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ObjectiveAs polar exploration develops, hull structure designs for ice routes are no longer limited to the traditional empirical formula method as more attention is paid to the actual ice load and structural response acting on the structure. The study of structural response calculation under ice load is crucial for the structural design of polar ships. MethodsFirst, the finite element method is used to numerically simulate the ice load cases of a polar navigation ship, such as crushed ice, floating ice and layered ice. Considering the influence of the material strain rate, the dynamic response of the structure under ice load is calculated. Second, based on the structural response equivalence, the static transformation of the dynamic response is completed, and the concept of the dynamic static transformation coefficient is proposed. Finally, the range of the dynamic static conversion coefficient under different ice load cases is obtained.ResultThe results show that the conversion coefficient of the dynamic-static equivalent conversion of the bow structure under different ice load cases is between 1.0 and 1.4.ConclusionThe quasi-static equivalent method of the ice-induced dynamic response of a bow structure is verified as reasonable and feasible.

Abstract Drones play an important role in modern cities, they bring convenience but also bring corresponding risks. Falling drones can cause casualties or damage to urban facilities and serious property damage, which increases the third-party risk problem. An effective way to reduce these third-party risks is to avoid high-risk areas in path planning, but most current path planning methods are optimized to minimize flight distance, and third-party risk costs are rarely considered. In this paper, a comprehensive risk-cost UAV path planning method is proposed, which evaluates urban risk by establishing a third-party risk model that incorporates obstacle risk, death risk, and property loss risk. This paper proposes a Min-cost A* algorithm based on city risk assessment, and smooths the generated low-risk path through the improved Floyd algorithm. The results show that the path planning method can effectively reduce the risk in the flight path, improve the reliability of the UAV flight path in the urban environment, and solve the problem of planning the third-party risk path of the UAV.

Abstract Objective This study aimed to examine whether diabetes mellitus is causally associated with osteonecrosis. Method Using publicly accessible genome-wide association study statistics, a bidirectional two-sample Mendelian randomization analysis was carried out. In order to determine whether diabetes has a causal effect on osteonecrosis and whether osteonecrosis has a causal effect on diabetes, we extracted six date on diabetes in Europeans from IEU OpenGWAS and GWAS Catalogue and osteonecrosis in Europeans from FinnGen. We then evaluated the data using inverse variance weighting, MR-Egger regression, weighted median, weighted mode, and simple mode. The results’ stability and dependability were then evaluated using sensitivity analysis and heterogeneity analysis. Finally, meta-analysis is used to further confirm if there is a relationship between diabetes and osteonecrosis. Results When diabetes was used as an exposure factor, MR-Egger regression showed that directional fold product was unlikely to bias the results. Cochran’s Q test showed only minor heterogeneity in a few data sets. Multidirectional tests Egger-intercept, MR-PRESSO and funnel plots for most data did not show multidirectional and asymmetry at the gene level. Most of the IVW results showed no causal relationship between diabetes mellitus and osteonecrosis. The results of meta-analysis of IVW methods further confirmed the absence of a causal relationship. Inverse MR analysis also showed no causal relationship between osteonecrosis and diabetes. Conclusion Results of bidirectional MR analysis show no evidence of causal relationship between diabetes and osteonecrosis.

Abstract Background Multiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries. Methods Twelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes. Results Respiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 h after surgery. The difference in measurements was not statistically significant between the two groups before surgery with P values greater than 0.05. However, the interior group canines had better RR and PO2 values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48th hour. It took longer operation time to complete the minimally invasive interior fixation surgery (P value less than 0.001), but the total blood loss was less than the exterior fixation group (P value less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility. Conclusions The investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes.

Abstract Various exciton species in transition metal dichalcogenides (TMDs), such as neutral excitons, trions (charged excitons), dark excitons, and biexcitons, have been individually discovered with distinct light-matter interactions. In terms of valley-spin locked band structures and electron-hole configurations, these exciton species demonstrate flexible control of emission light with degrees of freedom (DOFs) such as intensity, polarization, frequency, and dynamics. However, it remains elusive to fully manipulate different exciton species on demand for practical photonic applications. Here, we investigate the contrasting light-matter interactions to control multiple DOFs of emission light in a hybrid monolayer WSe2-Ag nanowire (NW) structure by taking advantage of various exciton species. These excitons, including trions, dark excitons, and biexcitons, are found to couple independently with propagating surface plasmon polaritons (SPPs) of Ag NW in quite different ways, thanks to the orientations of transition dipoles. Consistent with the simulations, the dark excitons and dark trions show extremely high coupling efficiency with SPPs, while the trions demonstrate directional chiral-coupling features. This study presents a crucial step towards the ultimate goal of exploiting the comprehensive spectrum of TMD excitons for optical information processing and quantum optics.

Abstract Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC.

Plant-based meat analogs (PBMAs) are promising sustainable food sources. However, their high moisture and protein contents make them prone to microbial deterioration, limiting their shelf life and sensory appeal. This study explored enhancing PBMAs’ shelf life using nanoemulsions of Litsea cubeba and cinnamon essential oils, emulsified with chitosan and Tween 80. The composite nanoemulsion, produced through high-pressure homogenization, exhibited a droplet size of 4.99 ± 0.03 nm, a polydispersity index (PDI) of 0.221 ± 0.008, and a zeta potential of 95.13 ± 2.67 mV, indicating remarkable stability (p < 0.05). Applied to PBMAs stored at 4 °C, it significantly improved color and pH balance and reduced thiobarbituric acid reactive substances and cooking loss. Most notably, it inhibited the growth of Escherichia coli and Staphylococcus aureus, curbing spoilage and protein oxidation, thereby extending the products’ shelf life and preserving sensory quality. As shown above, the encapsulation of LCEO/CEO in nanoemulsions effectively inhibits spoilage and deterioration in PBMAs, improving flavor and quality more than direct addition. Future studies should explore using various essential oils and emulsifiers, as well as alternative encapsulation techniques like microcapsules and nanoparticles, to further prevent PBMA deterioration.

Salt stress has become a major environmental problem affecting plant growth and development. Some WRKY transcription factors have been reported to be involved in the salt stress response in plants. However, there are few studies on the involvement of WRKYs in the salt stress response in Rosa rugosa. In this study, we isolated a salt tolerance gene, RrWRKY1, from R. rugosa. RrWRKY1 was found to belong to Group I of the WRKY family, and it was specifically expressed in leaves and petals. RrWRKY1 expression was upregulated under NaCl stress in rose leaves. After silencing RrWRKY1 in R. rugosa, transgenic plants showed dry leaves and black and brown veins, indicating sensitivity to salt stress. At the same time, the transcription levels of the salt tolerance-related genes RrNHX1, RrABF2, RrRD22, RrNCED1, and RrHKT1 also changed significantly. The superoxide dismutase (SOD) and peroxidase (POD) activities decreased, the proline content decreased, and the malondialdehyde (MDA) content in the gene-silenced plants increased, indicating that RrWRKY1 regulates the salt tolerance of R. rugosa. In addition, the overexpression of RrWRKY1 in Arabidopsis thaliana improved the germination rate and the average of the main root and lateral root lengths, and the transgenic plants had a larger number of lateral roots than the WT plants under salt stress. This study provides candidate gene resources for salinity tolerance breeding and a theoretical basis for analyzing the salinity tolerance mechanism of the WRKY gene.

For an offshore photovoltaic helical pile foundation, significant horizontal cyclic loading is imposed by wind and waves. To study a fixed offshore PV helical pile’s horizontal cyclic bearing performance, a numerical model of the helical pile under horizontal cyclic loading was established using an elastic–plastic boundary interface constitutive model of the clay soil. This model was compared with a monopile of the same diameter under similar conditions. The study examined the effects of horizontal cyclic loading amplitude, period, and vertical loads on the horizontal cyclic bearing performance. The results show that under horizontal monotonic loading, the bearing capacities of a helical pile and monopile in a serviceability limit state are quite similar. However, as the amplitude of horizontal cyclic loading increases, soil stiffness deteriorates significantly, leading to greater horizontal displacement accumulation for both types of piles. The helical pile’s bearing capacity under horizontal cyclic loadings is approximately 60% of that under monotonic loading. With shorter cyclic loading periods, horizontal displacement accumulates rapidly in the initial stage and stabilizes over a shorter duration. In contrast, longer cyclic loading periods lead to slower initial displacement accumulation, but the total accumulated displacement at stabilization is greater. When vertical loads are applied, the helical pile exhibits more stable horizontal cyclic bearing performance than the monopile.

An experimental study was undertaken to investigate the problem of the substantial variability in water content in unrotted sheep dung, which leads to a lack of universality and practicality in calibrating its discrete element simulation parameters. The stacking angle was used as the response value in these experiments. The objective of this study was to establish precise simulation parameters for the composting process. A model for water content-stacking angle was established using the cylinder-lifting technique, resulting in a correlation value of 0.997. Utilizing the Hertz–Mindlin with JKR bonding model, three EDEM particle models were developed, each with distinct particle sizes, based on the particle size distribution of sheep dung. The JKR surface energy was determined using the Plackett–Burman test, the steepest-climbing test, and the Box–Behnken test using a set of 10 parameters. A subsequent study was conducted on the JKR surface energy, rolling friction factor, and static friction factor utilizing the Plackett–Burman test and Box–Behnken test. A parameter model for stacking angle–discrete elements was developed that achieved a p-value below 0.0001 and a relative inaccuracy of 3.46% or less. The regression model for the water content–discrete element parameter was derived by combining the water content–stacking angle model with the stacking angle–discrete element parameter model. Validation of this model was conducted using both the pumping plate technique and the hopper approach, resulting in a relative error of 4.89% or less. The findings demonstrate that the specific characteristics of sheep manure may be accurately anticipated by considering its water content. This approach offers a valid and universally applicable way of predicting the specific characteristics of sheep dung in the simulation of composting equipment.

Hollow Enemy Towers, as iconic structures of the Ming Great Wall, are renowned for their roles in defense surveillance, weapon storage, and firearm operation. Recent studies have indicated that certain Hollow Enemy Towers along the Ji Town section of the Ming Great Wall also serve the function of Beacon Towers for beacon signaling. However, previous studies have not definitively determined if these towers were distinctively marked, nor have they provided a comprehensive account of their current distribution and original historical appearance. This paper initially examined the historical documentation of white lime markings employed on the outer walls of certain Hollow Enemy Towers, which served as Beacon Towers during the middle and late Ming periods. Utilizing multidisciplinary methodologies, this research identified remains of lime markings of the Beacon-Equipped Hollow Enemy Towers along the Ji Town section of the Ming Great Wall, illustrating their extensive distribution. We analyzed the material composition and construction techniques of the lime mortar. This analysis clarifies the scope of lime plastering on the exterior walls of these towers and offers a point of reference for restoring their original historical appearance. The results make a significant supplement to the types of signaling structures on the Great Wall, enriching existing understanding of the original appearance of the Great Wall’s historical landscape.

The objectives of this study were (1) to determine the net energy requirements for the maintenance of gestating sows based on indirect calorimetry, and (2) to explore the feasibility of predicting the net energy requirements for the maintenance of gestating sows based on daily heart rate monitoring. In Exp. 1, six Landrace × Yorkshire crossbred reproductive sows with an initial body weight of 229.5 ± 14.9 kg at d 56 of gestation were randomly assigned to six diverse energy feeding levels using a 6 × 6 Latin square design. The experimental diet was formulated using corn, soybean meal, and wheat bran as major ingredients, and the six feeding levels were set as 1.2, 1.4, 1.6, 1.8, 2.0, and 2.2 times metabolizable energy for maintenance (100 kcal ME/kg BW0.75·d−1), respectively. The animal trial lasted for six periods with 9 days per period, encompassing 5 days of adaptation, 3 days of calorimetry in fed state, and 1 day of calorimetry in fasting state. In Exp. 2, six Landrace × Yorkshire crossbred pregnant sows with an initial body weight of 232.5 ± 12.5 kg at d 64 were fed a corn–soybean meal diet. All sows were tested in a respiratory calorimetry chamber for a 4 day calorimetry test. The heat production of the gestation sows was measured every 5 min using indirect calorimetry, and the heart rate of the gestating sows was recorded every minute using a belt-shape monitor. The results showed that the net energy requirements for the maintenance of gestating sows significant increased as the gestational stage progressed (p < 0.05), and a linear regression model revealed the average net energy requirement for the maintenance of gestating sows was 410 kJ/BW0.75 d−1 during late gestation (days 70–110). Moreover, the average heart rate of the gestating sows was 84 bpm, and the mathematical model developed to predict the net energy requirements for the maintenance of gestating sows was NEm(kcal/h)=19901+exp⁡[136−HR(bpm)43]. In conclusion, the average net energy requirement for the maintenance of sows during late gestation was 410 kJ/BW0.75 d−1, and the utilization of the heart rate monitoring method was found to provide a relevant, accurate prediction for the net energy requirements of sows.

This study introduces a novel thermoacoustic (TA) focusing system enhanced by Airy beam-based acoustic metasurfaces, significantly improving acoustic focusing and efficiency. The system integrates a TA emitter, fabricated from carbon nanotube (CNT) films, with a binary acoustic metasurface capable of generating quasi-Airy beams. Through finite element simulations, the system’s heat conduction, acoustic focusing, and self-healing properties were thoroughly analyzed. The results demonstrate that the system achieves superior sub-wavelength focusing, tunable focal length via frequency control, and robust self-healing, even in the presence of obstacles. These findings address current limitations in TA emitters and suggest broader applications in medical ultrasound and advanced technology.

The Inner Mongolia Autonomous Region, known for its famous Mongolian horses, faces significant environmental challenges due to the large-scale rearing of these animals, which produces a substantial amount of manure. If not managed effectively, this manure can lead to severe environmental pollution. The aim of this study was to investigate whether a small-scale intelligent aeration and heating composting system is effective in treating Mongolian horse manure, with the objective of enhancing composting efficiency and resource utilization to support sustainable agricultural development in the region. The equipment was utilized to treat a compost mixture of Mongolian horse manure and corn stover, allowing for an analysis of the changes in key indicators throughout the composting process. The results demonstrated that the equipment maintained high temperatures for up to eight days during the composting process, effectively inactivating pathogens and promoting the efficient decomposition of organic matter. The system also successfully controlled humidity to 12.7% and maintained oxygen concentration within the optimal range. Post-composting analysis revealed that the final compost contained 2.3% nitrogen, 1.3% phosphorus, and 1.2% potassium, with a pH of 6.4 and conductivity of approximately 5.2 mS/cm. Additionally, the carbon-to-nitrogen ratio decreased significantly from 27.3 to 15.9, indicating substantial organic matter degradation. Seed germination tests showed germination rates of 80%, 86%, and 75% for corn, mung bean, and wheat, respectively, with a final seed germination index of 104%. This study concluded that the small aeration and heating composting equipment is highly effective in treating Mongolian horse manure, producing high-quality organic fertilizers that significantly enhance soil fertility and demonstrate considerable potential for supporting sustainable agricultural practices and improving environmental management in the Inner Mongolia Autonomous Region.

Procypris mera (Lin, 1933), also known as the Chinese ink carp, currently has a second-class protection status in China. Understanding the structure and characteristics of mitochondrial genes provides essential information for resource conservation and phylogenetic studies of P. mera. Here, we sequenced the mitochondrial genomes of three P. mera (WYL1-3) from three sites and performed phylogenetic analysis. The generated three genomes were 16,587 bp in length, comprising 13 protein-coding genes (PCGs), 22 tRNAs, two rRNAs, and two non-coding regions (control region (CR), D-loop, and light-stranded replication start OL), with a preference for codons ending in A or C. The mitochondrial genomes of WYL2 and WYL3 were identical, differing from that of WYL1 by only five single-nucleotide polymorphisms (SNPs). All mitochondrial PCGs had Ka/Ks ratios of less than one, suggesting purifying selection. Phylogenetic tree analysis based on amino acid sequences suggested that the genus Puntioplites is sister to all other genera of the subfamily Cyprinidae of China; the genus Procypris forms a monophyletic group; and the genera Carassioides, Carassius, and Cyprinus form a monophyletic group. This study contributes to our understanding of the phylogenetic relationships in subfamily Cyprininae in China and lays the foundation for resource conservation and management of P. mera.

Skin injuries pose significant health challenges, with conditions like burns and diabetic, venous, and pressure ulcers presenting complex wound management scenarios. Effective wound care strategies for these injuries encompass a range of interventions, from simple wound dressings to bioactive materials and surgical procedures involving skin substitutes and skin grafting. This review explores the potential of natural polymers, including silk, collagen, gelatin, elastin, cellulose, chitosan, alginate, and hyaluronic acid, in wound management. Natural polymers offer several advantages, including abundance, biodegradability, and compatibility with traditional and modern material fabrication techniques, and have demonstrated safety and efficacy in clinical applications, modulating various facets of the wound healing process. Highlighting preclinical and clinical studies, along with commercial products, this review showcases the versatility and utility of natural polymers in wound management and provides insights into emerging developments, such as 3D bioprinting and stimuli‐responsive materials, which hold promise for personalized wound treatments. Additionally, we discuss the importance of the material format and morphology in engineering the next generation of wound dressings and skin substitutes, offering a pathway to optimize natural polymers for enhanced wound healing outcomes.

Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture.

Abstract Objective Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non‐Hodgkin's lymphoma (NHL), especially B‐cell non‐Hodgkin's lymphoma (B‐NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. Methods The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression‐free survival (PFS), and overall survival (OS) of HBV‐positive and negative B‐NHL subtypes were compared according to HBV infection. Results The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p

Abstract Diabetic ketoacidosis (DKA) is a life‐threatening acute complication of diabetes characterized by the accumulation of ketone bodies in the blood. Breath acetone, a ketone, directly correlates with blood ketones. Therefore, monitoring breath acetone can significantly enhance the safety and efficacy of diabetes care. In this work, the design and fabrication of an InP/Pt/chitosan nanowire array‐based chemiresistive acetone sensor is reported. By incorporation of chitosan as a surface‐functional layer and a Pt Schottky contact for efficient charge transfer processes and photovoltaic effect, self‐powered, highly selective acetone sensing is achieved. The sensor has exhibited an ultra‐wide acetone detection range from sub‐ppb to >100 000 ppm level at room temperature, covering those in the exhaled breath from healthy individuals (300–800 ppb) to people at high risk of DKA (>75 ppm). The nanowire sensor has also been successfully integrated into a handheld breath testing prototype, the Ketowhistle, which can successfully detect different ranges of acetone concentrations in simulated breath samples. The Ketowhistle demonstrates the immediate potential for non‐invasive ketone monitoring for people living with diabetes, in particular for DKA prevention.

Abstracts: Background: Pre-eclampsia (PE) is a syndrome with no specific pathological mechanism and is specific to pregnancy. The combined analysis of proteomics and transcriptomics possesses many benefits for treating this disease. m6A modification plays a major role in PE; however, mechanism have not been studied clearly. This study investigated the potential mechanism underlying the role of m6A in PE. Methods: Mass spectrometry-based label-free quantitative proteomics and transcriptomics experiments were conducted on the placenta of patients with pre-eclampsia and normal pregnancies, and the two omics were followed by joint analysis. Total m6A modification in placental tissues, HTR8/SVneo cells, and JEG-3 cells was measured by dot blot. The levels of RBM15 and CD82 in tissues and cells were detected using qPCR. The protein levels of G3BP1, RBM15, MMP-2, YTHDF2, and MMP-9 were measured by western blotting. The function, migration, and invasion characteristics of HTR8/SVneo and JEG-3 cells were measured using Transwell assays. SRAMP predicted the m6A modification site in the CD82 mRNA 3′UTR, and this was confirmed using luciferase activity and YTHDF2-RIP. Results: m6A modification was promoted in the PE group, and the RBM15 abundance was increased. Overexpression of RBM15 increased m6A modification. However, overexpression of RBM15 suppressed the expression of MMP-2 and MMP-9 and also the migratory and invasive capabilities of HTR8/SVneo and JEG-3 cells. CD82 expression levels were decreased in PE, and CD82 expression was confirmed via qPCR, western blotting and immunofluorescence. Furthermore, RBM15 overexpression reduced CD82 mRNA and protein levels. Luciferase activity and YTHDF2-RIP results verified that overexpression of RBM15 promoted the binding ability between YTHDF2 and the CD82 3′UTR, thereby decreasing CD82 expression. Finally, CD82 overexpression reversed the effect of RBM15 overexpression on the expression of MMP-2 and MMP-9 and on the migratory and invasive capabilities of the cells. Conclusions: Overexpression of RBM15 hindered the migratory and invasive capabilities of trophoblasts, while concurrently enhancing m6A modification. The potential mechanism was that overexpression of RBM15 promoted the binding capability between YTHDF2 and CD82 3′UTR and decrease the expression of CD82. Thus, this study provides a theoretical basis for the treatment of PE.

Combination therapies can enhance the sensitivity of cancer to drugs, lower drug doses, and reduce side effects in cancer treatment. However, differences in the physicochemical properties and pharmacokinetics of different therapeutic agents limit their application. To avoid the above dilemma and achieve accurate control of the synergetic ratio, a nanoscale co-delivery system (NCDS) has emerged as a prospective tool for combined therapy in cancer treatment, which is increasingly being used to co-load different therapeutic agents. In this study, we have summarized the mechanisms of therapeutic agents in combination for cancer therapy, nanoscale carriers for co-delivery, drug-loading strategies, and controlled/targeted co-delivery systems, aiming to give a general picture of these powerful approaches for future NCDS research studies.

IntroductionMicroplastics (MPs), identified as emerging contaminants, have been detected across diverse environmental media. Their enduring presence and small size facilitate the adsorption of organic pollutants and heavy metals, leading to combined pollution effects. MPs also accumulate in the food chain thus pose risks to animals, plants, and human health, garnering significant scholarly attention in recent years. Aerobic granular sludge (AGS) technology emerges as an innovative approach to wastewater treatment. However, the impacts of MPs on the operational efficiency and microbial characteristics of AGS systems has been insufficiently explored.MethodsThis study investigated the effects of varying concentration (10, 50, and 100 mg/L) of biodegradable MPs (Polylactic Acid, PLA) and non-biodegradable MPs (Polyethylene Terephthalate, PET) on the properties of AGS and explored the underlying mechanisms.Results and discussionsIt was discovered that low and medium concentration of MPs (10 and 50 mg/L) showed no significant effects on COD removal by AGS, but high concentration (100 mg/L) of MPs markedly diminished the ability to remove COD of AGS, by blocking most of the nutrient transport channels of AGS. However, both PLA and PE promoted the nitrogen and phosphorus removal ability of AGS, and significantly increased the removal efficiency of total inorganic nitrogen (TIN) and total phosphorus (TP) at stages II and III (P < 0.05). High concentration of MPs inhibited the growth of sludge. PET noticeably deteriorate the sedimentation performance of AGS, while 50 mg/L PLA proved to be beneficial to sludge sedimentation at stage II. The addition of MPs promoted the abundance of Candidatus_Competibacter and Acinetobacter in AGS, thereby promoting the phosphorus removal capacity of AGS. Both 50 mg/L PET and 100 mg/L PLA caused large amount of white Thiothrix filamentous bacteria forming on the surface of AGS, leading to deterioration of the sludge settling performance and affecting the normal operation of the reactor. Comparing with PET, AGS proved to be more resistant to PLA, so more attention should be paid to the effect of non-biodegradable MPs on AGS in the future.

Background Only a subset of patients with gastric cancer experience long-term benefits from immune checkpoint inhibitors (ICIs). Currently, there is a deficiency in precise predictive biomarkers for ICI efficacy. The aim of this study was to develop and validate a pathomics-driven ensemble model for predicting the response to ICIs in gastric cancer, using H&E-stained whole slide images (WSI).Methods This multicenter study retrospectively collected and analyzed H&E-stained WSIs and clinical data from 584 patients with gastric cancer. An ensemble model, integrating four classifiers: least absolute shrinkage and selection operator, k-nearest neighbors, decision trees, and random forests, was developed and validated using pathomics features, with the objective of predicting the therapeutic efficacy of immune checkpoint inhibition. Model performance was evaluated using metrics including the area under the curve (AUC), sensitivity, and specificity. Additionally, SHAP (SHapley Additive exPlanations) analysis was used to explain the model’s predicted values as the sum of the attribution values for each input feature. Pathogenomics analysis was employed to explain the molecular mechanisms underlying the model’s predictions.Results Our pathomics-driven ensemble model effectively stratified the response to ICIs in training cohort (AUC 0.985 (95% CI 0.971 to 0.999)), which was further validated in internal validation cohort (AUC 0.921 (95% CI 0.839 to 0.999)), as well as in external validation cohort 1 (AUC 0.914 (95% CI 0.837 to 0.990)), and external validation cohort 2 (0.927 (95% CI 0.802 to 0.999)). The univariate Cox regression analysis revealed that the prediction signature of pathomics-driven ensemble model was a prognostic factor for progression-free survival in patients with gastric cancer who underwent immunotherapy (p

Abstract This study systematically analyzed the molecular mechanism and function of nuclear factor kappa B subunit 2 (NFKB2) in colorectal cancer (CRC) to investigate the potential of NFKB2 as a therapeutic target for CRC. Various experimental techniques, including RNA sequencing, proteome chip assays, and small molecule analysis, were used to obtain a deeper understanding of the regulation of NFKB2 in CRC. The results revealed that NFKB2 was upregulated in a significant proportion of patients with advanced hepatic metastasis of CRC. NFKB2 played an important role in promoting tumor growth through CD8+ T‐cell exhaustion. Moreover, NFKB2 directly interacted with signal transducer and activator of transcription 2 (STAT2), leading to increased phosphorylation of STAT2 and the upregulation of programmed death ligand 1 (PD‐L1). Applying a small molecule inhibitor of NFKB2 (Rg5) led to a reduction in PD‐L1 expression and improved response to programmed death‐1 blockade‐based immunotherapy. In conclusion, the facilitated NFKB2‐STAT2/PD‐L1 axis may suppress immune surveillance in CRC and targeting NFKB2 may enhance the efficacy of immunotherapeutic strategies. Our results provide novel insights into the molecular mechanisms underlying the contribution of NFKB2 in CRC immune escape.

BackgroundAreca Nut (AN) is the fourth most commonly abused drug after nicotine, ethanol, and caffeine, due to its psychoactive properties provided by bioactive substances. Although previous studies have demonstrated AN’s anxiolytic-like activity and potential benefits in ameliorating symptoms of depression and schizophrenia, there remains limited awareness regarding its association with brief psychotic disorder.Case presentationThis case report presents the clinical profile of a 30-year-old male patient with a history of betel nut chewing for the past 2 years, who exhibited sudden onset delusions, hallucinations, and disorganized speech and behavior upon increasing the dosage of betel nut consumption. The patient displayed a positive response to antipsychotic treatment, and symptoms resolved upon discontinuation of betel nut consumption. However, one month after discharge, the patient experienced a recurrence of auditory hallucinations upon resuming betel nut chewing. Through counseling and support, the importance of abstaining from betel nut use and maintaining medication compliance was emphasized, resulting in no recurrence of psychotic symptoms during the six-month follow-up.ConclusionsThis case report highlights the related role of betel nut with brief psychotic disorder, especially when the chewing dosage is abruptly increased. It underscores the importance of considering betel nut as a potential precipitant related to acute psychiatric disorders in clinical settings.

BackgroundParkinson's disease (PD) is a progressive neurodegenerative condition. Chinese medicine therapies have demonstrated effectiveness for PD in controlled settings. However, the utilization of Chinese medicine therapies for PD in real-world clinical practice and the characteristics of patients seeking these therapies have not been thoroughly summarized.MethodThe study retrospectively analyzed initial patient encounters (PEs) with a first-listed diagnosis of PD, based on electronic medical records from Guangdong Provincial Hospital of Chinese Medicine between July 2018 and July 2023.ResultsA total of 3,206 PEs, each corresponding to an individual patient, were eligible for analyses. Approximately 60% of patients made initial visits to the Chinese medicine hospital after receiving a PD diagnosis, around 4.59 years after the onset of motor symptoms. Over 75% of the patients visited the Internal Medicine Outpatient Clinic at their initial visits, while a mere 13.85% visited PD Chronic Care Clinic. Rest tremor (61.98%) and bradykinesia (52.34%) are the most commonly reported motor symptoms, followed by rigidity (40.70%). The most commonly recorded non-motor symptoms included constipation (31.88%) and sleep disturbance (25.27%). Integration of Chinese medicine and conventional medicine therapies was the most common treatment method (39.15%), followed by single use of Chinese herbal medicine (27.14%). The most frequently prescribed herbs for PD included Glycyrrhiza uralensis Fisch. (gan cao), Astragalus mongholicus Bunge (huang qi), Atractylodes macrocephala Koidz. (bai zhu), Angelica sinensis (Oliv.) Diels (dang gui), Rehmannia glutinosa (Gaertn.) DC. (di huang), Paeonia lactiflora Pall. (bai shao), Bupleurum chinense DC. (chai hu), Citrus aurantium L. (zhi qiao/zhi shi/chen pi), Panax ginseng C. A. Mey. (ren shen), and Poria cocos (Schw.) Wolf (fu ling). These herbs contribute to formulation of Bu zhong yi qi tang (BZYQT).ConclusionPatients typically initiated Chinese medical care after the establishment of PD diagnosis, ~4.59 years post-onset of motor symptoms. The prevalent utilization of CHM decoctions and patented Chinese herbal medicine products, underscores its potential in addressing both motor and non-motor symptoms. Despite available evidence, rigorous clinical trials are needed to validate and optimize the integration of CHM, particularly BZYQT, into therapeutic strategies for PD.

The outcome of AL amyloidosis remains poor, particularly in patients with advanced organ involvement which takes long time to recovery. We conducted an observational study of two patients with AL amyloidosis treated with SDd regimen. Both patients successfully achieved significant hematological and organ responses without severe adverse events, and the time to organ response was remarkably shorter than previously reported. Notably, an over 15% reduction in interventricular septal thickness (IVST) was observed in patient#2 within 6 months. Up to now, SDd therapy has not been previously reported in AL amyloidosis and may be a promising option for these patients.

Determining the timing of landslide occurrence is crucial for establishing an accurate, comprehensive and systematic landslide inventory while assessing the potential for reducing landslide risk. Unfortunately, many existing landslide inventories lack temporal information such as the precise time of landslide events. Optical and Synthetic Aperture Radar (SAR) sensors are the most commonly used remote sensing technologies for landslide detection. Unlike optical sensors, SAR sensors are not affected by cloudy conditions and provide valuable imagery regardless of sunlight availability. Therefore, SAR-derived parameters, i.e., SAR amplitude, interferometric coherence, and polarimetric features (alpha and entropy), offer a higher temporal resolution for detecting landslide occurrence times compared to optical data. Despite the advantages, there is currently no universally accepted automatic method for determining the time of landslide events using SAR data. This is due to the lack of anomaly labels and the high time-series volatility in detecting landslide occurrence times. Despite advances in deep-learning methods for anomaly detection in time-series, only a few of them can address these challenges in our case. In this paper, we propose an unsupervised multivariate transformed-based deep-learning model to automatically and efficiently estimate landslide occurrence times using multivariate SAR-derived parameters time-series analysis. The designed gated relative position can increase robustness and temporal context information, by learning global temporal trends in the time-series. Subsequently, the time-series of the anomaly score derived from the proposed Transformer model is analyzed using an adaptive thresholding strategy to dynamically and automatically mark anomalies related to the landslide occurrence. Our research focuses on collapsed landslides characterized by dramatic changes in ground surface topography, with a particular attention for the need of a prior knowledge about landslide boundaries. We assess the performance of the proposed methodology for several collapsed landslides including the July 21, 2020 Shaziba and 23 July, 2019 Shuicheng landslides in China, March 19, 2019 Takht landslide in Iran, June 15, 2018 Jalgyz-Jangak and May 25, 2018 Kugart landslides in Kyrgyzstan, July 7, 2018 Hitardalur landslide in Iceland, and January 25, 2019 Brumadinho landslide in Brazil. In comparison to commonly used neural networks like the LSTM algorithm, our proposed framework leads to a more accurate estimate for the time of landslide failure using time-series of SAR-derived parameters. Furthermore, our results suggest the great potential of SAR data to narrow the time period detected from optical data when used in conjunction with them.

ObjectiveThis study aims to evaluate the origin of the neonatal gut microbiota on the 14th day and probiotic intervention in the third trimester.MethodsSamples were obtained from a total of 30 pregnant individuals and their offspring, divided into a control group with no intervention and a probiotic group with live combined Bifidobacterium and Lactobacillus tablets, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition of them. Non-metric multidimensional scaling and SourceTracker were used to evaluate the origin of neonatal gut microbiota.ResultsWe found that the microbiota in the neonatal gut at different times correlated with that in the maternal microbiota. The placenta had more influence on meconium microbiota. Maternal gut had more influence on neonatal gut microbiota on the 3rd day and 14th day. We also found that the maternal gut, vaginal, and placenta microbiota at full term in the probiotic group did not have a significantly different abundance of Bifidobacterium, Lactobacillus, or Streptococcus. However, some other bacteria changed in the maternal gut and their neonatal gut in the probiotic group.

Many researchers have focused on inequalities in income and energy consumption, but research on the regional disparities in natural gas consumption (NGC) is insufficient, which presents a gap about the development of informed policies for sustainable consumption. Increasing provincial NGC is a substantial measure to improve environmental protection, clean production, and the living standards of local citizens. It is necessary to determine the leading causes of inequality in gas consumption to improve the NGC in China’s provinces. To fill this research gap, we use the Gini coefficient and Lorenz curve to measure NGC inequality and apply hierarchical cluster analysis and a regression model with Partial R2 to estimate the factors of provincial NGC. The empirical results show a consistently increasing trend in China’s NGC over 1997–2019, which has not been accompanied by a steady decrease in inequality, and low inequality is mainly caused by several major natural gas-consuming provinces. Further, the NGC in coastal provinces is more significantly affected by GDP, foreign direct investment, and financial liberation, and the impact of urbanization level and population on provincial NGC has different patterns.

ObjectiveThe aim of this study was to evaluate the present status of self-management behavior and glycemic control in individuals diagnosed with Type 2 Diabetes Mellitus (T2D), as well as to examine the impact of health quotient (HQ) and time management skills on both self-management behavior and glycemic control.MethodsBetween October 2022 and March 2023, a purposive sampling method had been utilized to select 215 participants with type T2D. The survey concluded a general information questionnaire, an HQ scale, a diabetes time management questionnaire and a self-management behavior questionnaire. The health quotient(HQ)encompasses the individuals’ knowledge, attitude toward health, and the ability to maintain their own well-being. The diabetes time management questionnaire was reverse-scored, with higher scores indicating an enhanced competence in time management. The path among variables was analyzed using structural equation modeling(SEM).ResultsSEM showed that the direct effect of HQ on time management was −0.566 (p

IntroductionAdolescent suicide is a prevalent issue globally, with various factors contributing to this phenomenon. This study aimed to investigate these factors and their interrelationships to better understand the causes of adolescent suicide and provide evidence for its prevention.MethodsThis study conducted among middle school students in Liaoning Province, China, from April to May 2016, A cross-sectional survey was administered to 1,028 students aged 10–19, using instruments such as the Behavior Questionnaire-Revised (SBQ-R), Children's Perception of Interparental Conflict Scale (CPIC), and revised version of Inventory of Parent Attachment (IPPA-R).ResultBinary logistic regression analysis revealed that adolescents aged 15–19, adolescents with strong perceptions of parental conflict were at high risk of suicide intention. Adolescents living in rural areas, adolescents with high mother-child attachment, adolescents with high father-child attachment were at low risk of suicide intention. Furthermore, parent-child attachment played a mediating role between two dimensions of parental conflict perception (resolved situations and response effect) and suicide intention.DiscussionThe study concludes that adolescents living in urban areas, older adolescents, adolescents with a high level of parental conflict intensity, and those with low levels of parent-child attachment are at high risk of suicide intention. parent-child attachment played a mediating role between two dimensions of parental conflict perception (resolved situations and response effect) and suicide intention. Interventions aimed at reducing family conflicts and improving parent-child relationships are recommended to decrease the incidence of adolescent suicide.

This study was conducted to investigate the effects of dietary energy levels on microorganisms and short-chain fatty acids (SCFAs) of rumen and the expression of tight junction proteins in Honghe Yellow cattle. A total of fifteen male Honghe Yellow cattle were randomly divided into three treatments (five replicates per treatment), consisting of formulated energy concentrations of 5.90 MJ/kg (high-energy diet, group H), 5.60 MJ/kg (medium-energy diet, group M) and 5.30 MJ/kg (low-energy diet, group L). The results showed that compared with group H, the expression of Claudin-1 in rumen epithelium of groups M and L was increased, but the expression of ZO-1 was decreased (p

Summary: It is imperative to explore biomarkers that are both precise and readily accessible in the comprehensive management of breast cancer. A multicenter cohort, including 512 breast cancer patients and 198 nonneoplastic individuals, was recruited to detect the level of tumor-derived extracellular vesicles using our method based on dual DNA tetrahedral nanostructures. The level of tumor-derived extracellular vesicles was significantly higher in newly diagnosed breast cancer patients than in nonneoplastic individuals at a cutoff value of 3.58 U/μL. For postoperative metastasis monitoring, the level of tumor-derived extracellular vesicles was significantly higher in breast cancer patients with metastasis than in those without metastasis at a cutoff value of 3.91 U/μL. Its efficacy of diagnosis and metastasis monitoring was superior to traditional tumor markers. Elevated level of tumor-derived extracellular vesicles served as a predictive biomarker for diagnosis and metastasis monitoring in breast cancer patients.

Summary: This study investigates the relationship and genetic mechanisms of liver and heart diseases, focusing on the liver-heart axis (LHA) as a fundamental biological basis. Through genome-wide association study analysis, we explore shared genes and pathways related to LHA. Shared genetic factors are found in 8 out of 20 pairs, indicating genetic correlations. The analysis reveals 53 loci with pleiotropic effects, including 8 loci exhibiting shared causality across multiple traits. Based on SNP-p level tissue-specific multi-marker analysis of genomic annotation (MAGMA) analysis demonstrates significant enrichment of pleiotropy in liver and heart diseases within different cardiovascular tissues and female reproductive appendages. Gene-specific MAGMA analysis identifies 343 pleiotropic genes associated with various traits; these genes show tissue-specific enrichment primarily in the liver, cardiovascular system, and other tissues. Shared risk loci between immune cells and both liver and cardiovascular diseases are also discovered. Mendelian randomization analyses provide support for causal relationships among the investigated trait pairs.

The key to achieving rockburst warning lies in the understanding of rockburst precursors. Considering the correlation characteristics of rockburst acoustic emission (AE) parameters, a self-organizing map neural network (SOMNN) based method for rockburst precursor inversion was proposed. The feature of this method lies in a cyclic data segmentation iteration process based on the thinking of “interference signal screening”, “key signal extraction”, and “precursor signal inversion”. The rationality of this method has been verified in three groups of rockburst experiments. The results revealed that rockburst AE precursor signals consist of a series of signals characterized by long duration, high energy, low average frequency, high energy amplitude, and low peak frequency. Subsequently, potential value in long term rockburst warning of the precursor obtained in this study was shown via the comparison of conventional precursors. Finally, a preliminary interpretation for rockburst precursor was proposed under the framework of AE parameters physical significance, and it is revealed that AE precursor signals are likely linked to the creation of large-scale tensile cracks before rockburst.

ObjectiveThis study aimed to translate and validate the reliability and validity of the Chinese version of the Philippines Sunlight Exposure Questionnaire.MethodsA total of 392 Chinese individuals aged at least 18 years, residing in various cities in Sichuan province for at least 1 year, were recruited. The reliability of the Chinese version of the questionnaire was measured through internal consistency, split-half reliability, and retest reliability, while validity was determined using the content validity index and the structure validity index.ResultsThe Chinese version of the Sunlight Exposure Questionnaire, which includes 19 items covering 5 factors, demonstrated McDonald’s omega coefficient of 0.788. The split-half reliability of the questionnaire was 0.823, and the retest reliability was 0.940. The content validity index (S-CVI) was 0.952. The five-factor structure, supported by eigenvalues, explained 66.2% of the total variance. Confirmatory factor analysis indicated favorable model fit.ResultsThe chi-square value degrees of freedom ratio (χ2/df) = 1.852, the goodness-of-fit index (GFI) = 0.938, the normed fit index (NFI) = 0.922, the incremental fit index (IFI) = 0.962, the comparative fit index (CFI) = 0.962, the Tucker–Lewis index (TLI) = 0.952, and root mean square error of approximation (RMSEA) = 0.047. The indicators of the fit of the model were within reasonable bounds.ConclusionThe Chinese version of the Sunlight Exposure Questionnaire shows validity and good reliability for assessing sun exposure among adults in a Chinese cultural context.

Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism resulting from autoantibody-induced stimulation of the thyroid gland. Despite recent advancements in understanding GD's pathogenesis, the molecular processes driving disease progression and treatment response remain poorly understood. In this study, we aimed to identify crucial immunogenic factors associated with GD prognosis and immunotherapeutic response. To achieve this, we implemented a comprehensive screening strategy that combined computational immunogenicity-potential scoring with multi-parametric cluster analysis to assess the immunomodulatory genes in GD-related subtypes involving stromal and immune cells. Utilizing weighted gene co-expression network analysis (WGCNA), we identified co-expressed gene modules linked to cellular senescence and immune infiltration in CD4+ and CD8+ GD samples. Additionally, gene set enrichment analysis enabled the identification of hallmark pathways distinguishing high- and low-immune subtypes. Our WGCNA analysis revealed 21 gene co-expression modules comprising 1,541 genes associated with immune infiltration components in various stages of GD, including T cells, M1 and M2 macrophages, NK cells, and Tregs. These genes primarily participated in T cell proliferation through purinergic signaling pathways, particularly neuroactive ligand-receptor interactions, and DNA binding transcription factor activity. Three genes, namely PRSS1, HCRTR1, and P2RY4, exhibited robustness in GD patients across multiple stages and were involved in immune cell infiltration during the late stage of GD (p

Guided bone regeneration (GBR) is a widely utilized technique for alveolar bone augmentation and the GBR membrane plays a crucial role in this procedure. However, developing a membrane that possesses both mechanical property and biodegradability still remains a challenge. In this study, MgNH4PO4·6H2O (MNP) and polycaprolactone (PCL) were utilized to prepare a novel MNP-PCL composite GBR membrane via 3D printing method, and five different radios of MNP were included (5, 10, 15, 20, 25 wt%). All samples were well prepared into 25 mm × 25 mm square membranes with a thickness of about 0.8 mm. The membranes exhibited promising interconnected network structure with great distribution uniformity, mechanical properties, and biodegradability. Additionally, the membranes also possessed the capacities of sustained magnesium ions release (4 weeks at least) and weakly alkaline environment maintainance (pH 8.0–––8.5), which might be beneficial for promoting bone formation, this hypothesis was then confirmed by in vitro and in vivo studies that the adhesion, proliferation, osteogenic differentiation of MC3T3-E1 and new bone formation were signicantly enhanced on 10 % and 15 % MNP-PCL surfaces. In summary, the MNP-PCL membrane may providing a new approach for the development of GBR membranes in the future.

Summary: This study aimed to investigate the prevalence of diabetes in valvular heart disease (VHD), as well as the relationship of diabetes with severity of valvular lesions and clinical outcome. A total of 11,862 patients with significant (≥moderate) VHD from the China Valvular Heart Disease study were included in the analysis. The primary outcome was the composite of all-cause death, hospitalization for heart failure, and myocardial infarction during two-year follow-up. The prevalence of diabetes was 14.5% (1,721/11,862) in VHD. After adjusting for patients’ demographics, diabetes was associated with a significantly lower risk of severe valvular lesion in aortic regurgitation and mitral regurgitation (MR). In multivariable analysis, diabetes was identified as an independent predictor of two-year outcome in patients with MR (hazard ratio: 1.345, 95% confidence interval: 1.069–1.692, p = 0.011). More efforts should be made to enhance our understanding and improve outcomes of concomitant VHD and diabetes.

Neuroinflammation induced by chronic cerebral hypoperfusion (CCH) plays a crucial role in the pathophysiologic mechanisms of vascular dementia (VD). A growing body of research has found that intestinal microbiota is associated with a variety of central nervous system disorders and that there is a relationship between intestinal microbiota dysbiosis and cognitive dysfunction and inflammatory responses. Baicalein belongs to the class of flavonoids and has a variety of biological functions, including anti-inflammatory, antioxidant and anti-apoptotic. Baicalein has a significant improvement in memory and learning, and can be used as a potential drug for the protection and treatment of central nervous system disorders. Whether baicalein has an ameliorative effect on cognitive impairment in VD, and whether its mechanism is related to the inhibition of inflammatory response and regulation of intestinal microbiota has not been reported. We used bilateral common carotid artery occlusion (BCCAO) to establish a VD rat model. Morris water maze (MWM) test showed that baicalein improved cognitive dysfunction in VD rats. We applied HE staining, immunofluorescence and ELISA to observe that baicalein treatment significantly improved CCH-induced neuronal damage in the CA1 region of the hippocampus, and reduced glial cell activation and release of pro-inflammatory factors. Western blot showed that baicalein inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway in VD rats. We applied 16 S rDNA sequencing to analyze the composition of the intestinal microbiota. The results showed that baicalein modulated the diversity and composition of the intestinal microbiota, and suppressed the relative abundance of inflammation-associated microbiota in VD rats. In conclusion, this study found that baicalein ameliorated cognitive impairment, attenuated hippocampal inflammatory responses, inhibited the TLR4/MyD88/NF-κB signaling pathway, and modulated intestinal microbiota in VD rats.

Abstract Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16Hi) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16Hi Vδ2 T cells as a viable therapeutic option for cancer treatment.

Abstract Realizing bicontinuous fibrillar charge transport networks in the photoactive layer has been considered a promising method to achieve high‐efficiency organic solar cells (OSCs); however, this has been rarely achieved due to the interference of molecular organization of donor and acceptor components during solution casting. In this contribution, the fibrillization of polymer donor PM6 and small molecular nonfullerene acceptor L8‐BO is realized with the assistance of conjugated polymer D18‐Cl. Atomic force microscopy and photo‐induced force microscopy reveal that PM6 and D18‐Cl co‐assemble into long and slender fibrils within wide blending ratios due to their high compatibility; in contrast, the fibrillization of L8‐BO can be encouraged with the incorporation of 1% D18‐Cl. By utilizing a pseudo‐bulk heterojunction (p‐BHJ) active layer fabricated by layer‐by‐layer deposition, the optimized PM6+20% D18‐Cl/L8‐BO+1% D18‐Cl OSCs obtain bicontinuous fibril networks, leading to enhanced exciton dissociation and charge transport processes and superior power conversion efficiency of 19.2% (certified 18.91%) compared to 18.8% of the PM6:D18‐Cl:L8‐BO ternary BHJ OSCs.

Abstract Background Extramedullary disease usually implies a dismal outcome in relapsed/refractory multiple myeloma patients, and requires novel treatment approaches. We designed a trial using Selinexor, a nuclear export protein 1 inhibitor, together with anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell product CT103A to treat these patients, and describe the first two cases in this report. Methods Selinexor was administered with a novel two-step schedule in bridging therapy and in maintenance. The clinical responses and adverse events were recorded after CAR-T infusion and Selinexor administration. In vitro analysis of the influence of Selinexor on CAR-T cell function was performed using myeloma cell lines. Results After infusion, both patients achieved stringent complete remission (sCR), and were maintained in sCR at data-cutoff, with survival over 13 and 10 months, respectively. Neither immune effector cell-associated neurotoxicity syndrome nor over grade 2 cytokine release syndrome was observed. Meanwhile, the patients showed good tolerance to the combination. In addition, we demonstrated that low dose of Selinexor could upregulate the expression of BCMA on plasma cell lines and subsequently enhance the function of CAR-T cell in vitro. Conclusions The combination of Selinexor and CT103A exerts preliminary synergistic effect, and can be developed as a promising strategy for relapsed/refractory extramedullary myeloma.

Abstract Micro-gyroscopes using micro-electro-mechanical system (MEMS) and micro-opto-electro-mechanical system (MOEMS) are the new-generation and recently well-developed gyroscopes produced by the combinations of the traditional gyroscope technology and MEMS/MOEMS technologies. According to the working principle and used materials, the newly-reported micro-gyroscopes in recent years include the silicon-based micromechanical vibratory gyroscope, hemispherical resonant gyroscope, piezoelectric vibratory gyroscope, suspended rotor gyroscope, microfluidic gyroscope, optical gyroscope, and atomic gyroscope. According to different sensitive structures, the silicon-based micromechanical vibratory gyroscope can also be divided into double frame type, tuning fork type, vibrating ring type, and nested ring type. For those micro-gyroscopes, in recent years, many emerging techniques are proposed and developed to enhance different aspects of performances, such as the sensitivity, angle random walk (ARW), bias instability (BI), and bandwidth. Therefore, this paper will firstly review the main performances and applications of those newly-developed MEMS/MOEMS gyroscopes, then comprehensively summarize and analyze the latest research progress of the micro-gyroscopes mentioned above, and finally discuss the future development trends of MEMS/MOEMS gyroscopes.

Thanks to the synergistic effect, the bimetallic catalysts show better catalytic activity than the single metal catalysts and become a focus of research in heterogeneous catalysis. In this study, we successfully prepared Pd-Pt icosahedra which show high peroxidase-like activity under the synergistic effects of Pd and Pt. Vmax of the Pd-Pt icosahedra was significantly enhanced by 1.66 times for 3,3’,5,5’-tetramethylbenzidine (TMB) as the substrate and 1.23 times for H2O2 as the substrate, compared to that of the Pd icosahedra alone. By harnessing the superior peroxidase-like activity of Pd-Pt icosahedra, we successfully utilized Pd-Pt icosahedral nanozymes in various biological analyses based on colorimetry. In most cases, using a Pd-Pt icosahedra/H2O2/TMB system, glucose, glutathione (GSH), acid phosphatase (ACP), and alkaline phosphatase (ALP) were detected over a wide range of 0.05∼0.20 mM, 0∼20 mM, 0∼10 U/L and 0∼12 U/L. In this study, we prepared a novel bimetallic nanozyme that exhibited excellent peroxidase-like activity owing to the bimetallic synergistic effect, thus demonstrating the promising potential of Pd-Pt icosahedra in the field of bioanalysis.

The Chinese longsnout catfish (Leiocassis longirostris) is a rare and valuable freshwater fish wildly distributed throughout China. Fish growth is one of the most economically important traits in fish farming. Cultured fish with high growth performance can often bring direct economic benefits while meeting human food demand. The hypothalamus is an important regulatory organ in fish metabolic processes and endocrine activities, directly or indirectly regulating fish growth. Although significant research on L. longirostris has been reported, the molecular mechanisms and key genes involved in its growth are still unclear. Therefore, we performed comparative transcriptomics analysis using Illumina high throughput sequencing technology and analyzed transcript profiles of the brains from fast-growth (FG) with average body mass of (534.02±53.68) g, and slow-growth (SG) with average body mass og (108.41±4.96) g L. longirostris individuals. A total of 267 404 674 clean reads were generated, and 518 differentially expressed genes were identified, of which 412 genes were up-regulated and 106 genes were down-regulated in fast-growth fishes. Then, we subjected all these differentially expressed genes to GO term enrichment and KEGG pathway analysis to find the underlying function annotation. Based on Gene Ontology analysis, plenty of differentially expressed genes were enriched in growth, growth factor activity, and hormone-mediated signaling pathway. KEGG enrichment analysis indicated that some differentially expressed genes involved in MAPK signaling pathway, TGF-beta signaling pathway, calcium signaling pathway, and neuroactive ligand-receptor interaction were enriched. With the differentially expressed genes identified from GO and KEGG enrichment analysis, several key genes related to the growth of L. longirostris were screened, such as gnrh, thr, egr1, fgf18, sst, gipr, cart, and crf. The results of this study enriched the gene resources and provided valuable references for further study on the regulation mechanism of growth of L. longirostris.

Response speed is vital for the railway environment monitoring system, especially for the sudden-onset disasters. The edge-cloud collaboration scheme is proved efficient to reduce the latency. However, the data characteristics and communication demand of the tasks in the railway environment monitoring system are all different and changeable, and the latency contribution of each task to the system is discrepant. Hence, two valid latency minimization strategies based on the edge-cloud collaboration scheme is developed in this paper. First, the processing resources are allocated to the tasks based on the priorities, and the tasks are processed parallelly with the allocated resources to minimize the system valid latency. Furthermore, considering the differences in the data volume of the tasks, which will induce the waste of the resources for the tasks finished in advance. Thus, the tasks with similar priorities are graded into the same group, and the serial and parallel processing strategies are performed intra-group and inter-group simultaneously. Compared with the other four strategies in four railway monitoring scenarios, the proposed strategies proved latency efficiency to the high-priority tasks, and the system valid latency is reduced synchronously. The performance of the railway environment monitoring system in security and efficiency will be promoted greatly with the proposed scheme and strategies.

Functional nucleic acids including aptamers and DNAzymes are a class of valuable molecular tool for biotechnology. However, DNA and RNA aptamers and catalysts suffer from low biological stability and limited chemical diversity. Xeno-nucleic acids (XNAs) refer to nucleic acid analogues containing sugar moieties that are structurally distinct from DNA and RNA and possess advantageous properties. In this article, we first focus on two types of XNAs, threose nucleic acid (TNA) and 2’-fluoroarabinose nucleic acid (FANA), and summarize recent in vitro selections of TNA and FANA aptamers and catalysts. We then review three classes of unnatural base pairs (UBPs) and highlight examples of UBP-containing DNA aptamers and DNAzymes. Lastly, we briefly describe an XNA-modified DNAzyme 10–23 (X10-23) and its application in RNA knockdown and virus detection. Functional XNAs provide important chemical biology tools for biomedical research and future interdisciplinary collaboration will boost XNA basic research and clinical translation.