Logic-Based Strategy for Spatiotemporal Release of Dual Extracellular Vesicles in Osteoarthritis Treatment.

To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic-gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL-10)+ EVs to promote M2 polarization of macrophage, and SRY-box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose-of-action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)-sensitive self-assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl-hydrogel microspheres (PGE), respectively. These materials are mixed to form a "microspheres-in-gel" KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL-10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor-α and IL-1ß levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti-inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic-gates strategies for OA treatment.

Protein extraction from chlorella pyrenoidosa microalgae: Green methodologies, functional assessment, and waste stream valorization for bioenergy production.

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.

Sirtuins in intervertebral disc degeneration: current understanding.

BACKGROUND: Intervertebral disc degeneration (IVDD) is one of the etiologic factors of degenerative spinal diseases, which can lead to a variety of pathological spinal conditions such as disc herniation, spinal stenosis, and scoliosis. IVDD is a leading cause of lower back pain, the prevalence of which increases with age. Recently, Sirtuins/SIRTs and their related activators have received attention for their activity in the treatment of IVDD. In this paper, a comprehensive systematic review of the literature on the role of SIRTs and their activators on IVDD in recent years is presented. The molecular pathways involved in the regulation of IVDD by SIRTs are summarized, and the effects of SIRTs on senescence, inflammatory responses, oxidative stress, and mitochondrial dysfunction in myeloid cells are discussed with a view to suggesting possible solutions for the current treatment of IVDD. PURPOSE: This paper focuses on the molecular mechanisms by which SIRTs and their activators act on IVDD. METHODS: A literature search was conducted in Pubmed and Web of Science databases over a 13-year period from 2011 to 2024 for the terms "SIRT", "Sirtuin", "IVDD", "IDD", "IVD", "NP", "Intervertebral disc degeneration", "Intervertebral disc" and "Nucleus pulposus". RESULTS: According to the results, SIRTs and a large number of activators showed positive effects against IVDD.SIRTs modulate autophagy, myeloid apoptosis, oxidative stress and extracellular matrix degradation. In addition, they attenuate inflammatory factor-induced disc damage and maintain homeostasis during disc degeneration. Several clinical studies have reported the protective effects of some SIRTs activators (e.g., resveratrol, melatonin, honokiol, and 1,4-dihydropyridine) against IVDD. CONCLUSION: The fact that SIRTs and their activators play a hundred different roles in IVDD helps to better understand their potential to develop further treatments for IVDD. NOVELTY: This review summarizes current information on the mechanisms of action of SIRTs in IVDD and the challenges and limitations of translating their basic research into therapy.

Muscle Strength Decline Caused by Eperisone Hydrochloride: A Case Report.

A 65-year-old female with thoracic spinal stenosis and incomplete paraplegia underwent T11-T12 posterior thoracic interbody fusion. During postoperative rehabilitation, she experienced thigh pain, involuntary lower limb convulsions, and muscle fatigue. Despite being prescribed eperisone hydrochloride for relief, her muscle strength decreased after 14 doses. This adverse effect, not listed in the latest Chinese medication instructions, subsided 4 days after discontinuation. This case suggests eperisone hydrochloride potentially caused reversible muscle strength decline, highlighting its potential unsuitability for incomplete paraplegia patients due to possible further muscle strength reduction. We propose updating the medication instructions to alert clinicians to this risk.

Maize MITOGEN-ACTIVATED PROTEIN KINASE 20 mediates high-temperature-regulated stomatal movement.

High temperature induces stomatal opening; however, uncontrolled stomatal opening is dangerous for plants in response to high temperature. We identified a high-temperature sensitive (hts) mutant from the ethyl methane sulfonate (EMS)-induced maize (Zea mays) mutant library that is linked to a single base change in MITOGEN-ACTIVATED PROTEIN KINASE 20 (ZmMPK20). Our data demonstrated that hts mutants exhibit substantially increased stomatal opening and water loss rate, as well as decreased thermotolerance, compared to wild-type plants under high temperature. ZmMPK20-knockout mutants showed similar phenotypes as hts mutants. Overexpression of ZmMPK20 decreased stomatal apertures, water loss rate, and enhanced plant thermotolerance. Additional experiments showed that ZmMPK20 interacts with MAP KINASE KINASE 9 (ZmMKK9) and E3 ubiquitin ligase RPM1 INTERACTING PROTEIN 2 (ZmRIN2), a maize homolog of Arabidopsis (Arabidopsis thaliana) RIN2. ZmMPK20 prevented ZmRIN2 degradation by inhibiting ZmRIN2 self-ubiquitination. ZmMKK9 phosphorylated ZmMPK20 and enhanced the inhibitory effect of ZmMPK20 on ZmRIN2 degradation. Moreover, we employed virus-induced gene silencing (VIGS) to silence ZmMKK9 and ZmRIN2 in maize and heterologously overexpressed ZmMKK9 or ZmRIN2 in Arabidopsis. Our findings demonstrated that ZmMKK9 and ZmRIN2 play negative regulatory roles in high-temperature-induced stomatal opening. Accordingly, we propose that the ZmMKK9-ZmMPK20-ZmRIN2 cascade negatively regulates high-temperature-induced stomatal opening and balances water loss and leaf temperature, thus enhancing plant thermotolerance.

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies.

Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb-preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/ß-catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD-1/PD-L1, MAPK, and NF-κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway-based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.

Supplementation of hyaluronic acid injections with vitamin D improve knee function by attenuating synovial fluid oxidative stress in osteoarthritis patients with vitamin D insufficiency.

Objectives: There is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA. Methods: We investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared. Results: The results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = -0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency. Conclusion: We conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid.

Analgesia with reduced incidence of adverse reactions using flurbiprofen axetil in combination with half standard-dose opioids in primary total knee arthroplasty.

OBJECTIVES: To determine the analgesic effect of flurbiprofen axetil (FBA) combined with half standard-dose opioids in patients undergoing primary unilateral total knee arthroplasty (TKA). MATERIALS AND METHODS: A total of 100 patients undergoing primary TKA were randomly divided into two groups, namely a control group and an experimental group, with 50 patients in each group. All patients received the same dose of FBA in the form of a patient-controlled intravenous analgesia but in the control group this was combined with a standard-dose of opioids and in the experimental group with a half standard-dose of opioids. RESULTS: A visual analogue scale, used to assess the level of pain 8 hours, 48 hours, and 5 days after TKA, showed that pain relief in the experimental group was equal to that in the control group (difference non-significant: p > 0.05). The knee flexion and extension activity in both groups reached target levels on the fifth day after TKA where differences were also not significant: p > 0.05. The incidence of nausea and vomiting after TKA in the experimental group was significantly less than in the control group (p < 0.05). CONCLUSION: The analgesic effect of FBA in combination with half standard-dose opioids was similar to that of FBA in combination with conventional standard-dose opioids, but the incidence of adverse effects involving nausea/vomiting in the experimental group were significantly reduced.

Ubiquitin-specific peptidases: Players in bone metabolism.

Osteoporosis is an ageing-related disease, that has become a major public health problem and its pathogenesis has not yet been fully elucidated. Substantial evidence suggests a strong link between overall age-related disease progression and epigenetic modifications throughout the life cycle. As an important epigenetic modification, ubiquitination is extensively involved in various physiological processes, and its role in bone metabolism has attracted increasing attention. Ubiquitination can be reversed by deubiquitinases, which counteract protein ubiquitination degradation. As the largest and most structurally diverse cysteinase family of deubiquitinating enzymes, ubiquitin-specific proteases (USPs), comprising the largest and most structurally diverse cysteine kinase family of deubiquitinating enzymes, have been found to be important players in maintaining the balance between bone formation and resorption. The aim of this review is to explore recent findings highlighting the regulatory functions of USPs in bone metabolism and provide insight into the molecular mechanisms governing their actions during bone loss. An in-deep understanding of USPs-mediated regulation of bone formation and bone resorption will provide a scientific rationale for the discovery and development of novel USP-targeted therapeutic strategies for osteoporosis.

Untargeted serum and liver metabolomics analyses reveal the gastroprotective effect of polysaccharide from Evodiae fructus on ethanol-induced gastric ulcer in mice.

This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.

Nucleus pulposus related lncRNA and mRNA expression profiles in intervertebral disc degeneration.

In the present study, we aimed to have a comprehensive understanding of nucleus pulposus related long noncoding RNA (lncRNA) and mRNA expression profiles in intervertebral disc degeneration (IDD). In total, 2418 mRNAs and 528 lncRNAs were found to be differentially expressed in the IDD group compared with the Control group. Combining microarray datasets and sequencing data, 5 overlapping DEMs and 7 overlapping DELs were identified. NF-κB signaling pathway, PI3K-Akt signaling pathway and Wnt/ß-catenin signaling pathway were strongly linked with enriched GO terms and KEGG pathways. The ceRNA network suggested that lnc-TMEM44-AS1-hsa-miR-206-HDAC4 may be one crucial axis in IDD. PPI network analysis was constructed with 309 nodes and 129 edges. And the highest connectivity degrees were ALB, APOB and CCL2. This study suggested that specific lncRNAs and ceRNA axes may be crucial in the development of IDD. It provides a new perspective for delaying IDD process and enhancing intervertebral disc repair.

Distinct effects of biochar addition on soil macropore characteristics at different depths in a double-rice paddy field.

Soil macropores largely control the water and nutrients transport as well as runoff processes in the soil. Biochar is frequently applied to soils to improve the macropore structure, but the effects remain controversial. To clarify depth-dependent soil macropore characteristics affected by biochar addition, the intact soil cores with a depth of 200 mm were collected from biochar-amended paddy field at addition rates of 0, 24, and 48 t ha-1 (CK, BC1, and BC2, respectively). The two biochar treatments did not change the overall soil pore indices (e.g., macroporosity, pore number, fractal dimension, and circularity), but showed distinct effects at different soil depths. At a soil depth of 0-50 mm, the biochar treatments had higher macroporosity (8.59-8.85 %) than CK (4.94 %) (p < 0.05), but relatively lower pore circularity (0.83-0.84) than CK (0.88) (p < 0.05). The connectivity of biochar treatments (88-97) was 9.5-10.4 times higher than that of CK (9.3). At a soil depth of 100-200 mm, the biochar treatments exhibited lower macroporosity, macropore number, connectivity, and fractal dimension than CK (p < 0.05). The macropore indices (except circularity) of BC1 were relatively higher than those of BC2 in the most soil depths. Whether biochar altered the soil macropore indices depended on the addition rate of biochar and soil depth. The expansion and occupying effects of biochar were dominant at soil depths of 0-50 and 100-200 mm, respectively; and the two effects were stronger in BC1 than in BC2. A combination of the expansion and occupying effects occurred at a soil depth of 50-100 mm. The distinct effects of biochar on soil pore structure at different depths could mitigate methane emission and nutrient runoff loss from the double-rice paddy. Therefore, soil depth-dependent macropore structure should be considered when assessing the influence of biochar on soil properties and the associated environmental effects.

Multiple cyclic nucleotide-gated channels function as ABA-activated Ca2+ channels required for ABA-induced stomatal closure in Arabidopsis.

Abscisic acid (ABA)-activated inward Ca2+-permeable channels in the plasma membrane (PM) of guard cells are required for the initiation and regulation of ABA-specific cytosolic Ca2+ signaling and stomatal closure in plants. But the identities of the PM Ca2+ channels are still unknown. We hypothesized that the ABA-activated Ca2+ channels consist of multiple CYCLIC NUCLEOTIDE-GATED CHANNEL (CNGC) proteins from the CNGC family, which is known as a Ca2+-permeable channel family in Arabidopsis (Arabidopsis thaliana). In this research, we observed high expression of multiple CNGC genes in Arabidopsis guard cells, namely CNGC5, CNGC6, CNGC9, and CNGC12. The T-DNA insertional loss-of-function quadruple mutant cngc5-1 cngc6-2 cngc9-1 cngc12-1 (hereafter c5/6/9/12) showed a strong ABA-insensitive phenotype of stomatal closure. Further analysis revealed that ABA-activated Ca2+ channel currents were impaired, and ABA-specific cytosolic Ca2+ oscillation patterns were disrupted in c5/6/9/12 guard cells compared with in wild-type guard cells. All ABA-related phenotypes of the c5/6/9/12 mutant were successfully rescued by the expression of a single gene out of the four CNGCs under the respective native promoter. Thus, our findings reveal a type of ABA-activated PM Ca2+ channel comprising multiple CNGCs, which is essential for ABA-specific Ca2+ signaling of guard cells and ABA-induced stomatal closure in Arabidopsis.

An all-silk-derived bilayer hydrogel for osteochondral tissue engineering.

Osteochondral repair remains a challenge in clinical practice nowadays despite extensive advances in tissue engineering. The insufficient recruitment of endogenous cells in the early stage and incomplete cell differentiation in the later stage constitute the major difficulty of osteochondral repair. Here, a novel all-silk-derived multifunctional biomaterial platform for osteochondral engineering is reported. The bilayer methacrylated silk fibroin (SilMA) hydrogel was fabricated through stratified photocuring as the basic provisional matrix for tissue regeneration. Platelet-rich plasma (PRP) incorporation promoted the migration and pre-differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the early stage of implantation. The long-term regulation of BMSCs chondrogenesis and osteogenesis was realized by the stratified anchoring of the silk fibroin (SF) microspheres respectively loaded with Kartogenin (KGN) and berberine (BBR) in the hydrogel. The composite hydrogels were further demonstrated to promote BMSCs chondrogenic and osteogenic differentiation under an inflammatory microenvironment and to achieve satisfying cartilage and subchondral bone regeneration with great biocompatibility after 8 weeks of implantation. Since all the components used are readily available and biocompatible and can be efficiently integrated via a simple process, this composite hydrogel scaffold has tremendous potential for clinical use in osteochondral regeneration.

[Effects of Chemical Fertilizer Reduction Combined with Straw Application on Diazotrophic Communities in a Double Rice Cropping System].

Based on a three-year field experiment, the effects of reduced chemical fertilizer combined with straw application on paddy yield, soil fertility properties, and community structure of diazotrophs in a double-rice cropping field three years after straw application were examined. Three treatments were applied:conventional fertilizer application (CF), chemical fertilizer reduction combined with a low straw application rate (CFLS, 3 t·hm-2), and a high straw application rate (CFHS, 6 t·hm-2). The results showed that CFLS and CFHS did not significantly reduce rice grain yield (P>0.05); significantly neutralized soil acidification; increased soil microbial biomass carbon and nitrogen, dissolved organic carbon, and organic carbon content (P<0.05); and significantly reduced soil redox potential, ammonium nitrogen, and nitrate nitrogen contents (P<0.05). This was more conducive to improve soil nitrogen use efficiency. Compared with those under the CF treatment, the natural nitrogen fixation functional communities of CFLS and CFHS increased the Shannon, PD, and Evenness indexes (P<0.05) due to the improvement of conditions such as the increase in soil carbon storage and the decrease in acidification degree. The relative abundance of microbial communities with nitrogen fixation, carbon fixation, and plant growth promotion functions such as Ferrigenium, Sulfurivermis, Methylomonas, Methylovulum, Ectothiorhodospira, and Nostoc increased significantly (P<0.05). In conclusion, the reduction in chemical fertilizer combined with 3 t·hm-2 and 6 t·hm-2 straw application was an effective measure to improve the community structure of soil diazotrophs and the potential of soil nitrogen fixation.

Phytochemicals, biological activity, and industrial application of lotus seedpod (Receptaculum Nelumbinis): A review.

Lotus (Nelumbo nucifera Gaertn.) is a well-known food and medicinal plant. Lotus seedpod (Receptaculum Nelumbinis) is the by-products during lotus products processing, which is considered as waste. Numerous studies have been conducted on its phytochemicals, biological activity and industrial application. However, the information on lotus seedpod is scattered and has been rarely summarized. In this review, summaries on preparation and identification of phytochemicals, the biological activities of extracts and phytochemicals, and applications of raw material, extracts and phytochemicals for lotus seedpod were made. Meanwhile, the future study trend was proposed. Recent evidence indicated that lotus seedpods extracts, obtained by non-organic and organic solvents, possessed several activities, which were influenced by extraction solvents and methods. Lotus seedpods were rich in phytochemicals categorized as different chemical groups, such as proanthocyanidins, oligomeric procyanidins, flavonoids, alkaloids, terpenoids, etc. These phytochemicals exhibited various bioactivities, including ameliorating cognitive impairment, antioxidation, antibacterial, anti-glycative, neuroprotection, anti-tyrosinase and other activities. Raw material, extracts and phytochemicals of lotus seedpods could be utilized as sources for biochar and biomass material, in food industry and as dye. This review gives well-understanding on lotus seedpod, and provides theoretical basis for its future research and application.

Downregulation of hsa_circ_0000885 suppressed osteosarcoma metastasis and progression via regulating E2F3 expression and sponging miR-16-5p.

Introduction: Accumulating evidence has shown that circular RNAs (circRNAs) have indispensable functions during tumor progression by regulating gene expression. A previous study found that upregulation of hsa_circ_0000885 indicated a poor clinical outcome of osteosarcoma (OS). However, the regulatory mechanism of this process is unclear. Methods: This investigation aimed to elucidate how hsa_circ_0000885 regulated OSs. The study used RT-qPCR to investigate hsa_circ_0000885 expression in OS cells. We conducted luciferase reporter assays and analyses to confirm the hsa_circ_0000885 downstream target. We transfected OS cells using different vectors and used Transwell migration, colony formation, western blotting, Matrigel invasion, proliferation, in vivo tumorigenesis, and metastasis assays to identify the role of hsa_circ_0000885 in OS. Results: The results showed that hsa_circ_0000885 expression altered OS cell lines, and that hsa_circ_0000885 downregulation suppressed OS cell proliferation and invasion using in vivo and in vitro experiments. Luciferase reporter assays verified that miR-16-5p and E2F3 were downstream targets of hsa_circ_0000885. E2F3 overexpression or miR-16-5p inhibition reversed OS cell invasion and proliferation after silencing hsa_circ_0000885. Furthermore, hsa_circ_0000885 affected cancer stem cell differentiation by regulating miR-16-5p/E2F3. Conclusions: Overall, the results showed that hsa_circ_0000885 downregulation suppressed OS progression and metastasis via regulating E2F3 expression and sponging miR-16-5p.

Influence path identification of topography, soil, hydrology and landscape on phosphorus buffering capacity in typical agricultural catchments in central subtropical China.

The catchment phosphorus buffering capacity (PBF) determines the pressure-state-response relationship between anthropogenic P inputs and aquatic ecosystems at a catchment scale, and is affected by biogeochemical, hydrological, and ecological catchment characteristics. However, the complex relationship between these catchment characteristic factors and their impact pathways on PBF remains ambiguous, leading to large uncertainty in balancing agricultural productivity and water conservation via improving BF through management practices. In this study, the short-term buffering index, calculated from net anthropogenic P input and riverine P exports, was used to quantify the spatiotemporal variations in PBF in source agricultural catchments in the Dongting Lake basin. Partial least squares structural equation modeling was used to investigate the relationship between the PBF and the catchment characteristics. The results indicate that catchment PBF was directly determined by soil properties and hydrological conditions, while landscape patterns significantly mediated the effects of topography on soil and hydrology. Considering the pathway preferences of the model, landscape patterns could be the priority for characterizing and regulating PBF. According to a change-point analysis, the probability of PBF weakening increases dramatically when the proportion of farmland (Farm%) > 24.6%, degree of patch interspersion (Contagion index) < 64.5%, and Perimeter-Area Ratio Distribution (PARA) > 348.7. These findings provide new insights into catchment buffering mechanisms and can be used to promote the simultaneous achievement of agricultural production and environmental conservation goals.

Natural selenium stress influences the changes of antibiotic resistome in seleniferous forest soils.

BACKGROUND: Metal(loid)s can promote the spread and enrichment of antibiotic resistance genes (ARGs) in the environment through a co-selection effect. However, it remains unclear whether exposure of microorganisms to varying concentrations of selenium (Se), an essential but potentially deleterious metal(loid) to living organisms, can influence the migration and distribution of ARGs in forest soils. RESULTS: Precisely 235 ARGs conferring resistance to seven classes of antibiotics were detected along a Se gradient (0.06-20.65 mg kg-1) across 24 forest soils. (flor)/(chlor)/(am)phenicol resistance genes were the most abundant in all samples. The total abundance of ARGs first increased and then decreased with an elevated available Se content threshold of 0.034 mg kg-1 (P = 2E-05). A structural equation model revealed that the dominant mechanism through which Se indirectly influences the vertical migration of ARGs is by regulating the abundance of the bacterial community. In addition, the methylation of Se (mediated by tehB) and the repairing of DNA damages (mediated by ruvB and recG) were the dominant mechanisms involved in Se resistance in the forest soils. The co-occurrence network analysis revealed a significant correlated cluster between Se-resistance genes, MGEs and ARGs, suggesting the co-transfer potential. Lelliottia amnigena YTB01 isolated from the soil was able to tolerate 50 µg mL-1 ampicillin and 1000 mg kg-1 sodium selenite, and harbored both Se resistant genes and ARGs in the genome. CONCLUSIONS: Our study demonstrated that the spread and enrichment of ARGs are enhanced under moderate Se pressure but inhibited under severe Se pressure in the forest soil (threshold at 0.034 mg kg-1 available Se content). The data generated in this pilot study points to the potential health risk associated with Se contamination and its associated influence on ARGs distribution in soil.

The role of m6A methylation in osteosarcoma biological processes and its potential clinical value.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults and has a poor prognosis. Recent developments in the field of high-throughput sequencing technology, particularly in methylated RNA immunoprecipitation sequencing (MeRIP-seq), have led to renewed interest in RNA methylation. Among the various RNA modifications, N6-methyladenosine (m6A) modifications are the most common. Emerging evidence suggests that m6A methylation can affect the complexity of cancer progression by regulating biological functions related to cancer. In this review, we will shed light on recent findings regarding the biological function of m6A methylation in OS and discuss future research directions and potential clinical applications of RNA methyltransferases in OS.