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Abstract Introduction As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. Method In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. Results We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. Conclusion Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA. Graphical Abstract

Abstract Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.

Volatile substances of silver carp surimi prepared under different meat mincing times (1, 2, 3, 4, and 5) were determined by GC-IMS, and their TBARS values were also measured. Additionally, correlation analysis between the flavor substances and the TBARS values were conducted to elucidate the effect of meat mincing times on the flavor characteristics of surimi. According to the GC-IMS result, a total of 58 volatile substances were detected in all the 5 surimi samples, with relatively high levels of nonanal, ethyl acetate, 2-acetone, ethanol, and 2-methylbutanal. Aldehydes (39.13%~40.91%), ketones (15.52%~21.74%), and alcohols (19.28%~26.59%) were the main types of volatile substances. As the number of meat mincing times increased, the proportion of aldehydes first decreased and then increased, the ketones gradually increased, while the alcohols fluctuated. The PCA and Euclidean distance results of volatile substances indicated that there was a significant difference in flavor characteristics between surimi sample prepared with one time of meat mincing and other samples. The TBARS value of surimi significantly (Pr>0.5), while phenol and phenylacetaldehyde were negatively correlated (−0.8

Hydrostatic pressure is a crucial tool to regulate the structure and properties of materials. However, the influence of hydrostatic pressure on the microstructure of metastable β-Ti alloys remains unclear. In this work, the microstructure and microhardness evolution of a metastable β-type Ti-30Zr-10Nb alloy under hydrostatic pressure (≤10 GPa) were investigated and compared with those under uniaxial pressure (≤1106 MPa). The results revealed that under hydrostatic pressure, Ti-30Zr-10Nb alloy formed a peculiar hierarchical microstructure composed of submicron-scaled α” plates with self-accommodating morphologies, nanoscale ω particles, and microscale shear bands containing nanoscale α” domains. The formation of a hierarchical microstructure effectively coordinates not only the isotropic macroscopic strains but also the local shear stresses under hydrostatic pressure. Compared to uniaxial pressure, the hydrostatic pressure facilitates the β to ω transformation, but hinders the β to α” transformation. The microhardness of the Ti3010 alloy reaches approximately 319 HV at a hydrostatic pressure of 10 GPa, which is 28 % higher than the highest microhardness obtained under uniaxial pressure. The current results highlight the promising potential of hydrostatic pressure in optimizing the mechanical properties of metastable β-Ti alloys.

Under the condition of the shield tunnel intersecting the ground fissure section at a right angle, a physical model test was conducted at a geometric scale ratio of 1:30. This test aimed to compare and analyze the force and deformation of the conventional shield tunnel and shield tunnel after adopting measures to mitigate the effects of ground fissure dislocation. Meanwhile, a finite-element numerical simulation of a conventional shield tunnel under the same working conditions was performed. The physical model test results align closely with the outcomes predicted by numerical calculations. The deformation observed in the shield tunnel primarily consisted of vertical shear deformation near the ground fissure, accompanied by a minor torsional deformation. In grade IV ground fissure sites, both the conventional shield tunnel and shield tunnel with mortise-groove cross-section after taking measures exhibit a basic level of safety. However, only the shield tunnel, after taking measures, is safe when the ground fissure develops to grade III. By contrast, the conventional shield tunnel generates significant shear deformation at the first circumferential seam in the footwall of the ground fissure, which easily causes the joints inside the circumferential seam to yield shear. When the ground fissure grade was raised to II, the conventional shield tunnel and shield tunnel with mortise-groove cross-section after taking measures experienced relatively serious damage.

In hippocampus, synaptic plasticity and rhythmic oscillations reflect the cytological basis and the intermediate level of cognition, respectively. Transcranial ultrasound stimulation (TUS) has demonstrated the ability to elicit changes in neural response. However, the modulatory effect of TUS on synaptic plasticity and rhythmic oscillations was insufficient in the present studies, which may be attributed to the fact that TUS acts mainly through mechanical forces. To enhance the modulatory effect on synaptic plasticity and rhythmic oscillations, transcranial magneto-acoustic stimulation (TMAS) which induced a coupled electric field together with TUS’s ultrasound field was applied. The modulatory effect of TMAS and TUS with a pulse repetition frequency of 100 Hz were compared. TMAS/TUS were performed on C57 mice for 7 days at two different ultrasound intensities (3 W/cm2 and 5 W/cm $^{{2}}\text {)}$ . Behavioral tests, long-term potential (LTP) and local field potentials in vivo were performed to evaluate TUS/TMAS modulatory effect on cognition, synaptic plasticity and rhythmic oscillations. Protein expression based on western blotting were used to investigate the under- lying mechanisms of these beneficial effects. At 5 W/cm2, TMAS-induced LTP were 113.4% compared to the sham group and 110.5% compared to TUS. Moreover, the relative power of high gamma oscillations (50-100Hz) in the TMAS group ( $1.060\pm 0.155$ %) was markedly higher than that in the TUS group ( $0.560\pm 0.114$ %) and sham group ( $0.570\pm 0.088$ %). TMAS significantly enhanced the synchronization of theta and gamma oscillations as well as theta-gamma cross-frequency coupling. Whereas, TUS did not show relative enhancements. TMAS provides enhanced effect for modulating the synaptic plasticity and rhythmic oscillations in hippocampus.

This study aimed to investigate altered static and dynamic functional network connectivity (FNC) and its correlation with clinical symptoms in patients with knee osteoarthritis (KOA). One hundred and fifty-nine patients with KOA and 73 age- and gender-matched healthy subjects (HS) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluations. Group independent component analysis (GICA) was applied, and seven resting-state networks were identified. Patients with KOA had decreased static FNC within the default mode network (DM), visual network (VS), and cerebellar network (CB) and increased static FNC between the subcortical network (SC) and VS (p < 0.05, FDR corrected). Four reoccurring FNC states were identified using k-means clustering analysis. Although abnormalities in dynamic FNCs of KOA patients have been found using the common window size (22 TR, 44 s), but the results of the clustering analysis were inconsistent when using different window sizes, suggesting dynamic FNCs might be an unstable method to compare brain function between KOA patients and HS. These recent findings illustrate that patients with KOA have a wide range of abnormalities in the static and dynamic FNCs, which provided a reference for the identification of potential central nervous therapeutic targets for KOA treatment and might shed light on the other musculoskeletal pain neuroimaging studies.

Afidopyropen has high activity against pests. However, it poses potential risks to the soil ecology after entering the environment. The toxicity of afidopyropen to earthworms (Eisenia fetida) was studied for the first time in this study. The results showed that afidopyropen had low level of acute toxicity to E. fetida. Under the stimulation of chronic toxicity, the increase of reactive oxygen species (ROS) level activated the antioxidant and detoxification system, which led to the increase of superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. Lipid peroxidation and DNA damage were characterized by the increase of malondialdehyde (MDA) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) contents. Meanwhile, the functional genes SOD, CAT, GST, heat shock protein 70 (HSP70), transcriptionally controlled tumor protein (TCTP), and annetocin (ANN) played a synergistic role in antioxidant defense. However, the comprehensive toxicity of high concentration still increased on the 28th day. In addition, strong histopathological damage in the body wall and intestine was observed, accompanied by weight loss, which indicated that afidopyropen inhibited the growth of E. fetida. The molecular docking revealed that afidopyrene combined with the surface structure of SOD and GST proteins, which made SOD and GST become sensitive biomarkers reflecting the toxicity of afidopyropen to E. fetida. Summing up, afidopyropen destroys the homeostasis of E. fetida through chronic toxic. These results provide theoretical data for evaluating the environmental risk of afidopyropen to soil ecosystem.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent consequences of diabetes, with a high incidence and disability rate. The DPN’s pathogenesis is extremely complex and yet to be fully understood. Persistent high glucose metabolism, nerve growth factor deficiency, microvascular disease, oxidative stress, peripheral nerve cell apoptosis, immune factors, and other factors have been implicated in the pathogenesis of DPN. Astragalus mongholicus is a commonly used plant used to treat DPN in clinical settings. Its rich chemical components mainly include Astragalus polysaccharide, Astragalus saponins, Astragalus flavones, etc., which play a vital role in the treatment of DPN. This review aimed to summarize the pathogenesis of DPN and the studies on the mechanism of the effective components of Astragalus mongholicus in treating DPN. This is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.

Abstract In this study, an adsorbent (LCB) with rich honeycomb structure was prepared from cork waste generated from furniture factories for efficient adsorption of excess phosphorus (P) from wastewater. This adsorbent was successfully prepared in only one step, in situ precipitation method, which greatly simplified the synthesis process. Kinetic studies showed that when the initial concentration (C0) of wastewater was 10 mg P L−1, the P in the water could be completely adsorbed within 20 min. The adsorption efficiency of phosphorus was significantly improved compared to previous studies. When the C0 of pollutant and the dosage of LCB were 20 mg P L−1 and 0.5 g L−1, respectively, the removal rate of P exceeded 99% in the pH range of 3–10, which indicates the wide applicability of LCB. In addition, the P adsorption capacity of LCB was 82.4% of its initial value after nine adsorption–desorption cycles, indicating that LCB has a high stability and can be widely used in different water environments. Therefore, LCB is a promising material for the treatment of P-containing wastewater. Graphical Abstract

Abstract The third most often diagnosed disease globally and the second most prevalent cause of cancer-related death is colorectal cancer (CRC). Numerous human malignancies have been identified to have high expression of ADORA2A. However, it is still ambiguous about its function in CRC. RNA-seq with stable transfected SETDB1 knockdown cells was used to identify differentially expressed genes. Further, knockdown of ADORA2A in CRC cell lines SW620 and HCT116 was performed with siRNA and over expression of ADORA2A in SW480 cells was conducted with plasmids. CCK8, colony formation, wound healing, and transwell assay were used to detect the effects of cell proliferation, migration, and invasion after knockdown and over expression of ADORA2A. Also, apoptosis was analyzed by flow cytometry, apoptosis-related proteins and key PI3K/AKT pathway proteins were detected using Western blotting. ADORA2A was identified after RNA-seq analysis and played an important role in CRC prognosis. ADORA2A was relatively high in SW620 and HCT116 cell lines compared to SW480 cell lines. ADORA2A knockdown in SW620 and HCT116 inhibited cell proliferation, migration, and invasion, while ADORA2A overexpression had the opposite effect. In addition, ADORA2A also impacted the expression of apoptosis-related proteins, including Bcl-2, Bax, Cleaved caspase-3 and Cleaved caspase-9, and reduced apoptosis. Furthermore, this process may include the PI3K/AKT signaling pathway. ADORA2A promotes CRC progression and inhibits apoptosis by the PI3K/AKT signaling pathway. It may contribute to the management and treatment of CRC.

Disassembly line balancing (DLB) is a crucial optimization item in the recycling and remanufacturing of waste products. Considering the variations in the number of operators assigned to each station, this study investigates DLBs with six distinct station configurations: single-manned, multi-manned, single-robotic, multi-robotic, single-manned–robotic, and multi-manned–robotic setups. First, a unified mixed-integer programming (MIP) model is established for Type-I DLBs with each configuration to minimize four objectives: the number of stations, the number of operators, the total disassembly time, and the idle balancing index. To obtain more solutions, a novel bi-metric is proposed to replace the quadratic idle balancing index and is used in lexicographic optimization. Subsequently, based on the unified Type-I models, a unified MIP model for Type-II DLBs is established to minimize the cycle time, the number of operators, the total disassembly time, and the idle balancing index. Finally, the correctness of the established unified models and the effectiveness of the proposed bi-metric are verified by solving two disassembly cases of lighters and hairdryers, which further shows that the mathematical integration method of unified modeling has significant theoretical value for the multi-objective optimization of the DLBs with six distinct station configurations.

The shakedown state of the subgrade is crucial for the sustainable design and long-term stability evaluation of pavement structures. In order to characterize the plastic deformation and shakedown behavior of subgrade soil in seasonal frozen regions, cyclic triaxial tests were conducted on the thawed subgrade soil after seven cycles of freeze-thaw. The influences of the numbers of cycle loading, the amplitude of cyclic deviator stress, and the confining stress were considered variables. The evolution features of accumulative plastic strain, accumulative plastic strain rate, and critical dynamic stress were experimentally analyzed. Based on the shakedown theory, the ensuing discoveries were that the accumulative plastic strain response-behavior of thawed subgrade soil was typically divided into plastic shakedown, plastic creep, and incremental collapse under the long-term cyclic loading. Furthermore, the shakedown standard for thawed subgrade soil was also proposed based on the evolution of the accumulative plastic strain rate. The critical dynamic stresses can be obtained by the proposal formula to determine the different plastic deformation ranges.

Abstract Luminescent materials that display quick spectral responses to thermal stimuli have attracted pervasive attention in sensing technologies. Herein, a programmable luminescence color switching in lanthanide‐doped LiYO2 under thermal stimuli, based on deliberate control of the monoclinic (β) to tetragonal (α) phase transition in the crystal lattice, is reported. Specifically, a lanthanide‐doping (Ln3+) approach to fine‐tune the phase‐transition temperature in a wide range from 294 to 359 K is developed. Accordingly, an array of Ln3+‐doped LiYO2 crystals that exhibit progressive phase transition, and thus sequential color switching at gradually increasing temperatures, is constructed. The tunable optical response to thermal stimuli is harnessed for colorimetric temperature indication and quantitative detection, demonstrating superior sensitivity and temperature resolution (Sr = 26.1% K−1, δT = 0.008 K). The advances in controlling the phase‐transition behavior of luminescent materials also offer exciting opportunities for high‐performance personalized health monitoring.

Background: Endometriosis is a common gynecological disease that affects approximately 5 %∼10 % of reproductive-aged women. Zinc (Zn), selenium (Se), copper (Cu), cobalt (Co) and molybdenum (Mo) are essential trace elements and are very important for human health. However, studies on the relationship between mixtures of essential trace elements and the risk of endometriosis are limited and inconsistent. In particular, studies confirming the association via different sample types are limited. Objective: This study aimed to investigate the associations between Zn, Se, Cu, Co and Mo concentrations in blood and follicular fluid (FF) and endometriosis risk in a Chinese population. Methods: A total of 609 subjects undergoing in vitro fertilization (IVF) were recruited; 836 samples were analyzed, including 451 blood samples (234 controls and 217 cases) and 385 FF samples (203 controls and 182 cases). In addition, 227 subjects provided both blood and FF samples. Zn, Se, Cu, Co and Mo concentrations in blood and FF were quantified via inductively coupled plasma−mass spectrometry (ICP−MS). The associations between the levels of Zn, Se, Cu, Co and Mo and the risk of endometriosis were assessed using single-element models (logistic regression models), and the combined effect of the trace elements on endometriosis risk was assessed using multielement models (Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression). Results: Based on the single-element models, significant associations of Zn concentrations in blood (high-level vs. low-level group: aOR = 14.17, 95 % CI: 7.31, 27.50) and FF (first tertile vs. second tertile group: aOR = 0.34, 95 % CI: 0.16, 0.71; third tertile vs. second tertile group: aOR = 2.32, 95 % CI: 1.38, 3.91, respectively) and Co concentrations in blood (first tertile vs. second tertile group, aOR = 0.24, 95 % CI: 0.12, 0.48) and FF (third tertile vs. second tertile group: aOR = 3.87, 95 % CI: 2.19, 6.84) with endometriosis risk were found after adjustment for all confounders. In FF, Cu and Mo levels were significantly greater among the cases than among the controls, with a positive association with endometriosis risk (Cu (first tertile vs. second tertile group: aOR = 0.39, 95 % CI: 0.19, 0.81; third tertile vs. second tertile group: aOR = 2.73, 95 % CI: 1.61, 4.66, respectively) and Mo (high-level vs. low-level group: aOR = 14.93, 95 % CI: 7.16, 31.12)). However, similar associations between blood Cu and Mo levels and endometriosis risk were not found. In addition, the levels of these five essential trace element mixtures in blood and in FF were significantly and positively associated with endometriosis risk according to the BKMR analyses; the levels of Zn and Cu in blood and the levels of Mo in FF were significantly related to the risk of endometriosis, and the posterior inclusion probabilities (PIPs) were 1.00, 0.99 and 1.00 for Zn and Cu levels in blood and Mo levels in FF, respectively. Furthermore, Zn and Mo were the highest weighted elements in blood and FF, respectively, according to WQS analyses. Conclusion: The risk of endometriosis was associated with elevated levels of several essential trace elements (Zn, Cu and Co). Elevated levels of these elements may be involved in the pathomechanism of endometriosis. However, further studies with larger sample sizes will be necessary to confirm these associations.

Abstract The essential branched‐chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs’ full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence‐associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation‐related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation of the catabolic enzyme BCAA transaminase 1 during onset of cellular senescence, leading to highly elevated intracellular BCAA levels in senescent cells. This, in turn, activates the mammalian target of rapamycin complex 1 (mTORC1) to establish the full SASP program. Transgenic Drosophila models further indicate that orthologous BCAA regulators are involved in the induction of cellular senescence and age‐related phenotypes in flies, suggesting evolutionary conservation of this metabolic pathway during aging. Finally, experimentally blocking BCAA accumulation attenuates the inflammatory response in a mouse senescence model, highlighting the therapeutic potential of modulating BCAA metabolism for the treatment of age‐related and inflammatory diseases.

Abstract Background Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding Protein (RBP) Immunoprecipitation]-seq were used to confirm the potential regulating role of peptidyl-tRNA hydrolase 1 homolog (PTRH1) on the stability of the PD-L1 mRNA. Postoperative specimens were used to identify the expression of PD-L1 and PTRH1 in pancreatic cancer. Co-culturing T cells with pancreatic cancer cells to explore the immunosuppressive effect of pancreatic tumor cells. Results Our results revealed that a high dose of glucose enhanced the stability of the PD-L1 mRNA in pancreatic tumor cells by downregulating PTRH1 through RAS signaling pathway activation following epidermal growth factor receptor (EGFR) stimulation. PTRH1 overexpression significantly suppressed PD-L1 expression in pancreatic cells and improved the proportion and cytotoxic function of CD8+ T cells in the pancreatic TME of diabetic mice. Conclusions PTRH1, an RBP, plays a key role in the regulation of PD-L1 by high glucose and is closely related to anti-tumor immunity in the pancreatic TME.

Abstract Background Most studies support parafunctions play an important role in temporomandibular disorders (TMD), whereas the association between tooth wear and TMD remains controversial. Betel nut chewing as a parafunction is popular in South and Southeast Asia. We therefore investigated the association of severely worn dentition resulting from betel nut chewing with TMD. Methods A cross-sectional analysis of 408 control participants (male: 380, female: 28, 43.62 ± 9.54 years) and 408 participants with betel nut chewing related severely worn dentition (male: 380, female: 28, 43.73 ± 8.93 years) who received dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Health Management Center, Xiangya Hospital was performed. Betel nut chewing related severely worn dentition meant all the natural teeth had moderate to severe tooth wear [Tooth Wear Index (TWI) ≥ 2)] including ≥ 2 severe wear teeth (TWI ≥ 3) due to betel nut chewing. Multivariable logistic regression analysis was used. Results After adjusting for age, gender, betel nut chewing related severely worn dentition, oral submucosal fibrosis, number of missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, variables of age, gender and betel nut chewing related severely worn dentition were significant for overall TMD. Multivariable analysis showed betel nut chewing related severely worn dentition was significantly associated with intra-articular TMD [odds ratio and 95% confidence intervals: 1.689 (1.271–2.244), P = 0.001] in a betel nut chewing dose-dependent manner. Conclusion Betel nut chewing related severely worn dentition was associated with intra-articular TMD.

This study is to explore underlying mechanism of skin wound healing by snakehead fish soup using rat and cell models. We assessed skin wound changes after administering wild and farmed snakehead fish soup intragastrically, then using CCK-8 and scratch tests to evaluate cell proliferation and migration, last assessed vessel tubule formation by HUVEC cells. The results showed that the skin wound healing rates of rats after 14 days of intragastrical administration of farmed and wild snakehead fish soup were 52.71% and 57.76%, respectively, which were substantially greater than the control group (39.84%). With the administration of the soups, the collagen tissue on the skin wound was more homogenous and thicker, and type I collagen was denser. Additionally, interleukin-6 level in rat serum during wound healing was significantly lower, while cyclin-D1 and fibroblast growth factor-2 levels were higher. Furthermore, the soups (particularly at 50 μg/mL) significantly increased the proliferation and migration rates of both the HACAT and NIH3T3 cells, and considerably promoted the tubule formation of HUVEC cells. The findings confirm that the soup can promote skin wound healing and the underlying mechanism involves multiple roles including anti-inflammation, cell proliferation, vessel tubule formation, and collagen expression.

Aiming at the noise and nonlinear characteristics existing in the deformation monitoring data of concrete dams, this paper proposes a dam deformation prediction model based on a multi-scale adaptive kernel ensemble. The model incorporates Gaussian white noise as a random factor and uses the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) method to decompose the data set finely. Each modal component is evaluated by sample entropy (SE) analysis so that the data set can be reconstructed according to the sample entropy value to retain key information. In addition, the model uses partial autocorrelation function (PACF) to determine the correlation between intrinsic modal function (IMF) and historical data. Then, the global search whale optimization algorithm (GSWOA) is used to accurately determine the parameters of kernel extreme learning machine (KELM), which forms the basis of the dam deformation prediction model based on multi-scale adaptive kernel function. The case analysis shows that CEEMDAN-SE-PACF can effectively extract signal features and identify significant components and trends so as to better understand the internal deformation trend of the dam. In terms of algorithm optimization, compared with the WOA algorithm and other algorithms, the results of the GSWOA algorithm are significantly better than other algorithms and have the optimal convergence. In terms of prediction performance, CEEMDAN-SE-PACF-GSWOA-KELM is superior to the CEEMDAN-WOA-KELM, GSWOA-KELM, CEEMDAN-KELM, and KELM models, showing higher accuracy and stronger stability. This improvement is manifested in the decrease of root mean square error (RMSE), mean square error (MSE), and mean absolute error (MAE) and the improvement of the R square (R2) value close to 1. These research results provide a new method for dam safety monitoring and evaluation.

Sufficient soil moisture is required to ensure the successful transplantation of sweet potato seedlings. Thus, reasonable water management is essential for achieving high quality and yield in sweet potato production. We conducted field experiments in northern China, planted on 18 May and harvested on 18 October 2021, at the Nancun Experimental Base of Qingdao Agricultural University. Three water management treatments were tested for sweet potato seedlings after transplanting: hole irrigation (W1), optimized drip irrigation (W2), and traditional drip irrigation (W3). The variation characteristics of soil volumetric water content, soil temperature, and soil CO2 concentration in the root zone were monitored in situ for 0–50 days. The agronomy, root morphology, photosynthetic parameters, 13C accumulation, yield, and yield components of sweet potato were determined. The results showed that soil VWC was maintained at 22–25% and 27–32% in the hole irrigation and combined drip irrigation treatments, respectively, from 0 to 30 days after transplanting. However, there was no significant difference between the traditional (W3) and optimized (W2) drip irrigation systems. From 30 to 50 days after transplanting, the VWC decreased significantly in all treatments, with significant differences among all treatments. Soil CO2 concentrations were positively correlated with VWC from 0 to 30 days after transplanting but gradually increased from 30 to 50 days, with significant differences among treatments. Soil temperature varied with fluctuations in air temperature, with no significant differences among treatments. Sweet potato survival rates were significantly lower in the hole irrigation treatments than in the drip irrigation treatments, with no significant difference between W2 and W3. The aboveground biomass, photosynthetic parameters, and leaf area index were significantly higher under drip irrigation than under hole irrigation, and values were higher in W3 than in W2. However, the total root length, root volume, and 13C partitioning rate were higher in W2 than in W3. These findings suggest that excessive drip irrigation can lead to an imbalance in sweet potato reservoir sources. Compared with W1, the W2 and W3 treatments exhibited significant yield increases of 42.98% and 36.49%, respectively. The W2 treatment had the lowest sweet potato deformity rate.

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic–acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aβ) plaque and synaptic plasticity in Alzheimer’s disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aβ. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aβ plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer’s disease.

Plastic film mulching, widely used in agriculture, leads to microplastic (MP) pollution in soils. While biodegradable polybutylene adipate terephthalate (PBAT) films may offer a solution, their impacts on subsurface soils and microorganisms remain unclear. To investigate the effects of conventional non-biodegradable polyethylene (PE) and biodegradable PBAT MPs on the properties of sub-surface soils and microbial communities, MPs were added at varying doses in a field experiment and incubated for 160 days. Physicochemical characteristics, nutrient dynamics, and microbial composition, diversity, and networks of soils were analyzed using standard techniques and 16S rRNA/ITS gene sequencing. Correlations between soil properties and microbes were assessed. Both MP types significantly altered soil characteristics, with PBAT-MP elevating pH and the levels of available phosphorus and potassium more than PE-MP. Microbial composition shifts occurred, with low-addition PBAT-MP promoting plastic-degrading genera. The assessment of α/β-diversity indicated that PBAT-MP predominantly influenced fungi while PE-MP impacted bacteria. An examination of microbial co-occurrence networks highlighted that PE-MP primarily disrupted fungal interactions, whereas PBAT-MP streamlined network complexity. Correlation analyses revealed that PBAT-MP promoted fungal diversity/network resilience correlating to nutrients. PE-MP and PBAT-MP significantly altered native soil/microbe relationships. PBAT-MP may exert greater, yet unknown, impacts over time through its biodegradation into newer and smaller fragments. Future research needs to integrate multi-omics and stable isotope science to elucidate the deep mechanistic impacts of degraded film-derived MPs on microbial ecological functions and biogeochemical cycles. Attention should also be paid to the long-term accumulation/transport of MPs in agricultural soils. Overall, this work deepens the impact and understanding of MPs from plastic film on sub-surface soil ecology. Furthermore, it provides a theoretical foundation for managing ‘white pollution’ in the film-covered farmlands of arid and semi-arid regions in China.

Abstract Facial expression recognition plays a significant role in the application of man–machine interaction. However, existing models typically have shortcomings with numerous parameters, large model sizes, and high computational costs, which are difficult to deploy in resource‐constrained devices. This paper proposes a lightweight network based on improved MobileNetV3 to mitigate these disadvantages. Firstly, we adjust the channels in the high‐level network to reduce the number of parameters and model size, and then, the coordinate attention mechanism is introduced to the network, which enhances the attention of the network with few parameters and low computing cost. Furthermore, a complementary pooling structure is designed to improve the coordinate attention mechanism, which enables it to assist the network in extracting salient features sufficiently. In addition, the network with the joint loss consisting of the softmax loss and centre loss is trained, which can minimize the intra‐class gap and improve the classification performance. Finally, the network is trained and tested on public datasets FERPlus and RAF‐DB, with the best accuracy of 87.5% and 86.6%, respectively. The FLOPs, parameters, and the memory storage size are only 0.19GMac, 1.3 M, and 15.9 MB, respectively, which is lighter than most state‐of‐the‐art networks. Code is available at https://github.com/RIS‐LAB1/FER‐mobilenet.

Abstract Background The aberrance of gray matter morphology in migraineurs has been widely investigated. However, it remains largely unknown whether there are illness duration-related hierarchical changes in the gray matter structure. Methods A total of 86 migraine without aura (MwoA) patients and 73 healthy controls were included. The Voxel-Based Morphometry approach was utilized to compare the gray matter volume (GMV) differences between MwoA patients and healthy controls. The Structural Covariance Network analysis was conducted to quantify the cross-regional synchronous alterations of gray matter structure in MwoA patients. The Causal Structural Covariance Network analysis was performed to describe the progressive and hierarchical changes in the gray matter network of patients in the pathological progression of migraine. Results MwoA patients had duration-stage related GMV hypertrophy in the left parahippocampus, as well as synergistic GMV aberrance in the parahippocampus and the medial inferior temporal gyrus and cerebellum. Moreover, the GMV alteration of the parahippocampus, and the surrounding hippocampus, amygdala, and bilateral anterior cerebellum, preceded and causally influenced the morphological changes of lateral parietal-temporal-occipital gyrus, as well as the motor cortex and prefrontal gyrus with the increasing illness duration in MwoA patients. Conclusion The current study indicated that gray matter structural alterations in the medial inferior temporal gyrus, especially the parahippocampus, is a critical pathological characteristic in MwoA patients, which drives the gray matter structure alteration of other regions. These findings provide further evidence for understanding the progressive gray matter morphological changes in migraine and may facilitate the development of neuromodulation therapies targeting this procession.

The conventional rough-and-tumble pattern of industrial development in the northeast has severely affected China's sustainable development in recent years. As a result, the industrial park emerged and prospered with the advantages of clear industrial positioning, optimized functional layout and complete support facilities. Nonetheless, for the environmental management of industrial parks, environmental impact assessment (EIA) should be better applied as an upstream environmental protection means. Thus, in three aspects, this study summarizes the research on EIA in the world and analyzes the effectiveness and development of EIA in Northeast China. First, this study analyzed the status and trends of international research in EIA, based on the Web of Science database and the CiteSpace scientometric software. The number of papers continues to rise. Some countries collaborate closely and bring forth new ideas. Research focuses on environmental management, EIA methodology, and energy issues. Research hotspots are public participation and life cycle methods. Second, to specifically investigate the effectiveness of the EIA of the Northeast Industrial Park in recent years has been profitable for the improvement of the Northeast EIA system and for promoting the environmental management approach of the EIA at the micro level. It has been demonstrated that the effect of 70% EIA implementation is relatively significant with high effectiveness. Third, using a SWOT analysis approach, it aims to identify internal strengths and weaknesses, external opportunities and challenges in the development of the Northeast Industrial Park EIA, and propose a future development strategy for the Northeast Industrial Park EIA at the macro level.

BackgroundThe prognosis of hepatocellular carcinoma combined with portal vein tumor thrombus is poor, with a median survival of only 3-6 months. PD-1 combined with targeted therapy may provide an opportunity for patients with BCLC C stage hepatocellular carcinoma combined with portal vein tumor thrombus to undergo radical surgery, significantly prolonging their survival time.Case presentationA middle-aged 51-year-old male who was diagnosed with hepatocellular carcinoma combined with portal vein main stem tumor thrombus at our center in May 2020, with a BCLC stage of C, liver cirrhosis, HBV infection, and preoperative evaluation as unresectable. The liver function was Child-Pugh A. The initial treatment was lenvatinib combined with PD-1 therapy, followed by one cycle of TACE treatment. The tumor and thrombus volume significantly reduced, followed by continuous TACE combined with immunotherapy and targeted therapy, leading to the appearance of portal vein main stem emboli. After multidisciplinary discussion, surgical resection was performed, and the embolus was removed, achieving a cure. The patient has been tumor-free for over 34 months.ConclusionPD-1 combined with lenvatinib and local TACE create conditions for radical surgery, and it is hoped that more real-world research data can provide better evidence for the transformational treatment of hepatocellular carcinoma combined with portal vein tumor thrombus.

Gemcitabine (Gem) is the first-line chemotherapy drug for pancreatic cancer, but the acquired chemoresistance also hinders its application. Therefore, research about Gem resistance plays a crucial role in enhancing the therapeutic effect of Gem. As a deubiquitinating enzyme, ubiquitin-specific protease 8 (USP8) was shown to play vital roles in the tumorigenesis processes of several cancers; however, the effect of USP8 on Gem resistance of pancreatic cancer still remains largely unknown. In the current study, we observed that the expression of USP8 was increased in pancreatic cancer patients, it is related to the recurrence of Gem chemotherapy, and USP8 expression could be induced by Gem application. Furthermore, USP8 was found to promote Gem resistance both in vivo and in vitro via regulating cell viability and apoptosis. Moreover, USP8 enhanced the activation of Nrf2 signaling which is dependent on its deubiquitinase ability. At last, we illustrated that USP8 interacted with Nrf2 directly and deubiquitinated K48-linked polyubiquitin chains from Nrf2, stabilizing the expression of Nrf2. In summary, the manuscript revealed the role of USP8 in Gem chemoresistance and suggested USP8 as a potential therapeutic target for pancreatic cancer.

This study aimed to investigate the effects of okara insoluble dietary fiber (IDF) with different particle sizes on the volatile organic compounds (VOCs) and characteristic aroma compounds of silver carp surimi gel. VOCs of nano-sized IDF (NIDF), micro-sized IDF (MIDF), and silver carp surimi gels with 0.8% (w/w) NIDF or 0.8% (w/w) MIDF were analyzed by electronic nose, gas chromatography-ion mobility spectrometry (GC-IMS) and Solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC–MS) combined with sensory evaluation. Results revealed that the addition of NIDF and MIDF could affect the VOCs of surimi gels. NIDF reduced the odor activity value of some fishy aroma compounds, such as hexanal, nonanal, (E,E)-2,4-heptadienal, and 1-octen-3-ol. Moreover, NIDF increased the concentrations of VOCs with branched chains or a benzene ring, such as 2-methylbutanal, 3-methylbutanal, benzaldehyde, and phenylacetaldehyde. The overall sensory preference of surimi gel could be improved with the addition of NIDF. This study provides new ideas for the applications of okara in aroma regulation of surimi products.

Abstract Background Congenitally missing tooth is the most common dental abnormality which leaves spaces in the arch, leads to numerous forms of malocclusion due to the Bolton index discrepancy and is even associated with abnormal craniofacial morphology. Even though the roles of malocclusion and tooth loss in temporomandibular disorders (TMD) development remain controversial, basic researches have found some common molecules are involved in osteoarthritis and dental agenesis. However, the association of congenitally missing teeth with TMD is unknown. We hence investigated the association of congenitally missing teeth with TMD. Methods A cross-sectional analysis of 586 control participants (male: 287, female: 299, 38.33 ± 11.65 years) and 583 participants with non-third molar congenitally missing teeth (male: 238, female: 345, 39.13 ± 11.67 years) who consecutively received routine dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders Axis I in Health Management Center, Xiangya Hospital was performed. Logistic regression analysis was used to study the association of congenitally missing teeth with TMD. Results The congenitally missing teeth group included 581 hypodontia and 2 oligodontia participants. The congenitally missing anterior teeth participants, the congenitally missing posterior teeth participants and participants with both congenitally missing anterior and posterior teeth accounted for 88.34%, 8.40% and 3.26% of the congenitally missing teeth group respectively. Congenitally missing teeth group had greater ratios of females and orthodontic history. Participants with congenitally missing teeth had a significantly higher prevalence of overall TMD (67.24%) in comparison to control participants (45.90%). After adjusting age, gender, presence of congenitally missing teeth, number of congenitally missing teeth, number of non-congenitally missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, the variables of age, gender, presence of congenitally missing teeth and number of dental quadrants with missing teeth were significant for overall TMD. Multivariable logistic regression analysis showed congenitally missing tooth was significantly related with overall TMD [odds ratio (OR):1.689(1.080–2.642), P = 0.022], intra-articular TMD [OR: 1.711(1.103–2.656), P = 0.017] and pain-related TMD [OR: 3.093(1.321–7.239), P = 0.009]. Conclusion Congenitally missing tooth is a risk factor for TMD. When treating the congenitally missing teeth population, TMJ evaluation and multidisciplinary strategies are necessary.

Ambient light interference stands as the primary source of noise encountered by the light detection and ranging (LiDAR) systems based on single-photon avalanche diode (SPAD), which seriously restricts the detection range and accuracy of sensors. Multi-event mode and time-gating method are extensively employed due to their effective suppression ability of the ambient light interference with easily implemented circuit structure. However, the current research on these two operational modes is limited to qualitative description, lacking a comprehensive theoretical analysis. This paper investigates the impact of the multi-event mode and time-gating method on enhancing the imaging capabilities of the sensor, employing a probability distribution perspective. A behavioral model is established, enabling the simulation of the comprehensive functionality of a SPAD-based LiDAR system in either first-hit mode or multi-event mode, including the histogramming, coincident detection, time- gating functions. The model can serve as a substitute for the actual circuit in system function validation and parameter optimization, thereby significantly reducing the design and simulation cycle.

Brain age prediction is important for understanding brain development and aging. Currently, researchers can predict brain age using resting-state functional MRI (rs-fMRI) data. However, there are differences in brain age development among different subjects, and the same subject also has different development at different ages. So far, how to accurately estimate brain age using rs-fMRI efficiently remains a challenging problem. Therefore, a brain age prediction model with the similarity metric convolutional neural network is proposed in this paper. Specifically, this paper first introduces a siamese convolutional neural network, which includes convolution, batch normalization, and pooling steps simultaneously learns the features of two groups of rs-fMRI, and designs a similarity measurement network. Subsequently, fMRI images of two groups of different subjects are input into the network, and a similarity metirc module is designed to calculate the similarity between the two groups of images. Then the network is optimized by a loss function, and finally, the average value of the three groups of sample labels with the greatest similarity is taken. The absolute mean error and correlation coefficients obtained from the model are 5.337 and 0.6279, respectively. Experimental results show that this method has low mean absolute error and high correlation coefficient on the longitudinal imaging data set of Southwest University.

The high-frequency trading framework for the price trend prediction model and trading strategy has been a popular approach for T+0 trading in the stock market. The prediction model is used to predict price trends, and the trading strategy is used to determine the price and volume of the order. Most trading strategies consist of multiple trading logic associated with certain tuning parameters. These parameters significantly affect the profitability of high-frequency trading frameworks. There are two main disadvantages of this framework: 1) the price trend prediction model can not adapt to the current market data distribution, and 2) the trading strategy can not adapt to the current market conditions automatically. Thus, the framework cannot always maintain positive revenue. To address this problem, we propose a novel dynamic parameter optimization algorithm based on reinforcement learning for stock prediction and trading, and to generate an adaptive trading framework. First, we use a rolling model training method for stock price trend prediction. Second, we regard each set of strategy parameters as action and devise an inverse reinforcement learning algorithm for the reward function to accurately estimate the reward of each action. Because of the T+1 trading rules of the Chinese stock market, we consider the constraint of limited short position in the reward function. Finally, a reward-enhanced upper confidence bound (UCB) selection algorithm is proposed to automatically optimize the parameters of the trading logic in real-time trading. The experimental results show that our method achieves competitive performance in the Chinese stock market.

BackgroundBloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have received much attention. However, few studies have identified risk factors for CRKP BSIs in comparison to CRKP non-bloodstream infections (non-BSIs). This study aimed to compare the epidemiology, risk factors, and outcomes of CRKP BSIs and CRKP non-BSIs.MethodsWe conducted a retrospective study of patients infected with CRKP in the ICU from January 2012 to December 2020. Clinical characteristics and outcomes were compared between CRKP BSIs and CRKP non-BSIs. Predictors associated with 28-day all-cause mortality in CRKP-infected patients were also evaluated.Results326 patients infected with CRKP were enrolled, including 96 patients with CRKP BSIs and 230 with CRKP non-BSIs. The rates of CRKP BSIs in CRKP infections were generally raised from 2012 (12.50%) to 2020 (45.76%). Multivariate logistic analysis indicated that the use of carbapenems within the prior 90 days was an independent risk factor for CRKP BSIs (p = 0.019). Compared to CRKP non-BSIs, CRKP isolates in the CRKP BSI group were found to be non-susceptible to more tested carbapenems (p = 0.001). Moreover, the CRKP BSI group exhibited a higher mortality rate (p = 0.036). The non-susceptibility of CRKP isolates to more tested carbapenems (p = 0.025), a high SOFA score (p = 0.000), and the use of antifungal drugs within the prior 90 days (p = 0.018) were significant factors for 28-day all-cause mortality in CRKP-infected patients.ConclusionThe proportion of CRKP BSI increased progressively in CRKP-infected patients over 9 years. The use of carbapenems within the prior 90 days was an independent risk factor for the development of CRKP BSIs. The non-susceptibility of CRKP isolates to more tested carbapenems and a higher mortality rate were found in the CRKP BSI group.

The replacement of plastic film with biodegradable film is important for reducing plastic film residual pollution in semi-arid regions of northern China. However, information on biodegradable film improvements based on the hydrothermal requirements of major food crops in the typical plastic film mulching area is limited. This study used a combination of field data measurements and curve fitting to assess the spatiotemporal distribution of soil hydrothermal variation and the corresponding maize yield in the field under biodegradable film mulching (BM), polyethylene film mulching (PM), and without mulching (CT). The warming effect of BM was between those of PM and CT and all treatments differed significantly from each other. The duration of the warming effect of BM was shorter than that of PM, and the warming effect of both disappeared at the early jointing stage of maize. The BM soil moisture was significantly lower compared with PM and CT throughout the soil profile (0–180 cm). Moreover, moisture fluctuations were observed in the 0–40 and 40–120 cm soil layers of BM after degradation, and the timing of fluctuations coincided with the filling period of maize. Consequently, the water use efficiency and yield of BM were lower than those of PM. Hence, we suggest that the conservation effect of biodegradable film mulching on soil moisture should persist until the end of the maize filling period, and that the start-up stage of degradation cannot be based solely on the disappearance of the warming effect.

Abstract Ovarian reserve (OR) and fertility are critical in women's healthcare. Clinical methods for encoding OR and fertility rely on the combination of tests, which cannot serve as a multi‐functional platform with limited information from specific biofluids. Herein, metabolic fingerprinting of follicular fluid (MFFF) from follicles is performed, using particle‐assisted laser desorption/ionization mass spectrometry (PALDI‐MS) to encode OR and fertility. PALDI‐MS allows efficient MFFF, showing fast speed (≈30 s), high sensitivity (≈60 fmol), and desirable reproducibility (coefficients of variation

Neuro-navigation is a key technology to ensure the clinical efficacy of TMS. However, the neuro-navigation system based on positioning sensor is currently unable to be promoted and applied in clinical practice due to its time-consuming and high-cost. In the present study, we designed I-Helmet system to promote an individualized and clinically friendly neuro-navigation approach to TMS clinical application. I-Helmet system is based on C++ with a graphical user interface that allows users to design a 3D-printed helmet model for coil navigation. Besides, a dedicated coil positioning accuracy detection method was promoted based on three-dimensional (3D) printing and 3D laser scanning for evaluation. T1 images were collected from 24 subjects, and based on each image, phantom were created to simulate skin and hair. Six 3D-printed helmets with the head positioning hole enlarged by 0–5% tolerance in 1% increments were designed to evaluate the influences of skin, hair, and helmet-tolerance on the positioning accuracy and contact force of I-Helmet. Finally, I-Helmet system was evaluated by comparing its positioning accuracy with three skin hardnesses, three hair styles, three operators, and with or without landmarks. The accuracy of the proposed coil positioning accuracy detection method was about 0.30 mm in position and 0.22° in orientation. Skin and hair had significant influences on positioning accuracy (p 0.05). The tolerance of the helmet presented significant influences on positioning accuracy (p

Background and objectiveIt has been proved that repetitive transcranial magnetic stimulation (rTMS) triggers the modulation of homeostatic metaplasticity, which causes the effect of rTMS to disappear or even reverse, and a certain length of interval between rTMS trains might break the modulation of homeostatic metaplasticity. However, it remains unknown whether the effects of high-frequency rTMS can be modulated by homeostatic metaplasticity by lengthening the train duration and whether homeostatic metaplasticity can be broken by prolonging the inter-train interval.MethodsIn this study, 15 subjects participated in two experiments including different rTMS protocols targeting the motor cortex. In the first experiment, high-frequency rTMS protocols with different train durations (2 s and 5 s) and an inter-train interval of 25 s were adopted. In the second experiment, high-frequency rTMS protocols with a train duration of 5 s and different inter-train intervals (50 s and 100 s) were adopted. A sham protocol was also included. Changes of motor evoked potential amplitude acquired from electromyography, power spectral density, and intra-region and inter-region functional connectivity acquired from electroencephalography in the resting state before and after each rTMS protocol were evaluated.ResultsHigh-frequency rTMS with 2 s train duration and 25 s inter-train interval increased cortex excitability and the power spectral density of bilateral central regions in the alpha frequency band and enhanced the functional connectivity between central regions and other brain regions. When the train duration was prolonged to 5 s, the after-effects of high-frequency rTMS disappeared. The after-effects of rTMS with 5 s train duration and 100 s inter-train interval were the same as those of rTMS with 2 s train duration and 25 s inter-train interval.ConclusionOur results indicated that train duration and inter-train interval could induce the homeostatic metaplasticiy and determine the direction of intensity of rTMS after-effects, and should certainly be taken into account when performing rTMS in both research and clinical practice.

Background At present, the avoidance of drug shortages mainly relies on expert experience. This study aimed to establish an evaluation index system for the risk of drug shortages in medical institutions in China and to apply the system to guide the graded management of drugs in short supply.Methods A two-round Delphi process was conducted to determine the indicators in the index system. The weight value of each indicator was calculated using analytic hierarchy process (AHP) methods. The data of drugs in short supply from January 1 to December 31, 2020 in Hunan province were collected and evaluated using this index system. The evaluation scores, which ranged from 0 to 100, were calculated.Results A three-level index system with four first-level indicators, 11 second-level indicators, and 36 third-level indicators was constructed by the two rounds of the Delphi process. The expert authority coefficient (Cr) of the first and second rounds of consultation were 0.88 and 0.90, respectively. The Kendall’s coefficients of concordance (Kendall’s W) for the two rounds of consultation were 0.44 and 0.50, respectively (P < .05). For the first-level indicators ‘supply stability,’ ‘causes of shortage,’ ‘medicine availability in medical institution’ and ‘pharmaceutical properties,’ the weight values were 0.3253, 0.2489, 0.2398, and 0.1860, respectively. Based on the risk evaluation score, drugs (dosage strength) at high risk of shortage included sodium thiosulfate (0.64 g), posterior pituitary lobe hormones (1 mL:6 IU), protamine sulfate (5 mL:50 mg), thrombin (500 U), urokinase (10 WU), and rotundine sulfate (2 mL:60 mg).Conclusion An indexed system for the risk assessment of drug shortages in China was established to guide the graded response to drug shortages in medical institutions and the implementation of differential management strategies to address these shortages.

Understanding of orchard nutrition status can facilitate the proper management of orchards for higher fruit yield and quality. From 2011 to 2019, the nutrition status of orchards in Hunan Province, a major citrus-producing area in china, were assessed. A total of 361 soil samples, 378 leaf samples and 285 fruit samples of sweet oranges including navel orange (citrus sinensis l. Osbeck ‘newhall’) and common sweet orange (citrus sinensis l. Osbeck ‘bingtangcheng’), and mandarins including satsuma mandarin (citrus unshiu marc. ‘miyagawa’) and ponkan (citrus reticulata blanco ‘xinnu’) were collected. These samples were from112 sweet orange orchards and 140 mandarin orchards. Parameters of soil, leaf and fruit nutrition and fruit quality were analyzed based on these samples. The results revealed that soil acidification occurred in 79.0% of sweet orange orchards (ph 3.56 to 8.12) and 74.7% of mandarin orchards (ph 2.75 to 8.15). Soil organic matter (om) was abundant in both sweet orange orchards (21.3 g/kg on average) and mandarin orchards (19.77 g/kg on average). Nutrient analysis demonstrated deficiencies of nitrogen (n), potassium (k) and boron (b) in soils and leaves of sweet orange and mandarin orchards. Zinc (zn) was abundant in soils but deficient in leaves, suggesting a low zn utilization efficiency in these orchards. Besides, excessive iron (fe), magnesium (mn) and copper (cu) were found in sweet orange and mandarin leaves, which may be associated with low soil ph and fungicides application in this area. The average contents of n, phosphorus (p) and k in the fruit were about 0.80%, 0.11% and 0.51%, respectively, with a ratio close to 1:0.14:0.6. Multiple linear regression (mlr) analysis revealed that leaf npk and molybdenum (mo) significantly affect fruit fresh fruit weight (ffw) and total soluble solids (tss), and leaf p is closely correlated with fruit titratable acid (ta).

Abstract Background Pulmonary hypertension (PH) is a progressive and fatal cardiopulmonary disease characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance and artery pressure. Vascular remodeling is associated with the excessive cell proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). In this paper, the effects of heat shock protein-110 (HSP110) on PH were investigated. Methods The C57BL/6 mice and human PASMCs (HPASMCs) were respectively exposed to hypoxia to establish and simulate PH model in vivo and cell experiment in vitro. To HSP110 knockdown, the hypoxia mice and HPASMCs were infected with adeno-associated virus or adenovirus carring the shRNAs (short hairpin RNAs) for HSP110 (shHSP110). For HSP110 and yes-associated protein (YAP) overexpression, HPASMCs were infected with adenovirus vector carring the cDNA of HSP110 or YAP. The effects of HSP110 on PH development in mice and cell proliferation, migration and autophagy of PASMCs under hypoxia were assessed. Moreover, the regulatory mechanisms among HSP110, YAP and TEA domain transcription factor 4 (TEAD4) were investigated. Results We demonstrated that expression of HSP110 was significantly increased in the pulmonary arteries of mice and HPASMCs under hypoxia. Moreover, knockdown of HSP110 alleviated hypoxia-induced right ventricle systolic pressure, vascular wall thickening, right ventricular hypertrophy, autophagy and proliferation of PASMCs in mice. In addition, knockdown of HSP110 inhibited the increases of proliferation, migration and autophagy of HPASMCs that induced by hypoxia in vitro. Mechanistically, HSP110 knockdown inhibited YAP and transcriptional co-activator with PDZ-binding motif (TAZ) activity and TEAD4 nuclear expression under hypoxia. However, overexpression of HSP110 exhibited the opposite results in HPASMCs. Additionally, overexpression of YAP partially restored the effects of shHSP110 on HPASMCs. The interaction of HSP110 and YAP was verified. Moreover, TEAD4 could promote the transcriptional activity of HSP110 by binding to the HSP110 promoter under hypoxia. Conclusions Our findings suggest that HSP110 might contribute to the development of PH by regulating the proliferation, migration and autophagy of PASMCs through YAP/TAZ-TEAD4 pathway, which may help to understand deeper the pathogenic mechanism in PH development.

Abstract Background The doctor/nurse and police officer population have some common typical characteristics of great professional pressure and night shift and past studies indicated oral mucosa lesions were closely associated with psychological factors and health-risking behaviors, however the prevalence of recurrent aphthous stomatitis (RAS) and the two commonly seen oral potentially malignant disorders of oral submucosal fibrosis (OSF) and oral leukoplakia in doctor/nurse and police officer in the Betel quid chewing city of Mainland China is unknown The cross-sectional study was to determine the prevalence differences of RAS, oral leukoplakia and OSF among doctor/nurse, police officer and non-doctor/nurse and non-police officer population aged 20–59 years. Methods RAS, OSF and oral leukoplakia were examined in doctor/nurse group (male: 659, female: 2439), police officer group (male: 839, female: 262) and non-doctor/nurse and non-police officer group (male: 7576, female: 8129) from 2020-11-01 to 2021-08-31 in Health Management Center, Xiangya Hospital in Changsha city, Hunan province. Results The prevalence rates of RAS, OSF, oral leukoplakia and oral leukoplakia combined with OSF in male and female non-doctor/nurse and non-police officer group are 8.32‰ and 10.83‰, 58.08‰ and 1.23‰, 11.75‰ and 0.25‰, 7.66‰ and 0.12‰ respectively. Compared with the non-doctor/nurse and non-police officer population, prevalence rates of RAS in male (24.27‰) and female (20.50‰) doctor/nurse population were significantly higher. Prevalence rates of OSF (21.24‰) and oral leukoplakia (3.03‰) in male doctor/nurse population were significantly less but prevalence rates of OSF (93.71‰), oral leukoplakia (20.17‰) and oral leukoplakia combined with OSF (15.42‰) for male police officer were significantly greater in comparison with male non-doctor/nurse and non-police officer group. OSF and oral leukoplakia prevalence rates were obvious lower for the female than the counterpart male group, but there were no significant differences of OSF and oral leukoplakia prevalence rates between the female non-doctor/nurse and non-police officer and female doctor/nurse group. Oral leukoplakia was not found in the female police officers. Conclusions Doctor/nurse population have higher prevalence of RAS. Male doctors/nurses have lower prevalence of OSF and oral leukoplakia, while male police officers have higher prevalence of OSF, oral leukoplakia and oral leukoplakia combined with OSF.

Objectives Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection/colonisation has been reported in hospitals. The clinical characteristics of CRKP infection/colonisation in the intensive care unit (ICU) have received little attention. This study aims to investigate the epidemiology and extent of K. pneumoniae (KP) resistance to carbapenems, the sources of CRKP patients and CRKP isolates, and the risk factors for CRKP infection/colonisation.Design Retrospective single-centre study.Data source Clinical data were obtained from electronic medical records.Participants Patients isolated with KP in the ICU from January 2012 to December 2020.Main outcome measures The prevalence and changing trend of CRKP were determined. The extent of KP isolates resistance to carbapenems, the specimen types of KP isolates, and the sources of CRKP patients and CRKP isolates were all examined. The risk factors for CRKP infection/colonisation were also assessed.Results The rate of CRKP in KP isolates raised from 11.11% in 2012 to 48.92% in 2020. CRKP isolates were detected in one site in 266 patients (70.56%). The percentage of CRKP isolates not susceptible to imipenem increased from 42.86% in 2012 to 98.53% in 2020. The percentage of CRKP patients from general wards in our hospital and other hospitals gradually converged in 2020 (47.06% vs 52.94%). CRKP isolates were mainly acquired in our ICU (59.68%). Younger age (p=0.018), previous admission (p=0.018), previous ICU stay (p=0.008), prior use of surgical drainage (p=0.012) and gastric tube (p=0.001), and use of carbapenems (p=0.000), tigecycline (p=0.005), β-lactams/β-lactamase inhibitors (p=0.000), fluoroquinolones (p=0.033), and antifungal drugs (p=0.011) within the prior 3 months were independent risk factors for CRKP infection/colonisation.Conclusions Overall, the rate of KP isolates resistance to carbapenems increased, and the severity of this resistance significantly increased. Intensive and local infection/colonisation control measures are necessary for ICU patients, especially those with risk factors for CRKP infection/colonisation.

BackgroundAnoikis is a programmed cell death process that was proven to be associated with cancer. Uroepithelial carcinoma of the bladder (BLCA) is a malignant disease of the urinary tract and has a strong metastatic potential. To determine whether anoikis-associated genes can predict the prognosis of BLCA accurately, we evaluated the prognostic value of anoikis-associated genes in BLCA and constructed the best model to predict prognosis.MethodThe BLCA transcriptome data were downloaded from TCGA and GEO databases, and genes with differential expression were selected and then clustered using non-negative matrix factorization (NMF). The genes with the most correlation with anoikis were screened and identified using univariate Cox regression, lasso regression, and multivariate Cox regression. The GEO dataset was used for external validation. Nomograms were created based on risk characteristics in combination with clinical variants and the performance of the model was validated with receiver operating characteristic (ROC) curves. The immunotherapeutic significance of this risk score was assessed using the immune phenomenon score (IPS). IC50 values of predictive chemotherapeutic agents were calculated. Finally, we used RT-qPCR to determine the mRNA expression of four genes, CALR, FASN, CASP6, and RAD9A.ResultWe screened 406 tumor samples and 19 normal tissue samples from the TCGA database. Based on anoikis-associated genes, we classified patients into two subtypes (C1 and C2) using NMF method. Subsequently, nine core genes were screened by multiple methods after analysis, which were used to construct risk profiles. The design of nomograms based on risk profiles and clinical variables, ROC, and calibration curves confirmed that the model could well have the ability to predict the survival of BLCA patients at 1, 3, and 5 years. By predicting the IC50 values of chemotherapeutic drugs, it was learned that the high-risk group (HRG) was more susceptible to paclitaxel, gemcitabine, and cisplatin, and the low-risk group (LRG) was more susceptible to veriparib and afatinib.ConclusionIn summary, the risk score of anoikis-associated genes can be applied as a predictor to predict the prognosis of BLCA in clinical practice.

Abstract Pancreatic ductal adenocarcinomas (PDAC) is one of the stiffest malignancies with strong solid stresses. Increasing stiffness could alter cellular behavior and trigger internal signaling pathways and is strongly associated with a poor prognosis in PDAC. So far, there has been no report on of an experimental model that can rapidly construct and stably maintain a stiffness gradient dimension in both vitro and in vivo. In this study, a gelatin methacryloyl (GelMA)‐based hydrogel was designed for in vitro and in vivo PDAC experiments. The GelMA‐based hydrogel has porous, adjustable mechanical properties and excellent in vitro and in vivo biocompatibility. The GelMA‐based in vitro 3D culture method can effectively form a gradient and stable extracellular matrix stiffness, affecting cell morphology, cytoskeleton remodeling, and malignant biological behaviors such as proliferation and metastasis. This model is suitable for in vivo studies with long‐term maintenance of matrix stiffness and no significant toxicity. High matrix stiffness can significantly promote PDAC progression and tumor immunosuppression. This novel adaptive extracellular matrix rigidity tumor model is an excellent candidate for further development as an in vitro and in vivo biomechanical study model of PDAC or other tumors with strong solid stresses.

BackgroundNeuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.MethodsEight databases were systematically searched for literature from inception to October 2022 with the keywords “Functional dyspepsia” and “Neuroimaging.” Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.ResultsA total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.ConclusionThe current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.

IntroductionTraditional acupuncture with reinforcing-reducing manipulation is essential for clinical effectiveness, whereas the underlying central mechanism of it remains unknown. This study with multiple-channels functional near-infrared spectroscopy (fNIRS) aims to explore cerebral-response modes during acupuncture with reinforcing-reducing manipulations.Materials and methodsFunctional near-infrared spectroscopy data were recorded from 35 healthy participants during the lifting-thrusting reinforcing manipulation, the lifting-thrusting reducing manipulation, and the even reinforcing-reducing manipulation with lifting-thrusting. The general linear model based (GLM) cortical activation analysis and the functional connectivity (FC) based on region of interest (ROI) analysis were combined to be conducted.ResultsIn comparison with the baseline, the results showed that three acupuncture with reinforcing-reducing manipulations similarly induced the hemodynamic responses in the bilateral dorsolateral prefrontal cortex (DLPFC) and increased FC between the DLPFC and primary somatosensory cortex (S1). Specifically, the even reinforcing-reducing manipulation deactivated the bilateral DLPFC, the frontopolar area (FP), the right primary motor cortex (M1), the bilateral S1, and the bilateral secondary somatosensory cortex (S2); The reducing manipulation deactivated the bilateral DLPFC; The reinforcing manipulation activated the bilateral DLPFC, the left S1, and the right S2. The between-group comparisons indicated that the reinforcing-reducing manipulation induced opposite hemodynamic responses in the bilateral DLPFC and the left S1 and exhibited different FC patterns in the left DLPFC-S1, within the right DLPFC, and between the left S1 and the left orbitofrontal cortex (OFC).ConclusionThese findings verified the feasibility of fNIRS for investigating cerebral functional activities of acupuncture manipulations, suggesting that the regulations on the DLPFC-S1 cortex may be the potential central mechanism for the realization of acupuncture with reinforcing-reducing manipulation’s effect.Clinical trial registrationClinicalTrials.gov, identifier, ChiCTR2100051893.

Abstract Background Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear. Methods This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes. Discussion We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD. Trial registration Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100049496. Registered on 2 August 2021