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Abstract The tripartite motif (TRIM) 22 and mitogen-activated protein kinase (MAPK) signaling pathways play critical roles in the growth of glioblastoma (GBM). However, the molecular mechanism underlying the relationship between TRIM22 and MAPK signaling remains unclear. Here, we found that TRIM22 binds to exon 2 of the sphingosine kinase 2 (SPHK2) gene. An ERK1/2-driven luciferase reporter construct identified TRIM22 as a potential activator of MAPK signaling. Knockout and overexpression of TRIM22 regulate the inhibition and activation of MAPK signaling through the RING-finger domain. TRIM22 binds to Raf-1, a negative regulator of MAPK signaling, and accelerates its degradation by inducing K48-linked ubiquitination, which is related to the CC and SPRY domains of TRIM22 and the C1D domain of Raf-1. In vitro and in vivo, an SPHK2 inhibitor (K145), an ERK1/2 inhibitor (selumetinib), and the nonphosphorylated mutant Raf-1S338A inhibited GBM growth. In addition, deletion of the RING domain and the nuclear localization sequence of TRIM22 significantly inhibited TRIM22-induced proliferation of GBM cells in vivo and in vitro. In conclusion, our study showed that TRIM22 regulates SPHK2 transcription and activates MAPK signaling through posttranslational modification of two critical regulators of MAPK signaling in GBM cells.

Author(s): X. J. Zhou (corresponding author) [1, 2]; T. Yoshida [1, 3]; A. Lanzara [1, 2]; P. V. Bogdanov [1]; S. A. Kellar [1]; K. M. Shen [1]; W. L. [...]

Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4-14.0; P < 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36-15.75; P < 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31-0.68; P < 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% P = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD., (© 2024. The Author(s).)

Renal fractional flow reserve (rFFR), a hemodynamic evaluation indicator for functional measurement, could be used for the detection of significant renal artery stenosis (RAS). In this study, we evaluated the correlation between color Doppler ultrasonography (CDU), angiography and rFFR in assessing RAS and to validate cut-off points of ultrasound parameters for significant RAS with rFFR<0.8. A total of 77 renal artery lesions from 58 patients with at least unilateral RAS were included into this study. All patients were participated in Fractional Flow Reserve to Determine the Appropriateness of Percutaneous Renal Artery Intervention in Atherosclerosis Renal Hypertension Patients (FAIR)-pilot study (NCT05732077). The rFFR was measured through a pressure wire after renal hyperemia induced by dopamine. Peak systolic velocity (PSV), renal-to-aortic ratio (RAR), resistive index (RI) and side-to-side differences of the intrarenal resistive indices (ΔRI) were obtained by CDU. The rFFR showed good correlation with both CDU and angiography assessment methods. Among CDU parameters, the best correlation was observed in rFFR with PSV (rho = -0.668, P < 0.0001) and RAR (rho = -0.597, P < 0.001). With a rFFR<0.80 as cut-off value for significant RAS, we computed sensitivity, specificity, and area under the curve (AUC) of CDU parameters. The most predicting cut-off points of CDU parameters were calculated as PSV for 2.415 m/s, RAR for 4.495, RI for 0.605 and ΔRI for 0.04, respectively. A PSV > 2.415 m/s provided a sensitivity of 90%, specificity of 75%, accuracy of 81% and AUC of 0.84 for detecting RAS with rFFR<0.8., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Data in terms of how active vitamin D supplementation affects muscle mass and function in end-stage renal disease (ESRD) patients has led to inconclusive results. The main goal of this research was to examine the association of active vitamin D supplementation and risk of the deterioration of muscle mass and function among ESRD patients on peritoneal dialysis (PD). Eligible ESRD patients on PD were prospectively included, and followed up at 3-month intervals in the tertiary care center. Based on the medications during the 12-month follow-up period, the patients were divided into two groups (vitamin D users and non-users). The deterioration of muscle mass and function was identified utilizing the criteria set by the Asian Working Group on Sarcopenia in 2019 (AWGS 2019). Primary outcome was defined as the deterioration of muscle mass and function at the end of the 12-month follow-up. The absolute diffecence and 95% confidence interval (CI) of the incidence of deterioration between vitamin D users and non-users was estimated. The association of vitamin D supplementation with risk of the deterioration of muscle mass and function during the 12-month follow-up period, was examined by employing multivariate logistic regression models. A total of 229 incident PD patients (6 of whom were lost in follow-up) were included. During the entire study period, 54.7% (122/223) of the remaining patients were considered users of oral active vitamin D. The incidence of deterioration in muscle mass and function was 30.5% (68/223) throughout the entire follow-up. In this regard, the rate was 23.0% (28/122) that received oral active vitamin D, while it was 39.6% (40/101) in the group that did not receive it, with an absolute diffecence of -16.6% (95% CI - 4.5, - 28.7) and an estimated relative risk (RR) of 0.784 (95% CI 0.651-0.943). After adjustment for potential confounding factors in logistic regression model, vitamin D users group was still associated with decreased risk of the deterioration of muscle mass and function (OR 0.330, 95% CI 0.159-0.683, P = 0.003). In secondary analysis, the relationship between oral active vitamin D and the deterioration of muscle mass and function remained consistent (≤ 0.25 µg per day vs. non-users; OR 0.300, 95% CI 0.131-0.688, P = 0.004); however, no significant relationship was identified in patients receiving a mean daily dose of > 0.25 µg compared with non-users (OR 0.389, 95% CI 0.146-1.034, P = 0.058). These results indicate that active vitamin D supplementation was significantly associated with a decreased risk of the deterioration of muscle mass and function in incident PD patients with ESRD. However, the amount and type of vitamin D used and the duration of the intervention warrant further randomized controlled trials to confirm the possibility that such medication improves sarcopenia in ESRD patients., (© 2024. The Author(s).)

Growing research has suggested an association between chronic inflammation and Intervertebral disc degeneration (IVDD), but whether there is a causal effect remains unknown. This study adopted two-sample Mendelian randomization (MR) approach to explore the etiological role of chronic inflammation in IVDD risk. Here, summary statistics for C-reactive protein (CRP), interleukin (IL)-1 α , IL-1 β , IL-6 expression and IVDD were obtained from genome-wide association studies (GWAS) of European ancestry. MR analyses were conducted by using inverse variance weighted (IVW), Wald Ratio, weighted median, and MR-Egger method. Sensitivity analyses were conducted to assess the robustness of the results. The MR analyses suggested a lack of causal association of CRP, IL-6 , and IL-1 α levels on IVDD (CRP-IVDD: odds ratio [OR] = 0.97, 95% confidence interval [CI] 0.86-1.09, P = 0.583; IL-6-IVDD: OR = 1.04, 95% CI 0.86-1.27, P = 0.679; IL-1 α -IVDD: OR = 1.09, 95%CI 1.00-1.18, P = 0.058). However, there was a sign of a connection between genetically elevated IL-1 β levels and a decreased IVDD incidence (OR = 0.87, 95%CI 0.77-0.99, P = 0.03). Our findings suggest a connection between IL-1 β levels and the risk of IVDD. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, the specific underlying mechanisms warrant further investigation., (© 2024. The Author(s).)

Monocular depth estimation is an important but challenging task. Although the performance has been improved by adopting various encoder-decoder architectures, the estimated depth maps lack structure details and clear edges due to simple repeated upsampling. To solve this problem, this paper presents the novel LapUNet (Laplacian U-shape networks), in which the encoder adopts ResNeXt101, and the decoder is constructed with the novel DLRU (dynamic Laplacian residual U-shape) module. The DLRU module based on the U-shape structure can supplement high-frequency features by fusing dynamic Laplacian residual into the process of upsampling, and the residual is dynamically learnable due to the addition of convolutional operation. Also, the ASPP (atrous spatial pyramid pooling) module is introduced to capture image context at multiple scales though multiple parallel atrous convolutional layers, and the depth map fusion module is used for combining high and low frequency features from depth maps with different spatial resolution. Experiments demonstrate that the proposed model with moderate model size is superior to other previous competitors on the KITTI and NYU Depth V2 datasets. Furthermore, 3D reconstruction and target ranging by utilizing the estimated depth maps prove the effectiveness of our proposed method., (© 2024. The Author(s).)

Stereotactic radiation therapy (SBRT) has emerged as a promising treatment modality for locally advanced pancreatic cancer. The aim of this study is to assess the dosimetric efficacy of online adaptive radiotherapy (ART) in comparison to image-guided radiation therapy (IGRT) for pancreatic cancer. We conducted a retrospective analysis involving 8 patients diagnosed with locally advanced pancreatic cancer. The gross tumor volume (GTV) delineates the visible extent of the tumor on imaging, while the planning tumor volume (PTV) was generated by expanding 5 mm from the GTV and ensuring a 3 mm distance from the small intestine, duodenum, and stomach simultaneously. Treatment planning was executed using the United Imaging Healthcare Treatment Planning System workstation. The control group underwent evaluation based on daily validated fan-beam CT (FBCT) scans, assessing both the dose delivered to actual organs at risk (OARs) and the target volume. Radiotherapy plans were developed utilizing simulation CT, and conventional radiotherapy with daily image-guided radiation therapy (IGRT) was administered using FBCT-Linac. Conversely, patients in the study group received daily validated FBCT-guided adaptive radiotherapy plans, with a focus on mean dose assessment of both the target volume and OARs. Subsequently, we compared the average outcomes of each treatment fraction between IGRT and online adaptive radiotherapy (ART). Comparison between ART and IGRT treatment plans revealed significant differences in various dosimetric parameters: For PTV: V98%: ART (96.28%) vs IGRT (89.73%), p = 0.000, V95%: ART (96.28%) vs IGRT (89.73%), p = 0.031, V90%: ART (98.58%) vs IGRT (93.65%), p = 0.000, Dmean: ART (4912.91) vs IGRT (4804.11), p = 0.000. For GTV: V100%: ART (97.96%) vs IGRT (94.85%), p = 0.314, V98%: ART (100.00%) vs IGRT (96.83%), p = 0.000, V90%: ART (100.00%) vs IGRT (97.75%), p = 0.000, Dmean: ART (4972.17) vs IGRT (4907.23), p = 0.000. For the duodenum: D0.5cc: ART (2883.92) vs IGRT (3359.35), p = 0.000, D1cc: ART (2726.32) vs IGRT (3128.66), p = 0.001, D5cc: ART (2051.96) vs IGRT (2273.93), p = 0.015, D10cc: ART (1650.73) vs IGRT (1731.74), p = 0.211. For the small bowel: D0.5cc: ART (3022.3) vs IGRT (3142.64), p = 0.037. D5cc: ART (2151.09) vs IGRT (2389.15), p = 0.043, D10cc: ART (1775.20) vs IGRT (1942.00), p = 0.079. For the stomach: D0.5cc: ART (3353.92) vs IGRT (4117.85), p = 0.000, D5cc: ART (2860.20) vs IGRT (3235.41), p = 0.000, D10cc: ART (2553.72) vs IGRT (2836.73), p = 0.000. For the Dmean of the left kidney and right kidney: Left kidney: ART (248.28) vs IGRT (239.65), p = 0.100. Right kidney: ART (314.55) vs IGRT (307.17), p = 0.345. These results suggest significant improvements in PTV coverage and sparing of OARs with ART compared to IGRT, indicating the potential of ART in optimizing treatment outcomes for pancreatic cancer patients. Compared to conventional IGRT-guided SBRT programs, ART-based SBRT for pancreatic cancer not only enhances the dose distribution to the target volume but also mitigates the radiation exposure to critical organs-at-risk (OARs) such as the duodenum, small intestine, and stomach. This approach may offer a more favorable safety profile while concurrently enhancing treatment efficacy., (© 2024. The Author(s).)

Diabetic ulcers (DUs) usually suffer from severe infections, persistent inflammation, and excessive oxidative stress during the healing process, which led to the microenvironmental alternation and severely impede DU healing, resulting in a delayed wound healing. Therefore, it is particularly important to develop a medical dressing that can address these problems simultaneously. To this end, self-healing composite hydrogels were prepared in this study utilizing Bletilla striata polysaccharide (BSP) and Berberine (BER) with borax via borate ester bond. The chemical and mechanical properties of the BSP/BER hydrogels were characterized, and their wound healing performance was investigated in vivo and in vitro. The results showed that the BSP/BER hydrogel significantly accelerated wound healing in DU mice with the healing rate of 94.90 ± 1.81% on the 14th day by using BSP/BER5, and this outstanding performance was achieved by the multi-targeted biological functions of antibacterial, anti-inflammatory and antioxidant, which provided favorable microenvironment for orderly recovery of the wound. Aside from exhibiting the antibacterial rate of over 90% against both Escherichia coli and Staphylococcus aureus, the BSP/BER5 hydrogel could significantly reduce NO levels 4.544 ± 0.32 µmol/L to exert its anti-inflammatory effects. Additionally, it demonstrated a hemolysis rate and promotes cell migration capabilities at (34.92 ± 1.66%). With the above features, the developed BSP/BER hydrogel in this study could be the potential dressing for clinical treatment of DU wound., (© 2024. The Author(s).)

Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market., (© 2024. The Author(s).)

The first-order second-moment checking point method was introduced to judge the instability probability and evaluate the stability of the TCURM. The frequency-response stability calculation and the reliability results were compared, and a frequency-response stability and reliability analysis method was proposed. Taking the Zengziyan W12 # unstable rock mass in Nanchuan, Chongqing, China, as an example, the calculation shows that the dynamic indexes and geological indexes decrease as the stiffness of the deterioration area decreases. According to the statistical data of the laboratory test and the field investigation, reliability theory is used to evaluate the stability of the TCURM, and the failure probabilities are 80.3% and 96.27% under natural and saturated conditions, which correspond to states of poor stability and instability, respectively. The reliability evaluation results are consistent with the conclusion of the frequency-response stability analysis. The new method can provide a theoretical basis for developing the dynamic monitoring and early warning indicators of the TCURM and disaster prevention and mitigation in mountainous areas., (© 2024. The Author(s).)

The association between insulin resistance (IR) and the risk of all-cause mortality and cardiovascular mortality among osteoarthritis (OA) patients remains uncertain. This study aims to clarify the correlation between a novel marker of IR, the triglyceride glucose-body mass index (TyG-BMI), and the risk of all-cause mortality and cardiovascular mortality in OA patients. Data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020 were analyzed. Multivariable Cox proportional hazards regression analysis and restricted cubic spline plots were employed to elucidate the association between the TyG-BMI index and the risk of all-cause mortality or cardiovascular mortality in OA patients. Additionally, subgroup analysis was conducted to explore potential interactions and identify populations at elevated risk of mortality. The study cohort comprised 4097 OA patients who were followed up for a period of 20 years, during which 1197 cases of all-cause mortality and 329 cases of mortality attributed to cardiovascular disease were recorded. Our findings revealed a U-shaped nonlinear relationship between the TyG-BMI index and the risk of all-cause mortality or cardiovascular mortality in OA patients, with the lowest mortality risk thresholds identified at 282 and 270, respectively. Moreover, surpassing these thresholds was associated with a 3% increase in the risk of all-cause mortality and a 5% increase in the risk of cardiovascular mortality for every 10-unit increment in TyG-BMI level. Among American OA patients, a U-shaped nonlinear relationship exists between the TyG-BMI index and the risk of all-cause mortality or cardiovascular mortality. These findings underscore the significant role of IR in the progression of OA., (© 2024. The Author(s).)

The linear ubiquitin chain assembly complex (LUBAC) mediates the linear ubiquitination of various proteins and is involved in NF-κB signaling and immune regulation. However, the function and mechanism of linear ubiquitination in regulating oncogenic signaling and tumor growth have remained poorly understood. Herein, we identified Gli proteins, key transcription factors in the Hedgehog (Hh) signaling pathway, as novel substrates of LUBAC. Linear ubiquitination stabilizes Gli proteins, leading to the noncanonical activation of Hh signaling in CRC cells. Furthermore, LUBAC facilitates tumor growth in CRC cells. Additionally, elevated expression of LUBAC components in CRC tissues was observed, and higher expression levels of these components correlated with poor prognosis in CRC patients. Interestingly, inhibition of LUBAC using either a small molecule agonist or RNA silencing specifically suppressed cell growth in CRC cells but had no effect on normal intestinal cells. Taken together, aberrant expression of LUBAC components activates Hh signaling noncanonically by mediating linear ubiquitination, promoting tumor growth in CRC, demonstrating the novel function of linear ubiquitination in regulating the protein stability of its substrates and highlighting the potential of targeting LUBAC as a therapeutic strategy in CRC., (© 2024. The Author(s).)

Data regarding the association of sarcopenia with hospitalization has led to inconclusive results in patients undergoing dialysis. The main goal of this research was to investigate the association between sarcopenia and hospitalization in Chinese individuals on continuous ambulatory peritoneal dialysis (CAPD). Eligible patients on CAPD were prospectively included, and followed up for 48 weeks in our PD center. Sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia in 2019 (AWGS 2019). Participants were categorized into sarcopenia (non-severe sarcopenia + severe sarcopenia) and non-sarcopenia groups. The primary outcome was all-cause hospitalization during the 48-week follow-up period. Association of sarcopenia with all-cause hospitalization was examined by employing multivariate logistic regression models. The risk of cumulative incidence of hospitalization in the 48-week follow-up was estimated using relative risk (RR and 95% CI). The cumulative hospitalization time and frequency at the end of 48-week follow-up were described as categorical variables, and compared by χ 2 test or fisher's exact test as appropriate. Subgroup and sensitivity analyses were also conducted to examine whether the potential association between sarcopenia and hospitalization was modified. A total of 220 patients on CAPD (5 of whom were lost in follow-up) were included. Prevalences of total sarcopenia and severe sarcopenia were 54.1% (119/220) and 28.2% (62/220) according to AWGS 2019, respectively. A total of 113 (51.4%) participants were hospitalized during the 48-week follow-up period, of which, the sarcopenia group was 65.5% (78/119) and the non-sarcopenia group was 34.7% (35/101), with an estimated RR of 1.90 (95%CI 1.43-2.52). The cumulative hospitalization time and frequency between sarcopenia and non-sarcopenia groups were significantly different (both P < 0.001). Participants with sarcopenia (OR = 3.21, 95%CI 1.75-5.87, P < 0.001), non-severe sarcopenia (OR = 2.84, 95%CI 1.39-5.82, P = 0.004), and severe sarcopenia (OR = 3.66, 95%CI 1.68-8.00, P = 0.001) demonstrated a significant association with all-cause hospitalization compared to individuals in non-sarcopenia group in the 48-week follow-up. Moreover, participants in subgroups (male or female; < 60 or ≥ 60 years) diagnosed with sarcopenia, as per AWGS 2019, were at considerably high risk for hospitalization compared to those with non-sarcopenia. In sensitivity analyses, excluding participants lost in the follow-up, the relationships between sarcopenia and hospitalization (sarcopenia vs. non-sarcopenia; severe sarcopenia/non-severe sarcopenia vs. non-sarcopenia) were consistent. This research involving Chinese patients on CAPD demonstrated a significant association between sarcopenia and incident hospitalization, thereby emphasizing the importance of monitoring sarcopenia health in this population., (© 2024. The Author(s).)

Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P < 0.001) and between IC with membrane PD-L1 positivity and CD8+ T cells (0.44; P < 0.001). There is high prevalence of PD-L1 expression in Chinese patients with MIUBC, suggesting that a sizable subset of patients could benefit from immunotherapy. The correlation of PD-L1 expression with tumor biomarkers provide clues for mechanisms underlying the effects of biomarkers for predicting efficacy., (© 2024. The Author(s).)

As an important pest on winter wheat, Rhopalosiphum padi (L.) causes damage to the wheat yield by sucking plant nutrients, transmitting plant viruses and producing mildew. R. padi has been reported to develop resistance to pyrethroids and neonicotinoids. To explore potential alternative approaches for R. padi control, the activity of 10 botanical insecticides was evaluated. Results suggested that the toxicity of rotenone and pyrethrins to R. padi were the highest and near to the commonly used chemical insecticides. When exposed to the low-lethal concentrations (LC 10 , LC 30 ) of rotenone or pyrethrins for 24 h, the lifespan and fecundity of adults in F0 generation decreased significantly compared to control. The negative effect could also be observed in the F1 generation, including the decreased average offspring, longevity of adult, and prolonged nymph period. The population parameters in F1 generation of R. padi were also inhibited by exposing to the low-lethal concentrations of rotenone or pyrethrins, including the decreased net reproductive rate, intrinsic rate of natural increase, finite rate of population increase, and gross reproduction rate. Co-toxocity factor results showed that mixtures of rotenone and thiamethoxam, pyrethrins and thiamethoxam showed synergistic effect. Our work suggested that rotenone and pyrethrins showed negative effect on the population growth under low-lethal concentrations. They are suitable for R. padi control as foliar spraying without causing population resurgence., (© 2024. The Author(s).)

This paper presents experimental and dynamic modeling research on the rubber bushings of the rear sub-frame. The Particle Swarm Optimization algorithm was utilized to optimize a Backpropagation (BP) neural network, which was separately trained and tested across two frequency ranges: 1-40 Hz and 41-50 Hz, using wideband frequency sweep dynamic stiffness test data. The testing errors at amplitudes of 0.2 mm, 0.3 mm, and 0.5 mm were found to be 1.03%, 3.05%, and 1.96%, respectively. Subsequently, the trained neural network was employed to predict data within the frequency range of 51-70 Hz. To incorporate the predicted data into simulation software, a dynamic model of the rubber bushing was established, encompassing elastic, friction, and viscoelastic elements. Additionally, a novel model, integrating high-order fractional derivatives, was proposed based on the frequency-dependent model for the viscoelastic element. An enhanced Particle Swarm Optimization algorithm was introduced to identify the model's parameters using the predicted data. In comparison to the frequency-dependent model, the new model exhibited lower fitting errors at various amplitudes, with reductions of 3.84%, 3.61%, and 5.49%, respectively. This research establishes a solid foundation for subsequent vehicle dynamic modeling and simulation., (© 2024. The Author(s).)

Persistent environmental colored compounds, resistant to biodegradation, accumulate and harm eco-systems. Developing effective methods to break down these pollutants is crucial. This study introduces Ag-MIL-101 (Ag-MIL-101) as a composite and reusable catalyst that efficiently degrades specific colored organic pollutants (COPs) like Methylene blue (MB), 4-Nitrophenol (4-NP), and 4-Nitroaniline (4-NA) using sodium borohydride at room temperature. The MIL-101 was synthesized using Terephthalic acid (TPA) derived from the degradation of Polyethylene Terephthalate (PET) plastic waste, with the assistance of zinc chloride. To further investigation, the kinetics of degradation reaction was studied under optimized conditions in the presence of Ag-MIL-101 as catalyst. Our results demonstrated the remarkable efficiency of the degradation process, with over 93% degradation achieved within just 8 min. The catalyst was characterized using FTIR, XRD, FESEM, and TEM. In this study, the average particle size of Ag-MIL-101 was determined using SEM and XRD analysis. These methods allow us to accurately and precisely determine the particle size. We determined the reaction rate constants for the degradation of each COP using a pseudo first-order kinetic equation, with values of 0.585, 0.597 and 0.302 min -1 for MB, 4-NP, and 4-NA, respectively. We also evaluated the recyclability of the catalyst and found that it could be reused for up to three cycles with only a slight decrease in efficiency (10-15%). Overall, our findings highlight the promising application of Ag-MIL-101 as an effective catalyst for the degradation of COPs, emphasizing the importance of optimizing reaction conditions to achieve enhanced efficiency., (© 2024. The Author(s).)

DNA double-strand break (DSB) sites that prevent the disjunction of broken DNA ends are formed through poly (ADP-ribose) (PAR) polymerase 1 (PARP1)-DNA co-condensation. The co-condensates apply mechanical forces to hold the DNA ends together and generate enzymatic activity for the synthesis of PAR. PARylation can promote the release of PARP1 from DNA ends and recruit various proteins, such as Fused in sarcoma (FUS) proteins, thereby stabilizing broken DNA ends and preventing their separation., (© 2024. The Author(s).)

CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive loss of motor neurons in the spinal cord, cerebral cortex and brain stem. ALS is characterized by gradual muscle atrophy and dyskinesia. The limited knowledge on the pathology of ALS has impeded the development of therapeutics for the disease. Previous studies have shown that autophagy and astrocyte-mediated neuroinflammation are involved in the pathogenesis of ALS, while 5HTR 2A participates in the early stage of astrocyte activation, and 5HTR 2A antagonism may suppress astrocyte activation. In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR 2A antagonist, in human SOD1 G93A (hSOD1 G93A ) ALS model mice, and elucidated the underlying mechanisms. HSOD1 G93A mice were administered DLT (20 mg·kg -1 ·d -1 , i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR 2A ) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. We showed that DLT administration significantly delayed ALS symptom onset time, prolonged lifespan and ameliorated movement disorders, gastrocnemius injury and spinal motor neuronal loss in hSOD1 G93A mice. Spinal cord-specific knockdown of 5HTR 2A by intrathecal injection of adeno-associated virus9 (AAV9)-si-5Htr2a also ameliorated ALS pathology in hSOD1 G93A mice, and occluded the therapeutic effects of DLT administration. Furthermore, we demonstrated that DLT administration promoted autophagy to reduce mutant hSOD1 levels through 5HTR 2A /cAMP/AMPK pathway, suppressed oxidative stress through 5HTR 2A /cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocyte neuroinflammation through 5HTR 2A /cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1 G93A mice. In summary, 5HTR 2A antagonism shows promise as a therapeutic strategy for ALS, highlighting the potential of DLT in the treatment of the disease. DLT as a 5HTR 2A antagonist effectively promoted autophagy to reduce mutant hSOD1 level through 5HTR 2A /cAMP/AMPK pathway, suppressed oxidative stress through 5HTR 2A /cAMP/AMPK/Nrf2-HO-1/NQO-1 pathway, and inhibited astrocytic neuroinflammation through 5HTR 2A /cAMP/AMPK/NF-κB/NLRP3 pathway in the spinal cord of hSOD1 G93A mice., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Titanium alloy with high corrosion resistance, high strength-to-density ratio, and excellent biocompatibility has a wide range of applications in the field of biomedical implants. Polishing experiments of titanium alloy with a small size and complex shapes were investigated using an ultrasonic assisted magnetorheological finishing (UMRF) device excited by a three-pole magnetic field generator. The models of the normal force and the shear force were first proposed based on the Preston equation to analyze the mechanism of material removal in the UMRF process. Subsequently, the single-factor experiments using titanium alloy nuts (M3) and the MR polishing fluid with silicon carbide abrasives were carried out. Furthermore, to improve the surface roughness and the change rate of surface roughness of nuts, orthogonal tests with a standard L 9 (3 4 ) orthogonal array were designed and performed based on the optimized process parameters obtained from the single-factor experiment. The results indicated the effect on surface roughness and change rate of surface roughness as applied current > roller speed > ultrasonic amplitude > spindle speed and applied current > roller speed > spindle speed > ultrasonic amplitude, respectively. Moreover, the surface roughness was improved from an initial 1.247 μm to a final 0.104 μm after the polishing for 80 min under these optimal process parameters., (© 2024. The Author(s).)

Arrhythmias are irregular heartbeat rhythms caused by various conditions. Automated ECG signal classification aids in diagnosing and predicting arrhythmias. Current studies mostly focus on 1D ECG signals, overlooking the fusion of multiple ECG modalities for enhanced analysis. We converted ECG signals into modal images using RP, GAF, and MTF, inputting them into our classification model. To optimize detail retention, we introduced a CNN-based model with FCA for multimodal ECG tasks. Achieving 99.6% accuracy on the MIT-BIH arrhythmia database for five arrhythmias, our method outperforms prior models. Experimental results confirm its reliability for ECG classification tasks., (© 2024. The Author(s).)

This study assesses the effect of stone content on the stability of soil-rock mixture slopes and the dynamics of ensuing large displacement landslides using a material point strength reduction method. This method evaluates structural stability by incrementally decreasing material strength parameters. The author created four distinct soil-rock mixture slope models with varying stone contents yet consistent stone size distributions through digital image processing. The initial conditions were established by linearly ramping up the gravity in fixed proportionate steps until the full value was attained. Stability was monitored until a sudden shift in displacement marked the onset of instability. Upon destabilization, the author employed the material point method to reconstruct the landslide dynamics. Due to the substantial computational requirements, the author developed a high-performance GPU-based framework for the material point method, prioritizing the parallelization of the MPM algorithm and the optimization of data structures and memory allocation to exploit GPU parallel processing capabilities. Our results demonstrate a clear positive correlation between stone content and slope stability; increasing stone content from 10 to 20% improved the safety factor from 1.9 to 2.4, and further increments to 30% and 40% ensured comprehensive stability. This study not only sheds light on slope stability and the mechanics of landslides but also underscores the effectiveness of GPU-accelerated methods in handling complex geotechnical simulations., (© 2024. The Author(s).)

Renal replacement therapy (RRT) is a crucial treatment for sepsis-associated acute kidney injury (S-AKI), but it is uncertain which S-AKI patients should receive immediate RRT. Identifying the characteristics of patients who may benefit the most from RRT is an important task. This retrospective study utilized a public database and enrolled S-AKI patients, who were divided into RRT and non-RRT groups. Uplift modeling was used to estimate the individual treatment effect (ITE) of RRT. The validity of different models was compared using a qini curve. After labeling the patients in the validation cohort, we characterized the patients who would benefit the most from RRT and created a nomogram. A total of 8289 patients were assessed, among whom 591 received RRT, and 7698 did not receive RRT. The RRT group had a higher severity of illness than the non-RRT group, with a Sequential Organ Failure Assessment (SOFA) score of 9 (IQR 6,11) vs. 5 (IQR 3,7). The 28-day mortality rate was higher in the RRT group than the non-RRT group (34.83% vs. 14.61%, p < 0.0001). Propensity score matching (PSM) was used to balance baseline characteristics, 458 RRT patients and an equal number of non-RRT patients were enrolled for further research. After PSM, 28-day mortality of RRT and non-RRT groups were 32.3% vs. 39.3%, P = 0.033. Using uplift modeling, we found that urine output, fluid input, mean blood pressure, body temperature, and lactate were the top 5 factors that had the most influence on RRT effect. The area under the uplift curve (AUUC) of the class transformation model was 0.068, the AUUC of SOFA was 0.018, and the AUUC of Kdigo-stage was 0.050. The class transformation model was more efficient in predicting individual treatment effect. A logistic regression model was developed, and a nomogram was drawn to predict whether an S-AKI patient can benefit from RRT. Six factors were taken into account (urine output, creatinine, lactate, white blood cell count, glucose, respiratory rate). Uplift modeling can better predict the ITE of RRT on S-AKI patients than conventional score systems such as Kdigo and SOFA. We also found that white blood cell count is related to the benefits of RRT, suggesting that changes in inflammation levels may be associated with the effects of RRT on S-AKI patients., (© 2024. The Author(s).)

Understanding user behavior via IP addresses is a crucial measure towards numerous pragmatic IP-based applications, including online content delivery, fraud prevention, marketing intelligence, and others. While profiling IP addresses through methods like IP geolocation and anomaly detection has been thoroughly studied, the function of an IP address-e.g., whether it pertains to a private enterprise network or a home broadband-remains underexplored. In this work, we initiate the first attempt to address the IP usage scenario classification problem. We collect data consisting of IP addresses from four large-scale regions. A novel continuous neural tree-based ensemble model is proposed to learn IP assignment rules and complex feature interactions. We conduct extensive experiments to evaluate our model in terms of classification accuracy and generalizability. Our results demonstrate that the proposed model is capable of efficiently uncovering significant higher-order feature interactions that enhance IP usage scenario classification, while also possessing the ability to generalize from the source region to the target one., (© 2024. The Author(s).)

Food consumption contributes to the degradation of air quality in regions where food is produced, creating a contrast between the health burden caused by a specific population through its food consumption and that faced by this same population as a consequence of food production activities. Here we explore this inequality within China's food system by linking air-pollution-related health burden from production to consumption, at high levels of spatial and sectorial granularity. We find that low-income groups bear a 70% higher air-pollution-related health burden from food production than from food consumption, while high-income groups benefit from a 29% lower health burden relative to their food consumption. This discrepancy largely stems from a concentration of low-income residents in food production areas, exposed to higher emissions from agriculture. Comprehensive interventions targeting both production and consumption sides can effectively reduce health damages and concurrently mitigate associated inequalities, while singular interventions exhibit limited efficacy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Vitamin C played pleiotropic roles in critical illness and vitamin C insufficiency was predictive of the development of multiple organ failure. Currently, the prevalence of vitamin C insufficiency in Chinese critically ill patients is rarely determined and there are no established bedside tools to predict hypovitaminosis C. To develop a nomogram to identify patients with high risk of hypovitaminosis C, we performed a bi-center prospective cohort study at two ICUs of the first and sixth medical center in PLA General Hospital, Beijing, China from May 6th to July 31st, 2021 We identified 322 eligible patients. 62.4% patients were hypovitaminosis C. 7 features, including source of infection, the level of serum albumin, age, male gender, sepsis, vascular disease, and wasting of vitamin C by the kidney, were selected using LASSO algorithm and therefore included in the nomogram. In the testing set, our model showed moderate discrimination ability with areas under the curve of 0.75 [0.64-0.84]. Variable importance evaluated by SHAP value highlighted two novel important predictors, i.e., abdominal infection and the level of serum albumin. In conclusion, we first reported a high burden of vitamin C insufficiency in Chinese adult patient in the ICU. We also constructed a prediction model to timely identify patients with high risk of hypovitaminosis C, which allows the clinicians to choose appropriate candidates for Vitamin C repletion in clinical practice or clinical trials., (© 2024. The Author(s).)

Returning organic nutrient sources (for example, straw and manure) to rice fields is inevitable for coupling crop-livestock production. However, an accurate estimate of net carbon (C) emissions and strategies to mitigate the abundant methane (CH 4 ) emission from rice fields supplied with organic sources remain unclear. Here, using machine learning and a global dataset, we scaled the field findings up to worldwide rice fields to reconcile rice yields and net C emissions. An optimal organic nitrogen (N) management was developed considering total N input, type of organic N source and organic N proportion. A combination of optimal organic N management with intermittent flooding achieved a 21% reduction in net global warming potential and a 9% rise in global rice production compared with the business-as-usual scenario. Our study provides a solution for recycling organic N sources towards a more productive, carbon-neutral and sustainable rice-livestock production system on a global scale., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Liver cancer, a chronic non-communicable disease, represents a serious public health problem. Long-term trends in the burden of liver cancer disease are heterogeneous across regions. Incidence and mortality of liver cancer, based on the Global Burden of Disease, were collected from the Chinese Centre for Disease Control and Prevention. Age-period-cohort model was utilized to reveal the secular trends and estimate the age, period and cohort effects on primary liver cancer due to specific etiologies. Both the age-standardized incidence and mortality rate of liver cancer in Hubei province were on the rise, although there were discrepancies between gender groups. From age-period-cohort analysis, both incidence and mortality of liver cancer due to Hepatitis B virus were the highest in all age groups. The incidence of all liver cancer groups increased with time period in males, while this upward trend was observed in females only in liver cancer due to alcohol use group. Cohort effects indicated the disease burden of liver cancer decreased with birth cohorts. Local drifts showed that the incidence of liver cancer due to specific etiologies was increasing in the age group of males between 40 and 75 years old. The impact of an aging population will continue in Hubei Province. the disease burden of liver cancer will continue to increase, and personalized prevention policies must be adopted to address these changes., (© 2024. The Author(s).)

Wireless traffic prediction is vital for intelligent cellular network operations, such as load-aware resource management and predictive control. Traditional centralized training addresses this but poses issues like excessive data transmission, disregarding delays, and user privacy. Traditional federated learning methods can meet the requirement of jointly training models while protecting the privacy of all parties' data. However, challenges arise when the local data features among participating parties exhibit inconsistency, making the training process difficult to sustain. Our study introduces an innovative framework for wireless traffic prediction based on split learning (SL) and vertical federated learning. Multiple edge clients collaboratively train high-quality prediction models by utilizing diverse traffic data while maintaining the confidentiality of raw data locally. Each participant individually trains dimension-specific prediction models with their respective data, and the outcomes are aggregated through collaboration. A partially global model is formed and shared among clients to address statistical heterogeneity in distributed machine learning. Extensive experiments on real-world datasets demonstrate our method's superiority over current approaches, showcasing its potential for network traffic prediction and accurate forecasting., (© 2024. The Author(s).)

Soil roadbed along the river suffers from water erosion at the bottom and collapse at the top under flood scouring, which leads to the suspension of upper pavement slab. In order to ensure the safety of soil roadbed along the river, this study explored the development mechanism of soil roadbed damage by flood in actual cases, and proposed the evolution process of instability under roadbed scouring. The stability law of roadbed along the river under flood scouring was analyzed, and the stability safety factor was corrected to analyze the sensitivity of water depth, flow rate, river bending angle and stability safety factor K in working conditions. The sensitivity of width and height of soil roadbed after flood scouring to water depth, flow velocity, river bending angle was investigated. Moreover, numerical simulation was carried out to determine the displacement nephogram and maximum shear stress nephogram of soil roadbed along the river under the conditions of road surface and roadbed load, vehicle loading or constant change of water depth. By comparing the above theories and engineering cases, the water damage mechanism of soil roadbed along the river was further verified., (© 2024. The Author(s).)

Approximately 36% of patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from severe visual and motor disability (blindness or light perception or unable to walk) with abnormalities of whole-brain functional networks. However, it remains unclear how whole-brain functional networks and their dynamic properties are related to clinical disability in patients with NMOSD. Our study recruited 30 NMOSD patients (37.70 ± 11.99 years) and 45 healthy controls (HC, 41.84 ± 11.23 years). The independent component analysis, sliding-window approach and graph theory analysis were used to explore the static strength, time-varying and topological properties of large-scale functional networks and their associations with disability in NMOSD. Compared to HC, NMOSD patients showed significant alterations in dynamic networks rather than static networks. Specifically, NMOSD patients showed increased occurrence (fractional occupancy; P < 0.001) and more dwell times of the low-connectivity state (P < 0.001) with fewer transitions (P = 0.028) between states than HC, and higher fractional occupancy, increased dwell times of the low-connectivity state and lower transitions were related to more severe disability. Moreover, NMOSD patients exhibited altered small-worldness, decreased degree centrality and reduced clustering coefficients of hub nodes in dynamic networks, related to clinical disability. NMOSD patients exhibited higher occurrence and more dwell time in low-connectivity states, along with fewer transitions between states and decreased topological organizations, revealing the disrupted communication and coordination among brain networks over time. Our findings could provide new perspective to help us better understand the neuropathological mechanism of the clinical disability in NMOSD., (© 2024. The Author(s).)

Bladder cancer (BLCA) is one of the most widespread malignancies worldwide, and displays significant tumor heterogeneity. Understanding the molecular mechanisms exploitable for treating aggressive BLCA represents a crucial objective. Despite the involvement of DLGAP5 in tumors, its precise molecular role in BLCA remains unclear. BLCA tissues exhibit a substantial increase in DLGAP5 expression compared with normal bladder tissues. This heightened DLGAP5 expression positively correlated with the tumor's clinical stage and significantly affected prognosis negatively. Additionally, experiments conducted in vitro and in vivo revealed that alterations in DLGAP5 expression notably influence cell proliferation and migration. Mechanistically, the findings demonstrated that DLGAP5 was a direct binding partner of E2F1 and that DLGAP5 stabilized E2F1 by preventing the ubiquitination of E2F1 through USP11. Furthermore, as a pivotal transcription factor, E2F1 fosters the transcription of DLGAP5, establishing a positive feedback loop between DLGAP5 and E2F1 that accelerates BLCA development. In summary, this study identified DLGAP5 as an oncogene in BLCA. Our research unveils a novel oncogenic mechanism in BLCA and offers a potential target for both diagnosing and treating BLCA., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Vesicular monoamine transporter 2 (VMAT2) accumulates monoamines in presynaptic vesicles for storage and exocytotic release, and has a vital role in monoaminergic neurotransmission 1-3 . Dysfunction of monoaminergic systems causes many neurological and psychiatric disorders, including Parkinson's disease, hyperkinetic movement disorders and depression 4-6 . Suppressing VMAT2 with reserpine and tetrabenazine alleviates symptoms of hypertension and Huntington's disease 7,8 , respectively. Here we describe cryo-electron microscopy structures of human VMAT2 complexed with serotonin and three clinical drugs at 3.5-2.8 Å, demonstrating the structural basis for transport and inhibition. Reserpine and ketanserin occupy the substrate-binding pocket and lock VMAT2 in cytoplasm-facing and lumen-facing states, respectively, whereas tetrabenazine binds in a VMAT2-specific pocket and traps VMAT2 in an occluded state. The structures in three distinct states also reveal the structural basis of the VMAT2 transport cycle. Our study establishes a structural foundation for the mechanistic understanding of substrate recognition, transport, drug inhibition and pharmacology of VMAT2 while shedding light on the rational design of potential therapeutic agents., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

TRAF-interacting protein (TRAIP), an E3 ligase containing a RING domain, has emerged as a significant contributor to maintaining genome integrity and is closely associated with cancer. Our study reveals that TRAIP shows reduced expression in bladder cancer (BLCA), which correlates with an unfavorable prognosis. In vitro and in vivo, TRAIP inhibits proliferation and migration of BLCA cells. MYC has been identified as a novel target for TRAIP, wherein direct interaction promotes K48-linked polyubiquitination at neighboring K428 and K430 residues, ultimately resulting in proteasome-dependent degradation and downregulation of MYC transcriptional activity. This mechanism effectively impedes the progression of BLCA. Restoring MYC expression reverses suppressed proliferation and migration of BLCA cells induced by TRAIP. Moreover, our results suggest that MYC may bind to the transcriptional start region of TRAIP, thereby exerting regulatory control over TRAIP transcription. Consequently, this interaction establishes a negative feedback loop that regulates MYC expression, preventing excessive levels. Taken together, this study reveals a mechanism that TRAIP inhibits proliferation and migration of BLCA by promoting ubiquitin-mediated degradation of MYC., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This study aimed to investigate the impact of tactical formations on the physical and technical performance of professional football players in the Chinese Super League (CSL). A sample of 800 games from the 2015-2021 CSL was analyzed, and players' physical (total distance covered, distance covered while ball in play, number of sprints, sprint distance, and high/middle/low-speed running) and technical (gain/loss of possession, ball retention percentage, challenges, challenge success percentage, passes, and pass success percentage) performance was assessed across six team formations: 3-5-2 (n = 137), 4-3-3 (n = 77), 4-2-3-1 (n = 391), 4-4-2 (n = 257), 3-4-3 (n = 41), and 4-1-4-1 (n = 107). Linear mixed models were used to assess variations in performance indicators across positions and formations. The results demonstrated that central defenders traveled significantly more total and low-speed running distances in the 3-5-2 formation than in the 4-2-3-1 formation (ES range: 0.33-0.34, p < 0.01). Fullbacks in the 3-5-2 formation demonstrated more high-speed running than did those in the 4-4-2 formation (ES = 0.27, p = 0.04). The central midfielders exhibited significantly more sprints and longer sprint distances in the 4-2-3-1 formation than in the 4-4-2 formation (ES range: 0.2-0.24, p < 0.01). Regarding technical performance, central defenders displayed significantly greater ball retention percentages, passes, and pass success rates in the 3-4-3 than in the 3-5-2 formations (ES range: 0.58-0.65, p < 0.01). Moreover, fullbacks and central midfielders executed markedly more passes with superior pass success rates in 4-back formations than in 3-5-2 formations (ES range: 0.2-0.53, p < 0.01). These findings can help coaches and academic staff understand the physical and technical requirements of various positions in various tactical formations, thus optimizing the training process., (© 2024. The Author(s).)

In this study, Penaeus monodon were gave basic feed supplemented with three levels of Enterococcus faecium. Then, the expression of non-specific immunity-related genes, and the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), malondialdehyde (MDA), acid phosphatase (ACP), alkaline phosphatase (AKP), phenol oxidase (PO) were evaluated. Meanwhile, the disease resistance test and intestinal flora determination were conducted. The results showed that the MDA levels of 2% and 5% E. faecium groups were significantly lower than that of the control group (P < 0.05). While the SOD and T-AOC and ACP and AKP of experimental groups were significantly higher (P < 0.05), the PO of experimental groups were significantly lower than that of the control group (P < 0.05). In addition, the expressions of immunity-related genes (tlr22, dorsal, lysozyme, crustin, imd, and relish) in the 2% and 5% E. faecalis groups were significantly greater than those in the control group (P < 0.05). After P. monodon was challenged with Vibrio parahaemolyticus for 7 days, the average cumulative mortality of P. monodon in the 2% and 5% groups were significantly lower than that in the 0% group (P < 0.05). With the increase of feeding time, the number of effective OTUs in each group showed a downward trend. At the 14th d, Proteobacteria, Bacteroidetes and Firmicutes, the dominant flora in the intestinal tract of P. monodon. In summary, supplied with E. faecium could increase the expression of non-specific immunity-related genes, enhance the immune capacity of P. monodon., (© 2024. The Author(s).)

Oxidative stress is the primary cause of ischaemic stroke and is closely related to circadian rhythm. However, the mechanism by which circadian rhythm regulates oxidative stress in ischaemic stroke remains elusive. The Silent Information Regulator 1 (SIRT1) controls circadian rhythm by activating the transcription of the circadian clock core protein Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) through deacetylation. Studies have shown that the SIRT1-BMAL1 pathway can regulate oxidative stress. To investigate its correlation with oxidative stress, we examined the expression levels and influencing factors of SIRT1-BMAL1 at different times in ischaemic stroke patients and analyzed their clinical indexes, oxidative stress, and inflammatory factor indicators. The expression levels of oxidative stress and inflammatory factor indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α), SIRT1, and BMAL1, were detected in ischaemic stroke patients within 4.5 h of onset and in non-stroke patients. Patients were divided into four subgroups based on onset time: subgroup 1 (0:00-05:59); subgroup 2 (06:00-11:59); subgroup 3 (12:00-17: 59); and subgroup 4 (18:00-23:59). Our results showed higher MDA, IL-6, and TNF-α levels, and lower SOD, SIRT1, and BMAL1 levels in ischaemic stroke patients compared to control patients (P < 0.05). Among the four subgroups, the content of MDA, IL-6, and TNF-α was highest in patients with ischaemic stroke onset from subgroup 2 (06:00-11:59), while the expression levels of SOD, BMAL1, and SIRT1 were lowest in patients with ischaemic stroke in subgroup 2. Additionally, myeloperoxidase (MPO) reached the highest value showing the same trends consistent with MDA, IL-6, and TNF-ɑ and opposite trends consistent with SOD, BMAL1, and SIRT1. However, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), immediate blood glucose, immediate diastolic blood pressure, immediate systolic blood pressure, and homocysteine (HCY) did not show any statistically significant circadian rhythm changes (P > 0.05). Our findings suggest that the SIRT1-BMAL1 pathway may be involved in early oxidative stress in ischaemic stroke, which may be related to MPO., (© 2024. The Author(s).)

The COVID-19 pandemic triggered an unprecedented level of restrictive measures globally. Most countries resorted to lockdowns at some point to buy the much-needed time for flattening the curve and scaling up vaccination and treatment capacity. Although lockdowns, social distancing and business closures generally slowed the case growth, there is a growing concern about these restrictions' social, economic and psychological impact, especially on the disadvantaged and poorer segments of society. While we are all in this together, these segments often take the heavier toll of the pandemic and face harsher restrictions or get blamed for community transmission. This study proposes a road-network-based networked approach to model mobility patterns between localities during lockdown stages. It utilises a panel regression method to analyse the effects of mobility in transmitting COVID-19 in an Australian context, together with a close look at a suburban population's characteristics like their age, income and education. Firstly, we attempt to model how the local road networks between the neighbouring suburbs (i.e., neighbourhood measure) and current infection count affect the case growth and how they differ between delta and omicron variants. We use a geographic information system, population and infection data to measure road connections, mobility and transmission probability across the suburbs. We then looked at three socio-demographic variables: age, education and income and explored how they moderate independent and dependent variables (infection rates and neighbourhood measures). The result shows strong model performance to predict infection rate based on neighbourhood road connection. However, apart from age in the delta variant context, the other variables (income and education level) do not seem to moderate the relationship between infection rate and neighbourhood measure. The results indicate that suburbs with a more socio-economically disadvantaged population do not necessarily contribute to more community transmission. The study findings could be potentially helpful for stakeholders in tailoring any health decision for future pandemics., (© 2024. The Author(s).)

In this study, silver nanoparticles (Ag-NPs) were synthesized using a green and biologically inspired approach by utilizing reducing compounds from Thyme plant leaves. Zeolite was used to immobilize the synthesized Ag-NPs (Ag@Z). The modified Zeolite served as a catalyst for the reduction reaction of various organic pollutant dyes (OPDs) including 4-nitrophenol (4-NP), 4-nitroaniline (4-NA), methylene blue (MB), and methyl orange (MO) with sodium borohydride. The degradation of OPDs was monitored by measuring changes in their maximum absorption wavelength intensity. A thorough examination of multiple parameters (catalyst, silver and sodium borohydride dosage, yield degradation, and reaction time) was carried out to identify the optimized conditions for the degradation of OPDs. The results showed that the Ag@Z catalyst achieved an efficiency of over 93% in less than 10 min for the degradation of OPDs. The recoverability and reusability of the catalyst were examined, revealing a partial loss in efficiency after four recovery stages. Structural analysis using XRD, SEM, and TEM techniques confirmed the characteristics and morphology of the synthesized catalyst., (© 2024. The Author(s).)

Identifying potential prognostic factors of CSM patients could improve doctors' clinical decision-making ability. The study retrospectively collected the baseline data of population characteristics, clinical symptoms, physical examination, neurological function and quality of life scores of patients with CSM based on the clinical big data research platform. The modified Japanese Orthopedic Association (mJOA) score and SF-36 score from the short-term follow-up data were entered into the cluster analysis to characterize postoperative residual symptoms and quality of life. Four clusters were yielded representing different patterns of residual symptoms and quality of patients' life. Patients in cluster 2 (mJOA RR 55.8%) and cluster 4 (mJOA RR 55.8%) were substantially improved and had better quality of life. The influencing factors for the better prognosis of patients in cluster 2 were young age (50.1 ± 11.8), low incidence of disabling claudication (5.0%) and pathological signs (63.0%), and good preoperative SF36-physiological function score (73.1 ± 24.0) and mJOA socre (13.7 ± 2.8); and in cluster 4 the main influencing factor was low incidence of neck and shoulder pain (11.7%). We preliminarily verified the reliability of the clustering results with the long-term follow-up data and identified the preoperative features that were helpful to predict the prognosis of the patients. This study provided reference and research basis for further study with a larger sample data, extracting more patient features, selecting more follow-up nodes, and improving clustering algorithm., (© 2024. The Author(s).)

Soil salinization substantially hampers the growth and development of wheat, potentially leading to plant death in severe cases, thus reducing grain yield and quality. This phenomenon poses a significant threat to food security in China. We investigated the effects of two exogenous plant growth regulators, sodium salicylate and folcisteine, on the wheat physiology and key characteristics under salt stress using hydroponics method. The results indicated that both regulators effectively mitigated the growth inhibition of wheat under salt stress. We assessed morphological and physiological indexes, including antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], peroxidase [POD]) and malondialdehyde (MDA) concentration in wheat after foliar application of sodium salicylate and folcisteine under salt stress. The findings revealed that sodium salicylate was more effective than folcisteine. However, folcisteine showed superior performance in reducing hydrogen peroxide (H 2 O 2 ) content and superoxide anion (O 2- ) level compared to sodium salicylate. Simultaneously, Concurrent application of both regulators synergistically enhanced their efficacy, yielding the most favorable outcomes. In addition, this study noted that while the initial effects of these regulators were not pronounced, their sustained application significantly improved wheat growth in stressful condition and alleviated the detrimental impacts of salt stress. This approach could effectively guarantee the food security and production in China., (© 2023. The Author(s).)

To clarify the risk of tuberculosis (TB) infection in patients with Takayasu arteritis (TAK). In this study, we conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, Cochrane, and Medline, from the inception of the Literature Library to May 16, 2023. Using a specific set of keywords, including "Takayasu Arteritis", "Tuberculosis", and "Mycobacterium tuberculosis", the main objective of this search was to identify all relevant observational studies, including case-control studies, cohort studies, and cross-sectional studies, that report the prevalence of TB in individuals diagnosed with TAK. Two independent evaluators rigorously screened the studies, extracted data, and assessed the study quality using the Joanna Briggs Institute (JBI) critical appraisal tools. Statistical analyses were conducted using R software version 4.3.0, which allowed for the synthesis of prevalence and subgroup analyses. Subgroup analyses were stratified based on quality scores, World Health Organization regional categorizations, and TB categories. Assessment of publication bias was performed using a funnel plot. The study included a total of 30 studies with 5548 participants. The findings showed that individuals with TAK exhibited an average prevalence of TB infection at 31.27% (95% CI 20.48-43.11%). Significantly, the prevalence of TB infection demonstrated notable regional disparities, ranging from 16.93% (95% CI 7.71-28.76%) in the Western Pacific Region to 63.58% (95% CI 35.70-87.66%) in the African Region. Moreover, the study revealed that patients with TAK displayed a high prevalence of latent TB infection (LTBI) at 50.01% (95% CI 31.25-68.77%) and active TB at 14.40% (95% CI 9.03-20.68%). The high heterogeneity observed in the data highlights significant variability in TB infection rates among the populations studied, with the African Region exhibiting the highest rates. The study concludes that there is a high prevalence of TB infection in the TAK population, with regional variations. Consideration should be given to  implementing rigorous TB screening measures and preventive interventions specifically tailored for the TAK population., (© 2023. The Author(s).)

Liver fibrosis is a wound-healing process characterized by excess formation of extracellular matrix (ECM) from activated hepatic stellate cells (HSCs). Previous studies show that both EZH2, an epigenetic regulator that catalyzes lysine 27 trimethylation on histone 3 (H3K27me3), and long non-coding RNA H19 are highly correlated with fibrogenesis. In the current study, we investigated the underlying mechanisms. Various models of liver fibrosis including Mdr2 -/- , bile duct ligation (BDL) and CCl 4 mice were adapted. We found that EZH2 was markedly upregulated and correlated with H19 and fibrotic markers expression in these models. Administration of EZH2 inhibitor 3-DZNeP caused significant protective effects in these models. Furthermore, treatment with 3-DZNeP or GSK126 significantly inhibited primary HSC activation and proliferation in TGF-β-treated HSCs and H19-overexpreesing LX2 cells in vivo. Using RNA-pull down assay combined with RNA immunoprecipitation, we demonstrated that H19 could directly bind to EZH2. Integrated analysis of RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) further revealed that H19 regulated the reprogramming of EZH2-mediated H3K27me3 profiles, which epigenetically promoted several pathways favoring HSCs activation and proliferation, including epithelial-mesenchymal transition and Wnt/β-catenin signaling. In conclusion, highly expressed H19 in chronic liver diseases promotes fibrogenesis by reprogramming EZH2-mediated epigenetic regulation of HSCs activation. Targeting the H19-EZH2 interaction may serve as a novel therapeutic approach for liver fibrosis., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)