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Abstract The potential association between red blood cell distribution width (RDW) at admission and prognosis in patients with sepsis-induced cardiomyopathy(SIC) remains uncertain. The purpose of this study was to explore the prognostic value of RDW on mortality in patients with SIC. Data for this retrospective study were obtained from the MIMIC IV2.2 database. We used propensity score matching (PSM) and Cox proportional hazards regression analysis to evaluate the main risk factors associated with mortality in SIC patients. This analysis was utilized to develop a predictive nomogram. To assess the predictive accuracy and clinical usefulness of the model, we employed the concordance index (C-index) and decision curve analysis. To define the high- and low-RDW groups among patients with SIC, we determined the optimal cut-off value by maximizing the Youden index. According to the screening criteria, we identified a cohort of 1051 patients diagnosed with SIC. When comparing the high-RDW group to the low-RDW group, it was found that the high-RDW group exhibited longer Los_ICU(4.5 days vs.3.8 days, respectively, P = 0.009) and higher mortality rates at 28 days (33.8% vs. 7.8%, respectively, P

ChatGPT has received considerable attention in education, particularly in programming education because of its capabilities in automated code generation and program repairing and scoring. However, few empirical studies have investigated the use of ChatGPT to customize a learning system for scaffolding students' computational thinking. Therefore, this article proposes an intelligent programming scaffolding system using ChatGPT following the theoretical framework of computational thinking and scaffolding. A mixed-method study was conducted to investigate the affordance of the scaffolding system using ChatGPT, and the findings show that most students had positive attitudes about the proposed system, and it was effective in improving their computational thinking generally but not their problem-solving skills. Therefore, more scaffolding strategies are discussed with the aim of improving student computational thinking, especially regarding problem-solving skills. The findings of this study are expected to guide future designs of generative artificial intelligence tools embedded in intelligent learning systems to foster students' computational thinking and programming learning.

Abstract Background Despite the adverse effects of ambient fine particulate matter (PM2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long‐term PM2.5 exposure was calculated using 1‐km resolution satellite‐based PM2.5 estimates. PM2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort‐stratified Cox proportional hazards models, individually and in combination. Results In 488,166 person‐years of follow‐up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM2.5 stratification (≤65.02 µg/m3) other than in high PM2.5 stratification (>65.02 µg/m3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66–0.85) and 1.10 (95% CI: 0.99–1.22), respectively. Similar results were observed for PA intensity. High PM2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR = 1.79, 95% CI: 1.59–2.01 for PA volume; HR = 1.82, 95% CI: 1.64–2.02 for PA intensity). Conclusion PA could reduce type 2 diabetes risk in low‐pollution areas, but high PM2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long‐term polluted residents.

Abstract Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5’-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.

Abstract Typical weak signal search experiments rely on resonant effects, where the resonance frequency is scanned over a broad range, resulting in significant time consumption. In this study, we demonstrate an accelerated strategy that surpasses the typical resonance-bandwidth limited scan step without compromising sensitivity. We apply this method to an alkali-noble-gas spin system, achieving an approximately 30-fold increase in scanning step size. Additionally, we obtain an ultrahigh sensitivity of 1.29 fT ⋅ Hz−1/2 at around 5 Hz, corresponding to an energy resolution of approximately 1.8 × 10−23eV ⋅ Hz−1/2, which is among the highest quantum energy resolutions reported. Furthermore, we use this sensor to search for axion-like particles, setting stringent constraints on axion-like particles (ALPs) in the 4.5–15.5 Hz Compton-frequency range coupling to neutrons and protons, improving on previous limits by several-fold. This accelerated strategy has potential applications in other resonant search experiments.

The process of urbanization generates substantial amounts of solid waste materials, including glass, red brick, concrete, and ceramic tile. Effective treatment methods for these waste materials are currently lacking, resulting in significant land wastage and environmental pollution. Utilizing these waste materials in the construction of asphalt pavements presents a viable solution for their high-quality and large-scale utilization. In this study, the properties of commonly produced urban solid waste materials, including glass, red brick, concrete, and ceramic tile, were investigated for their suitability as limestone porous asphalt mixtures. The physical and chemical properties of the coarse aggregate were examined using four groups of preliminary tests, including leakage analysis, scattering, rutting, and freeze-thaw splitting tests. The results revealed that the apparent relative density varied for different particle sizes within the range of 2.36–4.75 mm, 4.75–9.5 mm, 9.5–16 mm, and 13.2–16 mm. However, the dynamic stability of the glass specimen was only 740 times/mm, which falls significantly below the technical requirement of 1500 times/mm. Additionally, the high-temperature stability of the glass specimen was deemed unsatisfactory. The red brick test piece exhibited inadequate water stability due to its high-water absorption rate. Therefore, reducing the amount of waste glass and minimizing the incorporation of waste red brick are recommended. The findings of this study contribute to the expansion of application methods and techniques for urban solid waste, improving the utilization rate of solid waste resources. Furthermore, the study sheds light on the changes in the performance of solid waste aggregates mixed with porous asphalt mixtures, providing valuable insights for road engineering endeavors.

Abstract Csn5 is subunit 5 of the COP9 signalosome (CSN), but the mechanism by which it strictly controls the pathogenicity of pathogenic fungi through autophagy remains unclear. Here, we found that Csn5 deficiency attenuated pathogenicity and enhanced autophagy in Magnaporthe oryzae. MoCSN5 knockout led to overubiquitination and overdegradation of MoTor (the core protein of the TORC1 complex [target of rapamycin]) thereby promoted autophagy. In addition, we identified MoCsn5 as a new interactor of MoAtg6. Atg6 was found to be ubiquitinated through linkage with lysine 48 (K48) in cells, which is necessary for infection-associated autophagy in pathogenic fungi. K48-ubiquitination of Atg6 enhanced its degradation and thereby inhibited autophagic activity. Our experimental results indicated that MoCsn5 promoted K48-ubiquitination of MoAtg6, which reduced the MoAtg6 protein content and thus inhibited autophagy. Aberrant ubiquitination and autophagy in ΔMocsn5 led to pleiotropic defects in the growth, development, stress resistance, and pathogenicity of M. oryzae. In summary, our study revealed a novel mechanism by which Csn5 regulates autophagy and pathogenicity in rice blast fungus through ubiquitination.

Background: The increasing prevalence of kidney diseases has become a significant public health issue, with a global prevalence exceeding 10%. In order to accurately identify biochemical changes and treatment outcomes associated with kidney diseases, novel methods targeting specific genes have been discovered. Among these genes, leucine-rich α-2 glycoprotein 1 (LRG1) has been identified to function as a multifunctional pathogenic signaling molecule in multiple diseases, including kidney diseases. This study aims to provide a comprehensive overview of the current evidence regarding the roles of LRG1 in different types of kidney diseases. Summary: Based on a comprehensive review, it was found that LRG1 was upregulated in the urine, serum, or renal tissues of patients or experimental animal models with multiple kidney diseases, such as diabetic nephropathy, kidney injury, IgA nephropathy, chronic kidney diseases, clear cell renal cell carcinoma, end-stage renal disease, canine leishmaniosis-induced kidney disease, kidney fibrosis, and aristolochic acid nephropathy. Mechanistically, the role of LRG1 in kidney diseases is believed to be detrimental, potentially through its regulation of various genes and signaling cascades, i.e., fibronectin 1, GPR56, vascular endothelial growth factor (VEGF), VEGFR-2, death receptor 5, GDF15, HIF-1α, SPP1, activin receptor-like kinase 1-Smad1/5/8, NLRP3-IL-1b, and transforming growth factor β pathway. Key Messages: Further research is needed to fully comprehend the molecular mechanisms by which LRG1 contributes to the pathogenesis and pathophysiology of kidney diseases. It is anticipated that targeted treatments focusing on LRG1 will be utilized in clinical trials and implemented in clinical practice in the future.

The fluid–structure interaction effect should not be disregarded when examining the vibration characteristics of hydraulic pipeline systems. The transfer matrix method (TMM) is an efficacious method for analyzing the vibration characteristics of hydraulic pipelines in the frequency domain, offering advantages such as simplicity and efficiency. However, the TMM suffers the problem of high frequency instability when dealing with long-span hydraulic pipelines, which restricts its practical application. Currently, several modified transfer matrix methods face challenges such as low computational efficiency and difficulties in handling complex boundaries. In response to these issues, this paper proposes a novel modified transfer matrix method known as the mixed variable transfer matrix method. This innovative method possesses clear physical significance and effectively prevents the transfer matrix from becoming singular without necessitating the subdivision of the pipeline length. Consequently, it addresses high-frequency instability while maintaining high computational efficiency. Moreover, this method is capable of addressing complex boundary problems by integrating boundary matrices, thereby demonstrating enhanced applicability compared to existing methods. The performance of the proposed method was validated through the utilization of classic Dubee pipeline impact test data, and the result shows maximum errors of 3.03% relative to the public data. Subsequently, an experiment was conducted on a section of hydraulic piping within a ship’s steering system. A hydraulic fluid noise generator was established to induce fluid pulsation excitation to the pipeline, thereby simulating the actual boundary conditions encountered in a ship’s hydraulic pipeline system so as to corroborate the efficacy of the proposed method in predicting the frequency domain vibration characteristics of a real hydraulic pipeline system. The experimental results indicate that the proposed method offers significant advantages in terms of high precision, efficiency, and stability, shows maximum errors of 4.35% relative to experimental data, and demonstrates promising prospects for engineering applications.

Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM2.5) has been documented, there remains disagreement among the related literature. Our study conducted a systematic review and meta-analysis of epidemiological studies to investigate the health effects of outdoor PM2.5 exposure on human TL after a thorough database search. To quantify the overall effect estimates of TL changes associated with every 10 μg/m3 increase in PM2.5 exposure, we focused on two main topics, which were outdoor long-term exposure and prenatal exposure of PM2.5. Additionally, we included a summary of short-term PM2.5 exposure and its impact on TL due to limited data availability.Our qualitative analysis included 20 studies with 483,600 participants. The meta-analysis showed a statistically significant association between outdoor PM2.5 exposure and shorter human TL, with pooled impact estimates (β) of −0.12 (95% CI: −0.20, −0.03, I2= 95.4%) for general long-term exposure and −0.07 (95% CI: −0.15, 0.00, I2= 74.3%) for prenatal exposure.In conclusion, our findings suggest that outdoor PM2.5 exposure may contribute to TL shortening, and noteworthy associations were observed in specific subgroups, suggesting the impact of various research variables. Larger, high-quality studies using standardized methodologies are necessary to strengthen these conclusions further.

AbstractIn this study, the complete mitochondrial genome of Chlorogomphus shanicus Wilson, 2002 was reported, and the maximum-likelihood (ML) phylogenetic tree was constructed using 13 protein-coding genes (PCGs). The total length of the mitogenome of C. shanicus was 15,497 bp. Twelve PCGs started with ATN codons, except cox1 began with TTG codon. Most transfer RNA genes (tRNAs) were predicted to fold in a typical cloverleaf structure, except the trnS1 (gct), which lacked a dihydrouridine arm that had been simplified to a loop. The phylogenetic tree showed that Anisoptera was split into two clades, and revealed that C. shanicus was closely related to Cordulegaster boltonii (Donovan, 1807) which is endemic to Europe.

Abstract Background To predict the microvascular invasion (MVI) in patients with cHCC-ICC. Methods A retrospective analysis was conducted on 119 patients who underwent CT enhancement scanning (from September 2006 to August 2022). They were divided into MVI-positive and MVI-negative groups. Results The proportion of patients with CEA elevation was higher in the MVI-positive group than in the MVI-negative group, with a statistically significant difference (P = 0.02). The MVI-positive group had a higher rate of peritumoral enhancement in the arterial phase (P = 0.01) whereas the MVI-negative group had more oval and lobulated masses (P = 0.04). According to the multivariate analysis, the increase in CEA (OR = 10.15, 95% CI: 1.11, 92.48, p = 0.04), hepatic capsular withdrawal (OR = 4.55, 95% CI: 1.44, 14.34, p = 0.01) and peritumoral enhancement (OR = 6.34, 95% CI: 2.18, 18.40, p

This paper investigates mechanical behaviours of sandstone during post-peak cyclic loading and unloading subjected to hydromechanical coupling effect, confirming the peak and residual strengths reduction laws of sandstone with water pressure, and revealing the influence of water pressure on the upper limit stress and deformation characteristics of sandstone during post-peak cyclic loading and unloading. Regarding the rock strength, the experimental study confirms that the peak strength σp and residual strength σr decrease as water pressure P increases. Especially, the normalized strength parameters σp/σpk and σr/σre was negatively and linearly correlated with the P/σ3. Moreover, the Hoek-Brown strength criterion can be applied to describe the relationship between effective peak strength and effective confining stress. During post-peak cyclic loading and unloading, both the upper limit stress σp(i) and crack damage threshold stress σcd(i) of each cycle tend to decrease with the increasing cycle number. A hysteresis loop exists among the loading and unloading stress–strain curves, indicating the unloading deformation modulus Eunload is larger than the loading deformation modulus Eload. Based on experimental results, a post-peak strength prediction model related to water pressure and plastic shear strain is established.

Abstract Synovial sarcoma (SS) is a rare malignant soft tissue sarcoma that originates from primitive mesenchymal cells with epithelial differentiation potential. It is most commonly found in the limbs and trunk. In the urinary system, it is mostly found in the kidneys. However, synovial sarcomas originating from the external urethra are extremely rare. Only one case of synovial sarcoma arising from the vulvar urethral orifice has been reported previously, and we report a second case of synovial sarcoma of the urethral orifice. In addition, a total of 16 vulvar synovial sarcomas were identified and the literature are analyzed in this report reviews from 1966 to the present.

Dental fluorosis, resulting from long-term environmental exposure to fluoride, is prevalent among diverse populations worldwide. Severe fluorosis not only compromises the aesthetic appeal of teeth but also impairs their functionality. This study aims to investigate the oral microbiome in dental fluorosis and the health individuals of adolescents living in the endemic fluorosis area of Guizhou, China through full-length 16S rDNA sequencing. Fourty-six individuals meet the sampling criteria, and we divided these samples into the following groups: a healthy group (H = 23) and a dental fluorosis group (F = 23), and two subgroups of Miao ethnicity: a healthy Miao group (Hm = 13) and a dental fluorosis Miao group (Fm = 15). A total of 660,389 high-quality sequences were obtained, and 12,007 Amplicon Sequence Variants (ASVs) were identified, revealing significant variations in oral microbiome between Fm and Hm groups. The composition of oral microbiota was similar between the H and F groups. At the genus level, Pseudopropionibacterium and at the species level, Streptococcus oralis_subsp.dentisani_clade_058 were less abundant in group F than in group H (P < 0.05). Further analysis revealed that the abundance of Capnocytophaga gingivalis and Kingella denitrificans was significantly lower in Fm fluorosis patients than in the Hm group (P < 0.05). Based on the LEfSe analysis, the potential core biomarkers in the oral of Fm fluorosis patients were identified at different taxonomic levels, ranging from phylum to species. These include Gammaproteobacteria, Prevotella sp_HMT_304, Gemella sanguinis, and Gracilibacteria_(GN02). Network analysis revealed that the microbiota in the fluorosis group exhibited more complex interactions with each other than the healthy group. Notably, within the Hm group, the potential biomarkers Capnocytophaga gingivalis and Kingella denitrificans exhibited a positive correlation. Finally, we employed PICRUSt2 analysis to explore the abundance clustering of the top 30 functional units in each sample, and we found that the metabolic pathway compositions of the four groups were similar. In summary, our findings suggest that the microbial composition of plaque in Hm patients with dental fluorosis is significantly altered, and we identified the potential marker microorganisms that contribute to these changes.

Abstract Background Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti‐inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) signaling pathway. Methods and results RAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate‐resistant acid phosphatase staining, F‐actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti‑inflammatory bone resorption, the expression of autophagy‐related proteins and NLRP3 signaling pathway factors in pre‐OCs were evaluated by western blot analysis, and the expression of OC‑specific molecules was analyzed using reverse transcription‑quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor‐α, whereas increased Interleukin‐10. In addition, SIM inhibited LPS‐induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC‑specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3‐related proteins expression while upregulating P62 under inflammatory conditions. Conclusions SIM may reduce autophagy secretion to attenuate LPS‐induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri‐implantitis.

Biodiversity of local communities has been found to generally decrease with elevation. However, the elevational patterns of intraspecific genetic diversity remain unclear, especially in passive dispersers and species with short life histories. In this study, we investigated the populations of a tropical dominant Cladoceran, Diaphanosoma dubium, along elevation in the largest watershed of South China. The studied populations were grouped into four regional groups based on elevation and habitat connectivity. No significant elevation pattern was observed for mitochondrial genetic diversity, but nuclear diversity was influenced by habitat type. The haplotype network showed a radial pattern with a common haplotype at the centre, and many private haplotypes existed in each regional group. Four clusters of D. dubium populations were identified and exactly corresponding to the four investigated regions, indicating a strong spatial genetic structure. Weak but significant isolation by distance (IBD) supported the critical role of environmental selection with elevation. Precipitation significantly explained population genetic variation at the watershed scale. Bidirectional gene flow was a common pattern that occurred among the four regional groups. Our results highlight that habitat selection with gene flow plays an important role in shaping the genetic pattern of tropical freshwater Cladocera along an elevational gradient.

Abstract IKKα has been shown to be responsible of multiple pro-tumorigenic functions and therapy resistance independent of canonical NF-κB, but its role in acquired chemotherapy resistance in breast cancer remains unclarified. In this study, we obtained pre-treatment biopsy and post-treatment mastectomy specimens from a retrospective cohort of triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy(NAC) (n = 43). Immunohistochemical methods were used to detect the expression of IKKα before and after NAC, and the relationship between IKKα and the pathologic response to NAC was examined. In addition, we developed a new ADR-resistant MDA-MB-231 cell line(MDA-MB-231/ADR) and analyzed these cells for changes in IKKα expression, the role and mechanisms of the increased IKKα in promoting drug resistance were determined in vitro and in vivo. We demonstrated that the expression of IKKα in residual TNBC tissues after chemotherapy was significantly higher than that before chemotherapy, and was positively correlated with lower pathological reaction. IKKα expression was significantly higher in ADR-resistant TNBC cells than in ADR-sensitive cells, IKKα knockdown results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, IKKα knockdown promotes chemotherapeutic drug-induced tumor cell death in an transplanted tumor mouse model. Functionally, we demonstrated that IKKα knockdown significantly upregulated the expression of cleaved caspase 3 and Bax and inhibited the expression of Bcl-2 upon ADR treatment. Our findings highlighted that IKKα exerts an important and previously unknown role in promoting chemoresistance in TNBC, combining IKKα inhibition with chemotherapy may be an effective strategy to improve treatment outcome in chemoresistant TNBC patients.

Inspired by the fact that therapeutic efficacy for triple negative breast cancer (TNBC) is weaken due to the enhancement of autophagy levels after long-term use of chemotherapeutic agents, a theranostic nanoplatform (CQ@ICG@PFH@PDA-PEG5k) integrating ultrasound (US) imaging and therapeutic functions is rationally designed based on the perfluorohexane (PFH) nanodroplet by loading autophagy inhibitor chloroquine (CQ) and photosensitizer indocyanine green (ICG). After CQ@ICG@PFH@PDA-PEG5k is delivered to tumor regions, CQ and ICG are co-released from the theranostic formulation, followed by liquid–gas phase transition of perfluorohexane (PFH) upon near-infrared (NIR) laser irradiation, assessing ultrasound (US) imaging function. For seeking a promising alternative for TNBC therapy, the antitumor therapeutic efficacy of CQ@ICG@PFH@PDA-PEG5k is compared with those of ICG@PFH@PDA-PEG5k + free CQ and ICG@PFH@PDA-PEG5k upon photothermal therapy (PTT) in vitro and in vivo. The tumor vascularity is investigated by color Doppler flow imaging (CDFI). CQ@ICG@PFH@PDA-PEG5k maybe has great potential for exploitation in TNBC therapy.

The symmetrical oil suction and discharge chambers and the reversing rotation condition of bidirectional involute internal gear pumps result in low oil absorption capacity and flow pulsation due to cavitation. However, efforts to address these issues suffer from an incomplete understanding of the effects of oil properties, suction chamber volume, suction pressure, and rotational speed on the oil absorption capacity and cavitation characteristics of these pumps. The present work addresses this issue by conducting detailed computational fluid dynamics (CFD) simulations. The results of analysis demonstrate that the degree of cavitation caused by changes in the mass fraction of dissolved gas in the oil is positively correlated with flow pulsation, while the degree of cavitation caused by changes in the suction port size, suction pressure, and rotational speed is negatively correlated with flow pulsation. The degree of cavitation in the oil suction cavity initially increases as the mass fraction of dissolved gas in the oil increases, and then decreases. The rotational speed exhibits a critical value, where the oil absorption capacity increases with increasing rotational speed below the critical value, and decreases with increasing rotational speed above the critical value. The results of this research are expected to be of great significance for guiding improvements in the design of bidirectional involute internal gear pumps and the determination of critical working conditions.

AimThis study aims to explore the association between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and relative grip strength in older adults in order to provide some references for the prevention and control of sarcopenia.MethodsFor this cross-sectional study, the demographic and clinical data of 1,404 individuals aged ≥60 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2011–2014. The definition of relative grip strength was the sum of the largest reading from each hand/body mass index (BMI) ratio. We used weighted univariate linear regression and stepwise regression analysis to screen the covariates. Weighted univariate and multivariate linear regression analyses were used to explore the association between the TG/HDL-C ratio and the relative grip strength. We also explored this relationship in subgroups of gender, diabetes mellitus (DM), cardiovascular disease (CVD), and arthritis. The evaluation index was β with 95% confidence intervals (CIs).ResultsA total of 1,306 older adults were eligible. After adjusting for the covariates including age, gender, race, marital status, physical activity, DM, CVD, arthritis, and chronic kidney disease (CKD), we found that the TG/HDL-C ratio was negatively linked to the relative grip strength (all p

Neurological disorders are the leading cause of disability and death globally. Currently, there is a significant concern about the therapeutic strategies that can offer reliable and cost-effective treatment for neurological diseases. Propofol is a widely used general intravenous anesthetic in the clinic. Emerging studies demonstrate that propofol exerts neuroprotective effects on neurological diseases and disorders, while its underlying pathogenic mechanism is not well understood. Autophagy, an important process of cell turnover in eukaryotes, has been suggested to involve in the neuroprotective properties developed by propofol. In this narrative review, we summarized the current evidence on the roles of autophagy in propofol-associated neurological diseases. This study highlighted the effect of propofol on the nervous system and the crucial roles of autophagy. According to the 21 included studies, we found that propofol was a double-edged sword for neurological disorders. Several eligible studies reported that propofol caused neuronal cell damage by regulating autophagy, leading to cognitive dysfunction and other neurological diseases, especially high concentration and dose of propofol. However, some of them have shown that in the model of existing nervous system diseases (e.g., cerebral ischemia-reperfusion injury, electroconvulsive therapy injury, cobalt chloride-induced injury, TNF-α-induced injury, and sleep deprivation-induced injury), propofol might play a neuroprotective role by regulating autophagy, thus improving the degree of nerve damage. Autophagy plays a pivotal role in the neurological system by regulating oxidative stress, inflammatory response, calcium release, and other mechanisms, which may be associated with the interaction of a variety of related proteins and signal cascades. With extensive in-depth research in the future, the autophagic mechanism mediated by propofol will be fully understood, which may facilitate the feasibility of propofol in the prevention and treatment of neurological disorders.

ABSTRACT Type III secretion system (T3SS) facilitates survival and replication of Edwardsiella piscicida in vivo. Identifying novel T3SS effectors and elucidating their functions are critical in understanding the pathogenesis of E. piscicida. E. piscicida T3SS effector EseG and EseJ was highly secreted when T3SS gatekeeper-containing protein complex EsaB-EsaL-EsaM was disrupted by EsaB deficiency. Based on this observation, concentrated secretomes of ΔesaB strain and ΔesaBΔesaN strain were purified by loading them into SDS-PAGE gel for a short electrophoresis to remove impurities prior to the in-the gel digestion and mass spectrometry. Four reported T3SS effectors and two novel T3SS effector candidates EseQ (ETAE_2009) and Trx2 (ETAE_0559) were unraveled by quantitative comparison of the identified peptides. EseQ and Trx2 were revealed to be secreted and translocated in a T3SS-dependent manner through CyaA-based translocation assay and immunofluorescent staining, demonstrating that EseQ and Trx2 are the novel T3SS effectors of E. piscicida. Trx2 was found to suppress macrophage apoptosis as revealed by TUNEL staining and cleaved caspase-3 of infected J774A.1 monolayers. Moreover, Trx2 has been shown to inhibit the p65 phosphorylation and p65 translocation into the nucleus, thus blocking the NF-κB pathway. Furthermore, depletion of Trx2 slightly but significantly attenuates E. piscicida virulence in a fish infection model. Taken together, an efficient method was established in unraveling T3SS effectors in E. piscicida, and Trx2, one of the novel T3SS effectors identified in this study, was demonstrated to suppress apoptosis and block NF- κB pathway during E. piscicida infection. IMPORTANCE Edwardsiella piscicida is an intracellular bacterial pathogen that causes intestinal inflammation and hemorrhagic sepsis in fish and human. Virulence depends on the Edwardsiella type III secretion system (T3SS). Identifying the bacterial effector proteins secreted by T3SS and defining their role is key to understanding Edwardsiella pathogenesis. EsaB depletion disrupts the T3SS gatekeeper-containing protein complex, resulting in increased secretion of T3SS effectors EseG and EseJ. EseQ and Trx2 were shown to be the novel T3SS effectors of E. piscicida by a secretome comparison between ∆esaB strain and ∆esaB∆esaN strain (T3SS mutant), together with CyaA-based translocation assay. In addition, Trx2 has been shown to suppress macrophage apoptosis and block the NF-κB pathway. Together, this work expands the known repertoire of T3SS effectors and sheds light on the pathogenic mechanism of E. piscicida.

Kawasaki disease (KD), an autoinflammatory disease primarily affecting young children, characterized by consisting of acute systemic vasculitis and coronary artery involvement in severe cases. Intravenous immunoglobulin gamma (IVIG) combined with aspirin therapy is the first-line regimen for the prevention of coronary aneurysms in the acute phase of KD. The etiology and pathogenesis of KD are unclear, but its incidence is increasing gradually, especially in the cases of IVIG-naïve KD and refractory KD. Conventional therapies for refractory KD have unsatisfactory results. At present, infliximab (IFX), a human-murine chimeric monoclonal antibody that specifically blocks tumor necrosis factor-α (TNF-α), has made great progress in the treatment of KD. This review revealed that IFX infusion (5 mg/kg) could effectively modulate fever, reduce inflammation, improve arthritis, diminish the number of plasma exchange, decrease hospitalizations, and prevent the progression of coronary artery lesions. The adverse effects of IFX administration included skin rash, arthritis, respiratory disease, infusion reaction, hepatomegaly, and vaccination-associated complications. But the incidence of these adverse effects is low. The clear optimal application protocol of the application of IFX for either initial combination therapy or salvage therapy in KD is still under investigation. In addition, there are no effective biomarkers to predict IFX resistance. Further multicenter trials with large sample size and long-term follow-up are still needed to validate the clinical efficacy and safety of IFX for IVIG-resistant KD or refractory KD.

Abstract Background The pattern of changes in the cervical spine and the spinal cord and their dynamic characteristics in patients with cervical spinal cord injury without fracture and dislocation remain unclear. This study aimed to evaluate the dynamic changes in the cervical spine and spinal cord from C2/3 to C7/T1 in different positions by using kinematic magnetic resonance imaging in patients with cervical spinal cord injury without fracture and dislocation. This study was approved by the ethics committee of Yuebei People's Hospital. Methods Using median sagittal T2-weighted images for 16 patients with cervical spinal cord injury without fracture and dislocation who underwent cervical kinematic MRI, the anterior space available for the cord, spinal cord diameter, posterior space available for the cord from C2/3 to C7/T1, and Muhle’s grade were determined. The spinal canal diameter was calculated by adding the anterior space available for the cord, spinal cord diameter, and posterior space available for the cord. Results The anterior space available for the cord, posterior space available for the cord, and spinal canal diameters at C2/3 and C7/T1 were significantly higher than those from C3/4 to C6/7. Muhle’s grades at C2/3 and C7/T1 were significantly lower than those at the other levels. Spinal canal diameter was lower in extension than in the neutral and flexion positions. In the operated segments, significantly lesser space was available for the cord (anterior space available for the cord + posterior space available for the cord), and the spinal cord diameter/spinal canal diameter ratio was higher than those in the C2/3, C7/T1, and non-operated segments. Conclusion Kinematic MRI demonstrated dynamic pathoanatomical changes, such as canal stenosis in different positions, in patients with cervical spinal cord injury without fracture and dislocation. The injured segment had a small canal diameter, high Muhle’s grade, low space available for the cord, and high spinal cord diameter/spinal canal diameter ratio.

The steering system noise is one of the main noise sources in submarine stealth condition. Combined with the composition of the steering system, the noise source of each component is sorted out systematically, and corresponding vibration and noise reduction design measures are proposed. As the main noise source of the steering system, emphasis is placed on analyzing the noise mechanism of the rudder hydraulic system, which is divided into two categories and six types according to steady state and transient operating conditions. Finally, it is pointed out that the new type electro-hydraulic steering gear, based on direct drive servo control principle, is the future development trend.

Abstract Objective To study the aggravation of clinical symptoms after discontinuation of metal chelating agent therapy in Wilson's disease (WD) patients, analyze the causes of aggravation, and observe the prognosis. Methods 40 WD patients (cerebral type 30 cases and hepatic type 10 cases) who stopped using metal chelating agent were selected, 40 WD patients with normal therapy, and 10 normal control cases were selected. All patients underwent neurological symptom evaluation using modified Young scale, Child‐Pugh liver function grading, metal metabolism, and disease typing. Magnetic sensitivity imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy imaging (MRS) were performed. According to the imaging results, WD patients were divided into metal deposition stage, fiber damage stage, and neuron necrosis stage. All patients were treated with metal chelating agent for 6 months. Results The score of modified Young scale in drug withdrawal group was lower than that in normal treatment group before drug withdrawal (p = .032). The score of modified Young scale was higher after drug withdrawal than before (p = .011). The number of Child‐Pugh B‐grade patients after drug withdrawal was more than that before drug withdrawal and in normal treatment group. The proportion of patients in the stage of neuronal necrosis after drug withdrawal (25%) was higher than that before drug withdrawal (10%) (p = .025). After drug withdrawal, urine copper was significantly higher than that before drug withdrawal and in the normal treatment group (p = .032, .039). After the withdrawal group resumed metal chelating agent treatment, 34.2% of neurological symptoms worsened. Conclusions WD patients showed neurological symptoms aggravation and increased liver injury after metal chelating agent withdrawal. Increased metal deposition and new nerve injury occurred in the brain. After re‐treatment, the aggravated neurological symptoms of WD patients are difficult to reverse.

IntroductionShift work has become an increasingly common work mode globally. This study aimed to investigate the association between shift work and the risk of incident gastroesophageal reflux disease (GORD), an upward gastrointestinal disorder disease worldwide, and to explore the mediating factors.MethodA total of 262,722 participants from the UK Biobank free of GORD and related gastrointestinal diseases were included to investigate the association and potential mediators between shift work and incident GORD. Multivariate-adjusted Cox models were used to evaluate the association between shift work status and GORD incidence.ResultsCompared to non-shift workers, shift workers had a 1.10-fold greater risk of incident GORD [95% confidence intervals (CIs): 1.03, 1.18], after adjusting for a range of potential confounders. However, the excess risk of GORD attenuated to the null after further adjusting for selected mediators. Specifically, the association was mediated by sleep patterns (25.7%), healthy behaviors (16.8%), depressive symptoms (20.2%), chronic conditions (13.3%), and biological factors (17.6%). After adjustment for all the mediators together, the association was attenuated by 71.5%.DiscussionOur findings indicated that long-term shift workers may have a higher risk of incident GORD, yet the excess risk may be explained by poor sleep quality, unhealthy behaviors, depressive symptoms, etc. This has positive implications for protecting the health of shift workers.

PurposeNephrolithiasis is thought to be a risk factor for osteoporosis, but data assessing if osteoporosis predisposes to the risk of nephrolithiasis are lacking. The present study aims to investigate whether patients with nephrolithiasis have a prominently higher prevalence of osteoporosis than the controls and vice versa via a cumulative analysis.MethodsFour databases were used to detect the eligible studies. We calculated the relative risk (RR) with a 95% confidence interval (CI) to assess the combined effect. The methodologies for conducting this study followed the PRISMA guidelines and were registered in the PROSPERO (ID: CRD42023395875),ResultsNine case-control or cohort studies with a total of 454,464 participants were finally included. Combined results indicated that there was a significantly higher prevalence of osteoporosis in patients with nephrolithiasis as compared to the general population without nephrolithiasis (overall RR from six studies= 1.204, 95%CI: 1.133 to 1.28, P< 0.001; heterogeneity: I2 = 34.8%, P= 0.162). Conversely, osteoporosis was significantly correlated to an increased risk of nephrolithiasis as compared to the controls without osteoporosis (overall RR from four studies= 1.505, 95%CI: 1.309 to 1.731, P< 0.001; I2 = 89.8%, P< 0.001). Sensitivity analysis on the two categories validated the above findings. No significant publication bias was identified in this study.ConclusionsThe present study highlighted a significantly high prevalence of osteoporosis in patients with nephrolithiasis and vice versa. This reciprocal association reminded the clinicians to conduct a regular follow-up assessment when managing patients with nephrolithiasis or osteoporosis, especially for the elderly.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42023395875.

This paper concerns an improved model-free adaptive fractional-order control with a high-order pseudo-partial derivative for uncertain discrete-time nonlinear systems. Firstly, a new equivalent model is obtained by employing the Grünwald–Letnikov (G-L) fractional-order difference of the input in a compact-form dynamic linearization. Then, the pseudo-partial derivative (PPD) is derived using a high-order estimation algorithm, which provides more PPD information than the previous time. A discrete-time model-free adaptive fractional-order controller is proposed, which utilizes more past input–output data information. The ultimate uniform boundedness of the tracking errors are demonstrated through formal analysis. Finally, the simulation results demonstrate the effectiveness of the proposed method.

Geopolymer enhances mechanical properties with polyvinyl alcohol (PVA) fibers, but there has been limited research exploring low PVA fiber dosages for mechanical properties in 3D printing or shotcrete. This study experimentally investigated slag and fly ash-based geopolymer mixtures reinforced with 0.1%, 0.15%, and 0.2% PVA fiber by volume as well as a control group without PVA fibers. These mixtures were prepared using fly ash, quartz sand, slag powder, silica fume, and an aqueous sodium silicate solution as the alkali activator, with the addition of PVA fiber to enhance composite toughness. The mechanical properties of the composites, encompassing dog-bone tensile properties, cubic compressive strength, bending and post-bending compressive strength, and prism compressive properties, were evaluated. Significantly, specimens with 0.15% PVA fibers exhibited optimal performance, revealing a notable 28.57% increase in tensile stress, a 36.45% surge in prism compressive strain, and a 47.59% rise in tensile strain compared to fiber-free specimens. Furthermore, environmental scanning electron microscopy observations were employed to scrutinize the microscopic mechanisms of composites incorporating PVA fibers, slag, and fly ash. In comparison to fiber-free specimens, prism compressive specimens with 0.15% PVA fibers demonstrated a 27.17% increase in post-cracking loading capacity, a 44.07% increase in post-cracking ductility, a 50.00% increase in peak strain energy, and a 76.36% increase in strain energy ratio.