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Let q ≥ 3 be an odd prime power and m ≥ 2 be an even integer. In this paper, a kind of narrow-sense constacyclic BCH codes over F q 2 with lengths n = q 2 m - 1 2 a (q + 1) are studied, where q ≡ a + 1 (mod 2 a) and a < q - 1 . The maximum designed distances such that narrow-sense constacyclic BCH codes over F q 2 with length q 2 m - 1 2 a (q + 1) containing their Hermitian dual codes are determined. We obtain some quantum codes with good parameters by such narrow-sense constacyclic BCH codes. The quantum codes that we construct have larger designed distances or dimensions than the ones with the same length in the literature. [ABSTRACT FROM AUTHOR]

This study uses discrete element method models to simulate the fragmentation and deposition of landslides with varying volumes on terrains with different slopes and heights. The slope motion process during the numerical simulations of the landslide movement can be divided into three stages based on changes in the kinetic energy. The variations in the kinetic and frictional energies throughout the mass motion are used to establish pertinent parameters to analyze the dynamics of the slider fragmentation characteristics. Building on prior research, the impact of the slope on the mobility and deposit morphology, including the apparent and equivalent friction coefficients and the ratio of the width to length as a deposit morphology model, is examined using motion models. Concurrently, the three experimental variables (the slope gradient, slope height, and sliding block volume) are analyzed and discussed in conjunction with the motion and deposit morphology models. Previous studies indicate that the quantification of landslide fragmentation is only applicable to rock landslides and has limitations. In the numerical simulations, distinct contact models for pre- and post-fragment particles are defined to enumerate the total number of intact particles. Subsequently, a dimensionless parameter is formulated to quantify the degree of slope fragmentation. The relationship of this parameter with the motion and deposition models is subsequently explored. The results show that increased fragmentation reduces the landslide mobility, indicating that fragmentation is an energy-consumptive process that hinders landslide motion. These findings provide insights into the mechanisms of long-runout landslides and contribute to the reproduction of landslide dynamics. [ABSTRACT FROM AUTHOR]

20-Hydroxyeicosatetraenoic acid (20-HETE) is associated with secondary damage in traumatic brain injury (TBI) of the immature brain. Microglial activation is pivotal in this process. However, the underlying mechanism of action remains unknown. While 20-HETE interacts with G protein-coupled receptor 75 (GPR75) in some pathological processes, their interaction in brain tissue remains uncertain. This study aimed to investigate whether 20-HETE can activate microglia by binding to GPR75 in TBI of the immature brain. Drug affinity responsive molecular target stability (DARTS) assays, cycloheximide (CHX) chase assays, and auto-dock assays were employed to analyze the interaction between 20-HETE and GPR75. The expression levels of cytochrome P450 4A (CYP4A) and GPR75 in activated microglia in an immature brain TBI model were observed by western blot and multiple immunofluorescence staining. The effects of different levels of 20-HETE expression and lentivirus-mediated GPR75 gene silencing on 20-HETE-induced inflammatory factor release from BV-2 cells were observed by enzyme-linked immunoassay (ELISA). The phosphorylation levels of the downstream Src kinase, epidermal growth factor receptor (EGFR), and nuclear factor (NF)-κB were assessed using western blot. Cell viability and apoptosis were detected by CCK-8 and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. 20-HETE bound to the GPR75 protein and inhibited its degradation. GPR75 gene silencing reversed the 20-HETE-induced inflammatory activation of BV-2 cells, effectively inhibiting the activation of the Src/EGFR/NF-κB pathway and the effects of 20-HETE on cell viability and the apoptosis rate. In contrast, overexpression of GPR75 had the opposite effect. In addition, after immature brain TBI, the 20-HETE and GPR75 expression levels were upregulated in microglia, with significant activation of the Src/EGFR/NF-κB pathway. Inhibition of 20-HETE synthesis with N-hydroxy-N’-(4-n-butyl-2-methylphenyl) formamidine (HET0016) produced the opposite effect. 20-HETE regulates the Src/EGFR/NF-κB signaling pathway via GPR75 to activate microglia, promoting immature brain TBI. These findings offer a novel target for promoting the brain injury effect of 20-HETE. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aims to assess the performance, methodological quality and reporting transparency in prediction models for the dental implant's complications and survival rates. Methods: A literature search was conducted in PubMed, Web of Science, and Embase databases. Peer-reviewed studies that developed prediction models for dental implant's complications and survival rate were included. Two reviewers independently evaluated the risk of bias and reporting quality using the PROBAST and TRIPOD guidelines. The performance of the models were also compared in this study. The review followed the PRISMA guidelines and was registered with PROSPERO (CRD42019122274). Results: The initial screening yielded 1769 publications, from which 14 studies featuring 43 models were selected. Four of the 14 studies predicted peri-implantitis as the most common outcome. Three studies predicted the marginal bone loss, two predicted suppuration of peri-implant tissue. The remaining five models predicted the implant loss, osseointergration or other complication. Common predictors included implant position, length, patient age, and a history of periodontitis. Sixteen models showed good to excellent discrimination (AUROC >0.8), but only three had undergone external validation. A significant number of models lacked model presentation. Most studies had a high or unclear risk of bias, primarily due to methodological limitation. The included studies conformed to 18–27 TRIPOD checklist items. Conclusions: The current prediction models for dental implant complications and survival rate have limited methodological quality and external validity. There is a need for enhanced reliability, generalizability, and clinical applicability in future models. [ABSTRACT FROM AUTHOR]

B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients, but there are still some patients who cannot achieve remission after treatment, or relapse after remission. Therefore, it is of great importance to overcome the drug resistance of CD19 CAR T cells after B-NHL treatment and reduce the recurrence rate of CD19 CAR T cells after B-NHL treatment. We found that low concentrations of chidamide did not enhance the ability of CD19 CAR T cells to kill B-NHL cells during and after preparation. B-NHL cells pretreated with chidamide were more likely to be killed by CD19 CAR T cells. CD19 CAR T cells secreted more cytokines (IL-2, TNF-α, and IFN-γ) after co-culture with B-NHL cells pretreated with chidamide. At the same time, the expression of CD19 on B-NHL cell surface was increased by chidamide. In vivo experiments showed that infusion of CD19 CAR T cells after chidamide bridging intervention can enhance the therapeutic effect of B-NHL and prolong the overall survival of mice. This study provides a new direction and theoretical foundation for CD19 CAR T cell therapy in B-NHL. [ABSTRACT FROM AUTHOR]

Currently, diabetes is one of the most dangerous diseases in modern society. Prevention is an extremely important aspect in the field of medicine, and the field of artificial intelligence and the healthcare industry are penetrating and integrating with each other, and combining machine models for prediction and diagnosis of diabetes is a big trend. In order to validate the advantages and potential of XGBoost model in the field of diabetes prediction, this study identified 10 key features by processing a medical examination dataset containing 556,495 sample size. Among them, glycated hemoglobin has high clinical value as a predictor. By constructing six machine models (XGBoost, Decision Tree, Logistic Regression, Random Forest, CatBoost, and LightGBM) and comparing their performances, we finally obtained that: the performance of XGBoost is relatively the best, with accuracy of 97.5%, recall of 97%, F1 score of 96.9%, and ROC-AUC score of 0.971. [ABSTRACT FROM AUTHOR]

This study aims to explore the application value of big data technology (BDT) in enterprise information security (EIS). Its goal is to develop a risk prediction model based on big data analysis to enhance the information security protection capability of enterprises. A big data analysis system that can monitor and intelligently identify potential security risks in real-time is constructed by designing complex network analysis algorithms and machine learning models. For different types of security threats, the system uses feature engineering and model training processes to extract key risk indicators and optimize model prediction performance. The experimental results show that the constructed risk prediction model has excellent performance on the test set, and its Area Under the Curve reaches 0.95, indicating that the model has good differentiation ability and high prediction accuracy. In addition, in the multi-class risk identification task, the model achieves an average precision of 0.87. Compared with the traditional method, it has remarkably improved the early warning accuracy and response speed of enterprises to various information security incidents. Therefore, this study confirms the effectiveness and feasibility of applying BDT to EIS risk management, and the successfully constructed prediction model provides strong technical support for EIS protection. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical outcomes of ultrasonography-guided aspiration and sclerotherapy and laparoscopic deroofing for the treatment of simple renal cysts in children, providing evidence for clinical decision-making in the management of pediatric renal cysts. Methods: A total of 49 patients with simple renal cysts were divided into two groups based on the treatment method: 29 patients (group 1) underwent laparoscopic deroofing, 20 patients (group 2) underwent ultrasonography-guided aspiration and sclerotherapy. The clinical efficacy differences between the two groups were compared. During the study period, optimizations were made to the aspiration and sclerotherapy procedure in terms of sclerosant injection volume, sclerosing time, frequency, and intervals. Results: The complete disappearance rate of cysts in group 2(95.0%) was significantly higher than that in group 1 (33.3%) (P < 0.001). The recurrence rate of cysts in group 2 was 0%, significantly lower than that in group 1 (33.3%) (P = 0.014). The group 2 had shorter hospital duration, indwelling catheterization duration, indwelling drainage duration, intraoperative blood loss, and operative time compared to the group 1 (P < 0.001). No severe complications such as intra-abdominal organ injury occurred in either group. However, in the group 2, 6 cases experienced transient low back pain and/or "alcoholic reaction", which resolved spontaneously. Conclusion: Compared to laparoscopic deroofing, aspiration and sclerotherapy for simple renal cysts in children demonstrates a higher complete disappearance rate. It is an economical, minimally invasive, and effective treatment option. The modified aspiration and sclerotherapy in this study showed good clinical outcomes and is worthy of further promotion. [ABSTRACT FROM AUTHOR]

Streamline visualization is crucial for understanding 3D vector fields, and seed placement is essential for high-quality streamlines. Current algorithms are either uniform, omitting vital information, or slow due to precalculation. We propose three novel techniques to build a topology-guided accelerated vector field streamline visualization framework. First, we convert the tracing process into an iterative one, dynamically generating seed points based on critical region detection and a cooldown mechanic. Second, we introduce "planar critical points" combined with traditional critical points to identify critical regions, and place new seed points according to their critical point types. During this process, we circumvent complex eigenvalue calculation with determining whether the eigenvalues are real, which is enough for our placement strategies. Third, we offer a fast streamline simplification technique based on global distortion to reduce clutter. Based on the proposed streamline visualization framework and various vector field visualization methods, we develop a CUDA-based application tool called AdaptiFlux, which achieves real-time visualization of vector fields more efficiently than those representative visualization tools. [ABSTRACT FROM AUTHOR]

Geopolitics events have a significant impact on financial markets in the process of global economic integration and financial liberalization. Focusing on the 2022 Russia-Ukraine conflict, this paper utilizes the TVP-VAR network connectedness approach to investigate its specific impacts on the connectedness of major global financial markets. It examines the dynamic evolution of high-frequency and low-frequency shocks on market correlations during the pre-conflict, initial, and stalemate stages, revealing the changes in risk transmission paths. Findings show that the conflict led to increased market interconnectedness. Low-frequency became a major part of the total spillover, signaling long-term structural changes. The stock and foreign exchange market initially responded swiftly, serving as starting points for risk diffusion. The commodity market has been risk receivers throughout the conflict period. Intra-market and cross-market linkages have also changed. The German stock market was the main source of risk spillovers in the conflict, influencing international market linkages. In the global financial market network, several stock markets were the primary risk transmitters in the early stage of the conflict, while foreign exchange markets took on this role during the stalemate period. In addition, gold continues to play a safe-haven role. Furthermore, the TVP-VAR model is used to quantitatively assess the extent of the impact of the conflict on the spillover effects of major global financial markets at different time points and lags. Based on these findings, this paper constructs diversified portfolios and proposes a series of targeted risk management recommendations, which provide a theoretical basis for future policy formulation under similar crises. [ABSTRACT FROM AUTHOR]

Dyskalemia are associated with an increased risk of mortality in patients undergoing maintenance hemodialysis (MHD). However, studies evaluating the impact of serum potassium variability on mortality in MHD patients are scarce. To investigate serum potassium variability and its association with prognosis in MHD patients, we conducted a retrospective study on maintenance hemodialysis patients from three campus of Renji Hospital between June 2018 and December 2022. The exposure of interest was serum potassium variability defined as the coefficient of variation of serum potassium levels (CVSP). Cox regression models and Kaplan-Meier survival analysis were used to assess the prognostic significance of serum potassium variability. In a subgroup analysis, the association between serum potassium variability and prognosis was investigated in patients within normal serum potassium concentration range. Total of 588 maintenance hemodialysis patients were included. During a median follow-up of 45 months (24, 54), 121 patients (20.6%) died. The survival analysis suggested significantly higher survival rates for both all-cause (p < 0.01) and cardiovascular (p < 0.01) death in patients in the highest group of CVSP (H-CVSP) compared with those in the the lowest group (L-CVSP). After adjustment, the all-cause mortality hazard ratio compared to L-CVSP was 2.17 [95% confidence interval (CI) 1.18, 3.97] for H-CVSP (p < 0.05) and was 2.53 [95%CI 1.03, 6.22] for cardiovascular mortality (p < 0.05). In the subgroup analysis, 493 patients (83.8%) presented normokalemia (the mean of serum potassium levels ≥ 3.5mmol/L and ≤ 5.0mmol/L) were included. Similar association was found between serum potassium variability and accumulated survival rates, and higher serum potassium variablity was remained an independent risk factor for cardiovascular mortality (2.69, 95% CI 1.07–6.78, p < 0.05) in patients within normal serum potassium concentration range. In conclusion, a higher serum potassium variability was associated with all-cause and cardiovascular mortality in maintenance haemodialysis patients, even in the normal range. [ABSTRACT FROM AUTHOR]

Reliability technology plays a significant role in ensuring the safe operation of the subsea control system. To perform a comprehensive analysis of the reliability of complex systems, a combination of Failure Mode and Effects Analysis (FMEA) and Fuzzy Fault Tree Approach (FFTA) is introduced. Firstly, the FMEA method is used to analyze the potential failure modes and causes of system failure by completing the qualitative analysis of system reliability from the perspective of multi-factor failure modes. And the risk matrix diagram is applied to determine the degree of harm of different failure modes to the system. Then, the system reliability is quantitatively analyzed using FFTA, and a fault tree model is established by dividing the system into "system-subsystem-component" and solving for the minimum cut set. In addition, the failure probability of the top-level event is quantitatively calculated by introducing fuzzy set theory, and the probabilistic importance of the bottom-level event is analyzed to find out the weak points of each subsystem. Finally, a qualitative and quantitative reliability analysis is conducted by using FMEA-FFTA method for subsea control system. Effective measures should be taken to focus on preventive protection and regular testing for the high risk, medium–high risk and medium risk modes for subsea control system. [ABSTRACT FROM AUTHOR]

Considering that conventional dynamic compaction (CDC) method has limitation in the effectiveness of improvement depth because the improved shallow soil layers prevent the impact energy further transmitted to the deep ground, a new technique of in-pipe deep dynamic compaction (IDDC) is proposed in which the tamper can compact soil from the deep to the shallow soil layers. In this paper, the main objective is to illustrate the work mechanism of IDDC. Firstly, main components of equipment and construction process of IDDC are introduced. Then, model tests of CDC and IDDC were conducted on loose sand to obtain the influence depth using the acceleration of soil particles during impact and the distribution of cone resistance and side friction through static cone penetration tests (CPTs) after impact. Finally, the analytical formulae of superimposed stress and settlement due to IDDC was derived based on the Mindlin's solution and equation of motion, and verified with model test results and a practical case. The results indicate that with the falling height of 1 m in model tests, the further impacts after the 6th impact of CDC could hardly improve ground, resulting in the improvement depth of around 45 cm, whereas the improvement depth of IDDC was over 80 cm. Moreover, at the falling height of 1 m, the average increment in cone resistance after IDDC is 82% greater than that after CDC. Finally, compared with experimental results, the errors of the predicted settlement and the superimposed stress are less than 26 and 14%, respectively, and the proposed formulae succeed to predict the improvement depth of IDDC applied in a coastal area of China. [ABSTRACT FROM AUTHOR]

For two graphs G and H, the Gallai–Ramsey number gr k (G : H) is defined as the minimum integer n such that any k-edge-coloring of K n must contain either a rainbow copy of G or a monochromatic copy of H. In this paper, we obtain the exact values of gr k (G : H) , where H is a path and G ∈ { K 1 , 3 , P 4 + , P 5 } is a small tree and P 4 + is the graph consisting of P 4 with one extra edge incident with an inner vertex. [ABSTRACT FROM AUTHOR]

Renal fibrosis, a progressive scarring of the kidney, lacks effective treatment. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) hold promise for treating kidney diseases due to their anti-inflammatory properties. This study investigates their potential to lessen renal fibrosis by targeting macrophage-to-myofibroblast transformation (MMT), a key driver of fibrosis. We employed a mouse model of unilateral ureteral obstruction (UUO) and cultured cells exposed to transforming growth factor-β (TGF-β) to mimic MMT. HucMSC-Exos were administered to UUO mice, and their effects on kidney function and fibrosis were assessed. Additionally, RNA sequencing and cellular analysis were performed to elucidate the mechanisms by which HucMSC-Exos inhibit MMT. HucMSC-Exos treatment significantly reduced kidney damage and fibrosis in UUO mice. They downregulated markers of fibrosis (Collagen I, vimentin, alpha-smooth muscle actin) and suppressed MMT (α-SMA + F4/80 + cells). Furthermore, ARNTL, a specific molecule, emerged as a potential target of HucMSC-Exos in hindering MMT and consequently preventing fibrosis. HucMSC-Exos effectively lessen renal fibrosis by suppressing MMT, suggesting a novel therapeutic strategy for managing kidney damage and fibrosis. [ABSTRACT FROM AUTHOR]

Objective: Exopolysaccharide (EPS1-1) exhibits immunomodulatory and antitumor activities; however, its mechanism of action remains unknown. We determined the antitumor activity and whether EPS1-1 could enhance the shift of tumor-associated macrophages (TAMs) toward the M1 phenotype. Methods: The viability of MC-38 was assessed by the CCK-8 assay. The phagocytic activity of primary peritoneal macrophages (PEMs) was assayed by immunofluorescence microscopy and the levels of TNF-α, IL-6, and NO were tested by ELISA kits, and NO assay kit. M1 polarization was analyzed by flow cytometry and Immunofluorescence staining. Results and Discussion: The viability of MC-38 cells did not exhibit a significant difference (p > 0.05). EPS1-1 significantly upregulated IL-6, TNF-α, and NO production as well as phagocytic activity. Furthermore, it significantly inhibited tumor growth (85.32%), increased the spleen and thymus indices, and elevated the proportion of M1 cells in vitro and in vivo. Conclusions: It indicated that EPS1-1 had no direct inhibitory effect on MC-38 cell viability, exhibited remarkable anti-tumor activity against MC-38 transplanted tumors, reduced the volume of transplanted tumors, and significantly activated TAMs polarization to an immunostimulatory M1 phenotype to modulate antitumor immune responses in C57BL/6J mice. [ABSTRACT FROM AUTHOR]

In this paper, a class of narrow-sense constacyclic BCH codes over F q 2 with length n = q 2 m - 1 2 q 2 - 1 is studied, where q ≥ 3 is an odd prime power and m ≥ 2 is even. The maximum designed distance such that narrow-sense constacyclic BCH codes over F q 2 with length n containing their Hermitian dual codes is determined. We obtain some new quantum codes by using such narrow-sense constacyclic BCH codes. Our constructions not only have larger designed distance but also have better parameters than the ones in the literature. [ABSTRACT FROM AUTHOR]

High IQ motif-containing GTPase activating protein 3 (IQGAP3) expression is considered to be associated with poor prognosis of colorectal cancer (CRC). However, its role in early-onset CRC (EOCRC) progress is unclear. The mRNA and protein levels of IQGAP3 and Parkin (PRKN) were examined by qRT-PCR and western blot. Cell proliferation, apoptosis and metastasis were determined by CCK8 assay, EdU assay, flow cytometry and transwell assay. ROS, MDA, GSH, Fe2+, ACSL4 and SLC7A11 levels were detected to assess cell ferroptosis. The interaction between PRKN and IQGAP3 was assessed by Co-IP assay and ubiquitination assay. Xenograft tumor models were constructed to explore the effect of PRKN and IQGAP3 on the tumorigenesis in vivo. IQGAP3 was upregulated, while PRKN was downregulated in EOCRC tissues and cells. IQGAP3 knockdown inhibited CRC cell proliferation, migration and invasion, while enhanced apoptosis and ferroptosis. PRKN ubiquitinated IQGAP3 to promote its degradation. PRKN overexpression suppressed CRC cell growth, metastasis and promoted ferroptosis, while these effects were reversed by upregulating IQGAP3. In animal study, upregulation of PRKN reduced CRC tumorigenesis by decreasing IQGAP3 expression in vivo. IQGAP3, ubiquitinated by PRKN, promoted EOCRC progression by enhancing cell proliferation, metastasis, repressing apoptosis and ferroptosis, which provided a novel target for EOCRC treatment. [ABSTRACT FROM AUTHOR]

Ionized amine group (R-NH2) and carboxyl group (R-COOH) within the active layer of polyamide (PA) nanofiltration membranes result in the formation of positive (R-NH3+) and negative (R-COO−) functional groups, respectively, which determines membrane performance and is essential for membrane fabrication and modification. Herein, a facile dye adsorption/desorption method using Orange II and Toluidine Blue O dyes was developed to measure the densities of R-NH2, R-NH3+, R-COOH, or R-COO− on surfaces of six PA membranes, and the correlation between the density of such groups and the zeta potential was established. The dye adsorption method was proven reliable due to its lower standard deviation, detection limit, and quantification limit values. Furthermore, the densities of R-NH3+ or R-COO− under different pH values were measured, fitting well with results calculated from the acid-base equilibrium theory. Additionally, a correlation was established between the net surface density ([R-NH3+] − [R-COO−]) and the surface charge density (σ) calculated via the Gouy–Chapman model based on zeta potential results. The resulted correlation (σ/(mC·m−2) = (3.67 ± 0.08) × ([R-NH3+] − [R-COO−])/(nmol·cm−2) + (0.295 ± 0.08)) effectively predicts the σ value of the membrane. This study provides a facile and reliable dye adsorption method for measuring the density of R-NH2, R-NH3+, R-COOH, or R-COO−, enabling an in-depth understanding of membrane charge properties. [ABSTRACT FROM AUTHOR]

Sleep disturbances (SD) are common in major depressive disorder (MDD) patients. Brain functional asymmetry is crucial for understanding MDD pathophysiology. Previous studies using the parameter of asymmetry (PAS) approach have found brain functional asymmetry disruption in MDD. However, this has not been explored in MDD patients with SD. This study examined 26 MDD patients with SD, 34 MDD patients without SD, and 34 healthy controls using resting-state functional magnetic resonance imaging scans. SD symptoms were quantified using the 17-item Hamilton Rating Scale for Depression. PAS approach was used to evaluate functional asymmetry. MDD patients with SD displayed increased PAS in the left middle frontal gyrus (MFG)/inferior frontal gyrus (IFG) and decreased PAS in the left parahippocampal gyrus (PHG) compared to MDD patients without SD. Increased PAS in the left MFG/IFG was positively correlated with SD severity, and a negative correlation was found between decreased PAS in the left PHG and SD scores in all MDD patients. Receiver operating characteristic analysis indicated that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may serve as potential neuroimaging markers to differentiate MDD patients with SD from those without SD with Area Under Curve values of 0.8157 and 0.8068, respectively. These results highlighted that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may be considered a prominent feature associated with SD symptoms of MDD patients, potentially serving as imaging markers to discriminate between MDD patients with and without SD. [ABSTRACT FROM AUTHOR]

Restricted Access Media-Methacrylic Resin with the ability of protein exclusion was prepared by the free radical polymerization using methacrylic acid, ethylene glycol dimethacrylate and glycidyl methacrylate as monomer, cross-linker and comonomer, respectively. Protein exclusion ability of this material was studied. The results showed that the material was able to eliminate 93.6% of protein after bovine serum albumin solution was added and shaken for 220 min. Adsorption kinetics and adsorption isotherms of Lamotrigine on this material were investigated. The experimental data were the most suitable for the pseudo-second-order kinetics model and Freundlich isotherm model. Restricted Access Media-Methacrylic Resin was used as sorbent for Solid-Phase Extraction to extract Lamotrigine from Human Plasma. The method for the determination of Lamotrigine in human plasma by SPE followed by the HPLC–UV presented linear range from 1.0 to 66.6 µg/mL with correlation coefficient 0.9930 for Lamotrigine, assay precision with relative standard deviation value 6.24%, and assay accuracy 94.7–104.7% with relative standard deviation values 4.33–5.81%. SPEs filled with this material were used at least 7 times without any significant changes in their performance. Analytical validation parameters demonstrated that the method could be applied to the determination of Lamotrigine at the therapeutic plasma levels without other treatments. [ABSTRACT FROM AUTHOR]

The rotational–translational loess landslides are widely distributed in northwest China, usually posing threats to the surrounding residents and infrastructure. These loess landslides are characterized by the formation of multiple slip surfaces during the run-out process, and the mechanisms of this phenomenon in loess landslides have not been sufficiently investigated. Therefore, in this paper, we integrated the elastic–plastic strain softening constitutive law into the original DualSPHysics code to extend its application in simulating rotational–translational loess landslides. Two benchmark cases are studied to validate the model, the failure process of a cohesive soil slope without strain softening and that of a sensitive clay slope with strain softening. The results illustrate that our model can effectively predict large deformation. Then, the run-out process of the Caijiapo landslide in northwest China is analyzed by the modified model to investigate its failure mechanism. The results illustrate that the failure pattern of the Caijiapo loess landslide is very different from the typical retrogressive failure of clay landslides. The main slip surface of the Caijiapo landslide is controlled by the pre-existing structural plane. The second and third slip surfaces of this landslide are formed inside the sliding mass due to stress redistribution during the run-out process. Three scarps are formed in the landslide deposit because of the formation of multiple slip surfaces. This deposition morphology can be well reproduced by the SPH model taking strain softening into account, while the results using an SPH model without considering strain softening cannot capture this essential deformation characteristic. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is one of the hallmarks in the pathophysiology of prion disease and other neurodegenerative diseases. Various metabolic dysfunctions are identified and considered to contribute to the progression of some types of neurodegenerative diseases. In this study, we evaluated the status of glycolysis pathway in prion-infected rodent and cell models. The levels of the key enzymes, hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) were significantly increased, accompanying with markedly downregulated mitochondrial complexes. Double-stained IFAs revealed that the increased HK2 and PFK distributed widely in GFAP-, Iba1-, and NeuN-positive cells. We also identified increased levels of AMP-activated protein kinase (AMPK) and the downstream signaling. Changes of AMPK activity in prion-infected cells by the AMPK-specific inhibitor or activator induced the corresponding alterations not only in the downstream signaling, but also the expressions of three key kinases in glycolysis pathway and the mitochondrial complexes. Transient removal or complete clearance of prion propagation in the prion-infected cells partially but significantly reversed the increases of the key enzymes in glycolysis, the upregulation of AMPK signaling pathway, and the decreases of the mitochondrial complexes. Measurements of the cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) showed lower OCR and higher ECAR in prion-infected cell line, which were sufficiently reversed by clearance of prion propagation. Those data indicate a metabolic reprogramming from oxidative phosphorylation to glycolysis in the brains during the progression of prion disease. Accumulation of PrPSc is critical for the switch to glycolysis, largely via activating AMPK pathway. [ABSTRACT FROM AUTHOR]

This paper identifies the presence of anomalies in Chinese urban construction investment bonds (UCIBs) market using variable ranking portfolio analysis and finds that liquidity anomalies, downside risk anomalies, and historical return anomalies significantly exist. By conducting Fama–MacBeth regressions on the cross-sectional returns of UCIBs and anomalies, we find that only the 6-month momentum in the historical return anomaly can generate statistically significant risk premium which cannot be explained by long-established bond pricing factors, and thus it's an anomaly for UCIBs. This paper also finds that portfolios constructed based on significant anomalies in the UCIBs market can generate more profits than other models through the out-of-sample cross-sectional return forecasting. [ABSTRACT FROM AUTHOR]

Sophisticated interactions between stromal and immune cells play crucial roles in various biological and pathological processes. In chronic rhinosinusitis with nasal polyps (CRSwNP), the upper airway inflammation in many patients is driven by TH2, ILC2, and eosinophils, thus being treated with glucocorticoids and anti-type 2 inflammation biologics. The resistance to these therapies is often associated with neutrophilic inflammation, which has also been widely identified in CRSwNP, but the underlying mechanisms remain unclear. Using single-cell analysis, spatial transcriptomics, and T-cell receptor sequencing, we identify an increased presence of granzyme K+(GZMK+) CD8+ T cells in NPs, which possess a phenotype distinct from the cytotoxic GZMB+ effector CD8+ T subset. GZMK+CD8+ T cells are found to express CXCR4 and interact with CXCL12-secreting fibroblasts, inducing the latter to produce neutrophil chemoattractants in a manner uniquely mediated by GZMK but not other granzymes. This GZMK+CD8+ T cell-fibroblast crosstalk is also observed in other inflammatory diseases. Furthermore, GZMK+CD8+ T cells exhibit a selective expansion of clones that recognize Epstein-Barr virus. Here, we show that GZMK marks a phenotypically distinct subset of effector CD8+ T cells that promote neutrophilic inflammation. Chronic rhinosinusitis with nasal polyps generally has a type 2 inflammatory eosinophilic profile but can have a treatment resistant neutrophilic phenotype. Here the authors characterise nasal polyps using single cell sequencing and spatial transcriptomics and show granzyme K+CD8+ T cells associated with neutrophilic inflammation which promote release of neutrophilic chemoattractants from fibroblasts. [ABSTRACT FROM AUTHOR]

Background: Infectious uveitis is a significant cause of visual impairment worldwide, caused by diverse pathogens such as viruses, bacteria, fungi, and parasites. Understanding its prevalence, etiology, pathogenesis, molecular mechanism, and clinical manifestations is essential for effective diagnosis and management. Methods: A systematic literature search was conducted using PubMed, Google Scholar, Web of Science, Scopus, and Embase, focusing on studies published in the last fifteen years from 2009 to 2023. Keywords included "uveitis," "infectious uveitis," "viral uveitis," and others. Rigorous inclusion and exclusion criteria were applied, and data were synthesized thematically. Gene symbols related to infectious uveitis were analyzed using protein-protein interaction (PPI) networks and pathway analyses to uncover molecular mechanisms associated with infectious uveitis. Results: The search from different databases yielded 97 eligible studies. The review identified a significant rise in publications on infectious uveitis, particularly viral uveitis, over the past fifteen years. Infectious uveitis prevalence varies geographically, with high rates in developing regions due to systemic infections and limited diagnostic resources. Etiologies include viruses (39%), bacteria (17%), and other pathogens, substantially impacting adults aged 20–50 years. Pathogenesis involves complex interactions between infectious agents and the ocular immune response, with key roles for cytokines and chemokines. The PPI network highlighted IFNG, IL6, TNF, and CD4 as central nodes. Enriched pathways included cytokine-cytokine receptor interaction and JAK-STAT signaling. Clinical manifestations range from anterior to posterior uveitis, with systemic symptoms often accompanying ocular signs. Diagnostic strategies encompass clinical evaluation, laboratory tests, and imaging, while management involves targeted antimicrobial therapy and anti-inflammatory agents. Conclusion: This review underscores the complexity of infectious uveitis, driven by diverse pathogens and influenced by various geographical and systemic factors. Molecular insights from PPI networks and pathway analyses provide a deeper understanding of its pathogenesis. Effective management requires comprehensive diagnostic approaches and targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Dance is one of the most popular art cultures in the world. The study investigates the transformative impact of dance education on the mental health of Chinese students, focusing on emotional regulation, cognitive function, and overall well-being. Utilizing a mixed-method approach, the research engages dance students from prominent academies in China, employing a carefully crafted questionnaire and interview process. The study reveals compelling findings, affirming the positive influence of dance education on reducing symptoms of anxiety and depression, enhancing self-esteem and body image, and fostering emotional regulation skills. Drawing on a diverse sample of 342 participants, the study employs robust statistical analyses, including reliability tests, correlation analysis, and hypothesis testing, to substantiate its claims. The results not only support the hypotheses formulated but also showcase the multifaceted benefits of dance education, bridging stress management, community building, positive attitudes towards physical activity, improved cognitive abilities, and enhanced academic performance. The extensive data analysis incorporates both quantitative and qualitative dimensions, providing a clear understanding of the profound connections between dance education and mental health. The study contributes significantly to the existing literature by offering empirical evidence that underscores the pivotal role of dance education in cultivating holistic well-being among students. These findings bear important implications for educators, policymakers, and mental health professionals, advocating for the integration of dance education as a proactive strategy for fostering positive mental health outcomes in educational settings. [ABSTRACT FROM AUTHOR]

The Indo-Pacific king mackerel, scientifically known as Scomberomorus guttatus, is a valued marine species that holds significant commercial importance in the Indo-Pacific region. However, the lack of genomic resources has hindered a comprehensive understanding of this species. In this study, we constructed a genome of Indo-Pacific king mackerel at the chromosome level using a combination of PacBio HiFi reads and a chromosome contact map (Hi-C). The resulting genome had high contig and scaffold N50 values of 8.84 Mb and 32.9 Mb, respectively. In the genome assembly, which is 797.66 Mb in size and consists of 24 chromosomes, we also identified 35.89% repetitive elements and predicted 25,886 protein-coding genes. Our study not only benefits to reveal the possible mechanism of adaptive evolution in this fish, but also offers insight for the future sustainable management of these valuable biological resources. [ABSTRACT FROM AUTHOR]

Introduction: Rice kernel smut, caused by Tilletia horrida, is becoming an increasingly serious disease in hybrid rice planting, leading to production losses and quality decline of male-sterile rice varieties. Successful infection requires an efficient energy source that the pathogen obtains from rice plants, such as carbohydrates. Glycoside hydrolases (GHs), one of the largest sub-families in the cell wall-degrading enzyme family, play a key role in the infection progress of pathogens. To investigate their roles in facilitating infection, in this study, we identified and characterized genes encoding GH family proteins of T. horrida and further explored the functions and structures of these genes. Materials and methods: Through genome-wide sequencing and bioinformatics analyses, 52 GH genes were identified from T. horrida, named ThGhd_1 to ThGhd_52. The subcellular location, conserved motifs, and structures of ThGhds were identified by bioinformatics analyses. Results: Phylogenetic analysis revealed that ThGhds with similar domains clustered together, although some proteins clustered in different branches, which might reflect functional diversity. Protein-protein interaction network analysis revealed that ThGhds interact with partner proteins involved in reactive oxygen species signaling, protein kinase activity, and plant hormone signal transduction pathways. RNA-sequencing analysis showed that the expression of ThGhd genes responded differently at different infection time points, with dynamic changes detected during the T. horrida infection process, indicating that these genes are involved in interactions with rice and have potential roles in pathogenic mechanisms. Conclusions: The results of this study provide valuable resources for the structure elucidation of GH family proteins of T. horrida and can help to further elucidate their roles in pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: The underlying mechanism by which lupus nephritis (LN) progresses to chronic kidney disease remains elusive. Fibrosis is a hallmark feature of chronic kidney disease, including LN. The chronicity index (CI) score, which incorporates glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis, summarizes the extent of kidney tissue fibrosis. Method: In this study, we employed label-free quantitative proteomics based on mass spectrometry to generate kidney protein profiles with varying CI scores. Results: A total of 98 proteins exhibiting linear correlation with CI scores were initially screened out by linear model (CI linearly related proteins), and subsequently, 12 key proteins were derived based on the CI linearly related proteins using Cytohubba. LN patients were stratified into two subtypes based on CI scores and epithelial-mesenchymal transition (EMT) characteristics. These subtypes exhibited significant disparities in immune infiltration and molecular pathways. The high EMT group exhibited heightened activation of immune cells, such as memory B cells, gamma delta T cells, and resting mast cells. Gene Set Enrichment Analysis (GSEA) uncovered substantial dysregulation in critical biological processes and signaling pathways, including NF-κB, JNK, PI3K/AKT/mTOR signaling pathway, lipoprotein biosynthetic process, and endocytosis, in both subgroups. Conclusion: In conclusion, this study establishes molecular subgroups based on the CI score, providing novel insights into the molecular mechanisms governing chronicity in the kidneys of diverse LN patients. Key Points • Fibrosis is a fundamental and characteristic pathological process underlying the NIH-CI in LN. • Different EMT status presented variant clinical characteristics, immune features in LN. [ABSTRACT FROM AUTHOR]

Background: The Aryl Hydrocarbon Receptor (AHR) is a transcription factor that regulates several biological processes. Its potential in anti-tumor immunotherapy is becoming clearer, yet no bibliometric studies on this topic exist. This study aims to understand the current research landscape and identify future directions through a bibliometric analysis of AHR's anti-tumor immunological effects. Methods : We conducted a comprehensive bibliometric analysis of AHR antitumor immunotherapy papers in the Web of Science Core Collection. Various aspects of the publications were analyzed, and research hotspots and future trends were identified using scientific bibliometric tools and statistical methods. Results: We collected 592 English papers published between 2010 and 2023, with an almost annual increase. Most publications were from the USA, followed by China, Germany, and Italy. The journal "Frontiers in Immunology" had the most papers, and the most cited paper was Christiane A. Opitz's "An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor." The research is centered around AHR gene expression, with a growing focus on intestinal disease and the development of Programmed cell death ligand 1 (PD-L1) drugs. Conclusion: This bibliometric study highlights the significance of AHR in immunomodulatory research, outlining the research trends and key contributors. It suggests AHR's immune effects may mediate the process of colitis cancer transformation, providing valuable insights for future anti-tumor immunotherapy strategies based on AHR. [ABSTRACT FROM AUTHOR]

Seawater electrolysis using renewable electricity offers an attractive route to sustainable hydrogen production, but the sluggish electrode kinetics and poor durability are two major challenges. We report a molybdenum nitride (Mo2N) catalyst for the hydrogen evolution reaction with activity comparable to commercial platinum on carbon (Pt/C) catalyst in natural seawater. The catalyst operates more than 1000 hours of continuous testing at 100 mA cm−2 without degradation, whereas massive precipitate (mainly magnesium hydroxide) forms on the Pt/C counterpart after 36 hours of operation at 10 mA cm−2. Our investigation reveals that ammonium groups generate in situ at the catalyst surface, which not only improve the connectivity of hydrogen-bond networks but also suppress the local pH increase, enabling the enhanced performances. Moreover, a zero-gap membrane flow electrolyser assembled by this catalyst exhibits a current density of 1 A cm−2 at 1.87 V and 60 oC in simulated seawater and runs steadily over 900 hours. Efficient catalysts for seawater electrolysis are crucial for sustainable hydrogen production but struggle with slow kinetics and low durability. Here, the authors report a molybdenum nitride catalyst that in situ generates ammonium groups, enhancing both performance and stability in natural seawater. [ABSTRACT FROM AUTHOR]

Constacyclic BCH codes are an interesting subclass of constacyclic codes because of their important theoretical and practical value. The purpose of this paper is to study the parameters of cyclic BCH codes of length n = q m - 1 and negacyclic BCH codes of length n = q m - 1 2 . We settle completely their dimensions. We also determine the minimum distances of a class of cyclic BCH codes of length n = q m - 1 and give a lower bound on the minimum distances of other classes of constacyclic BCH codes. As seen by the code examples in this paper, the lower bound on the minimum distances of constacyclic BCH codes we gave is very close to the true minimum distances. These q -ary codes have good parameters in general. [ABSTRACT FROM AUTHOR]

The Shiyang River is an important ecological pillar in northwest China, sustaining Minqin oasis and its surrounding society. However, the basin has long been plagued by water scarcity and ecological fragility. Although the river classification is critical for understanding the complexity, diversity, and ecological functions of rivers, and the foundation of river management and watershed ecological restoration, it has not received adequate attention in this region. To obtain a deeper and comprehensive understanding of the Shiyang River, this study utilizes the Rosgen stream classification system to assess the river morphology, geomorphic features, and hydrologic processes. The results showed that seven first-level and fourteen second-level river types can be identified along 53 river sections of the Shiyang River. Further comparison analysis on the hydrologic parameters for each river type demonstrated a strong positive correlation between discharge and all river parameters. As discharge increased, channels with moderate to high width/depth ratios experienced significant lateral adjustments. A consistent channel gradient, coupled with higher discharge, facilitated the transition from single to multiple channels. Braiding tendencies were more pronounced in rivers where riverbeds were wider and shallower with higher stream power. Additionally, water-flow shear stress decreased with the increase in the width/depth ratio. This study offered critical insights into the Shiyang River's forms and processes and for the river management and ecological restoration practices. [ABSTRACT FROM AUTHOR]

Neuroinflammation is a common pathological feature in a number of neurodegenerative diseases, which is mediated primarily by the activated glial cells. Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome-associated neuroinflammatory response is mostly considered. To investigate the situation of the NLRP3-related inflammation in prion disease, we assessed the levels of the main components of NLRP3 inflammasome and its downstream biomarkers in the scrapie-infected rodent brain tissues. The results showed that the transcriptional and expressional levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein (ASC) in the brains of scrapie-infected rodents were significantly increased at terminal stage. The increased NLPR3 overlapped morphologically well with the proliferated GFAP-positive astrocytes, but little with microglia and neurons. Using the brain samples collected at the different time-points after infection, we found the NLRP3 signals increased in a time-dependent manner, which were coincidental with the increase of GFAP. Two main downstream cytokines, IL-1β and IL-18, were also upregulated in the brains of prion-infected mice. Moreover, the gasdermin D (GSDMD) levels, particularly the levels of GSDMD-NT, in the prion-infected brain tissues were remarkably increased, indicating activation of cell pyroptosis. The GSDMD not only co-localized well with the astrocytes but also with neurons at terminal stage, also showing a time-dependent increase after infection. Those data indicate that NLRP3 inflammasomes were remarkably activated in the infected brains, which is largely mediated by the proliferated astrocytes. Both astrocytes and neurons probably undergo a pyroptosis process, which may help the astrocytes to release inflammatory factors and contribute to neuron death during prion infection. [ABSTRACT FROM AUTHOR]

The dosing of fluconazole for young infants remains empirical because of the limited pharmacokinetic (PK) data. We aimed to establish a population PK model and assess the systematic exposure-response of commonly used regimens of fluconazole in Chinese infants. We included infants with a postnatal age of less than 120 days and received intravenous fluconazole. Both scheduled and scavenged plasma samples were collected, and fluconzaole concentration was determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using Phoenix NLME, and then Monte Carlo simulation was conducted to predict the probability of target attainment (PTA) of empirically used regimens of both prophylactic and therapeutic purposes. Based on 304 plasma samples from 183 young infants, fluconazole concentration data was best described by a one-compartment model with first-order elimination. Gestational Age (GA), postnatal age (PNA), and body weight (BW) were included in the final model as CL = 0.02*(GA/214)2.77*(PNA/13)0.24*exp(nCL); V = 1.56*(BW/1435)0.90*exp(nV). Model validation revealed the final model had qualified stability and acceptable predictive properties. Monte Carlo simulation indicated that under the same minimum inhibitory concentration (MIC) value and administration regimen, PTA decreased with GA and PNA. The commonly used prophylactic regimens can meet the clinical need, while higher doses might be needed for treatment of invasive candidiasis. This population PK model of fluconazole discriminated the impact of GA and PNA on CL and BW on V. Dosing adjustment was needed according to the GA and PNA of infants to achieve targeted exposures. [ABSTRACT FROM AUTHOR]

Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC. [ABSTRACT FROM AUTHOR]

The role of circadian rhythm genes (CRGs) in gastric cancer (GC) is poorly understood. This study aimed to develop a CRG signature to improve understanding of prognosis and immunotherapy responses in GC patients. We integrated the The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) dataset with CRGs to develop a prognostic signature for GC. The signature's predictive ability was validated using Kaplan-Meier and ROC curves. The CIBERSORT algorithm evaluated immune cell proportions, and tumor immune dysfunction and exclusion score, as well as immune phenotype score, determined the response to immunotherapy for STAD patients. Finally, we assessed signature genes expression using real-time quantitative polymerase chain reaction. We developed a 4-CRG signature for STAD, demonstrating accurate prognostic ability. The low-risk group showed increased B cell memory and CD8 + T cells, and decreased M2 Macrophages compared to the high-risk group. Patients in the low-risk group had a higher likelihood of benefiting from immunotherapy. Additionally, gastric cancer tissues exhibited elevated expression of OPN3 and decreased expression of TP53 compared to adjacent tissue. This study successfully established a prognostic signature for CRGs, accurately predicting prognosis and immunotherapeutic response among STAD patients, providing insights for the development of personalized therapeutic strategies for these patients. [ABSTRACT FROM AUTHOR]

This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P < 0.05). There was a notable relationship between blood Mn and NAFLD in crude model 1, which was still significant upon adjustment of all the identified covariates (all P < 0.05). Under Mn exposure, the cotinine-exposed group had a higher risk of NAFLD than the cotinine-unexposed group. In conclusion, blood Mn level is an independent risk factor for pediatric NAFLD, and cotinine exposure can enhance this relationship to some degree. Therefore, reducing cotinine exposure may alleviate detrimental consequences related to exposure to heavy metals in children. [ABSTRACT FROM AUTHOR]

Cellular communication network factor 2 (CCN2) is a secreted extracellular matrix-associated protein, and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis, chronic inflammation, or tissue injury, which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders. However, human phenotypes associated with CCN2 deficiency have remained enigmatic; variants in CCN2 have not yet been associated with a human phenotype. Here, we collected families diagnosed with spondyloepimetaphyseal dysplasia (SEMD), and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing. We identified a monoallelic variant in signal peptide of CCN2 (NM_001901.2: c.65 G > C [p.Arg22Pro]) as the cause of SEMD in 14 subjects presenting with different degree of short stature, premature osteoarthritis, and osteoporosis. Affected subjects showed decreased serum CCN2 levels. Cell lines harboring the variant displayed decreased amount of CCN2 proteins in culture medium and an increased intracellular retention, indicating impaired protein secretion. And the variant weakened the stimulation effect of CCN2 on osteogenesis of bone marrow mesenchymal stem cells. Zebrafish ccn2a knockout model and osteoblast lineage-specific Ccn2-deficient mice (Ccn2fl/fl;Prx1Cre) partially recapitulated the phenotypes including low bone mass observed in affected subjects. Pathological mechanism implicated in the skeletal abnormality in Ccn2fl/fl;Prx1Cre mice involved decreased bone formation, increased bone resorption, and abnormal growth plate formation. Collectively, our study indicate that monoallelic variants in CCN2 lead to a human inherited skeletal dysplasia, and highlight the critical role of CCN2 in osteogenesis in human. [ABSTRACT FROM AUTHOR]

To address the issue of low accuracy in soft sensor modeling of key variables caused by multi-variable coupling and parameter sensitivity in complex processes, this paper introduces a TSK-type-based self-evolving compensatory interval type-2 fuzzy Long short-term memory (LSTM) neural network (TSECIT2FNN-LSTM) soft sensor model. The proposed TSECIT2FNN-LSTM integrates the LSTM neural network with the interval type-2 fuzzy inference system to address long-term dependencies in sequence data by utilizing the gate mechanism of the LSTM neural network. The TSECIT2FNN-LSTM structure learning algorithm uses the firing strength of the network rule antecedent to decide whether to generate new rules to improve the rationality of the network structure. TSECIT2FNN-LSTM parameter learning utilizes the gradient descent method to optimize network parameters. However, unlike other interval type-2 fuzzy neural network gradient calculation processes, the error term in the LSTM node parameter gradient of TSECIT2FNN-LSTM is propagated backwards in the time dimension. Additionally, the error term is simultaneously transferred to the upper layer network to enhance network prediction accuracy and memory capabilities. The TSECIT2FNN-LSTM soft sensor model is utilized to predict the alcohol concentration in wine and the nitrogen oxide emission in gas turbines. Experimental results demonstrate that the proposed TSECIT2FNN-LSTM soft sensing model achieves higher prediction accuracy compared to other models. [ABSTRACT FROM AUTHOR]

This paper focuses on a question raised by Holm and Jørgensen, who asked if the induced cotorsion pairs (Φ(X), Φ(X)⊥) and (⊥Ψ(Y), Ψ(Y)) in Rep(Q, A)—the category of all A-valued representations of a quiver Q—are complete whenever (X, Y) is a complete cotorsion pair in an abelian category A satisfying some mild conditions. We give an affirmative answer if the quiver Q is rooted. As an application, we show under certain mild conditions that if a subcategory L, which is not necessarily closed under direct summands, of A is special precovering (resp., preenveloping), then Φ(L)(resp., Ψ(L)) is special precovering (resp., preenveloping) in Rep(Q, A). [ABSTRACT FROM AUTHOR]

A two-phase flow model accelerated by graphical processing unit (GPU) is developed to solve fluid-solid interaction (FSI) using the sharp-interface immersed boundary method (IBM). This model solves the incompressible Navier-Stokes equations using the projection-based fractional step method in a fixed staggered Cartesian grid system. A volume of fluid (VOF) method with second-order accuracy is employed to trace the free surface. To represent the intricate surface geometry, the structure is discretized using the unstructured triangle mesh. Additionally, a ray tracing method is employed to classify fluid and solid points. A high-order stable scheme has been introduced to reconstruct the local velocity at interface points. Three FSI problems, including wave evolution around a breakwater, interaction between a periodic wave train and a moving float, and a 3-D moving object interacting with the free surface, were investigated to validate the accuracy and stability of the proposed model. The numerical results are in good agreement with the experimental data. Additionally, we evaluated the computational performance of the proposed GPU-based model. The GPU-based model achieved a 42.29 times speedup compared with the single-core CPU-based model in the three-dimension test. Additionally, the results regarding the time cost of each code section indicate that achieving more significant acceleration is associated with solving the turbulence, advection, and diffusion terms, while solving the pressure Poisson equation (PPE) saves the most time. Furthermore, the impact of grid number on computational efficiency indicates that as the number of grids increases, the GPU-based model outperforms the multi-core CPU-based model. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs. ibrutinib to treat relapsed/refractory (R/R) CLL/SLL. Here we report results from the subgroup of Chinese patients. Adults with R/R CLL/SLL were randomized 1:1 to receive zanubrutinib (160 mg twice-daily) or ibrutinib (420 mg once-daily) until disease progression or unacceptable toxicity. Endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Data were analyzed descriptively. Ninety patients were randomized in China (zanubrutinib, n = 47; ibrutinib, n = 43). Baseline characteristics were balanced between groups, with fewer male patients in the zanubrutinib vs. ibrutinib group (55.3% vs. 69.8%). Median age was 60.5 years, 11% had del(17p) mutation, and 32% had tumor protein 53 (TP53) mutation. With median 25.3 months follow-up, ORR was 80.9% with zanubrutinib vs. 72.1% with ibrutinib. PFS was improved with zanubrutinib vs. ibrutinib (HR = 0.34 [95% CI, 0.15, 0.77]), and the HR for OS was 0.45 (95% CI, 0.14, 1.50). Rates of Grade ≥ 3 treatment-emergent adverse events (TEAEs; 64.4% vs. 72.1%), AEs leading to discontinuation (6.4% vs. 14.0%), and serious TEAEs (35.6% vs. 51.2%) were lower with zanubrutinib vs. ibrutinib. Zanubrutinib demonstrated improved ORR, PFS, and OS vs. ibrutinib and a more favorable safety profile in patients with R/R CLL/SLL in China. These results are consistent with the full global population of ALPINE. ClinicalTrials.gov: NCT03734016, registered November 7, 2018. [ABSTRACT FROM AUTHOR]

This study aimed to develop an interpretable diagnostic model for subtyping of pulmonary adenocarcinoma, including minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), and invasive adenocarcinoma (IAC), by integrating 3D-radiomic features and clinical data. Data from multiple hospitals were collected, and 10 key features were selected from 1600 3D radiomic signatures and 11 radiological features. Diverse decision rules were extracted using ensemble learning methods (gradient boosting, random forest, and AdaBoost), fused, ranked, and selected via RuleFit and SHAP to construct a rule-based diagnostic model. The model's performance was evaluated using AUC, precision, accuracy, recall, and F1-score and compared with other models. The rule-based diagnostic model exhibited excellent performance in the training, testing, and validation cohorts, with AUC values of 0.9621, 0.9529, and 0.8953, respectively. This model outperformed counterparts relying solely on selected features and previous research models. Specifically, the AUC values for the previous research models in the three cohorts were 0.851, 0.893, and 0.836. It is noteworthy that individual models employing GBDT, random forest, and AdaBoost demonstrated AUC values of 0.9391, 0.8681, and 0.9449 in the training cohort, 0.9093, 0.8722, and 0.9363 in the testing cohort, and 0.8440, 0.8640, and 0.8750 in the validation cohort, respectively. These results highlight the superiority of the rule-based diagnostic model in the assessment of lung adenocarcinoma subtypes, while also providing insights into the performance of individual models. Integrating diverse decision rules enhanced the accuracy and interpretability of the diagnostic model for lung adenocarcinoma subtypes. This approach bridges the gap between complex predictive models and clinical utility, offering valuable support to healthcare professionals and patients. [ABSTRACT FROM AUTHOR]

Aberrant long non-coding RNA (lncRNA) expression has been shown to be involved in the pathological process of pre-eclampsia (PE), yet only a small portion of lncRNAs has been characterized concerning the function and molecular mechanisms involved in PE. This study aimed to investigate the regulatory mechanism of the lncRNA AC092100.1 (AC092100.1) in angiogenesis in PE. In our study, bioinformatics analysis was performed to screen for differentially expressed lncRNAs between normal subjects and PE patients. The levels of AC092100.1 in placental tissues of patients with or without PE were validated using qRT-PCR. The effect of AC092100.1 overexpression on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was investigated. The binding of AC092100.1 and YT521-B homology domain-containing 2 (YTHDC2) was predicted and verified. The effect of AC092100.1/YTHDC2 on the expression of vascular endothelial growth factor-A (VEGFA) in HUVECs was determined. Finally, a PE mice model was conducted. Fetal mouse growth, the abundance of mesenchymal morphology markers, including hypoxia-inducible factor 1-alpha (HIF-1α), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), Slug, and Vimentin, and endothelial markers, including placental growth factor (PLGF), CD31, and vascular endothelial (VE)-cadherin, in placental tissues were assessed. Here, we found that AC092100.1 was abnormally downregulated in placental tissues from PE patients. We established that AC092100.1 overexpression promoted HUVEC proliferation, migration, and tube formation in vitro. Mechanistically, AC092100.1 induced the accumulation of YTHDC2 and VEGFA through binding to YTHDC2 in HUVECs. Inhibition of YTHDC2 or VEGFA reversed AC092100.1-promoted tube formation. AC092100.1 overexpression contributed to alleviating fetal growth disorder, decreased levels of sEng, HIF-1α, sFlt-1, Slug, and Vimentin, and increased levels of VEGFA, PLGF, CD31, and VE-cadherin in PE mice. Our findings provided evidence supporting the role of the AC092100.1/YTHDC2/VEGFA axis in regulating angiogenesis, which demonstrated a therapeutic pathway for PE targeting angiogenesis. [ABSTRACT FROM AUTHOR]

Objective: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. Methods: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. Results: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. Conclusion: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC. [ABSTRACT FROM AUTHOR]

In this study, we have reported spatial and temporal variation in particulate matter (PM), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3) over five provincial capital cities in northwestern China during 2013–2020. Regarding the seasonal variation, all pollutants (except ozone) exhibited the lowest concentration during summer and the highest concentration during winter, which could be attributed to increased anthropogenic activities (like coal burning) and conducive meteorological features. The highest monthly mean concentrations were primarily observed during December-February, whereas ozone exhibited the highest concentration during April-August, with different cities experiencing the highest concentration during different seasons. Regarding the diurnal variation exhibited by the pollutants, the lowest concentration of pollutants (except O3) was observed during the late afternoon (17:00–18:00) period. Ozone posed the urban site diurnal variation characteristic (peak during afternoon hour) over all sites. Urumqi had the highest PM2.5/PM10 ratio during November-March and the lowest ratio during April-October. Compared to the WHO revised guideline, the annual mean PM2.5 concentration was about 8–12 times higher, whereas the annual PM10 concentration was exceeded by a factor of up to 7. Most pollutants exhibited reduced concentration during the spring festival period. Analysis using HYSPLIT back trajectories indicated that the air masses affecting the five sites primarily originated from the northwestern area of China, although the impact of long-range pollution transport from remote regions should not be overlooked. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model's performance was evaluated using Harrell's C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P < 0.001) and 8.16 in the internal test set (95% CI: 2.5, 26.8; P < 0.001). The multimodal model demonstrated a C-index of 0.76 in the internal test set and a C-index of 0.64 in the external test set. Comparative analysis against FIGO staging revealed an NRI of 0.06 (P < 0.001) for the multimodal model. The model presents opportunities for prognostic assessment, treatment strategizing, and ongoing patient monitoring. [ABSTRACT FROM AUTHOR]