] vs. 18 [4.2%], p = 0.026), and fatal pulmonary embolism (PE) (3 [0.7%] vs. 12 [2.8%], p = 0.019), compared with those without green tea intake (n = 425). No intake of green tea was correlated with an increase in VTE development (multivariate hazard ratio (HR) 1.758 [1.476–2.040], p

The increasingly improved transportation infrastructure network is the prerequisite and foundation for driving regional development. Scientifically investigating the mechanisms by which the transport superiority degree (TSD) in arid regions affects the health of ecosystems holds significant practical value and importance for ecosystem protection and regional sustainable development. This study investigates the impact of the TSD on the Ecosystem Health Levels (EHL) in Southern Xinjiang, China, an area characterized by its arid climate and ecological vulnerability. Arid regions, such as Southern Xinjiang, often face unique ecological challenges, including water scarcity, soil erosion, and biodiversity loss, which can be exacerbated by human activities including transportation infrastructure development. By leveraging multi-source remote sensing data, this research aims to uncover the intricate dynamics between TSD and EHL in such a fragile ecological context. The findings of this study are critical for understanding the balance between infrastructural development and environmental conservation in arid regions and provide valuable insights for sustainable planning and policy-making in similar ecological settings. The research results show the following: (1) Over the study period, county-scale TSD in southern Xinjiang generally increased, while the conditions of EHL deteriorated, with higher EHL in the eastern counties than in the western counties. (2) Bivariate spatial autocorrelation analysis reveals a significant spatial dependency between county-scale TSD and EHL, with primary relationship types being LH (Low TSD − High EHL) and HL (High TSD − Low EHL). (3) Spatial regression model results indicate that an increase in TSD leads to the deterioration of county-scale EHL, and during the study period, it was observed that the interference of TSD on EHL gradually weakened.

By enhancing the type 1–3 piezoelectric composite material, a highly sensitive hydroacoustic transducer sensitive element structure is suggested for uses in sonar systems, such as small target identification and fine imaging. A lower metal plate, a piezoelectric ceramic column array, and an upper metal plate make up the piezoelectric material structure. The resonance frequency of the bimetal plate type piezoelectric ceramic array material was theoretically analyzed, the sensitive element geometry of the bimetal plate piezoelectric material was studied using finite element simulation, the material choice for the metal plate affected the material’s performance, and the parameters of each size of the sensitive element were determined. These findings served as a guide for the production of a highly sensitive hydroacoustic transducer, as well as the structure of the piezoelectric material transducer in the water performance test. Results indicate that the structure transducer has a maximum transmit voltage response of 178 dB and a −3 dB bandwidth of approximately 25 kHz; the transducer may be efficiently tuned for a maximum receive sensitivity of −172 dB.

Abstract Tislelizumab, an anti‐programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first‐in‐human, dose‐finding BGB‐A317‐001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5–10 mg/kg every 2 weeks (q2w), 2–5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune‐mediated AEs, and infusion‐related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure–response (E–R) analyses by logistic regression using data from study BGB‐A317‐001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018–2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E–R relationship. Overall, the totality of data, including efficacy, safety, and E–R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.

The high momentum tail (HMT) of nucleons, as a signature of the short-range correlations in nuclei, has been investigated by the high-energy bremsstrahlung γ rays produced in 86Kr+124Sn at 25 MeV/nucleon. The energetic photons are measured by a CsI(Tl) hodoscope mounted on the spectrometer CSHINE. The energy spectrum ≥35 MeV can be reproduced by the Isospin- and Momentum-Dependent Boltzmann-Uehling-Uhlenbeck model calculations incorporating the photon production channel from np process in which the HMTs of nucleons is considered. A non-zero HMT ratio of about 15% is favored by the data. The effect of the capture channel np→dγ is demonstrated.

Abstract Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases.