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This paper presents a review of research progress on photovoltaic direct current arc detection based on VOSviewer bibliometric analysis. This study begins by introducing the basic concept and hazards of photovoltaic DC arcing faults, followed by a summary of commonly used arc detection techniques. Utilizing VOSviewer, the relevant literature is subjected to clustering and visualization analysis, offering insights into research hotspots, trends, and interconnections among different fields. Based on the bibliometric analysis method of VOSviewer software, this paper analyzes the articles published in the last 10 years (2014–2023) on photovoltaic DC fault diagnosis. We analyzed the specific characteristics of 2195 articles on arc failures, including year of publication, author, institution, country, references, and keywords. This study reveals the development trend, global cooperation model, basic knowledge, research hotspots, and emerging frontier of PV DC arc. Future research directions and development trends for photovoltaic DC arc detection are proposed which provides valuable references for further studies and applications in this domain. This comprehensive analysis indicates that photovoltaic DC arc detection technology is expected to find broader applications and greater promotion in the future.

Over the past decades, the cryosphere has changed significantly in High Mountain Asia (HMA), leading to multiple natural hazards such as rock–ice avalanches, glacier collapse, debris flows, landslides, and glacial lake outburst floods (GLOFs). Monitoring cryosphere change and evaluating its hydrological effects are essential for studying climate change, the hydrological cycle, water resource management, and natural disaster mitigation and prevention. However, knowledge gaps, data uncertainties, and other substantial challenges limit comprehensive research in climate–cryosphere–hydrology–hazard systems. To address this, we provide an up-to-date, comprehensive, multidisciplinary review of remote sensing techniques in cryosphere studies, demonstrating primary methodologies for delineating glaciers and measuring geodetic glacier mass balance change, glacier thickness, glacier motion or ice velocity, snow extent and water equivalent, frozen ground or frozen soil, lake ice, and glacier-related hazards. The principal results and data achievements are summarized, including URL links for available products and related data platforms. We then describe the main challenges for cryosphere monitoring using satellite-based datasets. Among these challenges, the most significant limitations in accurate data inversion from remotely sensed data are attributed to the high uncertainties and inconsistent estimations due to rough terrain, the various techniques employed, data variability across the same regions (e.g., glacier mass balance change, snow depth retrieval, and the active layer thickness of frozen ground), and poor-quality optical images due to cloudy weather. The paucity of ground observations and validations with few long-term, continuous datasets also limits the utilization of satellite-based cryosphere studies and large-scale hydrological models. Lastly, we address potential breakthroughs in future studies, i.e., (1) outlining debris-covered glacier margins explicitly involving glacier areas in rough mountain shadows, (2) developing highly accurate snow depth retrieval methods by establishing a microwave emission model of snowpack in mountainous regions, (3) advancing techniques for subsurface complex freeze–thaw process observations from space, (4) filling knowledge gaps on scattering mechanisms varying with surface features (e.g., lake ice thickness and varying snow features on lake ice), and (5) improving and cross-verifying the data retrieval accuracy by combining different remote sensing techniques and physical models using machine learning methods and assimilation of multiple high-temporal-resolution datasets from multiple platforms. This comprehensive, multidisciplinary review highlights cryospheric studies incorporating spaceborne observations and hydrological models from diversified techniques/methodologies (e.g., multi-spectral optical data with thermal bands, SAR, InSAR, passive microwave, and altimetry), providing a valuable reference for what scientists have achieved in cryosphere change research and its hydrological effects on the Third Pole.

An appropriate drying method is crucial for producing high-quality dried apricots. In this study, the effects of four drying methods, hot air drying (HAD), infrared drying (IRD), pulse vacuum drying (PVD), and vacuum freeze-drying (VFD), on the drying kinetics and physical and nutritional characteristics of apricot slices were evaluated. PVD required the shortest time (16.25 h), followed by IRD (17.54 h), HAD (21.39 h), and VFD (34.64 h). VFD resulted in the best quality of apricot slices, with the smallest color difference (ΔE = 13.64), lowest water activity (0.312 ± 0.015) and browning degree (0.35), highest color saturation (62.84), lowest hardness (8.35 ± 0.47 N) and shrinkage (9.13 ± 0.65%), strongest rehydration ability (3.58 ± 0.11 g/g), a good microstructure, and high nutrient-retention rates (ascorbic acid content: 53.31 ± 0.58 mg/100 g, total phenolic content: 12.64 ± 0.50 mg GAE/g, and carotenoid content: 24.23 ± 0.58 mg/100 g) and antioxidant activity (DPPH: 21.10 ± 0.99 mmol Trolox/g and FRAP: 34.10 ± 0.81 mmol Trolox/g). The quality of PVD-treated apricot slices was second-best, and the quality of HAD-treated apricot slices was the worst. However, the energy consumption required for VFD was relatively high, while that required for PVD was lower. The results of this study provide a scientific basis for the large-scale industrial production of dried apricots.

Reproductive disorders and declining fertility rates are significant public health concerns affecting birth rates and future populations. Male infertility, often due to spermatogenesis defects, may be linked to environmental pollutants like nickel nanoparticles (Ni NPs). Ni NPs are extensively utilized across different industries. Nevertheless, their potential adverse effects cannot be overlooked. Previous studies have linked the reproductive toxicity induced by Ni NPs with disturbances in mitochondrial function. Mitochondrial division/fusion dynamics are crucial to their proper function, yet little is known about how Ni NPs perturb these dynamics and whether such perturbation contributes to the impairment of the male reproductive system. Herein, we demonstrated that the exposure of Ni NPs to the mouse-derived spermatogonia cell line (GC-1 cells) triggered DRP1-mediated mitochondrial division and the enhanced impairment of mitochondria, consequently promoting mitochondria-dependent cell apoptosis. Notably, both the mitochondrial division inhibitor (Mdivi-1) and lentiviral-transfected cells with low expression of Dnm1l-DK in these cells could mitigate the toxic effects induced by Ni NPs, pointing to the potential role of mitochondrial dynamics in Ni NP-induced reproductive toxicity. Collectively, our work contributes to the understanding of the mechanisms by which Ni NPs can impact male reproductive function and identifies mitochondrial division as a potential target for intervention.

Lactarius hatsudake is a common ectomycorrhizal edible mushroom in Pinus massoniana forests, and has important ecological and potential economic values. However, there are only a few reports on the establishment of Pinus massoniana–Lactarius hatsudake symbiosis. Here, we isolated a new strain of L. Lactarius hatsudake (GX01) from a local masson pine forest and established its ectomycorrhizal symbiosis with the P. massoniana. Potato dextrose agar (PDA) medium was optimal for the growth of L. hatsudake GX01. The saffron-to-brown ectomycorrhiza formed by L. hatsudake GX01 are usually bifurcated or coralloid shape, with a rod and a smooth surface, without emanating hyphae. The characteristic mantle and Hartig net structures of ectomycorrhizae were confirmed by microscope and scanning electron microscope (SEM). L. hatsudake GX01 can significantly promote the formation and development of lateral roots of P. massoniana seedlings during the early interaction. This study thus lays the foundation for subsequent study of the symbiotic molecular mechanism and application of P. massoniana–L. hatsudake symbiosis.

This study explores the challenges and advances in the estimation of the state of charge (SOC) of lithium-ion batteries (LIBs), which are crucial to optimizing their performance and lifespan. This review focuses on four main techniques of SOC estimation: experimental measurement, modeling approach, data-driven approach, and joint estimation approach, highlighting the limitations and potential inaccuracies of each method. This study suggests a combined approach, incorporating correction parameters and closed-loop feedback, to improve measurement accuracy. It introduces a multi-physics model that considers temperature, charging rate, and aging effects and proposes the integration of models and algorithms for optimal estimation of SOC. This research emphasizes the importance of considering temperature and aging factors in data-driven approaches. It suggests that the fusion of different methods could lead to more accurate SOC predictions, an important area for future research.

To evaluate the impact of different momentum control variable (CV) schemes (CV5, the momentum control variable option with ψχ and CV7, the momentum control variable option with UV) on radar data assimilation (DA) in weather research and forecasting model data-assimilation (WRFDA) systems, a heavy snowfall in central and eastern regions of China, which started on 6 February 2022, was taken as a case in this study. The results of the wind-field increments from the single observation tests indicated that the wind-field increments had a larger range of influence when stream function and velocity potential (ψχ) were used as momentum control variables in CV5. Some spurious increments were also generated in the wind-field analysis, since CV5 tended to maintain the integrated value of the wind field. When U-wind and V-wind were used as control variables in CV7, the wind-field increments had a smaller impact range, and there was less dependence among different locations on the wind increments. For the heavy snow case, the CV7 schemes displayed some improvements in simulating the composite reflectivity compared to the other two experiments, since the composite reflectivity in the CV5 and control experiments were overestimated to some level. It was also found that the RMSEs were lower in the CV7 compared to those in the CV5 in the short-term forecasts during the data-assimilation cycles. Results also indicated that the CV7 had a more significant effect on the 6 h accumulated precipitation forecasts. Meanwhile, the experiment Exp_CV7 achieved the best ETS and FSS scores among the three groups of experiments, while Exp_CV5 appeared to be generally superior to the CTRL. In summary, the precipitation of Exp_CV7 yielded the rainfall intensity and location most close to the observation compared to those from both the CTRL and Exp_CV5 experiments.

In this study, a Pt@Co-Al LDH hybrid structure was fabricated by assembling the metal precursor PtCl62− with the exfoliated LDH nanosheets followed by in situ reduction by NaBH4. The morphology, composition and microstructure of the hybrid were characterized by FESEM, HRTEM, XRD, XPS and BET techniques. Pt nanoparticles (NPs) with an average particle size of 3.1 nm were successfully and uniformly loaded on the surface of LDH nanosheets. The catalytic activity of the Pt@Co-Al LDH hybrid was tested for the reduction of 4-nitrophenol, which is one of the most frequent pollutants in wastewater effluent from the pharmaceutical and textile industries. The hybrid displays superior catalytic activity and stability in the reduction of 4-NP under environmental conditions with NaBH4 as a reducing agent. The hybrid can be recovered in a simple way and still shows high catalytic activity after five reuses.

Cellulose-based hierarchical porous beads exhibit significant application potential in adsorption and separation systems due to their degradation and biocompatibility. However, the current fabrications of cellulose beads show poor mechanical properties and a difficult-to-regulate hierarchical porous structure, reducing their lifespan of use and limiting their application in fine separation. Here, we reported the facile creep–drop method to prepare cellulose beads that enabled systemic regulation of the macro-size, micropore structures, and mechanical properties by optimizing injection nozzle diameter, the composition of the coagulation bath, the temperature of the coagulation bath, and cellulose concentration. Notably, during the molding process, the H2SO4-Na2SO4 composite solidification bath endowed cellulose beads with a dense shell layer and a loose core layer, which achieved the integration of mechanical properties and high porosity. The cellulose beads exhibited high porosity (93.38–96.18%) and high sphericity (86.78–94.44%) by modulating the shell thickness of the cellulose beads. In particular, the cellulose beads exhibited excellent mechanical properties with a high compressive strength of 544.24 kPa at a 5% cellulose concentration. It is expected that these cellulose beads with tunable microstructures can realize their potential for applications in the fields of wastewater treatment, chemical engineering, bioengineering, medicine, and pharmaceuticals.

Nanostructured lipid carriers (NLC) for the encapsulation and protection of phytosterol (PS) were prepared using walnut oil as liquid lipid by high-pressure homogenization method. The average particle size, polydispersity index, Zeta potential and encapsulation efficiency were used as the main evaluation indexes to optimize the preparation process parameters and formulations，and the morphology and stability of the optimized PS-NLC were investigated. The optimal ratio for the preparation of PS-NLC was determined by orthogonal tests as 10% of total lipid concentration, 2:3 of stearic acid and walnut oil, and 1.2% of soy lecithin. The prepared PS-NLC had a spherical appearance, small particle size and uniform distribution. The stability results of PS-NLC showed that PS-NLC was stable in storage at 4 ℃ for 28 days. It was diluted 5~100 times with good dilution stability, when used. And the addition of 2% sucrose had the best effect on the lyophilization protection of PS-NLC. Walnut oil was used as the wall material of NLC to provide a suitable lipid delivery system for phytosterols, which could provide technical support for the construction of PS-NLC in food industry.

Highlights A novel strategy was developed to construct ultrathin microfiber composite hydrogel films (< 5 μm) by embedding an electrospun fiber network into a hydrogel. The microfiber composite hydrogel offers tunable modulus in a broad range (from ~ 5 kPa to tens of MPa), which matches the modulus of most biological tissues and organs. The ultrathin configuration and ultrasoft nature allow the microfiber composite hydrogel seamlessly attaching to various rough surfaces.

Abstract The knowledge of acoustic wave propagation in a borehole embedded in gas hydrate-bearing sediments is of great significance for the exploitation of gas hydrate. A gas hydrate-bearing sediment is a typical three-phase porous medium containing two solids and one fluid. However, until now, the borehole acoustic wavefield and its component waves within such a porous medium have never been calculated. In this work, a real-axis integration method is proposed to calculate the borehole acoustic field embedded in a three-phase porous medium based on the Biot-type three-phase theory. Meanwhile, a component wave approach, combined with the branch-cut integral method and the residue theorem, including residues at leaky poles is proposed to study the borehole wave propagation of a three-phase porous medium. The branch points and poles of the potential acoustic wave function are obtained, which correspond to the normal and leaky modes on various Riemann sheets. On this basis, the excitation intensity and waveforms of each component are obtained. The result shows that the waveform summed up from all individual waves agrees well with the full waveform calculated by real-axis integration, which provides a theoretical basis for the subsequent inversion of reservoir parameters by using the information of various mode waves.

Abstract The construction of efficient artificial light-harvesting systems (ALHSs) is of vital importance in utilizing solar energy. Herein, we report the non-covalent syntheses of double helicates PCP-TPy1/2 and R p,R p-PCP-TPy1/2 by metal-coordination interaction and their applications in ALHSs and white light-emitting diode (LED) device. All double helicates exhibit significant aggregation-induced emission in tetrahydrofuran/water (1:9, v/v) solvent. The aggregated double helicates can be used to construct one-step or sequential ALHSs with fluorescent dyes Eosin Y (EsY) and Nile red (NiR) with the energy transfer efficiency up to 89.3%. Impressively, the PMMA film of PCP-TPy1 shows white-light emission when doped 0.075% NiR, the solid of double helicates (R p,R p-) PCP-TPy2 can be used as the additive of a blue LED bulb to achieve white-light emission. In this work, we provided a general method for the preparation of novel double helicates and explored their applications in ALHSs and fluorescent materials, which will promote future construction and application of helicates as emissive devices.

Abstract Telomeres, at the ends of chromosomes, protect chromosomes from fusion and preserve genomic stability. However, the molecular mechanisms underlying telomere attrition-induced genome instability remain to be understood. We systematically analyzed the expression of retrotransposons and performed genomic sequencing of different cell and tissue types with telomeres of varying lengths due to telomerase deficiency. We found that critically short telomeres altered retrotransposon activity to promote genomic instability in mouse embryonic stem cells, as evidenced by elevated numbers of single nucleotide variants, indels and copy number variations (CNVs). Transpositions of retrotransposons such as LINE1 resulting from the short telomeres can also be found in these genomes with elevated number of mutations and CNVs. Retrotransposon activation is linked to increased chromatin accessibility, and reduced heterochromatin abundance correlates with short telomeres. Re-elongation of telomeres upon recovery of telomerase partly represses retrotransposons and heterochromatin accumulation. Together, our findings suggest a potential mechanism by which telomeres maintain genomic stability by suppressing chromatin accessibility and retrotransposon activity.

Abstract Background There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention. Methods We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism. Results After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations. Conclusions Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management. Trial registration The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).

Abstract Background Myeloid neoplasms (MN) tend to relapse and deteriorate. Exploring the genomic mutation landscape of MN using next‐generation sequencing (NGS) is a great measure to clarify the mechanism of oncogenesis and progression of MN. Methods This multicenter retrospective study investigated 303 patients with MN using NGS from 2019 to 2021. The characteristics of the mutation landscape in the MN subgroups and the clinical value of gene variants were analyzed. Results At least one mutation was detected in 88.11% of the patients (267/303). TET2 was the most common mutation in the cohort, followed by GATA2, ASXL1, FLT3, DNMT3A, and TP53. Among patients with myeloid leukemia (ML), multivariate analysis showed that patients aged ≥60 years had lower overall survival (OS, p = 0.004). Further analysis showed TET2, NPM1, SRSF2, and IDH1 gene mutations, and epigenetic genes (p

Abstract Background Diabetes mellitus is a major cause of high mortality and poor prognosis in patients with pulmonary infections. However, limited data on the application of metagenomic next-generation sequencing (mNGS) are available for diabetic patients. This study aimed to evaluate the diagnostic performance of mNGS in diabetic patients with pulmonary infections. Methods We retrospectively reviewed 184 hospitalized patients with pulmonary infections at Guizhou Provincial People’s Hospital between January 2020 to October 2021. All patients were subjected to both mNGS analysis of bronchoalveolar lavage fluid (BALF) and conventional testing. Positive rate by mNGS and the consistency between mNGS and conventional testing results were evaluated for diabetic and non-diabetic patients. Results A total of 184 patients with pulmonary infections were enrolled, including 43 diabetic patients and 141 non-diabetic patients. For diabetic patients, the microbial positive rate by mNGS was significantly higher than that detected by conventional testing methods, primarily driven by bacterial detection (microbes: 95.3% vs. 67.4%, P = 0.001; bacteria: 72.1% vs. 37.2%, P = 0.001). mNGS and traditional tests had similar positive rates with regard to fungal and viral detection in diabetic patients. Klebsiella pneumoniae was the most common pathogen identified by mNGS in patients with diabetes. Moreover, mNGS identified pathogens in 92.9% (13/14) of diabetic patients who were reported negative by conventional testing. No significant difference was found in the consistency of the two tests between diabetic and non-diabetic groups. Conclusions mNGS is superior to conventional microbiological tests for bacterial detection in diabetic patients with pulmonary infections. mNGS is a valuable tool for etiological diagnosis of pulmonary infections in diabetic patients.

Abstract The low-cycle fatigue life of 316 stainless steel is a significant basis for safety assessment. Usually, many factors affect the low-cycle fatigue life of stainless steel, and the relationship between the influencing factors and fatigue life is complicated and nonlinear. Therefore, it is hard to predict fatigue life using the traditional empirical formula. Based on this, a machine learning algorithm is proposed. In this paper, based on the large amount of existing experimental data, machine learning methods are used to predict the low circumferential fatigue life of 316 stainless steel. The results show that the prediction accuracy of nu-SVR and ELM models is high and can meet engineering needs.

Abstract With the development of big traffic data, bus schedules should be changed from the traditional "empirical" rough scheduling to "responsive" accurate scheduling to meet the travel needs of passengers. Based on passenger flow distribution, considering passengers' feelings of congestion and waiting time at the station, we establish a Dual-Cost Bus Scheduling Optimization Model (Dual-CBSOM) with the optimization objectives of minimizing bus operation and passenger travel costs. Improving the classical Genetic Algorithm (GA) by adaptively determining the crossover probability and mutation probability of the algorithm. We use an Adaptive Double Probability Genetic Algorithm (A_DPGA) to solve the Dual-CBSOM. Taking Qingdao city as an example for optimization, the constructed A_DPGA is compared with the classical GA and Adaptive Genetic Algorithm (AGA). By solving the arithmetic example, we get the optimal solution that can reduce the overall objective function value by 2.3%, improve the bus operation cost by 4.0%, and reduce the passenger travel cost by 6.3%. The conclusions show that the Dual_CBSOM built can better meet the passenger travel demand, improve passenger travel satisfaction, and reduce the passenger travel cost and waiting for cost. It is demonstrated that the A_DPGA built in this research has faster convergence and better optimization results.

Abstract In recent years, tumor immunotherapy has made significant progress. However, tumor immunotherapy, particularly immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors), benefits only a tiny proportion of patients in solid cancers. The tumor microenvironment (TME) acts a significant role in tumor immunotherapy. Studies reported that tumor-associated macrophages (TAMs), as one of the main components of TME, seriously affected the therapeutic effect of PD-1/PD-L1 inhibitors. In this review, we analyzed TAMs from epigenetic and single-cell perspectives and introduced the role and mechanisms of TAMs in anti-programmed death protein 1(anti-PD-1) therapy. In addition, we summarized combination regimens that enhance the efficacy of tumor PD-1/PD-L1 inhibitors and elaborated on the role of the TAMs in different solid cancers. Eventually, the clinical value of TAMs by influencing the therapeutic effect of tumor PD-1/PD-L1 inhibitors was discussed. These above are beneficial to elucidate poor therapeutic effect of PD-1/PD-L1 inhibitors in solid tumors from the point of view of TAMs and explore the strategies to improve its objective remission rate of solid cancers.

Abstract Background Depression increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Physical activity has been shown to improve depressive symptoms in this population, but the relationship of sedentary behavior with depression has not been studied. In this study, we examined the relationship between sedentary behavior and depression in patients with chronic kidney disease. Methods This cross-sectional study included 5,205 participants aged ≥ 18 years with chronic kidney disease participating in the 2007–2018 National Health and Nutrition Examination Survey. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Recreation activity, work activity, walking or cycling for transportation, and sedentary behavior were measured using the Global Physical Activity Questionnaire. A series of weighted logistic regression models were used to investigate the aforementioned relationship. Results The prevalence of depression among US adults with chronic kidney disease was 10.97% in our study. In addition, sedentary behavior was strongly associated with higher levels of depressive symptoms, as measured by the PHQ-9 (P

Abstract Exosome is a subgroup of extracellular vesicles, which has been serving as an efficient therapeutic tool for various diseases. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. After appropriate modification, engineered exosomes are able to deliver antitumor drugs to tumor sites efficiently and precisely with fewer treatment-related adverse effects. However, there still exist many challenges for the clinical translation of engineered exosomes. For instance, what sources and modification strategies could endow exosomes with the most efficient antitumor activity is still poorly understood. Additionally, how to choose appropriately engineered exosomes in different antitumor therapies is another unresolved problem. In this review, we summarized the characteristics of engineered exosomes, especially the spatial and temporal properties. Additionally, we concluded the recent advances in engineered exosomes in the cancer fields, including the sources, isolation technologies, modification strategies, and labeling and imaging methods of engineered exosomes. Furthermore, the applications of engineered exosomes in different antitumor therapies were summarized, such as photodynamic therapy, gene therapy, and immunotherapy. Consequently, the above provides the cancer researchers in this community with the latest ideas on engineered exosome modification and new direction of new drug development, which is prospective to accelerate the clinical translation of engineered exosomes for cancer-targeted therapy.

Abstract Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

The polyoxometalates-based electrochromic energy storage devices (POMs-EESDs) were constructed using P2W17O6111− coated TiO2 as the working electrode and MnO2 film as the counter electrode. The MnO2 films with different thicknesses acted as the charge balancing layer. The device showed bifunctional of enhanced EC and energy storage properties along with high durability and cycle stabilities after the introduction of MnO2 film. The optimistic thickness of MnO2 was found to be 345 nm through balancing the optical modulation and the energy storage properties. For the EC aspect, the optical contrast was enhanced by four times under the potential step of −2.0/1.0 V. The MnO2 film also introduces high capacitance leading to the device can be used as a transparent capacitor. It is the first time to construct high-performance POMs-based EESD only by introducing a simple charge balancing (MnO2) layer in the device. Moreover, the mechanism of the MnO2 layer towards the performance improvement of the POMs-based EESDs was also explained.

Polymeric biomaterials have emerged as a highly promising candidate for drug delivery systems (DDS), exhibiting significant potential to enhance the therapeutic landscape of osteoarthritis (OA) therapy. Their remarkable capacity to manifest desirable physicochemical attributes, coupled with their excellent biocompatibility and biodegradability, has greatly expanded their utility in pharmacotherapeutic applications. Nevertheless, an urgent necessity exists for a comprehensive synthesis of the most recent advances in polymeric DDS, providing valuable guidance for their implementation in the context of OA therapy. This review is dedicated to summarizing and examining recent developments in the utilization of polymeric DDS for OA therapy. Initially, we present an overview of the intricate pathophysiology characterizing OA and underscore the prevailing limitations inherent to current treatment modalities. Subsequently, we introduce diverse categories of polymeric DDS, including hydrogels, nanofibers, and microspheres, elucidating their inherent advantages and limitations. Moreover, we discuss and summarize the delivery of bioactive agents through polymeric biomaterials for OA therapy, emphasizing key findings and emerging trends. Finally, we highlight prospective directions for advancing polymeric DDS, offering a promising approach to enhance their translational potential for OA therapy.

Metabolic reprogramming at a cellular level contributes to many diseases including cancer, yet few assays are capable of measuring metabolic pathway usage by individual cells within living samples. Here, autofluorescence lifetime imaging is combined with single-cell segmentation and machine-learning models to predict the metabolic pathway usage of cancer cells. The metabolic activities of MCF7 breast cancer cells and HepG2 liver cancer cells were controlled by growing the cells in culture media with specific substrates and metabolic inhibitors. Fluorescence lifetime images of two endogenous metabolic coenzymes, reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD), were acquired by a multi-photon fluorescence lifetime microscope and analyzed at the cellular level. Quantitative changes of NADH and FAD lifetime components were observed for cells using glycolysis, oxidative phosphorylation, and glutaminolysis. Conventional machine learning models trained with the autofluorescence features classified cells as dependent on glycolytic or oxidative metabolism with 90%–92% accuracy. Furthermore, adapting convolutional neural networks to predict cancer cell metabolic perturbations from the autofluorescence lifetime images provided improved performance, 95% accuracy, over traditional models trained via extracted features. Additionally, the model trained with the lifetime features of cancer cells could be transferred to autofluorescence lifetime images of T cells, with a prediction that 80% of activated T cells were glycolytic, and 97% of quiescent T cells were oxidative. In summary, autofluorescence lifetime imaging combined with machine learning models can detect metabolic perturbations between glycolysis and oxidative metabolism of living samples at a cellular level, providing a label-free technology to study cellular metabolism and metabolic heterogeneity.

BackgroundIn vitro fertilization (IVF) is the main technique to address the infertility issue in the patient-oriented strategy encompassing individualized oocyte number (POSEIDON) population. Adopting appropriate protocols for assisted reproduction technologies (ART) cycles in the POSEIDON group may attain more favorable pregnancy outcomes.ObjectivesThis study aimed to compare the effectiveness of modified long gonadotropin-releasing hormone agonist protocol and non-downregulation protocol in POSEIDON patients undergoing ART, and to identify the factors affecting the pregnancy outcomes in this group.DesignThis study was designed as a propensity score-matched (PSM) retrospective analysis.ParticipantsThe study cohort consisted of 910 patients diagnosed with ovarian hyporesponsiveness and treated by IVF from January 2020 to June 2022. They were followed up until the transfer of the last embryo of the IVF cycle and/or pregnancy at 12 weeks. The study was conducted at the Center of Reproductive Medicine, Tongji Medical College, Wuhan Union Hospital, Huazhong University of Science and Technology.MethodsThe patients were divided into Group I and Group II. Group I was treated with modified long gonadotropin-releasing hormone agonist protocol while Group II was put on a non-downregulation protocol. Propensity score matching (PSM) was used to select patients for each group. The subjects were compared in terms of the baseline level, process of controlled ovarian hyperstimulation, and pregnancy outcomes. Binary logistic regression analysis was performed to assess the difference in the cumulative pregnancy rate between the two groups.ResultsOf the 910 POSEIDON patients who underwent IVF, 213 received the modified long gonadotropin-releasing hormone agonist protocol and 697 were subjected to the non-downregulation protocol. From the original cohort, PSM matched 174 pairs of patients. No statistically significant difference was found in total gonadotropin (Gn) dose between the two PSM groups, but the average daily Gn dose was lower in Group I and the duration of Gn lasted longer. The number of retrieved oocytes, the number of metaphase II (MII) ooctyes retrieved, normal fertilization, and normal cleavage embryos was significantly higher in Group I than in Group II, but there existed no significant difference in the number of high-quality embryos between the two groups. The single-cycle CPR (cumulative pregnancy rate) was higher in Group I than in Group II (for Group I: before PSM, CPR = 52.6%; after PSM, CPR = 51.7%; for Group II: before PSM, CPR = 34.0%; after PSM, CPR = 34.5%), and the difference was statistically significant. A binary logistic regression analysis in the unmatched patients showed that the CPR of Group II was 0.486 times that of Group I (95% CI: 0.303 to 0.779).ConclusionsThe modified long gonadotropin-releasing hormone agonist protocol can be used as an optimal protocol for IVF or ICSI (Intracytoplasmic sperm injection) in POSEIDON patients.Level of evidenceLevel III

ObjectiveThe immune response assumes a pivotal role in the underlying mechanisms of urticaria pathogenesis. The present study delves into an investigation of the genetic causal connections between urticaria and prevalent autoimmune afflictions, notably rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn’s disease (CD).MethodsA bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationships involving four autoimmune diseases and urticaria. The genome-wide association study (GWAS) summary data of four autoimmune disease were sourced from the IEU OpenGWAS database. The GWAS summary data for urticaria were derived from the Finnish consortium dataset. The principal analytical approach employed in this study was the random-effects inverse variance weighted (IVW) method. Subsequently, a series of sensitivity analyses were performed, encompassing assessments of heterogeneity, horizontal pleiotropy, outliers, “Leave-one-out” analyses, and tests for adherence to the assumption of normal distribution.ResultsThe random-effects IVW analysis indicate a positive genetic causal association between RA and urticaria (P < 0.001, OR 95% CI = 1.091 [1.051-1.133]). Conversely, SLE, UC, and CD do not exhibit a significant genetic causal relationship with urticaria. The reverse MR analysis reveals a positive genetic causal linkage between urticaria and SLE (P = 0.026, OR 95% CI = 1.289 [1.031-1.612]). However, the analysis demonstrates no substantial genetic causal relationship between urticaria and RA, UC, or CD. Importantly, the genetic causal assessment absence of heterogeneity, horizontal pleiotropy, and outliers. Furthermore, it remains unaffected by any individual single nucleotide polymorphism (SNP), demonstrating adherence to a normal distribution.ConclusionThis investigation establishing RA as a predisposing factor for urticaria. Moreover, urticaria as a plausible risk determinant for SLE. Heightened vigilance is recommended among RA patients to monitor the manifestation of urticaria within clinical settings. Similarly, individuals afflicted by urticaria should duly acknowledge the prospective susceptibility to SLE.

Rationale & objectiveA causal relationship concerning diabetic retinopathy (DR) and diabetic nephropathy (DN) has been studied in many epidemiological observational studies. We conducted a two-sample mendelian randomization study from the perspective of genetics to assess these associations.Methods20 independent single nucleotide polymorphisms (SNPs) associated with diabetic retinopathy were selected from the FinnGen consortium. Summary-level data for diabetic nephropathy were obtained from the publicly available genome-wide association studies (GWAS) database, FinnGen and CKDGen consortium. Inverse variance weighted (IVW) was selected as the primary analysis. MR-Egger, weighted median (WM), simple mode and weighted mode were used as complementary methods to examine causality. Additionally, sensitivity analyses including Cochran’s Q test, MR-Egger, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analyses were conducted to guarantee the accuracy and robustness of our MR analysis.ResultsOur current study demonstrated positive associations of genetically predicted diabetic retinopathy with diabetic nephropathy (OR=1.32; P=3.72E-11), type 1 diabetes with renal complications (OR=1.96; P= 7.11E-11), and type 2 diabetes with renal complications (OR=1.26, P=3.58E-04). Further subtype analysis and multivariate mendelian randomization (MVMR) also reached the same conclusion. A significant casualty with DN was demonstrated both in non-proliferative DR (OR=1.07, P=0.000396) and proliferative DR (OR=1.67, P=3.699068E-14). All the findings were robust across several sensitivity analyses.ConclusionConsistent with previous clinical studies, our findings revealed a positive correlation between DR and DN, providing genetic evidence for the non-invasive nature of DR in predicting DN.

Objectives: In this study, we aimed to establish the trimester-specific RIs of renal function tests (RFTs) in singleton pregnant women and investigate the associations between adverse perinatal outcomes and abnormal renal function laboratory results. Methods: The results of RFTs and the associated medical records were retrieved from 16489 singleton pregnant women who underwent first- and third-trimester prenatal screening and gave a live birth at out institute between August 2018 and December 2019. The RFTs were performed on the automated immunochemistry platform ARCHITECT ci16200 (Abbott Laboratories Ltd, Abbott Park, Illinois, US) in the clinical laboratory of our institute. The nonparametric 2.5th-97.5th percentile intervals and the indirect Hoffmann methods were used to define the trimester-specific RIs. The associations between abnormal RFTs and adverse pregnancy outcomes was assessed statistically by logistic regression. Results: There was no significant difference between the direct observational and the indirect Hoffmann methods in establishing RIs of RFTs. Compared with RFTs in the first trimester, the concentrations of serum BUN and Crea were slightly decreased (p

To determine the fates of the persistent pollutants cadmium (Cd) and micro-plastics in agricultural soils, an in-depth understanding of the interactions between Cd and mulching film is required. In the present work, pot experiments are conducted under natural conditions to study the influence of various Cd concentrations on the aging process of polyethylene mulching film in soil collected from Changzhi, Shanxi Province. The results indicate that during 150 days, the aging degree of the mulch film increases gradually as the increased Cd concentration in the soil. Further, the results of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectrometry and X-ray photoelectron spectroscopy (XPS) demonstrate that the average vinyl index (VI) of the aging mulch film increases from 1.29 to 1.82, while the oxygen-to-carbon (O/C) ratio of the mulch film decreases significantly from 0.344 to 0.045, as the Cd concentration is increased from 0 to 10 mg kg–1. When the aging time exceeds 90 days, the oxygen-containing functional groups (C–O and CO) generated consumed by the adsorbed Cd. In addition, electron paramagnetic resonance (EPR) measurements indicate that Cd both enhances the formation of hydroxyl radical (·OH) on the surface of the mulch film and prevents the combination of ·OH and electrons, thereby accelerating the aging of the mulch. Hence, the present study indicates that the presence of Cd will hasten the decomposition of mulch, which will inevitably result in the faster release of micro-plastics from the mulch into the soil environment.

Non-coding RNAs (ncRNAs) act as important modulators of gene expression and they have been confirmed to play critical roles in the physiology and development of malignant tumors. Understanding the synergism of multiple ncRNAs in competing endogenous RNA (ceRNA) regulation can provide important insights into the mechanisms of malignant tumors caused by ncRNA regulation. In this work, we present a framework, SCOM, for identifying ncRNA synergistic competition. We systematically construct the landscape of ncRNA synergistic competition across 31 malignant tumors, and reveal that malignant tumors tend to share hub ncRNAs rather than the ncRNA interactions involved in the synergistic competition. In addition, the synergistic competition ncRNAs (i.e. ncRNAs involved in the synergistic competition) are likely to be involved in drug resistance, contribute to distinguishing molecular subtypes of malignant tumors, and participate in immune regulation. Furthermore, SCOM can help to infer ncRNA synergistic competition across malignant tumors and uncover potential diagnostic and prognostic biomarkers of malignant tumors. Altogether, the SCOM framework (https://github.com/zhangjunpeng411/SCOM/) and the resulting web-based database SCOMdb (https://comblab.cn/SCOMdb/) serve as a useful resource for exploring ncRNA regulation and to accelerate the identification of carcinogenic biomarkers.

The COVID-19 pandemic, caused by SARS-CoV-2 virus, has been one of the top public health threats across the world over the past three years. Mycobacterium bovis BCG is currently the only licensed vaccine for tuberculosis, one of the deadliest infectious diseases in the world, that is caused by Mycobacterium tuberculosis. In the past decades, recombinant M.bovis BCG has been studied as a novel vaccine vector for other infectious diseases in humans besides tuberculosis, such as viral infections. In the current study, we generated a recombinant M. bovis BCG strain AspikeRBD that expresses a fusion protein consisting of M. tb Ag85A protein and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using synthetic biology technique. Our results show that the recombinant M. bovis BCG strain successfully expressed this fusion protein. Interestingly, the recombinant M. bovis BCG strain AspikeRBD significantly induced SARS-CoV-2 spike-specific T cell activation and IgG production in mice when compared to the parental M.bovis BCG strain, and was more potent than the recombinant M.bovis BCG strain expressing SARS-CoV-2 spike RBD alone. As expected, the recombinant M. bovis BCG strain AspikeRBD activated an increased number of M. tb Ag85A-specific IFNγ-releasing T cells and enhanced IgG production in mice when compared to the parental M.bovis BCG strain or the BCG strain expressing SARS-CoV-2 spike RBD alone. Taken together, our results indicate a potential application of the recombinant M. bovis BCG strain AspikeRBD as a novel dual vaccine against SARS-CoV-2 and M. tb in humans.

This study employs a Bayesian panel vector autoregressive model to examine the impact of economic uncertainty on public health, using an annual, country-level panel dataset of 103 emerging markets and developing countries spanning the years 1995 through 2019. The results from the full sample suggest that the immediate effects of heightened economic uncertainty on health are marginal, yet it may engender prolonged life expectancy and lowered mortality rates. The analysis unveils considerable heterogeneities among various country classifications. The health-enhancing effects of economic uncertainty are predominantly discernible in emerging markets, low-income and upper-middle-income countries. Additionally, a diminution in suicide rates, attributed to escalated economic uncertainty, is uniquely detected in upper-middle-income countries. Furthermore, economic growth and healthcare expenditure emerge as paramount determinants in bolstering overall population health, particularly in lower-middle-income countries. The detrimental effect of environmental pollution on health is more pronounced in emerging markets and middle-income nations. Excluding high-income countries, it is essential to emphasize the beneficial health outcomes resulting from financial development and globalization, as well as the deleterious effects of environmental pollution. Lastly, several policy implications aligned with the findings are outlined, providing a roadmap for decision-makers in these diverse economies to promote better health outcomes.

Cationic lead/cadmium and anionic arsenic exhibit opposite geochemical behaviors in soils, which makes the synchronous remediation of As, Cd, and Pb challenging. In this study, we developed an iron-manganese modified biochar (BC-Fe-Mn) that prepared from straw with iron (Fe) and manganese (Mn) loading at a pyrolysis temperature of 550 °C. After BC-Fe-Mn immobilization for 90 days, the simultaneous immobilization efficiency of Pb, Cd, and As reached 57%, 51%, and 35%, respectively. Speciation distributions shows that As transformed from specific bound state into weakly low crystallinity iron bound state. Cd transformed from carbonate fraction into Fe-Mn oxide bound fraction, and Pb transformed from carbonate fraction into residual state. During the procedure, simultaneous immobilization mechanisms might involve heavy metal morphological transformation, precipitation/co-precipitation, and surface complexation. Cd and Pb absorbed onto BC-Fe-Mn. Then the increased free iron oxides (Fed) reacted with the dissolved As to form iron-arsenic precipitation. The results show that BC-Fe-Mn is a promising material for the simultaneous immobilization of Pb, Cd, and As in multi-metal contaminated soil.

IntroductionStreptococcus pneumoniae is an important human pathogen that may cause severe invasive pneumococcal diseases (IPDs) in young children and the elderly. A comprehensive comparative whole-genome analysis of invasive and non-invasive serotype strains offers great insights that are applicable to vaccine development and disease control.MethodsIn this study, 58 invasive (strains isolated from sterile sites) and 71 non-invasive (serotypes that have not been identified as invasive in our study) pneumococcal isolates were identified among the 756 pneumococcal isolates obtained from seven hospitals in Zhejiang, China (2010–2022). Serotyping, antimicrobial resistance tests, and genomic analyses were conducted to characterize these strains.Results and discussionThe three most invasive serotypes were 23F, 14, and 6B. The invasive pneumococcal isolates' respective resistance rates against penicillin, ceftriaxone, tetracycline, and erythromycin were 34.5%, 15.5%, 98.3%, and 94.7%. Whole-genome sequencing indicated that the predominant invasive clonal complexes were CC271, CC876, and CC81. The high rate of penicillin non-susceptible Streptococcus pneumoniae (PNSP) is related to the clonal distribution of resistance-conferring penicillin-binding proteins (PBP). Interestingly, we found a negative correlation between invasiveness and resistance in the invasive pneumococcal serotype strains, which might be due to the proclivity of certain serotypes to retain their β-lactam resistance. Moreover, the mutually exclusive nature of zmpC and rrgC+srtBCD suggests their intricate and potentially redundant roles in promoting the development of IPD. These findings reveal significant implications for pneumococcal vaccine development in China, potentially informing treatment strategies and measures to mitigate disease transmission.

PurposeThyroid hormones sensitivity is a newly proposed clinical entity closely related with metabolic health. Prior studies have reported the cross-sectional relationship between thyroid hormones sensitivity and diabetes; however, the longitudinal association is unclear to date. We aimed to explore the relationship between impaired thyroid hormone sensitivity at baseline and diabetes onset using a cohort design.MethodsThis study enrolled 7283 euthyroid participants at the first visit between 2008 and 2009, and then annually followed until diabetes onset or 2019. Thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured to calculate thyroid hormone sensitivity by thyroid feedback quantile-based index (TFQI), Chinese-referenced parametric thyroid feedback quantile-based index (PTFQI), thyrotropin index (TSHI), thyrotroph thyroxine resistance index (TT4RI) and FT3/FT4 ratio. Cox proportional hazard model and cross-lagged panel analysis were used.ResultsThe mean baseline age was 44.2 ± 11.9 years, including 4170 (57.3%) male. During a median follow-up of 5.2 years, 359 cases developed diabetes. There was no significant association between thyroid hormones sensitivity indices and diabetes onset, and adjusted hazard ratios per unit (95% CIs) were 0.89 (0.65-1.23) for TFQI, 0.91 (0.57-1.45) for PTFQI, 0.95 (0.70-1.29) for TSHI, 0.98 (0.70-1.01) for TT4RI and 2.12 (0.17-5.78) for FT3/FT4 ratio. Cross-lagged analysis supported the temporal association from fasting glucose to impaired thyroid hormones sensitivity indices.ConclusionsOur findings could not demonstrate that thyroid hormones sensitivity status is a predictor of diabetes onset in the euthyroid population. Elevated fasting glucose (above 7.0 mmol/L) appeared to precede impaired sensitivity indices of thyroid hormones.

Background: The Double Roundhouse Kick (DRK) is one of the major scoring tools and athletes employ the leg of the dominant side (DS) or the non-dominant side (NS) for always attacking in an alternating state. The purpose is to examine the discrepancies in the biomechanical characteristics of the DS and NS of the leg of the DRK skills of sub-elite taekwondo athletes. Methods: Using the Vicon, Kistler, and Daedo brand Electronic Body Protector (EBP), collection of the DRK data (attack time, joint angle, joint angular velocity, joint moment, ground reaction force, etc.) of 12 sub-elite taekwondo athletes (19.6 ± 2.0 yr, 180 ± 7.3 cm, 70 ± 9.8 kg) with the DS leg and NS leg. The measured data analyses via Visual3D, and statistical methods using nonparametric tests paired with samples based on the Wilcoxon signed-rank test (The significance level is set as significant for P0.05) and shift of the center of gravity (P>0.05). (ii) Attacking leg (AL): the maximum knee flexion angle (Knee-MFA) (P

The cone is a crucial component of the whole life cycle of gymnosperm and an organ for sexual reproduction of gymnosperms. In Pinus koraiensis, the quantity and development process of male and female cones directly influence seed production, which in turn influences the tree’s economic value. There are, however, due to the lack of genetic information and genomic data, the morphological development and molecular mechanism of female and male cones of P. koraiensis have not been analyzed. Long-term phenological observations were used in this study to document the main process of the growth of both male and female cones. Transcriptome sequencing and endogenous hormone levels at three critical developmental stages were then analyzed to identify the regulatory networks that control these stages of cones development. The most significant plant hormones influencing male and female cones growth were discovered to be gibberellin and brassinosteroids, according to measurements of endogenous hormone content. Additionally, transcriptome sequencing allowed the identification of 71,097 and 31,195 DEGs in male and female cones. The synthesis and control of plant hormones during cones growth were discovered via enrichment analysis of key enrichment pathways. FT and other flowering-related genes were discovered in the coexpression network of flower growth development, which contributed to the growth development of male and female cones of P. koraiensis. The findings of this work offer a cutting-edge foundation for understanding reproductive biology and the molecular mechanisms that control the growth development of male and female cones in P. koraiensis.

Summary: The innate immune response must be terminated in a timely manner at the late stage of infection to prevent unwanted inflammation. The role of m6A-modified RNAs and their binding partners in this process is not well known. Here, we develop an enzymolysis-based RNA pull-down (eRP) method that utilizes the immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) to fish out m6A-modified RNA-associated proteins. We apply eRP to capture the methylated single-stranded RNA (ssRNA) probe-associated proteins and identify YT521-B homology domain-containing 2 (YTHDC2) as the m6A-modified interferon β (IFN-β) mRNA-binding protein. YTHDC2, induced in macrophages at the late stage of virus infection, recruits IFN-stimulated exonuclease ISG20 (IFN-stimulated exonuclease gene 20) to degrade IFN-β mRNA, consequently inhibiting antiviral innate immune response. In vitro and in vivo deficiency of YTHDC2 increases IFN-β production at the late stage of viral infection. Our findings establish an eRP method to effectively identify RNA-protein interactions and add mechanistic insight to the termination of innate response for maintaining homeostasis.

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.

Myxobacteria are widely distributed in various habitats of soil and oceanic sediment. However, it is unclear whether soil-dwelling myxobacteria tolerate a saline environment. In this study, a salt-tolerant myxobacterium Myxococcus sp. strain MxC21 was isolated from forest soil with NaCl tolerance >2% concentration. Under 1% salt-contained condition, strain MxC21 could kill and consume bacteria prey and exhibited complex social behaviors such as S-motility, biofilm, and fruiting body formation but adopted an asocial living pattern with the presence of 1.5% NaCl. To investigate the genomic basis of stress tolerance, the complete genome of MxC21 was sequenced and analyzed. Strain MxC21 consists of a circular chromosome with a total length of 9.13 Mbp and a circular plasmid of 64.3 kb. Comparative genomic analysis revealed that the genomes of strain MxC21 and M. xanthus DK1622 share high genome synteny, while no endogenous plasmid was found in DK1622. Further analysis showed that approximately 21% of its coding genes from the genome of strain MxC21 are predominantly associated with signal transduction, transcriptional regulation, and protein folding involved in diverse niche adaptation such as salt tolerance, which enables social behavior such as gliding motility, sporulation, and predation. Meantime, a high number of genes are also found to be involved in defense against oxidative stress and production of antimicrobial compounds. All of these functional genes may be responsible for the potential salt-toleration. Otherwise, strain MxC21 is the second reported myxobacteria containing indigenous plasmid, while only a small proportion of genes was specific to the circular plasmid of strain MxC21, and most of them were annotated as hypothetical proteins, which may have a direct relationship with the habitat adaptation of strain MxC21 under saline environment. This study provides an inspiration of the adaptive evolution of salt-tolerant myxobacterium and facilitates a potential application in the improvement of saline soil in future.

Background/objectiveThe outbreak of COVID-19 in China since 2019 has had a significant impact on the mental health of people in Hubei Province during the three-year pandemic period. Therefore, studying the prevalence of depression among the population of Hubei Province since the pandemic is of great significance.MethodsBased on opportunity and stress theory, we collected provincial-level data from Hubei (N = 3,285) to examine the impact of declining economic status on depressive symptoms and to investigate the moderating effect of psychological resilience during the period of economic adjustment.ResultsWe used propensity score matching to estimate the treatment effect of economic status decline on depression severity and confirmed the moderating effect of psychological resilience. We found that the more that an individual’s economic status declines, the more severe that his or her depressive symptoms become. Specifically, each unit decrease in economic status is associated with an increase of approximately 0.117 units in depression level. In addition, our results indicated that psychological resilience significantly moderated the relationship between economic decline and depression (−0.184*).Conclusions and implicationsOur study confirms the role of economic status in depressive symptoms. Compared with traditional research on the relationship between economic status and mental illness, this paper expands the research regarding the two in the context of a major public health emergency. Furthermore, we suggest ways to improve people’s mental health following the pandemic.

Indole-3-acetic acid (IAA) is a crucial growth regulator involved in the accumulation of polycyclic aromatic hydrocarbons (PAHs). However, the precise physiological and molecular mechanisms underlying IAA-mediated plant growth and PAH accumulation are not yet fully understood. In this study, two distinct IAA-sensitive genotypes of Arabidopsis thaliana (wild type and Axr5 mutant) were chosen to investigate the mechanisms of fluoranthene (Flu) uptake and accumulation in plant tissues (roots and leaves) through physiological and molecular analyses. The results revealed that the Flu concentration in Axr5 leaves was significantly higher than that in wild-type (WT) leaves. In roots, the Flu content decreased significantly with increasing IAA treatment, while no significant changes were observed with lower IAA treatment. Principal component analysis demonstrated that Flu accumulation in Arabidopsis roots was associated with IAA concentrations, whereas Flu accumulation in leaves was dependent on the genotype. Moreover, Flu accumulation showed a positive correlation with the activity of glutathione S-transferase (GST) and root length and a positive correlation with catalase (CAT) and peroxidase (POD) activity in the leaves. Transcriptome analysis confirmed that the expression of the ethylene-related gene ATERF6 and GST-related genes ATGSTF14 and ATGSTU27 in roots, as well as the POD-related genes AtPRX9 and AtPRX25 and CAT-related gene AtCAT3 in leaves, played a role in Flu accumulation. Furthermore, WRKY transcription factors (TFs) in roots and NAC TFs in leaves were identified as important regulators of Flu accumulation. Understanding the mechanisms of Flu uptake and accumulation in A. thaliana provides valuable insights for regulating PAH accumulation in plants.

Abstract Background Exosome is crucial mediator and play an important role in tumor angiogenesis. Tip cell formation is a prerequisite for persistent tumor angiogenesis which causes tumor metastasis. However, the functions and underlying mechanisms of tumor cell-derived exosomes in angiogenesis and tip cell formation remain less understood. Methods Exosomes derived from serum of colorectal cancer (CRC) patients with metastasis/non-metastasis and CRC cells were isolated by ultracentrifugation. CircRNAs in these exosomes were analyzed by circRNA microarray. Then, exosomal circTUBGCP4 was identified and verified by quantitative real-time PCR (qRT–PCR) and in situ hybridization (ISH). Loss- and gain-of-function assays were performed to explore the effect of exosomal circTUBGCP4 on vascular endothelial cell tipping and colorectal cancer metastasis in vitro and in vivo. Mechanically, bioinformatics analysis, biotin-labeled circTUBGCP4/ miR-146b-3p RNA pulldown, RNA immunoprecipitation (RIP), and luciferase reporter assay were used to confirm the interaction among circTUBGCP4, miR-146b-3p, and PDK2. Results Here, we showed that exosomes derived from CRC cells enhanced vascular endothelial cell migration and tube formation via inducing filopodia formation and endothelial cell tipping. We further screened the upregulated circTUBGCP4 in serum of CRC patients with metastasis compared to non-metastasis. Silencing circTUBGCP4 expression in CRC cell-derived exosomes (CRC-CDEs) inhibited endothelial cell migration, tube formation, tip cell formation, and CRC metastasis. Overexpression of circTUBGCP4 had opposite results in vitro and in vivo. Mechanically, circTUBGCP4 upregulated PDK2 to activate Akt signaling pathway by sponging miR-146b-3p. Moreover, we found that miR-146b-3p could be a key regulator for vascular endothelial cell dysfunction. Exosomal circTUBGCP4 promoted tip cell formation and activated the Akt signaling pathway by inhibiting miR-146b-3p. Conclusions Our results suggest that colorectal cancer cells generate exosomal circTUBGCP4, which causes vascular endothelial cell tipping to promote angiogenesis and tumor metastasis by activating Akt signaling pathway.

Abstract In recent years, breakthroughs have been made in tumor immunotherapy. However, tumor immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective in only a small percentage of patients in solid cancer. How to improve the efficiency of cancer immunotherapy is an urgent problem to be solved. As we all know, the state of the tumor microenvironment (TME) is an essential factor affecting the effectiveness of tumor immunotherapy, and the cancer-associated fibroblasts (CAFs) in TME have attracted much attention in recent years. As one of the main components of TME, CAFs interact with cancer cells and immune cells by secreting cytokines and vesicles, participating in ECM remodeling, and finally affecting the immune response process. With the in-depth study of CAFs heterogeneity, new strategies are provided for finding targets of combination immunotherapy and predicting immune efficacy. In this review, we focus on the role of CAFs in the solid cancer immune microenvironment, and then further elaborate on the potential mechanisms and pathways of CAFs influencing anti-PD-1/PD-L1 immunotherapy. In addition, we summarize the potential clinical application value of CAFs-related targets and markers in solid cancers.

Abstract Background Rituximab (RTX) is a standard therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the most frequently used dose may lead to severe adverse effects (SAEs). We explored the efficacy and safety of low-dose RTX in Chinese patients with AAV. Methods A total of 22 Chinese patients diagnosed with AAV with renal involvement, including 8 treated with low-dose RTX (400 mg of RTX total over 4 weeks) and 14 treated with cyclophosphamide (CYC), were evaluated. The baseline clinical and pathological data and laboratory parameters during follow-up at months 1, 3, 6, and 12 were collected retrospectively. Results The baseline data showed no significant differences between the two groups. The median peripheral CD19+ cell counts in the RTX group decreased from 315.0/μL to 1.5/μL at 2 weeks, and to 2.5/μL at 1 month after the first dose. The median SCr level decreased from 267.8 μmol/L before treatment to 151.45 μmol/L at 1 month, 132.75 μmol/L at 3 months, 123.2 μmol/L at 6 months, and 151.9 μmol/L at 12 months in RTX-treated patients. The improvements in renal function, proteinuria, and ANCA titre were not significantly different between the two groups. The SAE rate was significantly lower in the RTX group (one SAE of pneumonia) compared with the CYC group. Conclusions This is the first report that low-dose RTX could be effective for the treatment of Chinese patients with AAV with renal involvement.