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Abstract Covalent probes coupled with chemical proteomics represent a powerful method for investigating small molecule and protein interactions. However, the creation of a reactive warhead within various ligands to form covalent probes has been a major obstacle. Herein, we report a convenient and robust process to assemble a unique electrophile, an α-acyloxyenamide, through a one-step late-stage coupling reaction. This procedure demonstrates remarkable tolerance towards other functional groups and facilitates ligand-directed labeling in proteins of interest. The reactive group has been successfully incorporated into a clinical drug targeting the EGFR L858R mutant, erlotinib, and a pan-kinase inhibitor. The resulting probes have been shown to be able to covalently engage a lysine residue proximal to the ATP-binding pocket of the EGFR L858R mutant. A series of active sites, and Mg2+, ATP-binding sites of kinases, such as K33 of CDK1, CDK2, CDK5 were detected. This is the first report of engaging these conserved catalytic lysine residues in kinases with covalent inhibition. Further application of this methodology to natural products has demonstrated its success in profiling ligandable conserved lysine residues in whole proteome. These findings offer insights for the development of new targeted covalent inhibitors (TCIs).

Abstract Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.

Here we propose a non-line-of-sight (NLOS) tracking scheme using only one single-pixel single-photon channel. It is demonstrated that sending multiple beams with proper time delay enables multiplexing of multi-echoes of the hidden object in the single channel. Based on the multiplexed temporal histograms, we achieve a retrieval of the object's position with centimeter precision. The experiment of following the target's linear motion is also performed, proving that our technique can reliably track the moving object. This time multiplexing-based NLOS tracking scheme provides a simple way to reduce the numbers of the detecting channels, which may contribute to low-cost NLOS applications.

In Wireless Sensor Networks (WSNs), where sensor batteries cannot be replaced or recharged easily, the limited availability of energy has motivated a variety of cluster-based routing protocols. The unit operation of these protocols is known as a round (aka. a cycle). A round has two phases: 1) sensor clustering for selecting cluster-heads, and 2) routing for transmitting sensed data from sensors to a base-station via cluster-heads in multi-hop. The cluster-based routing protocols face the dilemma of energy-saving and energy-balance in both phases. Simply speaking, we have to trade off energy-saving for energy-balance and vice versa. First, frequent clustering can improve the energy-balance by rotating cluster-heads often among sensors, but the overhead for clustering increases quickly. Second, the multi-hop routing saves the energy of cluster-heads far away from transmitting data directly to base-station, but it deteriorates energy-balance since the cluster-heads near the base-station suffer more energy consumption for transmitting data of their own clusters and data from other cluster-heads as relays. Even though the related issues have been discussed and investigated widely, no learning-based solution has been proposed yet. This study attempts to fill the gap. Instead of proposing a new cluster-based routing protocol, this study adapts reinforcement learning to make two decisions concurrently for the existing protocols: 1) whether to redo sensor clustering for each round and 2) which cluster-heads should be excluded from being relays in multi-hop routing for each round. With several tailored techniques, the reinforcement learning-based solution could significantly boost the existing protocols by improving energy-saving and energy-balance, as evidenced by extensive experiments.

Primary health care institutions should be the main force of China's medical and health service system and the cornerstone of the national health care system. During the COVID-19 pandemic, China's primary health care institutions played a critical role, but many deficiencies and weaknesses were also highlighted. Through systematic literature search and analysis, this article finds that China's primary health care institutions have some problems such as low demand for patient care, weak integration of the health system, weak service foundation, and insufficient emergency response capacity for public health emergencies. Accordingly, we put forward a strategy for the construction of primary health care institutions based on the 'Three Forces Theory', which aims to improve the primary medical and health care service system, upgrade the capacity of primary medical and health care services, and better fulfill the strategic goal of 'Healthy China 2030'.

Abstract The utilization of the dispersive Fourier transformation approach has enabled comprehensive observation of the birth process of dissipative solitons in fiber lasers. However, there is still a dearth of deep understanding regarding the extinction process of dissipative solitons. In this study, we have utilized a combination of experimental and numerical techniques to thoroughly examine the breathing dynamics of dissipative solitons during the extinction process in an Er-doped mode-locked fiber laser. The results demonstrate that the transient breathing dynamics have a substantial impact on the extinction stage of both steady-state and breathing-state dissipative solitons. The duration of transient breathing exhibits a high degree of sensitivity to variations in pump power. Numerical simulations are utilized to produce analogous breathing dynamics within the framework of a model that integrates equations characterizing the population inversion in a mode-locked laser. These results corroborate the role of Q-switching instability in the onset of breathing oscillations. Furthermore, these findings offer new possibilities for the advancement of various operational frameworks for ultrafast lasers. Graphical abstract

To understand the stability of deep underground engineering rocks at high temperatures, it is necessary to conduct comprehensive tests on the mechanical properties of the rocks. In this study, a series of true triaxial tests (TTT) were conducted on sandstones using a self-developed true triaxial testing system combined with XRD, FE-SEM and CT analyses. The study systematically examined the microstructural characteristics, physical phase behavior, deformation properties and internal fracture development of the sandstone before and after heat treatment. The results of the study show that sandstone has temperature-dependent true triaxial mechanical properties after heat treatment. The stress-strain characteristic curves of the post-peak portion from room temperature to 800 °C show a significant stress-reducing segment, indicating the presence of brittle behavior. In addition, when the temperature exceeds 1000 °C, the sandstone exhibits brittle-ductile change characteristics, with a peak stress threshold observed at 800 °C. Notably, the peak stresses corresponding to 800 °C increased by 84.5 %, 63.1 %, 47 %, and 49.8 %, respectively, compared with the room temperature intermediate principal stresses(IPS) ranging from 20 MPa to 50 MPa, respectively. Importantly, the linear Mogi-Coulomb criterion remains valid for the peak strength of the high-temperature sandstone, while the internal fracture damage pattern of the specimens shows an inverted ''Y'' or inverted ''W'' configuration. The internal fracture network of rock samples above 800 °C is more complex. Intergranular crack is the main form of microcracking. This experimental study on the mechanical properties of sandstone under the combined effects of high temperature and real triaxial stresses provides valuable guidance for the selection of sandstone parameters and safety evaluation of coal underground gasification roofs.

The solute carrier family 12 (SLC12) of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl− extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl− loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs. Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs. These techniques include the ammonium pulse technique, radioactive or nonradioactive rubidium ion uptake-assay, and thallium ion-uptake assay. CCCs' activity can also be indirectly observed by measuring γ-aminobutyric acid (GABA) activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes, radiotracer 36Cl−, and fluorescent dyes. Other techniques include directly looking at kinase regulatory sites phosphorylation, flame photometry, 22Na+ uptake assay, structural biology, molecular modeling, and high-throughput drug screening. This review summarizes the role of CCCs in genetic disorders and cell volume regulation, current methods applied in studying CCCs biology, and compounds developed that directly or indirectly target the CCCs for disease treatments.

Abstract Background Bladder cancer (BLCA) is a prevalent urinary system malignancy. Understanding the interplay of immunological and metabolic genes in BLCA is crucial for prognosis and treatment. Methods Immune/metabolism genes were extracted, their expression profiles analyzed. NMF clustering found prognostic genes. Immunocyte infiltration and tumor microenvironment were examined. Risk prognostic signature using Cox/LASSO methods was developed. Immunological Microenvironment and functional enrichment analysis explored. Immunotherapy response and somatic mutations evaluated. RT-qPCR validated gene expression. Results We investigated these genes in 614 BLCA samples, identifying relevant prognostic genes. We developed a predictive feature and signature comprising 7 genes (POLE2, AHNAK, SHMT2, NR2F1, TFRC, OAS1, CHKB). This immune and metabolism-related gene (IMRG) signature showed superior predictive performance across multiple datasets and was independent of clinical indicators. Immunotherapy response and immune cell infiltration correlated with the risk score. Functional enrichment analysis revealed distinct biological pathways between low- and high-risk groups. The signature demonstrated higher prediction accuracy than other signatures. qRT-PCR confirmed differential gene expression and immunotherapy response. Conclusions The model in our work is a novel assessment tool to measure immunotherapy’s effectiveness and anticipate BLCA patients’ prognosis, offering new avenues for immunological biomarkers and targeted treatments.

Abstract The anomalous Hall effect (AHE) that emerges in antiferromagnetic metals shows intriguing physics and offers numerous potential applications. Magnets with a rutile crystal structure have recently received attention as a possible platform for a collinear-antiferromagnetism-induced AHE. RuO2 is a prototypical candidate material, however the AHE is prohibited at zero field by symmetry because of the high-symmetry [001] direction of the Néel vector at the ground state. Here, we show AHE at zero field in Cr-doped rutile, Ru0.8Cr0.2O2. The magnetization, transport and density functional theory calculations indicate that appropriate doping of Cr at Ru sites reconstructs the collinear antiferromagnetism in RuO2, resulting in a rotation of the Néel vector from [001] to [110] while maintaining a collinear antiferromagnetic state. The AHE with vanishing net moment in the Ru0.8Cr0.2O2 exhibits an orientation dependence consistent with the [110]-oriented Hall vector. These results demonstrate that material engineering by doping is a useful approach to manipulate AHE in antiferromagnetic metals.

Newcastle disease virus (NDV) is an oncolytic virus whose F protein cleavage activity is associated with viral infectivity. To explore the potential of modifying F protein cleavage activity to enhance antitumor effects, we constructed a recombinant NDV LaSota strain by replacing its F protein cleavage site with that from the mesogenic Beaudette C (BC) strain using reverse genetics techniques. The resulting virus, rLaSota-BC-RFP, demonstrated significantly enhanced infectivity and tumor cell suppression on the murine melanoma B16F10 cell, characterized by higher cytotoxicity and increased apoptosis compared to its parental strain, rLaSota-RFP. In vivo, rLaSota-BC-RFP treatment of B16F10 tumors in C57BL/6 mice resulted in significant tumor growth inhibition, improved survival rate, and induction of tumor-specific apoptosis and necrosis. Additionally, the rLaSota-BC-RFP treatment enhanced immunostimulatory effects within the tumor microenvironment (TME), characterized by increased infiltration of CD4+ and CD8+ T cells and elevated levels of antitumor immune modulator cytokines, including mouse IL-12, IFN-γ, IL-15, and TNF-α, in the rLaSota-BC-RFP-treated tumor tissues. Collectively, these findings demonstrate that the mesogenic F protein cleavage site enhances the oncolytic potential of the NDV LaSota strain, suggesting that rLaSota-BC-RFP is a promising oncolytic viral vector for gene delivery in cancer immunotherapy.

Mastitis is a common disease worldwide that affects the development of the dairy industry due to its high incidence and complex etiology. Precise regulation of cell death and survival plays a critical role in maintaining internal homeostasis, organ development, and immune function in organisms, and regulatory abnormalities are a common mechanism of various pathological changes. Recent research has shown that regulated cell death (RCD) plays a crucial role in mastitis. The development of drugs to treat cell death and survival abnormalities that can be widely used in mastitis treatment has important clinical significance. This paper will review the molecular mechanisms of apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis and their regulatory roles in mastitis to provide a new perspective for the targeted treatment of mastitis.

Oral diseases and conditions affect children’s oral health and negatively influence their overall health. Early detection and intervention are important in mitigating these negative consequences. However, dental fear and anxiety (DFA) regarding dental procedures often hinder children from seeking necessary dental care. Non-pharmacological behavior management strategies, such as distraction techniques, are commonly adopted to manage children’s behaviors. Distraction techniques have been developed rapidly in recent years and are widely accepted by both health professionals and parents due to their noninvasive and low-cost nature. This concise review aims to summarize current distraction techniques applied during dental treatments, especially for children. The most commonly reported techniques for children are audio distraction, audio-visual distraction, tactile distraction, olfactory distraction, and gustatory distraction. Audio distraction techniques involving music and storytelling help children relax. Audio-visual distraction techniques help to divert children’s attention from the dental treatment. Tactile stimuli can reduce the transmission of pain signals. Olfactory stimuli can help children feel comfortable and relaxed. Gustatory distraction involving sweet substances can create a positive environment. These distraction techniques effectively reduce DFA in children and improve their satisfaction with dental procedures. As technology continues to develop, further research is needed to provide more robust, evidence-based guidance for dentists using distraction techniques.

Glaesserella parasuis cytolethal distending toxin (GpCDT) can induce cell cycle arrest and apoptosis. Our laboratory’s previous work demonstrated that GTPase 4b (Rab4b) is a key host protein implicated in GpCDT-induced cytotoxicity. This study investigated the probable involvement of Rab4b in the process. Our study used CRISPR/Cas9 technology to create a Rab4b-knockout cell line. The results showed greater resistance to GpCDT-induced cell cytotoxicity. In contrast, forced Rab4b overexpression increased GpCDT-induced cytotoxicity. Further immunoprecipitation study reveals that GpCDT may bind with Rab4b. In PK-15 cells, GpCDT is transported to the early endosomes and late endosomes, while after knocking out Rab4b, GpCDT cannot be transported to the early endosome via vesicles. Rab4b appears essential for GpCDT-induced cytotoxicity in PK-15 cells.

This study aims to alleviate the serious deformation of surrounding rock (SR) in an extremely soft and fragile fully mechanized caving face roadway (ESFFMCFR, the 8# coal seam, Huaibei mining area) under a conventional support. Laboratory tests of roadway SR were conducted. The results show that in this coal seam, the extremely soft and fragile coal body has a high clay mineral content, so it is of low strength and breaks and softens easily. With reference to the mechanical tests on coal and rock mass around the coal seam and the monitoring results of roadway deformation, the roadway deformation is mainly caused by the development of fractures in the roadway SR, the separation of the support body and SR and the loose supporting structure. Considering the engineering environment and deformation characteristics of SR in the ESFFMCFR (the 8# coal seam, Huaibei mining area), this study proposed a synergistic support system of “lowering, drilling, anchoring, grouting and flatting (LDAGF)” for the ESFFMCFR based on the synergistic mechanism of support and SR under the basic principles of synergetics. Specifically, the synergistic support system of “LDAGF” includes the following measures: floor breaking and side lowering, bolt advance support, anchor cable support, advance water injection and grouting and flat-roof U-shaped steel shed support. Furthermore, this synergistic support system was applied on the ESFFMCFR in the 8# coal seam of Xinhu and Guobei coal mines, Huaibei mining area. The on-site application results reveal that when the synergistic support system is adopted, the maximum subsidence values in the above roadway roofs are 117 mm and 121 mm and the maximum displacement values of the two sides are 66 mm and 74 mm, respectively, which proves an excellent support effect. The synergistic support system, which can effectively control the serious deformation of the SR in ESFFMCFRs and ensure long-term stability and safety of the roadways, is suitable for the support of ESFFMCFRs and is of great guiding significance for roadways of the same type.

Soybean (Glycine max L.) is an important oil, food and economic crop in the world. High salinity severely affects the growth and yield of soybean. Overexpressing a specific anti‐retroviral transcription factor by biotechnology is an effective way to cultivate new stress‐tolerant varieties of soybean. TGA transcription factor is a subfamily of bZIP and plays an important role in abiotic stress responses.A TGA subfamily gene GmTGA13 was cloned and the gene expression, subcellular localization and transcriptional activity were measured. Through the Ag. tumefaciens mediated flower dip method and the Ag. rhizogenes mediated transformation of soybean hairy roots, the transgenic Arabidopsis and the 'combination' soybean plants of overexpressing GmTGA13 were obtained. The two types of transgenic plants were treated with salt stress respectively, and the related physiological indexes were determined. Furthermore, the expression levels of five abiotic stress responsive genes were analyzed in GmTGA13 overexpression hairy roots.GmTGA13 gene was highly expressed in roots and significantly induced by saline stress in soybean. GmTGA13 encoded a nuclear localization protein and had transcriptional activation activity. Overexpression of GmTGA13 enhanced the saline stress tolerance of transgenic Arabidopsis and the 'combination' soybean plants. Furthermore, overexpression of GmTGA13 enhanced the expression of the stress responsive genes in transgenic soybean hairy roots.In conclusion, overexpression of GmTGA13 is beneficial to the absorption of K+ and Ca2+ by the cell, thereby regulating the ion homeostasis in the cell balance. GmTGA13 enhanced salt resistance of plants by regulating the expression of many stress‐responsive genes. [ABSTRACT FROM AUTHOR]

Gynostemma pentaphyllum (Thunb.) Makino is an important producer of dammarene-type triterpenoid saponins. These saponins (gypenosides) exhibit diverse pharmacological benefits such as anticancer, antidiabetic, and immunomodulatory effects, and have major potential in the pharmaceutical and health care industries. Here, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptomes of more than 50,000 cells derived from G. pentaphyllum shoot apexes and leaves. Following cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Each cell type displayed substantial transcriptomic heterogeneity both within and between tissues. Examining gene expression patterns across various cell types revealed that gypenoside biosynthesis predominantly occurred in mesophyll cells, with heightened activity observed in shoot apexes compared to leaves. Furthermore, we explored the impact of transposable elements (TEs) on G. pentaphyllum transcriptomic landscapes. Our findings the highlighted the unbalanced expression of certain TE families across different cell types in shoot apexes and leaves, marking the first investigation of TE expression at the single-cell level in plants. Additionally, we observed dynamic expression of genes involved in gypenoside biosynthesis and specific TE families during epidermal and vascular cell development. The involvement of TE expression in regulating cell differentiation and gypenoside biosynthesis warrant further exploration. Overall, this study not only provides new insights into the spatiotemporal organization of gypenoside biosynthesis and TE activity in G. pentaphyllum shoot apexes and leaves but also offers valuable cellular and genetic resources for a deeper understanding of developmental and physiological processes at single-cell resolution in this species.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

Abstract Vibrio is a salt‐tolerant heterotrophic bacterium that occupies an important ecological niche in marine environments. However, little is known about the contribution of resource diversity to the marine Vibrio diversity and community stability. In this study, we investigated the association among resource diversity, taxonomic diversity, phylogenetic diversity, and community stability of marine Vibrio in the Beibu Gulf. V. campbellii and V. hangzhouensis were the dominant groups in seawater and sediments, respectively, in the Beibu Gulf. Higher alpha diversity was observed in the sediments than in the seawater. Marine Vibrio community assembly was dominated by deterministic processes. Pearson's correlation analysis showed that nitrite (NO2−‐N), dissolved inorganic nitrogen (DIN), ammonium (NH4+‐N), and pH were the main factors affecting marine Vibrio community stability in the surface, middle, and bottom layers of seawater and sediment, respectively. Partial least‐squares path models (PLS‐PM) demonstrated that resource diversity, water properties, nutrients, and geographical distance had important impacts on phylogenetic and taxonomic diversity. Regression analysis revealed that the impact of resource diversity on marine Vibrio diversity and community stability varied across different habitats, but loss of Vibrio diversity increases community stability. Overall, this study provided insights into the mechanisms underlying the maintenance of Vibrio diversity and community stability in marine environments.

Microorganisms, especially rare microbial species, are crucial in estuarine ecosystems for driving biogeochemical processes and preserving biodiversity. However, the understanding of the links between ecosystem multifunctionality (EMF) and the diversity of rare bacterial taxa in estuary ecosystems remains limited. Employing high-throughput sequencing and a variety of statistical methods, we assessed the diversities and assembly process of abundant and rare bacterioplankton and their contributions to EMF in a subtropical estuary. Taxonomic analysis revealed Proteobacteria as the predominant phylum among both abundant and rare bacterial taxa. Notably, rare taxa demonstrated significantly higher taxonomic diversity and a larger species pool than abundant taxa. Additionally, our findings highlighted that deterministic assembly processes predominantly shape microbial communities, with heterogeneous selection exerting a stronger influence on rare taxa. Further analysis reveals that rare bacterial beta-diversity significantly impacts to EMF, whereas alpha diversity did not. The partial least squares path modeling (PLS-PM) analysis demonstrated that the beta diversity of abundant and rare taxa, as the main biotic factor, directly affected EMF, while temperature and total organic carbon (TOC) were additional key factors to determine the relationship between beta diversity and EMF. These findings advance our understanding of the distribution features and ecological knowledge of the abundant and rare taxa in EMF in subtropical estuaries, and provide a reference for exploring the multifunctionality of different biospheres in aquatic environments.

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Abstract China's severe particle pollution could affect the regional climate and weather conditions that consequently threaten local to global food security. Yet, the underlying mechanisms and quantitative assessment of aerosols on crop yields remain unknown. Here, by integrating a meteorology–chemistry model and a crop model, we show the impacts of atmospheric aerosols on China's meteorology and soybean yields. We find that the potential yields of soybean would decrease in most parts of China due to direct aerosol radiation effects, while showing diverse responses in parts of the Northeast and North China Plain. Moreover, because of the high sensitivity of soybean growth to water, potential yield fluctuations are closely related to aerosol‐induced precipitation changes in most soybean‐growing regions of China. In particular, aerosols play the most important role during soybean's pod‐filling stage, in which the influence of both precipitation perturbations and negative solar radiative forcing is about 5–10 times that of air temperature on crop yield. Our study thereby identifies aerosol mitigation can bring a notable increase in crop yields, highlighting the potential for important co‐benefits in food security across polluting developing countries.

Abstract Titanium (Ti) dental implants face risks of early failure due to bacterial adhesion and biofilm formation. It is thus necessary to endow the implant surface with antibacterial ability. In this study, magnesium oxide (MgO) coatings were prepared on Ti by combining micro-arc oxidation (MAO) and electrophoretic deposition (EPD). The MgO nanoparticles homogeneously deposited on the microporous surface of MAO-treated Ti, yielding increasing coverage with the EPD time increased to 15 to 60 s. After co-culture with Porphyromonas gingivalis (P. gingivalis) for 24 h, 48 h, and 72 h, the coatings produced antibacterial rates of 4–53 %, 27–71 %, and 39–79 %, respectively, in a dose-dependent manner. Overall, EPD for 45 s offered satisfactory comprehensive performance, with an antibacterial rate 79 % at 72 h and a relative cell viability 85 % at 5 d. Electron and fluorescence microscopies revealed that, both the density of adherent bacterial adhesion on the surface and the proportion of viable bacteria decreased with the EPD time. The morphology of cells on the surface of each group was intact and there was no significant difference among the groups. These results show that, the MgO coating deposited on MAO-treated Ti by EPD had reasonably good in vitro antibacterial properties and cytocompatibility.

Abstract Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been proven to have little effect. Ferroptosis is a newly discovered type of programmed cell death that has been found to be involved in the process of ischemia‒reperfusion in multiple organs throughout the body. Studies have shown that it is also present in retinal ischemia‒reperfusion injury. A rat model of retinal ischemia‒reperfusion injury was constructed and treated with deferoxamine. In this study, we found the accumulation of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), and the consumption of glutathione (GSH) via ELISA testing; increased expression of transferrin; and decreased expression of ferritin, SLC7A11, and GPX4 via Western blotting (WB) and real-time PCR testing. Structural signs of ferroptosis (mitochondrial shrinkage) were observed across multiple cell types, including retinal ganglion cells (RGCs), photoreceptor cells, and pigment epithelial cells. Changes in visual function were detected by F-VEP and ERG. The results showed that iron and oxidative stress were increased in the retinal ischemia‒reperfusion injury model, resulting in ferroptosis and tissue damage. Deferoxamine protects the structural and functional soundness of the retina by inhibiting ferroptosis through the simultaneous inhibition of hemochromatosis, the initiation of transferrin, and the degradation of ferritin and activating the antioxidant capacity of the System Xc-GSH-GPX4 pathway.

Abstract Background Breast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer. Methods The Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells. Results GREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis. Conclusion These results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.

Abstract Objective To explore the DPP4 expression changes and functions in ovarian cancer (OV), as well as the regulation mechanism for DDP4. Methods GEPIA2, GSE18520, GSE26712 and UALCAN were used to analyze differences in DPP4 expression between OV tumors and control tissues. Serum DPP4 levels were measured by ELISA. The prognostic values of DPP4 were evaluated using a Kaplan–Meier (KM) plotter. Small interfering RNA was used for DPP4 knockdown in OVCAR-3 and SKOV-3 cells. CCK-8 and scratch healing assays were used to determine the cells’ proliferation and migration abilities. Flow cytometry (FCM) was used to detect the cell cycle and apoptosis. A dual-luciferase assay was designed to confirm the regulatory effect of miR-29a-3p on DPP4. Results The expressions of DPP4 mRNA and protein were decreased in OV tumor tissues. Serum DPP4 levels decreased in OV patients. KM plotter analysis showed correlation between high DPP4 expression and a poor prognosis in OV patients. By targeting knockdown of DPP4, we found that OVCAR-3 and SKOV-3 cells’ proliferation was inhibited, while cell’s migration ability was significantly promoted. FCM analysis showed that DPP4 knockdown induced a decrease in the S phase. Furthermore, DPP4 was shown to be downregulated by miR-29a-3p and TGFβ1 in OVCAR-3 cells, and miR-29a-3p expression was upregulated by TGFβ1. The effects of miR-29a-3p and TGFβ1 on OVCAR-3 cells’ biological behaviors were consistent with DPP4 knockdown. Conclusion DPP4 was downregulated in OV patients. DPP4 knockdown significantly inhibited OVCAR-3 and SKOV-3 cell proliferation and promoted cell migration. DDP4 can be downregulated by TGFβ1 through the upregulation of miR-29a-3p in OV cells.

Abstract In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of prophase in meiosis I (MI) after synapsis and recombination of homologous chromosomes, which cannot be segregated. Within the follicle, the maintenance of oocyte meiotic arrest is primarily attributed to high cytoplasmic concentrations of cyclic adenosine monophosphate (cAMP). Depending on the specific species, oocytes can remain arrested for extended periods of time, ranging from months to even years. During estrus phase in animals or the menstrual cycle in humans, the resumption of meiosis occurs in certain oocytes due to a surge of luteinizing hormone (LH) levels. Any factor interfering with this process may lead to impaired oocyte maturation, which in turn affects female reproductive function. Nevertheless, the precise molecular mechanisms underlying this phenomenon has not been systematically summarized yet. To provide a comprehensive understanding of the recently uncovered regulatory network involved in oocyte development and maturation, the progress of the cellular and molecular mechanisms of oocyte nuclear maturation including meiosis arrest and meiosis resumption is summarized. Additionally, the advancements in understanding the molecular cytoplasmic events occurring in oocytes, such as maternal mRNA degradation, posttranslational regulation, and organelle distribution associated with the quality of oocyte maturation, are reviewed. Therefore, understanding the pathways regulating oocyte meiotic arrest and resumption will provide detailed insight into female reproductive system and provide a theoretical basis for further research and potential approaches for novel disease treatments.

Objective: To explore the correlation between hepatocellular carcinoma (HCC) gene variation profile and clinical characteristics in Han nationality with HBV infection in Sichuan province. Methods: The clinical data and HCC tissues were obtained from the enrolled patients. Whole exome sequencing and bioinformatics analysis were performed on formalin-fixed and paraffin-embedded samples from HCC. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Results: Sixteen high-frequency mutated genes with differential expressions were identified by WES. SMG1 gene variation could be positively correlated with satellite lesions. AMY2B and RGPD4 gene mutation seemed to have a greater chance of vascular invasion. The patients with TATDN1 variation have bigger diameters and greater chances of vascular and microvascular invasion (all P

Abstract Background Rehabilitation post-knee arthroplasty is integral to regaining knee function and ensuring patients’ overall well-being. The debate over the relative effectiveness and safety of outpatient versus home-based rehabilitation persists. Methods A thorough literature review was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across four databases. Two researchers independently identified eligible studies centering on knee arthroplasty patients undergoing either outpatient or home-based rehabilitation. Study quality was assessed using the Cochrane Collaboration’s risk of bias tool, while continuous outcomes were subject to meta-analyses using Stata 17 software. Results Our analysis identified no significant differences in primary outcomes, including Range of Motion, Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Oxford Knee Score, and the Knee Society Score, between home-based and outpatient rehabilitation across different follow-up points. Adverse reactions, readmission rates, the need for manipulation under anesthesia, reoperation rate, and post-surgery complications were also similar between both groups. Home-based rehabilitation demonstrated cost-effectiveness, resulting in substantial annual savings. Furthermore, quality of life and patient satisfaction were found to be comparable in both rehabilitation methods. Conclusions Home-based rehabilitation post-knee arthroplasty appears as an effective, safe, and cost-efficient alternative to outpatient rehabilitation. Despite these findings, further multicenter, long-term randomized controlled trials are required to validate these findings and provide robust evidence to inform early rehabilitation choices post-knee arthroplasty.

Influenced by increasing global extreme weather and the uneven spatiotemporal distribution of water resources in monsoon climate areas, the balance of agricultural water resources supply and demand currently faces significant challenges. Conducting research on the spatial allocation trade-offs and synergistic mechanisms of agricultural water resources in monsoon climate areas is extremely important. This study takes the spatial layout of reservoir site selection in water conservancy projects as an example, focusing on Shandong Province as the research area. During the site selection process, the concept of water resource demand is introduced, and the suitability of reservoir siting is integrated. It clarifies ten influencing factors for suitability degree and five influencing factors for demand. A bi-objective optimization model that includes suitability degree and demand degree is established. Utilizing machine learning methods such as the GA_BP neural network model and the GA-bi-objective optimization model to balance and coordinate the supply and demand relationship of agricultural water resources in the monsoon region. The study found that: (1) in the prediction of suitability degree, the influencing factors are most strongly correlated with the regulatory storage capacity (regulatory storage capacity > total storage capacity > regulating storage coefficient); (2) compared with single-objective optimization of suitability degree, the difference between water supply and demand can be reduced by 74.3% after bi-objective optimization; (3) according to the spatial layout optimization analysis, the utilization of water resources in the central and western parts of Shandong Province is not sufficient, and the construction of agricultural reservoirs should be carried out in a targeted manner. This study provides new ideas for promoting the efficient use of water resources in monsoon climate zones and the coordinated development of humans and nature, reflecting the importance of supply and demand balance in the spatial allocation of agricultural water resources, reducing the risk of agricultural production being affected by droughts and floods.

Enunciating the carbon storage across various types of forests is a precondition for comprehending forest ecosystem carbon cycling. However, previous studies regarding forest carbon storage were primarily conducted in the general temperature zones, with a limited understanding of carbon storage in different forest types within climate transition zones. In this study, we employed biomass models to explore the carbon storage in three types of natural secondary forests (Pinus armandii forest, Quercus aliena forest, and Q. aliena–P. armandii mixed forest) in the transition zone between the northern subtropical and warm temperate regions of China. Furthermore, we used the variance decomposition analysis and random forest model to determine the key factors influencing carbon storage in three types of natural secondary forests. Our results indicated that the carbon storage of wood and soil layers in the Q. aliena–P. armandii mixed forest was significantly higher than that in the P. armandii and Q. aliena forests. Total carbon storage was ranked as follows: Q. aliena–P. armandii mixed forest (266.09 t/ha) > P. armandii forest (222.89 t/ha) > Q. aliena forest (212.46 t/ha). Our results also revealed that carbon storage of the wood layer was jointly regulated by environmental factors, plant physiological characteristics, and soil properties, while soil carbon storage was mainly affected by soil properties. These results highlight the significant advantages of mixed conifer–broadleaf forests in carbon storage, emphasizing the importance of mixed natural secondary forests in carbon cycling and ecosystem services. This study provides scientific evidence for enhancing forest carbon sink functions and developing forest conservation and management policies to combat climate change.

Exploring species diversity along elevational gradients is important for understanding the underlying mechanisms. Our study focused on analyzing the species diversity of fungal communities and their subcommunities at different trophic and taxonomic levels across three high mountains of the Korean Peninsula, each situated in a different climatic zone. Using high-throughput sequencing, we aimed to assess fungal diversity patterns and investigate the primary environmental factors influencing fungal diversity. Our results indicate that soil fungal diversity exhibits different elevational distribution patterns on different mountains, highlighting the combined effects of climate, soil properties, and geographic topology. Notably, the total and available phosphorus contents in the soil emerged as key determinants in explaining the differences in diversity attributed to soil properties. Despite the varied responses of fungal diversity to elevational gradients among different trophic guilds and taxonomic levels, their primary environmental determinants remained remarkably consistent. In particular, total and available phosphorus contents showed significant correlations with the diversity of the majority of the trophic guilds and taxonomic levels. Our study reveals the absence of a uniform diversity pattern along elevational gradients, underscoring the general sensitivity of fungi to soil conditions. By enriching our understanding of fungal diversity dynamics, this research enhances our comprehension of the formation and maintenance of elevational fungal diversity and the response of microbial communities in mountain ecosystems to climate change. This study provides valuable insights for future ecological studies of similar biotic communities.

Elucidating the water utilization strategy of trees during forest succession is a prerequisite for predicting the direction of forest succession. However, the water utilization characteristics of trees in forests across a successional gradient remain unclear. Here, we utilized the hydrogen and oxygen stable isotopes combined with the Bayesian mixed model (MixSIAR) to analyze the water utilization of dominant trees (Pinus massoniana, Castanea henryi, and Schima superba) in forests along a successional gradient in the Dinghushan Biosphere Reserve of China. Furthermore, we determined the primary factor affecting the water utilization of various trees based on variation partitioning analysis and a random forest model. Our results illustrated that in the early-successional forest, the water utilization ratios from shallow soil layers by P. massoniana were significantly lower than that in the mid-successional forest (51.3%–61.7% vs. 75.3%–81.4%), while its water utilization ratios from deep soil layers exhibited the opposite pattern (26.1%–30.1% vs. 9.0%–15.0%). Similarly, the ratios of water utilization from shallow soil layers by C. henryi (18.9%–29.5% vs. 32.4%–45.9%) and S. superba (10.0%–25.7% vs. 29.2%–66.4%) in the mid-successional forest were relatively lower than in the late-successional forest, whereas their water utilization ratios from deep soil layers showed the contrary tendency. Moreover, our results demonstrated that the diverse water utilization of each tree in different successional forests was mainly attributed to their distinct plant properties. Our findings highlight the increased percentage of water utilization of trees from shallow soil layers with forest succession, providing new insights for predicting the direction of forest succession under changing environments.

The timing of potato tuberization is affected by potato ripeness, environmental factors, and polygene regulation. The accurate control of the transition to tuberization has both scientific and practical production value, but the key factors regulating this transition remain unclear. This study grafted an early-maturing potato variety (Favorita) scion to the late-maturing Qingshu 9 variety and demonstrated that a heterologous early-maturing scion can induce early potato formation on a late-maturing rootstock. The transcriptome of functional leaves and stolons of grafted plants was comprehensively analyzed and 593 differentially expressed genes (DEGs) were identified, including 38 transcription factors. Based on gene molecular function analysis and previous reports, we propose that PIF5, bHLH93, CBF3, ERF109, TCP19, and YABBY1 are the key DEGs that induce tuber formation in early- and late-maturing potatoes. The YABBY1 gene was subjected to functional verification. The leaf area of StYABBY1-overexpressing plants was smaller than the wild type and no potato tubercles were formed, while an RNA interference plant line showed no change in leaf area and formed tubers, indicating that StYABBY1 has a role in leaf size regulation and tuber formation.

Carnivore protoparvovirus-1, feline parvovirus (FPV), and canine parvovirus (CPV) continue to spread in companion animals all over the world. As a result, FPV and CPV underwent host-to-host transfer in carnivorous wild-animal hosts. Here, a total of 82 fecal samples of suspected cat FPV infections were collected from Henan Province from 2020 to 2022. The previously published full-length sequence primers of VP2 and NS1 genes were used to amplify the targeted genes of these samples, and the complete gene sequences of 11 VP2 and 21 NS1 samples were obtained and analyzed. Analysis showed that the amino acid homology of the VP2 and NS1 genes of these isolates was 96.1–100% and 97.6–100%, respectively. The phylogenetic results showed that the VP2 and NS1 genes of the local isolates were mainly concentrated in the G1 subgroup, while the vaccine strains were distributed in the G3 subgroup. Finally, F81 cells were inoculated with the local endemic isolate Luoyang-01 (FPV-LY strain for short) for virus amplification, purification, and titer determination, and the pathogenesis of FPV-LY was detected. After five generations of blind transmission in F81 cells, cells infected with FPV-LY displayed characteristic morphological changes, including a round, threadlike, and wrinkled appearance, indicative of viral infection. The virus titer associated with this cytopathic effect (CPE) was measured at 1.5 × 106 TCID50/mL. Subsequent animal regression tests confirmed that the virus titer of the PFV-LY isolate remained at 1.5 × 106 TCID50/mL, indicating its highly pathogenic nature. Cats exposed to the virus exhibited typical clinical symptoms and pathological changes, ultimately succumbing to the infection. These results suggest that the gene mutation rate of FPV is increasing, resulting in a complex pattern of gene evolution in terms of host preference, geographical selection, and novel genetic variants. The data also indicate that continuous molecular epidemiological surveillance is required to understand the genetic diversity of FPV isolates.

Mycotoxins are secondary metabolites produced by several fungi and moulds that exert toxicological effects on animals including immunotoxicity, genotoxicity, hepatotoxicity, teratogenicity, and neurotoxicity. However, the toxicological mechanisms of mycotoxins are complex and unclear. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a multimeric cytosolic protein complex composed of the NLRP3 sensor, ASC adapter protein, and caspase-1 effector. Activation of the NLRP3 inflammasome plays a crucial role in innate immune defence and homeostatic maintenance. Recent studies have revealed that NLRP3 inflammasome activation is linked to tissue damage and inflammation induced by mycotoxin exposure. Thus, this review summarises the latest advancements in research on the roles of NLRP3 inflammasome activation in the pathogenesis of mycotoxin exposure. The effects of exposure to multiple mycotoxins, including deoxynivalenol, aflatoxin B1, zearalenone, T-2 toxin, ochratoxin A, and fumonisim B1, on pyroptosis-related factors and inflammation-related factors in vitro and in vivo and the pharmacological inhibition of specific and nonspecific NLRP3 inhibitors are summarized and examined. This comprehensive review contributes to a better understanding of the role of the NLRP3 inflammasome in toxicity induced by mycotoxin exposure and provides novel insights for pharmacologically targeting NLRP3 as a novel anti-inflammatory agent against mycotoxin exposure.

Deoxynivalenol (DON) is a global contaminant found in crop residues, grains, feed, and animal and human food. Biodegradation is currently the best solution for addressing DON pollution. However, efficient detoxification bacteria or enzymes that can be applied in complex matrices are lacking. The aim of this study was to isolate a DON-detoxifying probiotic strain with a high degradation rate, a good safety profile, and a clear genetic background. One hundred and eight bacterial strains were isolated from 300 samples collected from a school farm and surrounding livestock farms. A new DON-degrading strain, Lactobacillus rhamnosus MY-1 (L. rhamnosus MY-1), with a degradation rate of 93.34% after 48 h and a comprehensive degradation method, was identified. Then, MY-1 at a concentration of 1 × 108 CFU/mL was administered to mice in a chronic intoxication experiment for 28 days. The experimental group showed significantly higher weight gain and exhibited good production performance compared to the control group. The length of the ileal villi in the experimental group was significantly longer than that in the control group. The expression of pro-inflammatory cytokines decreased, while the expression of anti-inflammatory factors increased in the experimental group. Whole-genome analysis revealed that most of the MY-1 genes were involved in carbohydrate metabolism and membrane transport, with a cluster of secondary metabolite genes encoding antimicrobial properties. In summary, this study successfully identified a Lactobacillus strain with good safety performance, high DON degradation efficiency, and a clear genetic background, providing a new approach for the treatment of DON contamination.

Fungi as heterotrophs are key participants in the decomposition of organic materials and the transformation of nutrients in agroecosystems. Ditch-buried straw return as a novel conservation management strategy can improve soil fertility and alter hydrothermal processes. However, how ditch-buried straw return strategies affect the soil fungal community is still unclear. Herein, a 7-year field trial was conducted to test the influences of burial depth (0, 10, 20, 30, and 40 cm) and the amount of ditch-buried straw (half, full, double) on the diversity, composition, and predicted functions of a soil fungal community, as well as the activities of carbon-degraded enzymes. Under the full amount of straw burial, the abundance of phylum Ascomycota was 7.5% higher as compared to other burial amount treatments. This further increased the activity of cellobiohydrolase by 32%, as revealed by the positive correlation between Ascomycota and cellobiohydrolase. With deeper straw burial, however, the abundance of Ascomycota and β-D-glucopyranoside activity decreased. Moreover, genus Alternaria and Fusarium increased while Mortierella decreased with straw burial amount and depth. FUNgild prediction showed that plant fungal pathogens were 1- to 2-fold higher, whilst arbuscular mycorrhizal fungi were 64% lower under straw buried with double the amount and at a depth of 40 cm. Collectively, these findings suggest that ditch-buried straw return with a full amount and buried at a depth less than 30 cm could improve soil nutrient cycles and health and may be beneficial to subsequent crop production.