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This study aimed to master the self-resetting performance and working mechanism of superelastic shape memory alloy fibers reinforced engineered cementitious composite (SMAF-ECC) beams. Four SMAF-ECC pre-cut beams were fabricated. The three-point bending test was used to analyze the changes in mid-span deflection and crack width under different shape memory alloy (SMA) fibers lengths and end forms. And the stress of SMA fiber was analyzed by ABAQUS. Finally, the working mechanism of SMA fiber was revealed. The results showed that SMAF-ECC specimens perform well in deformation recovery and crack closure. Among them, the maximum deflection self-recovery rate of the specimen was 83.6%. And compared to the engineered cementitious composite (ECC) specimen, the residual crack width was reduced by 76.62% to 84.01%. In addition, reducing the length and diameter of the SMA fiber increased its stress. However, the length of SMA fiber had little effect on the deflection self-recovery rate of SMAF-ECC specimens, and the maximum difference between the specimens with different SMA fiber lengths was only 1.1%. The working mechanism of SMA fiber included four stages: linear elastic, descent, platform, and deformation strengthening stage. After the SMA fiber entered the platform phase, the residual deformation of the specimen was significantly reduced. When entering the deformation strengthening stage, the SMA fiber not only improved the bearing capacity of the specimen, but also provided greater restoring force, considerably improved the specimen's self-resetting performance. This paper offered a theoretical basis for the design of self-resetting beams. [ABSTRACT FROM AUTHOR]

AbstractThis paper presented a mechanics-based method to address the typical lateral stability issue of railway trains. A Base Electric Multiple Unit (Base EMU) and an upgraded EMU were used as the research objects. Mechanics-based models were developed for both systems; the Base EMU model was validated using actual test data. Different wheel-rail equivalent conicity values and suspension parameters were investigated. The results showed that inadequate wheel-rail guiding capacity under low conicity can led to the occurrence of lateral stability issues. When the train is pushed by motor cars, coupler lateral forces aggravate stability issues. Altering the yaw damper’s angle and damping properties can significantly reduce lateral swaying and improve the ride index. This represents a low-cost and favored solution. Decreasing the stiffness of the axle box pull rod is also effective in mitigating low-frequency lateral swaying. [ABSTRACT FROM AUTHOR]

Calcium sulfoaluminate (CSA) cement was used as an internal admixture to replace some of the magnesium oxide (MgO) in magnesium ammonium phosphate cement (MAPC) coatings. This experiment resulted in improved corrosion resistance and production cost savings for MAPC coatings on carbon steel surfaces. The corrosion resistance of coated carbon steel with different CSA doping concentrations was evaluated by electrochemical methods including Tafel polarization curves and electrochemical impedance spectroscopy (EIS). At the same time, 7-day flexural and compressive tests, Low-field nuclear magnetic resonance spectroscopy (NMR) test, X-ray diffraction (XRD), scanning electron microscope (SEM), and thermogravimetric and differential thermogravimetric techniques (TG-DTG) were performed on the modified coatings. Neutral salt spray tests confirmed the improved corrosion resistance of the coated carbon steel. Based on the results of the study, the best ratio of CSA-modified MAPC coatings was finalized. The addition of CSA improved the flexural and compressive strength of MAPC. At later stages of immersion, there was an increase in the polarization resistance value, and a significant increase in the anodic slope of the polarization curve. Furthermore, the overall low-frequency impedance value, coatings resistance, and charge transfer resistance all experienced a substantial increase. The microstructural study revealed that Ca4Al6O12(SO4) gradually hydrated during immersion to produce amorphous hydrated calcium sulfoaluminate gel, significantly improving the anticorrosion performance of the coated carbon steel. After the coated carbon steel were exposed to a neutral salt spray environment for 1,440 h, there was no bulging or flaking of the coatings surface, and no rusting of the carbon steel surface. The modified coatings effectively served as a protective layer. [ABSTRACT FROM AUTHOR]

AbstractFor the integrated system incorporating a low-cost inertial measurement unit (IMU) and global navigation satellite system (GNSS), rapid and accurate initial heading alignment is still a significant challenge, especially for marine applications in challenging ocean conditions. To overcome this difficulty, we propose an in-motion coarse heading alignment method using single-antenna GNSS and a low-grade IMU based on the basic principle of trajectory similarity. The heading angle is determined by dead reckoning (DR)-derived trajectory and GNSS-derived trajectory using gyro measurements and GNSS positioning solutions. The proposed alignment method can be implemented in real-time and the alignment period is just 1s, which indicates that the method could continuously output heading when the carrier is in motion. Therefore, the continuous heading output calculated by the proposed algorithm can be applied to the state and fault detection of the carrier. Experimental results show that the heading could be determined with an accuracy of 0.48°, 3.14°, and 2.43° at a 95% confidence level for the land vehicle, unmanned surface vessel (USV), and unmanned underwater vehicle (UUV) tests, respectively. Besides, the RMS of the alignment errors calculated by our method reaches 0.20°, 1.42°, and 1.22° for the land vehicle, USV, and UUV tests, respectively. [ABSTRACT FROM AUTHOR]

A new wave of research interests on train braking dynamics has been raised which requires more accurate and faster train braking dynamics simulations. Simulations with fully nonlinear fluid dynamic air brake models and nonlinear friction draft gear models are more accurate, however these are not yet available. This paper developed a model that has combined both of these aspects. Simulations were achieved by using a parallel co-simulation method which requires minimum working loads to merge legacy codes. A case study was carried out to simulate a heavy haul train braking commencing with a minimum service brake and then followed by a full-service brake before the minimum service brake was fully executed. Such transient simulations were not able to be accurately conducted by using empirical air brake models, but only by using fluid dynamic air brake models. Influences of co-simulation synchronization frequencies on computing time and results of the simulations were also investigated. Simulation results have recommended a synchronization frequency of 100 Hz. The corresponding simulation was 43% faster than real-time for a 152-vehicle train. [ABSTRACT FROM AUTHOR]

We investigated Andreev reflection of graphene-based normal/superconductor single and double junctions under the modulation of non-resonant circularly polarized light, staggered potential, and exchange field. In the graphene-based normal/superconductor single junction, we discovered that the circularly polarized light can adjust the bandgap of retro Andreev reflection and specular Andreev reflection. The exchange field can change the position of the transition point between retro Andreev reflection and specular Andreev reflection. In the graphene-based normal/superconductor/normal double junction, when the light field is modulated from left circularly polarized light to right circularly polarized light, the valley-spin switching effect between pure elastic co-tunneling and pure crossed Andreev reflection can be realized. By changing the exchange field, we achieved the conversion of non-local transport between pure elastic co-tunneling and pure crossed Andreev reflection. In addition, the energy location and range of crossed Andreev reflection and elastic co-tunneling can be controlled by the staggered potential and the exchange field. Our results suggest that the device can implement light and exchange field control of the Andreev reflection process and the spin-valley switch. [ABSTRACT FROM AUTHOR]

Recent studies suggest a shared genetic architecture between muscle and bone, yet the underlying molecular mechanisms remain elusive. This study aims to identify the functionally annotated genes with shared genetic architecture between muscle and bone using the most up-to-date genome-wide association study (GWAS) summary statistics from bone mineral density (BMD) and fracture-related genetic variants. We employed an advanced statistical functional mapping method to investigate shared genetic architecture between muscle and bone, focusing on genes highly expressed in muscle tissue. Our analysis identified three genes, EPDR1, PKDCC, and SPTBN1, which are highly expressed in muscle tissue and previously unlinked to bone metabolism. About 90% and 85% of filtered Single-Nucleotide Polymorphisms were in the intronic and intergenic regions for the threshold at P≤5×10−8 and P≤5×10−100, respectively. EPDR1 was highly expressed in multiple tissues, including muscles, adrenal glands, blood vessels, and the thyroid. SPTBN1 was highly expressed in all 30 tissue types except blood, while PKDCC was highly expressed in all 30 tissue types except the brain, pancreas, and skin. Our study provides a framework for using GWAS findings to highlight functional evidence of crosstalk between multiple tissues based on shared genetic architecture between muscle and bone. Further research should focus on functional validation, multi-omics data integration, gene-environment interactions, and clinical relevance in musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

The design of aqueous zinc (Zn) chemistry energy storage with high rate‐capability and long serving life is a great challenge due to its inhospitable coordination environment and dismal interfacial chemistry. To bridge this big gap, herein, we build a highly reversible aqueous Zn battery by taking advantages of the biomass‐derived cellulose nanocrystals (CNCs) electrolyte additive with unique physical and chemical characteristics simultaneously. The CNCs additive not only serves as fast ion carriers for enhancing Zn2+ transport kinetics but regulates the coordination environment and interface chemistry to form dynamic and self‐repairing protective interphase, resulting in building ultra‐stable Zn anodes under extreme conditions. As a result, the engineered electrolyte system achieves a superior average coulombic efficiency of 97.27 % under 140 mA cm−2, and steady charge–discharge for 982 h under 50 mA cm−2, 50 mAh cm−2, which proposes a universal pathway to challenge aqueous Zn chemistry in green, sustainable, and large‐scale applications. [ABSTRACT FROM AUTHOR]

The design of aqueous zinc (Zn) chemistry energy storage with high rate‐capability and long serving life is a great challenge due to its inhospitable coordination environment and dismal interfacial chemistry. To bridge this big gap, herein, we build a highly reversible aqueous Zn battery by taking advantages of the biomass‐derived cellulose nanocrystals (CNCs) electrolyte additive with unique physical and chemical characteristics simultaneously. The CNCs additive not only serves as fast ion carriers for enhancing Zn2+ transport kinetics but regulates the coordination environment and interface chemistry to form dynamic and self‐repairing protective interphase, resulting in building ultra‐stable Zn anodes under extreme conditions. As a result, the engineered electrolyte system achieves a superior average coulombic efficiency of 97.27 % under 140 mA cm−2, and steady charge–discharge for 982 h under 50 mA cm−2, 50 mAh cm−2, which proposes a universal pathway to challenge aqueous Zn chemistry in green, sustainable, and large‐scale applications. [ABSTRACT FROM AUTHOR]

Detailed simulations of car and train platoons are critical steps towards successful implementations of the platooning technologies. This paper developed a simulation method that can be used for both car and train platoon simulations. The method includes three main parts: (1) a scalable adaptive longitudinal space controller, (2) 2D multibody dynamics simulations that consider wheel-rail contact (Polach model), tyre-road contact (Magic Formula), suspensions and in-train forces, and (3) a scalable parallel computing method that processes the dynamics simulation of each individual vehicle (one car or one carriage) by using one independent computer core. Two case studies were conducted to simulate a 6-car platoon and a 3-train platoon on real-world road and track. The maximum space errors for the car platoon and the train platoon results were about 0.32 and 0.23 m, respectively. When the platoons were running at a steady speed, space errors were well controlled within ±0.05 m for both car and train platoons. Example dynamics results were presented including wheel-rail contact forces, tyre-road contact forces, and carbody vibrations. This information can be used to conduct a wide range of related studies such as passenger ride comfort and system damage assessments. [ABSTRACT FROM AUTHOR]

The information that automated train control (ATO) systems use to improve safety and reduce power usage is limited by on-board and wayside monitoring applications and computing power. This paper presents an augmented digital twin for railway applications that enables real-time consideration of derailment risk in train operations. The augmented digital twin implements a surrogate model with the results of a massive multibody dynamics numerical program and machine learning models to predict the instantaneous wagon derailment risk. A case study for a heavy haul iron ore wagon with three-piece bogies was conducted to test the augmented digital twin. A multibody simulation numerical program comprising 2100 simulation cases was completed. The surrogate model was developed using linear, polynomial, decision tree and ensemble forest regression models on the results of the numerical program. A longitudinal train simulator was used to calculate the speed and lateral coupler force throughout a train trip. The surrogate model effectively predicted the derailment index for empty and loaded conditions accounting for lateral coupler forces, vehicle speeds and curve radius. The proposed augmented digital twin can be further developed to accomplish other train operational benefits such as the reduction of rail damage. [ABSTRACT FROM AUTHOR]

Through questionnaire data and in-depth interview analysis, based on the perspective of villagers' perception, the vulnerability of tourism development and overall rural vulnerability in Hetou Village of Guangdong Province are systematically evaluated. Research has shown that the tourism industry has improved economic benefits and living conditions, but it has also brought pressure to the life of villagers. While promoting the inheritance of distinctive culture, the tourism industry faces problems of excessive commercialization and uneven development, which affects the social atmosphere. The perception of villagers towards tourism development includes the understanding of an increase in employment barriers, low economic benefits, and insufficient skills training. The income instability and changes in social atmosphere in the tourism industry have attracted attention, but there are also positive effects such as promoting the development of festival culture. In terms of environment, it includes environmental pollution, damage to traditional buildings, and chaotic management of tourism development. In terms of rural vulnerability, sensitivity is the main factor, followed by adaptability and exposure risk. There are problems in the development of Hetou Village, including limited land use, limited development of stakeholders, loss of young labor force, poor stability of livelihood capital, immature industrial development model, incomplete product research and development chain, weak investment willingness of villagers, unexplored historical and cultural factors, lack of professional technical training, and inadequate talent cultivation system. Finally, optimization suggestions are put forward from the aspects of protecting the ecological environment, reducing natural disaster risks, increasing villagers participation, introducing and retaining talents, enriching business models, promoting industrial integration, focusing on agricultural development, and improving capital stability, in order to increase employment channels, improve industrial development levels, stabilize village collective income, improve people's quality of life, and reduce the risk of returning to poverty. [ABSTRACT FROM AUTHOR]

Streptomyces are one of the most prolific sources of bioactive and structurally diverse secondary metabolites for natural product drug discovery. Genome sequencing and bioinformatics analysis revealed that the genomes of Streptomyces harbor a wealth of cryptic secondary metabolite biosynthetic gene clusters that could encode novel compounds. In this work, a genome mining approach was employed to investigate the biosynthetic potential of Streptomyces sp. HP-A2021, isolated from rhizosphere soil of Ginkgobiloba L. The complete genome of HP-A2021 was sequenced and contained the 9,607,552 base pair linear chromosome with a GC content of 71.07%. The annotation results revealed the presence of 8534 CDSs, 76 tRNA genes, and 18 rRNA genes in HP-A2021. The highest dDDH and ANI values based on genome sequences between HP-A2021 and the most closely related type strain, Streptomycescoeruleorubidus JCM 4359, were 64.2% and 92.41%, respectively. In total, 33 secondary metabolite biosynthetic gene clusters with an average length of 105,594 bp were identified, including the putative thiotetroamide, alkylresorcinol, coelichelin, and geosmin. The antibacterial activity assay confirmed that the crude extracts of HP-A2021 showed potent antimicrobial activity against human pathogenic bacteria. Our study demonstrated that Streptomyces sp. HP-A2021 will propose a potential use in biotechnological and novel bioactive secondary metabolite biosynthetic applications. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs)-based therapy in proficient mismatch repair (pMMR)/non-microsatellite instability-high (non-MSI-H) metastatic colorectal cancer (mCRC). Methods: Electronic databases were screened to identify relevant trials. The primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). Stratified analysis was accomplished on ICIs-based regimens, treatment lines and RAS status. Results: Totally, 1723 mCRC patients from 39 cohorts were included. The pooled ORR, DCR, 12-month overall survival (OS) rate and 6-month progression-free survival (PFS) rate of ICIs-based therapy in pMMR/non-MSI-H mCRC were 8.5% (95% CI: 4.4%-13.5%), 48.2% (95% CI: 37.8%-58.6%), 52.3% (95% CI: 46.4%-58.1%) and 32.8% (95% CI: 23.5%-42.7%) respectively. As a whole, no significantly differences were shown between ICIs-based and non-ICIs-based therapy for pMMR/non-MSI-H mCRC in terms of both PFS (HR = 1.0, 95% CI: 0.9–1.1, P = 0.91) and OS (HR = 1.0, 95% CI: 0.9–1.2, P = 0.51). It was worth noting that the addition of ICIs to anti-vascular endothelial growth factor (VEGF) agent plus chemotherapy displayed excellent efficacy in pMMR/non-MSI-H mCRC (ORR = 42.4%, 95% CI: 10.0%-78.6%; DCR = 92.0%, 95% CI: 68.3%-100.0%; 12-month OS rate = 71.4%, 95% CI: 50.0%-89.1%; 6-month PFS rate = 55.2%, 95% CI: 24.8%-83.8%; and PFS (compared with non-ICIs-based therapy): HR = 0.9, 95% CI: 0.8–1.0, P = 0.02), especially served as first-line therapy (ORR = 74.2%, 95% CI: 61.4%-85.4%; DCR = 98.7%, 95% CI: 92.0%-100.0%); and without additional treatment related adverse events (TRAEs) were observed. Conclusions: ICIs-based combination therapy, especially the addition of ICIs to first-line anti-VEGF agent plus chemotherapy, is promising in pMMR/non-MSI-H mCRC with good efficacy and controllable toxicity. [ABSTRACT FROM AUTHOR]

This paper developed a parallel computing architecture for high-fidelity virtual coupling simulations. Multi-body train dynamics models considered various nonlinear components including wheel-rail contact, suspensions, and inter-vehicle connections. A virtual coupling controller was developed which can be implemented under various train-to-train communication topologies. The controller also allows existing trains to leave the platoon and new trains to merge into the platoon without re-designing the controller. The parallel computing architecture is also scalable and not limited by: the number of vehicles in each train; the number of trains in each train platoon and the topology of train-to-train communications. A case study by simulating a three-train (18 vehicles in total) platoon on a real-world track section was conducted. The results show that, by using 19 computer cores, parallel computing speed is nearly twice as fast as real-time. Parallel computing is about 17 times faster than serial computing. The results also show that the maximum spacing errors of the follower trains were about 0.22 m. Dynamics results such as wheel-rail contact forces, suspension forces, carbody vibrations and inter-vehicle forces were obtained; these results can be used to conduct system assessments in terms of passenger ride comfort, mechanical wear, etc. [ABSTRACT FROM AUTHOR]

Although graphene has excellent electrical and mechanical properties, the giant delocalized π-electron system makes it chemically inert. Here, we propose an idea to design two-dimensional (2D) carbon allotropes via incorporating multiple rings in sp2-hybridized carbon networks, which can break the π-bonding network and enhance the surface reactivity. By assembling molecule of cyclobut(a)acenaphthylene, we predict a monolayer 2D carbon material, named as R12-graphene, which is composed of quadrilateral, pentagonal, hexagonal, and dodecagonal carbon rings. It shows great stability in energetic, dynamic, thermodynamic, and mechanical aspects. It exhibits high-performance as an anode material for potassium-ion batteries (PIBs), including an intrinsic metallic behavior, a high theoretical capacity (632 mA h g−1), a low K diffusion barrier (0.33 eV), and a low average open-circuit voltage (0.5 V). The presence of electrolytes can provide better K ion adsorption and diffusion capability compared to that in vacuum. Furthermore, R12-graphene has excellent wettability toward some commonly used electrolytes, which is beneficial for improving the charge/discharge rate for PIBs. [ABSTRACT FROM AUTHOR]

Background: This study targeted at developing a robust, prognostic signature based on super-enhancer-related genes (SERGs) to reveal survival prognosis and immune microenvironment of breast cancer. Methods: RNA-sequencing data of breast cancer were retrieved from The Cancer Genome Atlas (TCGA), 1069 patients of which were randomly assigned into training or testing set in 1:1 ratio. SERGs were downloaded from Super-Enhancer Database (SEdb). After which, a SERGs signature was established based on the training set, with its prognostic value further validated in the testing set. Subsequently, we identified the potential function enrichment and tumor immune infiltration of the model. Moreover, in vitro experiments were completed to further explore the biological functions of ZIC2 gene (one of the risk genes in the prognostic model) in breast cancer. Results: A risk score system of prognostic value was constructed with 6 SERGs (ZIC2, NFE2, FOXJ1, KLF15, POU3F2 and SPIB) to find patients in high-risk group with significantly worse prognosis in both training and testing sets. In addition, a multivariate regression was established via integrating the 6 genes with age and N stage, indicating well performance by calibration, time-dependent receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Further analysis demonstrated that tumor-associated pathological processes and pathways were significantly enriched in the high-risk group. In general, the novel SERGs signature could be applied to screen breast cancer with immunosuppressive microenvironment for the risk score was negatively correlated with ESTIMATE score, tumor-infiltration lymphocytes (such as CD4 + and CD8 + T cell), immune checkpoints and chemotactic factors. Furthermore, down-regulation of ZIC2 gene expression inhibited the cell viability, cellular migration and cell cycle of breast cancer cells. Conclusions: The novel SERGs signature could predict the prognosis of breast cancer; and SERGs might serve as potential therapeutic targets for breast cancer. [ABSTRACT FROM AUTHOR]

All-solid-state Tm lasers have a wider wavelength range and higher output power compared to other types of lasers. In this work, we demonstrate an all-solid-state, high repetition, Tm:YAP laser Q-switched by a graphdiyne (GDY) saturable absorber. The high-quality optical nonlinear material GDY, synthesized by a cross-coupling method, exhibits a strong nonlinear optical response. The application of GDY as a saturable absorber in the passively Q-switched (PQS) Tm:YAP of an all-solid-state laser has been realized with the shortest pulse duration of ~785 ns and repetition frequency of ~199.6 kHz at a central wavelength of 1985.8 nm. This represents the shortest pulse duration and the highest repetition frequency achieved from GDY in a solid-state Tm laser to date. Our work demonstrates the remarkable nonlinear optical properties of GDY, which holds promising potential in the field of optoelectronics. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of personalized nursing on the therapeutic effect on patients with laryngeal squamous cell carcinoma (LSCC) combined with Helicobacter pylori (HP) infection after surgery. Methods: This study enrolled 46 patients with LSCC as research subjects. The patients were divided into an experimental group and a control group using the random number table method. Routine nursing was provided in the control group, and individualized nursing intervention was conducted in the experimental group based on routine nursing. The incidence of adverse reactions (ARs) and the patients' nursing satisfaction were compared between the two groups. Results: Compared with the control group, the individualized nursing intervention reduced the incidence of ARs of esophageal reflux (P < 0.05) and improved nursing satisfaction (P < 0.05). Conclusion: Individualized nursing intervention reduced the incidence of esophageal reflux ARs in patients with LSCC and HP infection after tracheotomy and improved both the therapeutic effect of the treatment and the satisfaction of the patients. [ABSTRACT FROM AUTHOR]

Mitochondria are a crucial energy source for maintaining neuronal growth and synaptic function. Neurons possess unique morphological characteristics, which make the proper regulation of mitochondrial transport essential for meeting their energy demands. Syntaphilin (SNPH) is capable of specifically targeting the outer membrane of axonal mitochondria, anchoring them to microtubules, and thereby preventing their transport. SNPH also interacts with other mitochondrial proteins to regulate mitochondrial transport. The regulation of mitochondrial transport and anchoring mediated by SNPH is indispensable for axonal growth during neuronal development, maintenance of ATP levels during neuronal synaptic activity, and regeneration of mature neurons following damage. Precise blocking of SNPH may be an effective therapeutic strategy for neurodegenerative diseases and related mental disorders. [ABSTRACT FROM AUTHOR]

Cell pyroptosis has a reciprocal relationship with various cancer treatment modalities such as chemotherapy. However, the tumor microenvironment, characterized by hypoxia, substantially restricts the development and application of tumor therapies that integrate cell pyroptosis. Therefore, the cascade amplification of oxidative stress by interfering with redox homeostasis in tumors may be a promising approach. In this study, black phosphorus (BP) nanosheets and a glutathione peroxidase 4 inhibitor (RSL3) were coloaded into a thermosensitive PDLLA-PEG-PDLLA (PLEL) hydrogel (RSL3/BP@PLEL). Owing to the photothermal property of BP nanosheets, the RSL3/BP@PLEL hydrogel may trigger the release of loaded drugs in a more controllable and on-demand manner. Investigation of the antitumor effect in a mouse liver tumor model demonstrated that local injection of the hydrogel formulation in combination with near infrared laser irradiation could efficiently suppress tumor growth by interfering with the redox balance in tumors. Mechanistic study indicated that the combined treatment of photothermal therapy and glutathione depletion based on this hydrogel efficiently induced cell pyroptosis through both caspase-1/GSDMD and caspase-3/GSDME pathways, thereby triggering the repolarization of tumor-associated macrophages from M2 to M1. Overall, we developed a biocompatible and biodegradable hydrogel formulation for application in combination cancer treatment, providing a new platform for enhancing the efficacy of cancer therapy by amplifying cell pyroptosis and apoptosis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian endometrioma patients and evaluate the influence on ovarian reserve. Materials and methods: This prospective randomized controlled study included 88 women with unilateral ovarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian endometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one cycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group LLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day 3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were measured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured at several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall were measured. Results: Before surgery, serum AMH levels decreased in both groups from preoperative to one week and six months postoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative one week and postoperative six months (1.87 ± 0.97 vs. 1.31 ± 0.93, P = 0.07; 1.91 ± 1.06 vs. 1.54 ± 0.93, P = 0.001). The mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP, significantly higher than those in group LLP (25.83% vs. 31.43%, P < 0.001). Ovarian endometrioma wall AMH of group LLP was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P < 0.001). Meanwhile, ovarian endometrioma LE concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). There was also a significant inverse correlation between leukocyte esterase and AMH concentration in an ovarian endometrioma cyst wall (r=-0.564, P<0.001). Conclusion(s): The optimal time for laparoscopic cystectomy for patients with first identified unilateral ovarian endometrioma is the late luteal phase, which reduces ovarian tissue loss and preserves ovarian reserve effectively and safely. [ABSTRACT FROM AUTHOR]

The actual protective performance of the coated reinforcement in coral concrete was investigated by measuring the chloride ion diffusion coefficient, electrochemical analysis, and numerical simulation. The test results show that the corrosion rate of coated reinforcement in coral concrete under the action of wet and dry cycles is kept at a low level, and the Rp value is always greater than 250 kΩ·cm2 during the test period, which is in the uncorroded state and has good protection performance. Moreover, the chloride ion diffusion coefficient D is in accordance with the power function relationship with the wet and dry cycle time, and a time-varying model of chloride ion concentration on the surface of coral concrete is established. The surface chloride ion concentration of coral concrete reinforcement was modeled as a time-varying model; the cathodic zone of coral concrete members was the most active, increasing from 0 V to 0.14 V from 0 to 20 years, with a large increase in potential difference before the 7th year, and a significant decrease in the increase after the 7th year. [ABSTRACT FROM AUTHOR]

Background: Previous study has established two polygenic scores (PGSs) related to femoral neck bone mineral density (BMD) (PGS_FNBMDldpred) and total body BMD (PGS_TBBMDldpred) that are associated with fracture risk. However, these findings have not yet been externally validated in an independent cohort. Objectives: This study aimed to validate the predictive performance of the two established PGSs and to investigate whether adding PGSs to the Fracture Risk Assessment Tool (FRAX) improves the predictive ability of FRAX in identifying women at high risk of major osteoporotic fracture (MOF) and hip fractures (HF). Methods: The study used the Women's Health Initiative (WHI) cohort of 9,000 postmenopausal women of European ancestry. Cox Proportional Hazard Models were used to assess the association between each PGS and MOF/HF risk. Four models were formulated to investigate the effect of adding PGSs to the FRAX risk factors: (1) Base model: FRAX risk factors; (2) Base model + PGS_FNBMDldpred; (3) Base model + PGS_TBBMDldpred; (4) Base model + metaPGS. The reclassification ability of models with PGS was further assessed using the Net Reclassification Improvement (NRI) and the Integrated discrimination improvement (IDI). Results: The study found that the PGSs were not significantly associated with MOF or HF after adjusting for FRAX risk factors. The FRAX base model showed moderate discrimination of MOF and HF, with a C-index of 0.623 (95% CI, 0.609 to 0.641) and 0.702 (95% CI, 0.609 to 0.718), respectively. Adding PGSs to the base FRAX model did not improve the ability to discriminate MOF or HF. Reclassification analysis showed that compared to the model without PGS, the model with PGS_TBBMDldpred (1.2%, p = 0.04) and metaPGS (1.7%, p = 0.05) improve the reclassification of HF, but not MOF. Conclusions: The findings suggested that incorporating genetic information into the FRAX tool has minimal improvement in predicting HF risk for elderly Caucasian women. These results highlight the need for further research to identify other factors that may contribute to fracture risk in elderly Caucasian women. [ABSTRACT FROM AUTHOR]

In this work, the authors present a detailed train-track interaction model of a long freight train operation to predict long-term rail surface damage. In addition to vehicles and track, intermediate maintenance actions in the form of cyclic grinding passes have also been modelled according to European standards to realistically represent the evolving wheel-rail interface. The influence of longitudinal train dynamics in the form of inter-vehicle interactions, traction, braking, gradients, etc is also included in this method to reflect their effect on damage evolution. The authors demonstrate that the novel 'Train-track interaction' formulation is more complete and therefore better suited to study long-term rail surface damage as opposed to existing 'vehicle-track' formulations since the former brings the system dynamics at play, significantly altering the wheel-rail interaction. A key highlight of this work is that the rail surface damage is expressed in the form of evolving rail profiles over a large tonnage passing and by depicting RCF-affected zones. This framework can be tuned into a digital twin to guide infrastructure managers regarding the condition of rail surface as a function of tonnage passage. This can in turn facilitate predictive maintenance of track depending on traffic and operation. [ABSTRACT FROM AUTHOR]

The efficacy of photodynamic therapy (PDT) is still limited by the inefficient utilisation of generated ROS in tumours due to cellular redox homeostasis. To improve the therapeutic efficacy for oral carcinoma, biomimetic cell membrane-coated mesoporous nanoplatform was tailored to interfere with cellular redox homeostasis for amplified PDT. In this study, CAL-27 cancer cell membrane (CM) was encapsulated onto the mesoporous silica NPs (MSN), which were preloaded with Chlorin e6 (Ce6) and Curcumin (Cur). The biomimetic nanoparticles displayed a size of around 120 nm, which had excellent cytotoxicity under a laser and increased uptake ability to tumour cell. After internalised by cancer cells, the released Cur could effectively disturb ROS-defence system by suppressing TrxR activity, and decreasing TrxR-2 expression (p < 0.05), leading to enhanced cancer cell killing ability of PDT. The biomimetic system was found to selectively accumulate in the tumour due to its homologous targeting capability and inhibit tumour growth significantly. In a word, the biomimetic nanoplatform apparently enhanced the therapeutic effect of PDT on tumours by Cur disturbing the ROS-defence system, which exhibited a new way to enhance PDT. [ABSTRACT FROM AUTHOR]

To study the effect of slenderness ratio on the ultimate bearing capacity of UHPC (ultra-high performance concrete)-encased concrete-filled steel tubular (UC-CFST) columns, a total of nine specimens under axial compression were tested. A finite element model, considering the effects of material nonlinearity and interaction between concrete and steel tube, was developed. A full-range analysis was carried out on the typical load–deformation response of the UC-CFST medium-long columns. The experimental and numerical analysis results showed that with the increase in slenderness ratio, the deformation capacity of the UC-CFST columns increased, the ultimate bearing capacity decreased, and the failure mode changed from exceedance of compressive strength to loss of stability. The internal forces and stress distributions at the mid-height section of the columns at different stages were also investigated. Finally, the applicability of various methods for calculating the ultimate bearing capacity of ordinary concrete-encased CFST (OC-CFST) columns to UC-CFST columns was discussed, including the methods recommended by Chinese standard T/CECS 188-2019, European standard Eurocode 4, Australian/New Zealand joint standard AS/NZS 5100.6 : 2017 and American standard ANSI/AISC 360-16. It was found that the method recommended in AS/NZS 5100.6 : 2017 was suitable for calculating the ultimate bearing capacity of UC-CFST medium-long columns. [ABSTRACT FROM AUTHOR]

Summary : Whether the PGS developed using data from European ancestry is predictive of fracture risk for minorities remains unclear. This study demonstrated that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry. Purpose: Large-scale genome-wide association studies (GWAS) on bone mineral density (BMD) have been conducted predominantly in European cohorts. Genetic models based on common variants associated with BMD have been evaluated using almost exclusively European data, which could potentially exacerbate health disparities due to different linkage disequilibrium among different ethnic groups. Methods: UK Biobank (UKB) is a large-scale population-based observational study starting in 2006 that recruited 502,617 individuals aged between 40 and 69 years with genotypic and phenotypic data available. Based on the summary statistics of two GWAS studies of femoral neck BMD and total body BMD, we derived four PGSs and assessed the association between each PGS and prevalent/incident fractures within each ethnic group separately using Multivariate logistic regressions and Cox proportional hazard models. All models were adjusted for age, sex, and the first four principal components. Results: We assessed four PGSs derived from European cohorts. Significant associations were observed between PGSs and fracture in European and Asian cohorts but not in the African cohort. Of all four PGSs, PGS _ TB ldpred performed the best. A standard deviation decreases in PGS _ TB ldpred were associated with an increased hazard ratio (HR) of 1.24 (1.22–1.27), 1.28 (0.83–1.99), and 1.34 (1.10–1.64) in European, African, and Asian ancestry, respectively. A low BMD-related PGS is associated with up to 2.35- and 4.31-fold increased fracture risk in European and Asian populations. Conclusions: These results showed that PGSs based on common BMD-related genetic variants discovered in the European ancestry cohort are predictive of fracture risk in people of Asian but not African ancestry. [ABSTRACT FROM AUTHOR]

Autonomic imbalance and metabolic inflammation are important pathological processes in diabetic cardiomyopathy. Gut microbiota dysbiosis and increased levels of bacterial component lipopolysaccharide (LPS) are associated with diabetic myocardial injury, but the mechanism by which gut microbes affect metabolic inflammation and cardiac injury remains unclear. We determined whether pyridostigmine (PYR), which inhibits cholinesterase to improve vagal activity, could regulate the disordered gut microbiota and attenuate gut barrier dysfunction, metabolic endotoxemia, and inflammation in diabetes. Db/db mice exhibited high blood glucose levels, insulin resistance, low vagal activity, and diabetic myocardial injury. Db/db mice also exhibited gut microbiota perturbations and subsequent disruption of gut barrier function, resulting in an influx of LPS, metabolic endotoxemia, and inflammation. PYR ameliorated the dysregulated glucose and lipid metabolism, modulated the overall structure of the gut microbiota, selectively enhanced the abundance of anti‐inflammatory bacteria, and reduced the abundance of proinflammatory and potentially pathogenic bacteria in db/db mice. Importantly, PYR enhanced vagal activity, restored gut microbiota homeostasis, and alleviated gut barrier dysfunction. Therefore, the LPS‐induced extracellular signal‐regulated kinase (ERK)/early growth response‐1 (Egr‐1) pathway and consequent metabolic inflammation were inhibited, and eventually, cardiac hypertrophy, fibrosis, oxidative stress, and dysfunction were ameliorated in db/db mice. In vitro cardiomyocyte injury was induced by exposing primary neonatal rat ventricular cardiomyocytes to high glucose (HG) and LPS. In vitro analyses showed that HG + LPS induced ERK1/2 phosphorylation, Egr‐1 expression, inflammation, and cell apoptosis, which were inhibited by acetylcholine (ACh). Alpha 7 nicotinic ACh receptor but not muscarinic 2 ACh receptor plays an important role in ACh‐mediated anti‐inflammatory effects and inhibiting the ERK/Egr‐1 pathway in HG + LPS‐administered neonatal rat ventricular cardiomyocytes. PYR and ACh ameliorated diabetic myocardial injury by inhibiting the LPS‐induced ERK/Egr‐1 pathway and metabolic inflammation. The vagus–gut–heart axis has provided new insights into the complex mechanisms of diabetes and offers novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BRCA) is the most common malignancy with high morbidity and mortality in women, and transcription factor (TF) is closely related to the occurrence and development of BRCA. This study was designed to identify a prognostic gene signature based on TF family to reveal immune characteristics and prognostic survival of BRCA. Methods: In this study, RNA-sequence with corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and GSE42568. Prognostic differentially expressed transcription factor family genes (TFDEGs) were screened to construct a risk score model, after which BRCA patients were stratified into low-risk and high-risk groups based on their corresponding risk scores. Kaplan–Meier (KM) analysis was applied to evaluate the prognostic implication of risk score model, and a nomogram model was developed and validated with the TCGA and GSE20685. Furthermore, the GSEA revealed pathological processes and signaling pathways enriched in the low-risk and high-risk groups. Finally, analyses regarding levels of immune infiltration, immune checkpoints and chemotactic factors were all completed to investigate the correlation between the risk score and tumor immune microenvironment (TIME). Results: A prognostic 9-gene signature based on TFDEGs was selected to establish a risk score model. According to KM analyses, high-risk group witnessed a significantly worse overall survival (OS) than low-risk group in both TCGA-BRCA and GSE20685. Furthermore, the nomogram model proved great possibility in predicting the OS of BRCA patients. As indicted in GSEA analysis, tumor-associated pathological processes and pathways were relatively enriched in high-risk group, and the risk score was negatively correlated with ESTIMATE score, infiltration levels of CD4+ and CD8+T cells, as well as expression levels of immune checkpoints and chemotactic factors. Conclusions: The prognostic model based on TFDEGs could distinguish as a novel biomarker for predicting prognosis of BRCA patients; in addition, it may also be utilized to identify potential benefit population from immunotherapy in different TIME and predict potential drug targets. [ABSTRACT FROM AUTHOR]

Ischemic stroke is characterized by the presence of reactive microglia. However, its precise involvement in stroke etiology is still unknown. We used metabolic profiling and showed that chemokine like factor 1 (CKLF1) causes acute microglial inflammation and metabolic reprogramming from oxidative phosphorylation to glycolysis, which was reliant on the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR)–hypoxia inducible factor 1α (HIF-1α) signaling pathway. Once activated, microglia enter a chronic tolerant state as a result of widespread energy metabolism abnormalities, which reduces immunological responses, including cytokine release and phagocytosis. Metabolically dysfunctional microglia were also found in mice using genome-wide RNA sequencing after chronic administration of CKLF1, and there was a decrease in the inflammatory response. Finally, we showed that the loss of CKLF1 reversed the defective immune response of microglia, as indicated by the maintenance its phagocytosis to neutrophils, thereby mitigating the long-term outcomes of ischemic stroke. Overall, CKLF1 plays a crucial role in the relationship between microglial metabolic status and immune function in stroke, which prepares a potential therapeutic strategy for ischemic stroke. [ABSTRACT FROM AUTHOR]

Some cellular enzymatic pathways are located within a single organelle, while most others involve enzymes that are located within multiple compartmentalized cellular organelles to realize the efficient multi‐step enzymatic process. Herein, bioinspired by enzyme‐mediated biosynthesis and biochemical defense, a compartmented nanoreactor (Burr‐NCs@GlSOD) was constructed through a self‐confined catalysis strategy with burr defect‐engineered molybdenum disulfide/Prussian blue analogues (MoS2/PBA) and an interfacial diffusion‐controlled hydrogel network. The specific catalytic mechanism of the laccase‐like superactivity induced hydrogelation and cascade enzyme catalytic therapy were explored. The confined hydrogelation strategy introduces a versatile means for nanointerface functionalization and provides insight into biological construction of simulated enzymes with comparable activity and also the specificity to natural enzymes. [ABSTRACT FROM AUTHOR]

Some cellular enzymatic pathways are located within a single organelle, while most others involve enzymes that are located within multiple compartmentalized cellular organelles to realize the efficient multi‐step enzymatic process. Herein, bioinspired by enzyme‐mediated biosynthesis and biochemical defense, a compartmented nanoreactor (Burr‐NCs@GlSOD) was constructed through a self‐confined catalysis strategy with burr defect‐engineered molybdenum disulfide/Prussian blue analogues (MoS2/PBA) and an interfacial diffusion‐controlled hydrogel network. The specific catalytic mechanism of the laccase‐like superactivity induced hydrogelation and cascade enzyme catalytic therapy were explored. The confined hydrogelation strategy introduces a versatile means for nanointerface functionalization and provides insight into biological construction of simulated enzymes with comparable activity and also the specificity to natural enzymes. [ABSTRACT FROM AUTHOR]

Summary: The potential of bone mineral density (BMD)-related genome-wide polygenic score (PGS) in identifying individuals with a high risk of fractures remains unclear. This study suggests that an efficient PGS enables the identification of strata with up to a 1.5-fold difference in fracture incidence. Incorporating PGS into clinical diagnosis is anticipated to increase the population-level screening benefits. Purpose: This study sought to construct genome-wide polygenic scores for femoral neck and total body BMD and to estimate their potential in identifying individuals with a high risk of osteoporotic fractures. Methods: Genome-wide polygenic scores were developed and validated for femoral neck and total body BMD. We externally tested the PGSs, both by themselves and in combination with available clinical risk factors, in 455,663 European ancestry individuals from the UK Biobank. The predictive accuracy of the developed genome-wide PGS was also compared with previously published restricted PGS employed in fracture risk assessment. Results: For each unit decrease in PGSs, the genome-wide PGSs were associated with up to 1.17-fold increased fracture risk. Out of four studied PGSs, P G S _ T B B M D 81 (HR: 1.03; 95%CI 1.01–1.05, p = 0.001) had the weakest and the P G S _ T B B M D l d p r e d (HR: 1.17; 95%CI 1.15–1.19, p < 0.0001) had the strongest association with an incident fracture. In the reclassification analysis, compared to the FRAX base model, the models with P G S _ F N B M D 63 , P G S _ T B B M D 81 , P G S _ F N B M D l d p r e d , and P G S _ T B B M D l d p r e d improved the reclassification of fracture by 1.2% (95% CI, 1.0 to 1.3%), 0.2% (95% CI, 0.1 to 0.3%), 1.4% (95% CI, 1.3 to 1.5%), and 2.2% (95% CI, 2.1 to 2.4%), respectively. Conclusions: Our findings suggested that an efficient PGS estimate enables the identification of strata with up to a 1.7-fold difference in fracture incidence. Incorporating PGS information into clinical diagnosis is anticipated to increase the benefits of screening programs at the population level. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is highly polygenic and heritable, with heritability ranging from 50 to 80%; most inherited susceptibility is associated with the cumulative effect of many common genetic variants. However, existing genetic risk scores (GRS) only provide a few percent predictive power for osteoporotic fracture. Methods: We derived and validated a novel genome-wide polygenic score (GPS) comprised of 103,155 common genetic variants to quantify this susceptibility and tested this GPS prediction ability in an independent dataset (n = 15,776). Results: Among postmenopausal women, we found a fivefold gradient in the risk of major osteoporotic fracture (MOF) (p < 0.001) and a 15.25-fold increased risk of severe osteoporosis (p < 0.001) across the GPS deciles. Compared with the remainder of the GPS distribution, the top GPS decile was associated with a 3.59-, 2.48-, 1.92-, and 1.58-fold increased risk of any fracture, MOF, hip fracture, and spine fracture, respectively. The top GPS decile also identified nearly twofold more high-risk osteoporotic patients than the top decile of conventional GRS based on 1103 conditionally independent genome-wide significant SNPs. Although the relative risk of severe osteoporosis for postmenopausal women at around 50 is relatively similar, the cumulative incident at 20-year follow-up is significantly different between the top GPS decile (13.7%) and the bottom decile (< 1%). In the subgroup analysis, the GPS transferability in non-Hispanic White is better than in other racial/ethnic groups. Conclusions: This new method to quantify inherited susceptibility to osteoporosis and osteoporotic fracture affords new opportunities for clinical prevention and risk assessment. [ABSTRACT FROM AUTHOR]

Extreme learning machines (ELMs) have recently attracted significant attention due to their fast training speeds and good prediction effect. However, ELMs ignore the inherent distribution of the original samples, and they are prone to overfitting, which fails at achieving good generalization performance. In this paper, based on expectile penalty and correntropy, an asymmetric C-loss function (called AC-loss) is proposed, which is non-convex, bounded, and relatively insensitive to noise. Further, a novel extreme learning machine called L1 norm robust regularized extreme learning machine with asymmetric C-loss (L1-ACELM) is presented to handle the overfitting problem. The proposed algorithm benefits from L1 norm and replaces the square loss function with the AC-loss function. The L1-ACELM can generate a more compact network with fewer hidden nodes and reduce the impact of noise. To evaluate the effectiveness of the proposed algorithm on noisy datasets, different levels of noise are added in numerical experiments. The results for different types of artificial and benchmark datasets demonstrate that L1-ACELM achieves better generalization performance compared to other state-of-the-art algorithms, especially when noise exists in the datasets. [ABSTRACT FROM AUTHOR]

Introduction: Personalized Medicine (PM) holds great potential in healthcare. A few existing surveys have investigated awareness, understanding, and interest regarding PM in the general public; however, studies investigating college students' opinions about PM are lacking. This study aimed to evaluate the college student's awareness, understanding, and interest in PM, and their opinion was also analyzed by their gender and major. Methods: The study samples were undergraduate students enrolled at the University of Nevada, Las Vegas (UNLV). A web-based survey with 42 questions was emailed to all UNLV undergraduate students. Overall survey results were analyzed by gender and each student's major. A chi-square test evaluated the significant association between responses to questions with regard to gender or major. Results: Among the participants, 1225 students completed the survey. This survey found that most college students had a neutral attitude to PM and were not entirely familiar with this field. For example, most students (57.6%) had a "neutral" attitude toward PM. In addition, 77.6% of students never received any personal genetic testing. More than 80% of students thought "interests" was the most important factor in using PM, and 50% of respondents chose "somewhat likely" to the recommendation about PM from the doctor. Also of importance was the finding that a significant association between the most important factor of using PM and gender was observed (p = 0.04), and the associations between a student's major affected his or her reaction to PM, how well informed she or he was about PM, his or her attitude toward a doctor's recommendation about using PM were all significant (all participant's p<0.004). Conclusion: UNLV undergraduate students had a neutral attitude to PM and were not entirely familiar with this field. [ABSTRACT FROM AUTHOR]

Developing highly active and stable non-noble metal bifunctional electrocatalysts are urgently demanded in overall water splitting. Herein, tunable precursor ratio synthesis of cobalt-based ZIFs as a template derived active cobalt embedded N-doped carbon (Co@NC) catalyst. The rational synthesis of ZIF templates significantly impacts the complex nanostructure and properties of the catalyst (Co@NC). Consequently, the different nanostructures on Co@NC exhibit significance for the electrocatalyst of hydrogen and oxygen evolution reactions. The optimized Co@NC-20 provides excellent electrocatalytic activity with the lowest overpotential of 172 and 301 mV for HER and OER, respectively, at the current density of 10 mA cm−2. The bifunctional Co@NC-20 reveals a potential for overall water splitting as low as 1.68 V of 10 mA cm−2. After continuously working for 24h, the exceptional stability activity maintains 75% of the catalytic performance on Co@NC-20. The beneficial character in the synergistic effects between high-active Co species with well-protection of the metal core by carbon shell promotes their excellent performance. This study provides an essential reference for the rational design of ZIF templates for electrocatalysts with more complex structures in the future. [Display omitted] • Rational fabrication Co-ZIF template for sacrificial into Co@NC. • Ratio precursors (M:L) impact in structure/morphologies Co-ZIF template. • High efficient Co@NC electrocatalysts of OER/HER for water splitting reaction. • High active Co/N species for superior bifunctional electrocatalytic performance. • The carbon shell's well-protected core active site indicates good long-time stability features. [ABSTRACT FROM AUTHOR]

In this paper, a new Fe(II) complex, [FeCl2(BBP)]·(IPA)2 (BBP = 1,3-bis(1H-benzimidazole-2-yl)propane, IPA = isopropanol), was synthesized and characterized by single crystal X-ray diffraction, elemental analysis, IR and UV/Vis spectroscopy. The crystal analysis showed that the Fe(II) complex is mononuclear, and its Fe(II) center is four coordinate in a slightly distorted tetrahedron. The electrocatalytic activity towards HER and the electrochemical sensing performance to H2O2 of the Fe(II) complex was investigated by fabricating a composite electrode (a carbon paste electrode doped with the Fe(II) complex, Fe-CPE for short). Electrochemical studies have shown that the Fe-CPE only required a low overpotential of −0.481 V to drive the current density of 10 mA cm−2 with a smaller Tafel slope of 0.142 V dec−1 for HER in 0.5 M H2SO4 at 298 K. Additionally, Fe-CPE serves as a H2O2 sensor with superior electrocatalytic activity and a low detection limit of 0.36 μM (S/N = 3) in a linear range from 5.0 × 10−7 to 4.0 × 10−3 M in 0.5 M NaOH at −0.7 V. The above studies prove that the Fe(II) complex can be used as an effective bi-functional molecular electrocatalyst for HER and H2O2 sensing. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the chloride ion transport in coral aggregate seawater concrete (CASC) with varying water–cement ratios under different loads. The ultimate compressive strength was obtained by conducting compression testing of three groups of CASC with different water–cement ratios. Steady loads of 0%, 10%, and 20% of their respective ultimate compressive strengths were applied to the concrete specimens with different water–cement ratios. After being subjected to a seawater erosion test for 30, 60, 90, 120, and 180 days, the chloride ion concentration at different depths was measured to determine the chloride ion diffusion coefficient. Meanwhile, the chloride ion diffusion coefficients of CASC were verified by comparing them with results obtained from numerical simulations performed using COMSOL software. The test results show that the internal pore space of CASC expands, leading to acceleration of the chloride ion transport rate when applied loads are increased. The initial chloride ion concentration of CASC rises as the water–cement ratio rises, and the concentration gradient formed with artificial seawater lowers, decreasing the chloride ion transport rate. When the water cement ratio decreases and the load increases, the diffusion coefficient increases. Using the numerical simulation method of COMSOL software, it was proved that the model has good applicability and accuracy in predicting chloride ion transport in CASC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predictors of residual disease in a hysterectomy following a loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 3. Methods: This retrospective study identified 421 patients with histologically confirmed CIN 3 who underwent LEEP and subsequently had a hysterectomy within 6 months. The clinical data included age, parity, type of transformation zone, cytology results, human papillomavirus (HPV) genotype test, endocervical curettage (ECC), and pathological data of LEEP and hysterectomy were obtained from the medical records. A logistic regression model was used to analyze the relationship between the variables and the risk of residual disease in the hysterectomy samples. Results: 186 (44.18%) patients had residual disease in the hysterectomy specimens. The predictive markers of residual disease following LEEP included positive ECC, positive margin of the samples from LEEP, type II or III transformation zone, HPV16 and HPV18 infection, and other high-risk HPV. HPV-18 positivity (OR, 7.13; 95% CI, 3.49 to 14.56; p < 0.001) and type III transformation zone (OR, 6.37; 95% CI, 2.91 to 13.94; p < 0.001) were the most indicative of residual disease following LEEP. Conclusion: Positive high-risk HPV, particularly HPV18, positive ECC, the positive margin of specimens from LEEP, and type II or III transformation zone were reliable prognostic markers of residual disease following a LEEP for CIN 3. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predictors of residual disease in a hysterectomy following a loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 3. Methods: This retrospective study identified 421 patients with histologically confirmed CIN 3 who underwent LEEP and subsequently had a hysterectomy within 6 months. The clinical data included age, parity, type of transformation zone, cytology results, human papillomavirus (HPV) genotype test, endocervical curettage (ECC), and pathological data of LEEP and hysterectomy were obtained from the medical records. A logistic regression model was used to analyze the relationship between the variables and the risk of residual disease in the hysterectomy samples. Results: 186 (44.18%) patients had residual disease in the hysterectomy specimens. The predictive markers of residual disease following LEEP included positive ECC, positive margin of the samples from LEEP, type II or III transformation zone, HPV16 and HPV18 infection, and other high-risk HPV. HPV-18 positivity (OR, 7.13; 95% CI, 3.49 to 14.56; p < 0.001) and type III transformation zone (OR, 6.37; 95% CI, 2.91 to 13.94; p < 0.001) were the most indicative of residual disease following LEEP. Conclusion: Positive high-risk HPV, particularly HPV18, positive ECC, the positive margin of specimens from LEEP, and type II or III transformation zone were reliable prognostic markers of residual disease following a LEEP for CIN 3. [ABSTRACT FROM AUTHOR]

Elevated levels of circulating fibroblast growth factor 21 (FGF21) have been reported in patients with hyperuricemia. However, the effect of FGF21 in hyperuricemic nephropathy (HN) remains unexplored. Here, we investigated the effect and mechanism of action of FGF21 on HN. HN model was induced with adenine and potassium oxysalt in wild‐type C57BL/6 mice and FGF21−/− mice. For in vitro studies, human renal tubular epithelial (HK‐2) cells were exposed to uric acid with/without FGF21 or β‐Klotho‐siRNA. Here, we reported aggravated renal dysfunction and structural damage in the FGF21−/− mice compared to the wild‐type mice. These were evident in the upsurge of inflammatory factors IL‐1β, TNF‐α, IL‐6, and IL‐18; fibrotic markers Collagen I and α‐SMA; and oxidation products ROS and MDA. However, exogenous administration of FGF21 to wild‐type HN mice significantly reversed these negative effects. In terms of mechanism, FGF21 significantly inhibited NF‐κB/NLRP3 and TGF‐β1/Smad3 pathways and promoted nuclear translocation of Nrf2 both in vivo and in vitro. Furthermore, the silencing of β‐Klotho was marked by the attenuation of the improved effect of FGF21 on cell damage. In conclusion, our studies revealed that exogenous FGF21 treatment significantly improved HN, which was achieved by the inhibition of inflammation, fibrosis, and oxidative stress. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a common chronic metabolic disease caused by significant accumulation of advanced glycation end products (AGEs). Atrial fibrillation (AF) is a common cardiovascular complication of DM. Here, we aim to clarify the role and mechanism of atrial myocyte senescence in the susceptibility of AF in diabetes. Rapid transesophageal atrial pacing was used to monitor the susceptibility of mice to AF. Whole‐cell patch‐clamp was employed to record the action potential (AP) and ion channels in single HL‐1 cell and mouse atrial myocytes. More importantly, anti‐RAGE antibody and RAGE‐siRNA AAV9 were used to investigate the relationship among diabetes, aging, and AF. The results showed that elevated levels of p16 and retinoblastoma (Rb) protein in the atrium were associated with increased susceptibility to AF in diabetic mice. Mechanistically, AGEs increased p16/Rb protein expression and the number of SA‐β‐gal‐positive cells, prolonged the action potential duration (APD), reduced protein levels of Cav1.2, Kv1.5, and current density of ICa,L, IKur in HL‐1 cells. Anti‐RAGE antibody or RAGE‐siRNA AAV9 reversed these effects in vitro and in vivo, respectively. Furthermore, downregulating p16 or Rb by siRNA prevented AGEs‐mediated reduction of Cav1.2 and Kv1.5 proteins expression. In conclusion, AGEs accelerated atrial electrical remodeling and cellular senescence, contributing to increased AF susceptibility by activating the p16/Rb pathway. Inhibition of RAGE or the p16/Rb pathway may be a potential therapeutic target for AF in diabetes. [ABSTRACT FROM AUTHOR]

Physician communication (PC) is central to influencing physician–patient relationship (PPR), and physician empathy (PE) is central to PC. A comprehensive and objective assessment of the mechanisms underlying PPR from the two-way perspective of physicians and patients are important for social development. However, the relationship between these three variables under the two-way perspective is not clear. To examine the effectiveness of PC in predicting PPR from a two-way perspective of physicians and patients and the underlying mechanisms that influence PPR. We selected 2665 physicians and 2983 patients in China and examined the effect of physician empathy on PPR and the mediating role of PC between PE and PPR using structural equation modeling. The results of the physician self-assessment showed that the link between PC and PPR was not significant, while the results of the patient other assessment showed that physician communication was not only effective in predicting the doctor–patient relationship but also mediated the relationship between physician empathy and PPR; further analysis of the underlying mechanisms affecting PPR revealed that the results of the physician self-assessment showed that PC mediated the relationship between perspective-taking and PPR; however, the results of the patient other assessment showed that physician However, patient ratings showed that PC mediated the relationship between perspective-taking and PPR, as well as between empathic concern and PPR. However, patient ratings indicate that PC mediates the relationship between perspective-taking and PPR and between empathic concern and the PPR. [ABSTRACT FROM AUTHOR]

Based on an integrated model of doctor–patient psychological mechanisms, the formation mechanism of doctor-–patient trust was systematically demonstrated from the healthcare professional (HCP)'s perspective integrating intergroup relations (expectations), interpersonal relations (communication), and psychosocial (stereotypes). The results of a survey of 3000 doctors and nurses from 14 provinces in eastern, central, and western China support the rationality of an integrated model of doctor–patient psychological mechanisms. The establishment of doctor–patient trust is influenced by the direct role of primary intergroup factors, the indirect role of immediate interpersonal interactions, and the moderating role of social psychology. Specifically, (1) doctor–patient trust is directly predicted by HCP's expectation and indirectly influenced by communication; (2) stereotypes regulate the relationship between HCP's expectation, communication, and doctor–patient trust: the activation of positive stereotypes enhances the positive relationship among the three; Negative stereotypes only positively contribute to mediated pathway-communication behaviors and have a weaker facilitation effect compared to positive stereotypes. [ABSTRACT FROM AUTHOR]

AMPA receptors are tetrameric ionic glutamate receptors, which mediate 90% fast excitatory synaptic transmission induced by excitatory glutamate in the mammalian central nervous system through the activation or inactivation of ion channels. The alternation of synaptic AMPA receptor number and subtype is thought to be one of the primary mechanisms that involve in synaptic plasticity regulation and affect the functions in learning, memory, and cognition. The increasing of surface AMPARs enhances synaptic strength during long-term potentiation, whereas the decreasing of AMPARs weakens synaptic strength during the long-term depression. It is closely related to the AMPA receptor as well as its subunits assembly, trafficking, and degradation. The dysfunction of any step in these precise regulatory processes is likely to induce the disorder of synaptic transmission and loss of neurons, or even cause neuropsychiatric diseases ultimately. Therefore, it is useful to understand how AMPARs regulate synaptic plasticity and its role in related neuropsychiatric diseases via comprehending architecture and trafficking of the receptors. Here, we reviewed the progress in structure, expression, trafficking, and relationship with synaptic plasticity of AMPA receptor, especially in anxiety, depression, neurodegenerative disorders, and cerebral ischemia. [ABSTRACT FROM AUTHOR]

The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody‒drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future. [ABSTRACT FROM AUTHOR]

This paper proposed a novel routing strategy with two tunable parameters, α 1 , β , based on the dynamic local information in a finite buffer network. The system behaves differently from that with a local routing strategy based on the degree with an adjustable parameter α 2 . Simulations show that, under dynamic local strategy, the maximal capacity of the network system increases with β whereas it increases with the decrement of α 1 in the case of all the nodes having identical delivering ability. The dynamic local routing performs much better than the local routing, which is demonstrated by a larger value of the critical packet generation rate. We found that buffer coefficient has a limited impact on the performance of network system. We also demonstrate that a smaller α 1 would be better if we want to have an excellent traffic capacity considering the travel time, average path length and waiting time. Our study will be helpful to improve traffic performance in finite buffer networks. [ABSTRACT FROM AUTHOR]

Extreme learning machines (ELMs) have gained acceptance owing to their high efficiency and outstanding generalization ability. As a key component of data preprocessing, feature selection methods can decrease the noise or irrelevant data for ELMs. However, ELMs still do not have their own practical feature selection method for their special mechanism. In this study, we proposed a feature selection method for the ELM, named FELM. The proposed algorithm achieves highly efficient dimensionality reduction due to the feature ranking strategy. The FELM can simultaneously complete the feature selection and classification processes. In addition, by incorporating a memorization–generalization kernel into the FELM, the nonlinear case of it is issued (called FKELM). The FKELM can achieve high classification accuracy and extensive generalization by applying the property of memorization of training data. According to the experimental results on different artificial and benchmark datasets, the proposed algorithms achieve significantly better classification accuracy and faster training than the other methods. [ABSTRACT FROM AUTHOR]