Species differences in carbon drawdown during marine phytoplankton growth.

Ocean alkalinity enhancement (OAE) has been proposed as a mitigation method for negative carbon emission. Its effects on marine phytoplankton communities would depend on species differences in tolerance to high pH, which results from phytoplankton photosynthetic drawdown of dissolved inorganic carbon (DIC). In this study, 20 marine phytoplankton species were grown in sealed batch cultures and DIC, pH and chlorophyll a (Chl-a) were measured at the peaks of biomass. These results revealed a wide range of species differences. The drawdown DIC (ΔDIC) vs. increases in pH (ΔpH) graph resembled a Michaelis-Menten curve: significantly linear for ΔDIC < ~1000 µM and starting to plateau at ΔDIC > 1000 µM. This indicated that two mechanisms were operating: CO2 limitation at ΔpH < 1.41 and biologically-mediated precipitation-CO2 released carbon uptake at ΔpH > 1.41. These findings suggest that the potential effects of OAE on the phytoplankton communities would depend on the species differences in oceans.

A sucrose ferulate cycle linchpin for ferulyolation of arabinoxylans in plant commelinids.

A transformation in plant cell wall evolution marked the emergence of grasses, grains and related species that now cover much of the globe. Their tough, less digestible cell walls arose from a new pattern of cross-linking between arabinoxylan polymers with distinctive ferulic acid residues. Despite extensive study, the biochemical mechanism of ferulic acid incorporation into cell walls remains unknown. Here we show that ferulic acid is transferred to arabinoxylans via an unexpected sucrose derivative, 3,6-O-diferuloyl sucrose (2-feruloyl-O-α-D-glucopyranosyl-(1'→2)-3,6-O-feruloyl-ß-D-fructofuranoside), formed by a sucrose ferulate cycle. Sucrose gains ferulate units through sequential transfers from feruloyl-CoA, initially at the O-3 position of sucrose catalysed by a family of BAHD-type sucrose ferulic acid transferases (SFT1 to SFT4 in maize), then at the O-6 position by a feruloyl sucrose feruloyl transferase (FSFT), which creates 3,6-O-diferuloyl sucrose. An FSFT-deficient mutant of maize, disorganized wall 1 (dow1), sharply decreases cell wall arabinoxylan ferulic acid content, causes accumulation of 3-O-feruloyl sucrose (α-D-glucopyranosyl-(1'→2)-3-O-feruloyl-ß-D-fructofuranoside) and leads to the abortion of embryos with defective cell walls. In vivo, isotope-labelled ferulic acid residues are transferred from 3,6-O-diferuloyl sucrose onto cell wall arabinoxylans. This previously unrecognized sucrose ferulate cycle resolves a long-standing mystery surrounding the evolution of the distinctive cell wall characteristics of cereal grains, biofuel crops and related commelinid species; identifies an unexpected role for sucrose as a ferulate group carrier in cell wall biosynthesis; and reveals a new paradigm for modifying cell wall polymers through ferulic acid incorporation.

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Spatial variability of throughfall (i.e. the non-uniform characteristics of throughfall at different canopy positions) and its temporal persistence (i.e. time stability) are related to the quantity and efficiency of soil moisture replenishment, and affect plant competition and community succession dynamics by affecting resource availability. We carried out a meta-analysis with 554 papers (from 2000 to 2022) retrieved from Web of Science and China National Knowledge Infrastructure (CNKI) based on keyword search, quantified and compared the amount, spatial heterogeneity, and temporal stability characteristics of penetrating rain in different climate zones and plant functional types. Our results that throughfall proportion was lower in arid regions (72.0%±13.6%) than humid (75.1%±9.3%) and semi-humid areas (79.9%±10.4%). Cold climates had lower values (74.1%±14.6%) than temperate (74.2%±7.5%) and tropical climates (80.9%±14.6%). Shrubs (68.9%±14.9%) generally had lower throughfall proportion than trees (76.7%±9.1%). Broad-leaved trees (75.2%±11.1%) and conifers (75.1%±9.9%) showed similar throughfall proportions, as did evergreen (76.7%±10.0%) and deciduous species (74.7%±11.9%). Additionally, spatial variability (coefficient of variation) did not significantly differ across rainfall zones, temperature zones, or vegetation types. The spatial distribution of throughfall was relatively stable. Canopy structure was the dominant factor affecting temporal stability of throughfall. However, there was a lack of comparison between typical geographic units (i.e. spatial units with basically consistent geographical environmental conditions) at various temporal scales. Future research should expand upwards to the summary of global spatial scale rules and downwards to the analysis of process based temporal scale mechanisms, to depict the dynamic distribution of penetrating rain and unify observation standards to enhance comparability of different studies, in order to efficiently promote research on canopy penetrating rain and provide ecological and hydrological basis for protecting nature, managing artificial activities, and restoring degraded ecosystems.

The tandem CD33-CLL1 CAR-T as an approach to treat acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by high heterogeneity, poor long-term survival, and a propensity for relapse. Exceptional efficacy in treating recurrent or refractory B-lymphoid malignancies has been demonstrated by Chimeric antigen receptor T cells (CAR-T cells). Given the therapeutic potential of targeting both CD33 and C-type lectin-like molecule-1 (CLL1) in AML, the development of a dual-targeting CD33-CLL1 CAR-T cells assumes significant importance. MATERIALS AND METHODS: The expressions of CD33 and CLL-1 antigens in peripheral blood cells and bone marrow cells from AML patients was assessed. Subsequently, a Chimeric Antigen Receptor (CAR) incorporating a dual-specific single-chain variable fragment targeting CLL1 and CD33 (CD33-CLL1-CAR-T) was engineered. The anti-tumor efficacy and potential side effects of CD33-CLL1-CAR-T cells were comprehensively investigated in both in vitro and in vivo settings. RESULTS: The constructed tandem CD33-CLL1 CAR-T exhibited potent cytotoxicity against leukemia cell lines and human primary AML cells in vitro. Co-cultivation of AML blasts with CD33-CLL1-CAR-T cells resulted in effective proliferation and the secretion of substantial quantities of GM-CSF and IFN-γ. Importantly, the impact of CD33-CLL1-CAR-T cells on normal hematopoietic stem cells was minimal, ensuring safety in vivo mouse models. Notably, significant anti-leukemic activity was observed in the mouse model, with CD33-CLL1-CAR-T cells leading to tumor eradication and prolonged survival. DISCUSSION: The tandem CD33-CLL1 CAR-T cells not only efficiently eliminated AML blasts but also exhibited low cytotoxicity toward normal hematopoietic stem cells (HSCs). These findings underscore the potential clinical applicability of the tandem CD33-CLL1 CAR-T cells as an effective and safe treatment strategy for AML, representing a noteworthy advancement in the field of CAR-T cells therapy.

Cumulative characteristics and ecological risk source analysis of soil potentially toxic elements in the northern margin of the Tibetan Plateau.

To understand the soil toxic and hazardous elements content, pollution level, and ecological risk status in the northern margin of the Tibetan Plateau, we collected and analyzed 8273 sets of surface soil samples. Evaluations were conducted using the single-factor pollution index, geo-accumulation, pollution load, and potential ecological risk indices, and source identification correlation and principal component analysis. The results revealed that, compared with the background levels in China, the accumulation of soil arsenic, cadmium, nickel, and chromium was greater in the surface soil of the study area. Additionally, in comparison with Qinghai Province, more mercury accumulated in the surface soil of the study area and owing to the influence of anthropogenic activities. Benchmarking against soil environmental quality standards, the study area exhibited pollution control zones primarily dominated by arsenic and cadmium (3.9%). The spatial distribution revealed distinct zones: a ridge mountain type characterized by arsenic-cadmium-chromium-nickel, a Daban mountain type with solely cadmium presence, and a Longyangxia-Jianzha South type dominated by arsenic. Compared with the Qinghai Province soil background values, evaluations using the Pollution loading index, Geological Cumulative Index, and Potential Ecological Risk Index methods revealed varying degrees of potentially toxic element content exceedance. From an ecological risk perspective, the individual element with the highest potential ecological risk coefficients were mercury, followed by cadmium and arsenic; however, the region's overall ecological risk index was classified as low. Three distinct sources were identified: natural sources leading to high background levels of chromium, nickel, copper, zinc, and mercury; mixed natural and industrial/agricultural sources contributing to elevated cadmium levels; and human activity-related mercury enrichment. Based on the evaluation results, synergistic monitoring of soil and biota in naturally occurring risk zones is recommended to ensure the safety of agricultural and pastoral products. Additionally, ecological impact assessments and pollution source mitigation studies should be conducted in regions influenced by human activities to curb the further degradation of soil ecological quality.

Treatment of bone-cartilage defects with dual-layer tissue-engineered scaffolds loaded with icariin and quercetin.

Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.

Global, regional, and national temporal trend in burden of major depressive disorder from 1990 to 2019: An analysis of the global burden of disease study.

Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Comprehensive description of the global burden of MDD and its attributable risk factors is essential for policymaking but currently lacking. In this study, we aim to estimate the burden of MDD in terms of incidence, prevalence, and years lived with disability (YLDs), along with its attributable risk factors at global, regional, and rational level between 1990 and 2019, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Data analysis was completed on July 1, 2023. In 2019, 274.80 million (95 % uncertainty interval [UI], 241.28 to 312.77) new cases of MDD were identified globally, with an increase of 59 % from 1990. A total of 37.20 million (25.65 to 51.22) YLDs were attributable to MDD, accounting for the largest proportion of mental disorder YLDs (29.7 %). Countries in the low sociodemographic index quantile exhibited the highest age-standardized incidence rate of MDD, with Uganda (7836.2, per 100,000 person-years, 6713.7 to 9181.1) and Palestine (7687.7, 6546.1 to 9023.9) reporting the highest rates among them. The United States had the highest increase in age-standardized rates, with an average annual percent change of 0.99. Females had 1.6 times higher age-standardised rates than males, ranging from 1.2 (Oceania) to 2.2 (tropical Latin America) times across 21 regions. Globally, the proportions of YLDs due to MDD attributable to bullying victimization, childhood sexual abuse, and intimate partner violence were 4.86 %, 5.46 %, and 8.43 % in 2019, respectively. The heavy burden of MDD serves as a stark reminder that a coordinated response from governments and health communities is urgently needed to scale up mental health services and implement effective interventions, particularly in low-income countries.

A bibliometric analysis of miRNAs in rheumatoid arthritis from 2001 to 2022: Research hotspots and trends.

BACKGROUND: MicroRNAs (miRNAs) are widely recognized in the pathogenesis of autoimmune disease. As a key regulatory factor, miRNAs have introduced new biomarkers for the early diagnosis of rheumatoid arthritis (RA) and provided a favorable research direction for the development of novel therapeutic targets. This study aimed to explore the hotspots of miRNA research related to RA published from different countries, organizations, and authors. METHODS: From 2001 to 2022, publications on miRNA related to RA were identified in the Web of Science database. The total and annual number of publishments, citations, impact factor, H-index, productive authors, and involved journals were collected for quantitative and qualitative comparisons. RESULTS: A total of 29 countries/regions in the world have participated in the research of miRNAs and RA over the past two decades, and China (760, 53.18%) and the United States (233, 16.31%) account for the majority of the total publications. China dominated in total citation (17881) and H-index (62). A total of 507 academic journals have published articles in related fields, and Frontiers in Immunology published the most (53, 3.71%). Chih-hsin Tang of the China Medical University has published the most papers (16, 1.2%). Stanczyk (2008) published the most cited article Altered expression of miRNAs in synovial fibroblasts and synovial tissue in rheumatoid arthritis in Arthritis and Rheumatism, with 660 citations. Inflammation is the high-frequency keyword outside of RA and miRNAs, and related researches have mainly focused on miR-146a and miR-155. CONCLUSIONS: In the past two decades, extensive and continuous research has been conducted to investigate the role of miRNAs in RA, and miRNAs are widely recognized in the pathogenesis of RA. Related research has mainly focused on miR-146a and miR-155 that have shown promising results as key factors in RA experimental models. Focusing on clinical applications and translational research may be the future research direction and hotspot based on molecular biology basic research and mechanism exploration.

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis.

Background: In the environment of cartilage injury, the activation of vascular endothelial cell (VEC), marked with excessive CD62E and reactive oxygen species (ROS), can affect the formation of hyaluronic cartilage. Therefore, we developed a CD62E- and ROS-responsive drug delivery system using E-selectin binding peptide, Thioketal, and silk fibroin (ETS) to achieve targeted delivery and controlled release of Clematis triterpenoid saponins (CS) against activated VEC, and thus promote cartilage regeneration. Methods: We prepared and characterized ETS/CS and verified their CD62E- and ROS-responsive properties in vitro. We investigated the effect and underlying mechanism of ETS/CS on inhibiting VEC activation and promoting chondrogenic differentiation of bone marrow stromal cells (BMSCs). We also analyzed the effect of ETS/CS on suppressing the activated VEC-macrophage inflammatory cascade in vitro. Additionally, we constructed a rat knee cartilage defect model and administered ETS/CS combined with BMSC-containing hydrogels. We detected the cartilage differentiation, the level of VEC activation and macrophage in the new tissue, and synovial tissue. Results: ETS/CS was able to interact with VEC and inhibit VEC activation through the carried CS. Coculture experiments verified ETS/CS promoted chondrogenic differentiation of BMSCs by inhibiting the activated VEC-induced inflammatory cascade of macrophages via OPA1-mediated mitochondrial homeostasis. In the rat knee cartilage defect model, ETS/CS reduced VEC activation, migration, angiogenesis in new tissues, inhibited macrophage infiltration and inflammation, promoted chondrogenic differentiation of BMSCs in the defective areas. Conclusions: CD62E- and ROS-responsive ETS/CS promoted cartilage repair by inhibiting VEC activation and macrophage inflammation and promoting BMSC chondrogenesis. Therefore, it is a promising therapeutic strategy to promote articular cartilage repair.

Mechanisms of vascular invasion after cartilage injury and potential engineering cartilage treatment strategies.

Articular cartilage injury is one of the most common diseases in orthopedic clinics. Following an articular cartilage injury, an inability to resist vascular invasion can result in cartilage calcification by newly formed blood vessels. This process ultimately leads to the loss of joint function, significantly impacting the patient's quality of life. As a result, developing anti-angiogenic methods to repair damaged cartilage has become a popular research topic. Despite this, tissue engineering, as an anti-angiogenic strategy in cartilage injury repair, has not yet been adequately investigated. This exhaustive literature review mainly focused on the process and mechanism of vascular invasion in articular cartilage injury repair and summarized the major regulatory factors and signaling pathways affecting angiogenesis in the process of cartilage injury. We aimed to discuss several potential methods for engineering cartilage repair with anti-angiogenic strategies. Three anti-angiogenic tissue engineering methods were identified, including administering angiogenesis inhibitors, applying scaffolds to manage angiogenesis, and utilizing in vitro bioreactors to enhance the therapeutic properties of cultured chondrocytes. The advantages and disadvantages of each strategy were also analyzed. By exploring these anti-angiogenic tissue engineering methods, we hope to provide guidance for researchers in related fields for future research and development in cartilage repair.

Associations between patterns of blood heavy metal exposure and health outcomes: insights from NHANES 2011-2016.

BACKGROUND: Extensive research has explored the association between heavy metal exposure and various health outcomes, including malignant neoplasms, hypertension, diabetes, and heart diseases. This study aimed to investigate the relationship between patterns of exposure to a mixture of seven heavy metals and these health outcomes. METHODS: Blood samples from 7,236 adults in the NHANES 2011-2016 studies were analyzed for levels of cadmium, manganese, lead, mercury, selenium, copper, and zinc. Cluster analysis and logistic regression identified three distinct patterns of mixed heavy metal exposure, and their associations with health outcomes were evaluated. RESULTS: Pattern 1 exhibited higher odds ratios (ORs) for malignancy during NHANES 2011-2012 (OR = 1.33) and 2015-2016 (OR = 1.29) compared to pattern 2. Pattern 3 showed a lower OR for malignancy during NHANES 2013-2014 (OR = 0.62). For hypertension, pattern 1 displayed higher ORs than pattern 2 for NHANES 2011-2012 (OR = 1.26), 2013-2014 (OR = 1.31), and 2015-2016 (OR = 1.41). Pattern 3 had lower ORs for hypertension during NHANES 2013-2014 (OR = 0.72) and 2015-2016 (OR = 0.67). In terms of heart diseases, pattern 1 exhibited higher ORs than pattern 2 for NHANES 2011-2012 (OR = 1.34), 2013-2014 (OR = 1.76), and 2015-2016 (OR = 1.68). Pattern 3 had lower ORs for heart diseases during NHANES 2013-2014 (OR = 0.59) and 2015-2016 (OR = 0.52). However, no significant trend was observed for diabetes. All three patterns showed the strongest association with hypertension among the health outcomes studied. CONCLUSIONS: The identified patterns of seven-metal mixtures in NHANES 2011-2016 were robust. Pattern 1 exhibited higher correlations with hypertension, heart disease, and malignancy compared to pattern 2, suggesting an interaction between these metals. Particularly, the identified patterns could offer valuable insights into the management of hypertension in healthy populations.

The significance of targeting lysosomes in cancer immunotherapy.

Lysosomes are intracellular digestive organelles that participate in various physiological and pathological processes, including the regulation of immune checkpoint molecules, immune cell function in the tumor microenvironment, antigen presentation, metabolism, and autophagy. Abnormalities or dysfunction of lysosomes are associated with the occurrence, development, and drug resistance of tumors. Lysosomes play a crucial role and have potential applications in tumor immunotherapy. Targeting lysosomes or harnessing their properties is an effective strategy for tumor immunotherapy. However, the mechanisms and approaches related to lysosomes in tumor immunotherapy are not fully understood at present, and further basic and clinical research is needed to provide better treatment options for cancer patients. This review focuses on the research progress related to lysosomes and tumor immunotherapy in these.

Down-expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenesis and accelerates age-related bone loss via PTEN/PI3K/AKT pathway.

Aims: To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods: In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results: The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion: Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway.

The effects of postoperative malrotation alignment on outcomes of Gartland type III/IV paediatric supracondylar humeral fractures treated by close reduction and percutaneous K-wire fixation.

PURPOSE: In this study, we aimed to investigate the effects of postoperative malrotation alignment on the outcomes of Gartland type III/IV paediatric supracondylar humeral fracture (SCHF) treated by close reduction and percutaneous K-wire fixation. METHODS: Between January 2014 and December 2021, 295 Gartland type III/IV paediatric SCHFs treated by close reduction and percutaneous K-wire fixation were selected for this retrospective study. The demographic, clinical and radiographic parameters of all cases were collected. The lateral rotation percentage (LRP) was measured on X-rays to evaluate postoperative malrotation alignment of the fracture. All cases were categorized into 4 groups according to LRP: LRP ≤ 10% (210, 71.2%), 10% < LRP ≤ 20% (41, 13.9%), 20% < LRP ≤ 30% (26, 8.8%) and LRP > 30% (18, 6.1%). The carrying angle, ranges of multidirectional motions, Mayo Elbow Performance Score (MEPS) and Flynn's Standard Score (FSS) of the injured elbow were assessed 6 months postoperation and compared among different groups. ROC analysis based on LRP and the excellent/good rate of FSS was performed to determine the acceptable maximum degree of postoperative malrotation alignment. RESULTS: There was no difference in the demographic characteristics (age, sex, injured side and fracture type), postoperative Baumann angle, carrying angle or range of forearm rotation among the 4 groups (P > 0.05). The operation time and time from operation to K-wire removal were longer in the 20% < LRP ≤ 30% and LRP > 30% groups than in the LRP < 10% and 10% < LRP ≤ 20% groups (P < 0.001). The shaft condylar angle, range of elbow flexion, MEPS and FSS of the injured elbow 6 months postoperatively were lower in the 20% < LRP ≤ 30% and LRP > 30% groups than in the LRP < 10% and 10% < LRP ≤ 20% groups (P < 0.001). ROC analysis based on LRP and the excellent/good rate of FSS showed an area under the curve of 0.959 (95% CI 0.936-0.983), with a cutoff value of 26.5%, sensitivity of 95.3% and specificity of 90.1%. CONCLUSION: A certain degree of residual malrotation alignment deformity of the SCHF may reduce the shaft condylar angle and extend the time from operation to removing the K-wire and affect elbow function, especially the range of elbow flexion. The acceptable maximum degree of residual malrotation deformity expressed as the LRP value was 26.5%.

Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.

BACKGROUND: Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying mechanism and bring a potential preventive strategy for postmenopausal osteoporosis in the future. METHODS: An ovariectomy (OVX)-induced rat osteoporosis model was established for in vivo experiments. Micro-computed tomography and three-point bending test were used to evaluate bone strength. Histological femur slices were processed for immunohistochemistry (IHC). Bone turnover markers and nitric oxide (NO) concentrations in serum were determined with enzyme-linked immunosorbent assay (ELISA). The mouse embryo osteoblast precursor (MC3T3-E1) cells were used for in vitro experiments. The cell viability was analysed with a Cell Counting Kit­8. We performed Alizarin Red S staining and alkaline phosphatase (ALP) activity assay to observe the differentiation status of osteoblasts. Western blotting was adopted to detect the expression of osteogenesis related proteins and AMP-activated protein kinase/endothelial nitric oxide synthase (AMPK/eNOS) in osteoblasts. DAF-FM diacetate was used for semi-quantitation of intracellular NO. RESULTS: In OVX rats, alamandine alleviated osteoporosis and maintained bone strength. The IHC showed alamandine increased osteocalcin and collagen type I α1 (COL1A1) expression. The ELISA revealed alamandine decreased bone turnover markers and restored NO level in serum. In MC3T3-E1 cells, alamandine promoted osteogenic differentiation. Western blotting demonstrated that alamandine upregulated the expression of osteopontin, Runt-related transcription factor 2 and COL1A1. The intracellular NO was also raised by alamandine. Additionally, the activation of AMPK/eNOS axis mediated the effects of alamandine on MC3T3-E1 cells and bone tissue. PD123319 and dorsomorphin could repress the regulating effect of alamandine on bone metabolism. CONCLUSION: Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.

Stachyose in combination with L. rhamnosus GG ameliorates acute hypobaric hypoxia-induced intestinal barrier dysfunction through alleviating inflammatory response and oxidative stress.

High altitude is closely related to intestinal mucosal damage and intestinal microbiota imbalance, and there is currently no effective prevention and treatment measures. In this study, the effects of stachyose (STA), L. rhamnosus GG (LGG) and their combination on inflammatory response, oxidatve stress and intestinal barrier function in mice exposed to acute hypobaric hypoxia were investigated. Our results indicated the combination of STA and LGG could more effectively regulate intestinal microbiota disorders caused by hypobaric hypoxia than STA or LGG alone. When mice were administered with STA + LGG, the content of short chain fatty acids (SCFAs) especially butyric acid significantly increased, which helped intestinal cells to form tight connections, improve the level of anti-inflammatory cytokine (TGF-ß) and antioxidant enzymes (SOD, CAT, GSH-Px), and decrease the expression of pro-inlammatory cytokines and hypoxia-inducing factors (IFN-γ, IL-1ß, IL-6, TNF-α and HIF-1α), thereby enhance the strong intestinal barrier function. Furthermore, the synbiotics significantly reduced the ratio of Firmicutes to Bacteroidetes, while significantly increased the relative abundance of Rikenella, Bacteroides, Odoribacter, Ruminiclostridium_5 and Gordonibacter, which were correlated with production of SCFAs and anti-inflammatory role. Correlation analysis showed that the protective effect of synbiotics on intestinal barrier function was associated with its anti-inflammatory activity and antioxidant capacity. It provided a strong foundation for further research on the role of STA and LGG in maintaining normal intestinal function at high altitude. Our study has identified and demonstrated a new synbiotic that may be one of the ideal intervention measures for preventing and treating intestinal dysfunction at high altitude.

LncRNA USP2-AS1 facilitates the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting KDM3A/ETS1/USP2 to activate the Wnt/ß-catenin signaling pathway.

Human bone marrow mesenchymal stem cells (HBMSCs) can promote new bone formation. Previous studies have proven the ability of long non-coding RNAs (lncRNAs) to modulate the osteogenic differentiation of mesenchymal stem cells. However, the molecular mechanism modulated by lncRNAs in affecting the osteogenic differentiation of HBMSCs remains largely unknown. Thus, this study aims to reveal the role of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) in regulating the osteogenic differentiation of HBMSCs and investigate its regulatory mechanism. Through bioinformatics analysis and RT-qPCR, we confirmed that USP2-AS1 expression was increased in HBMSCs after culturing in osteogenic differentiation medium (OM-HBMSCs). Moreover, we uncovered that knockdown of USP2-AS1 inhibited the osteogenic differentiation of HBMSCs. Further exploration indicated that USP2-AS1 positively regulated the expression of its nearby gene USP2. Mechanistically, USP2-AS1 recruited lysine demethylase 3A (KDM3A) to stabilize ETS proto-oncogene 1 (ETS1), transcription factor that transcriptionally activated USP2. Additionally, USP2-induced Wnt/ß-catenin signalling pathway activation via deubiquitination of ß-catenin protein. In summary, our study proved that lncRNA USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by targeting KDM3A/ETS1/USP2 axis to activate the Wnt/ß-catenin signalling pathway.

Impact of recombinant human brain natriuretic peptide on emergency dialysis and prognosis in end-stage renal disease patients with type 4 cardiorenal syndrome.

Recombinant human brain natriuretic peptide (rhBNP) effects on type 4 cardiorenal syndrome (CRS) and adverse events such as heart failure rehospitalization and all-cause mortality have not been assessed in large-scale research. This study evaluated the impact of rhBNP on emergency dialysis and prognosis in end-stage renal disease (ESRD) patients with type 4 CRS, and the risk factors of emergency dialysis. This retrospective cohort study included patients with type 4 CRS and ESRD admitted for decompensated heart failure between January 2016 and December 2021. Patients were divided into the rhBNP and non-rhBNP cohorts, according to whether they were prescribed rhBNP. The primary outcomes were emergency dialysis at first admission and cardiovascular events within a month after discharge. A total of 77 patients were included in the rhBNP cohort (49 males and 28 females, median age 67) and 79 in the non-rhBNP cohort (47 males and 32 females, median age 68). After adjusting for age, residual renal function, and primary diseases, Cox regression analysis showed that rhBNP was associated with emergency dialysis (HR = 0.633, 95% CI 0.420-0.953) and cardiovascular events (HR = 0.410, 95% CI 0.159-0.958). In addition, multivariate logistic regression analysis showed that estimated glomerular filtration rate (eGFR) (OR = 0.782, 95% CI 0.667-0.917, P = 0.002) and procalcitonin (PCT) levels (OR = 1.788, 95% CI 1.193-2.680, P = 0.005) at the first visit were independent risk factors for emergency dialysis while using rhBNP was a protective factor for emergency dialysis (OR = 0.195, 95% CI 0.084-0.451, P < 0.001). This study suggests that RhBNP can improve cardiac function and reduce the occurrence of emergency dialysis and cardiovascular events in ESRD patients with type 4 CRS.

Trends in the prevalence and treatment of comorbid depression among US adults with and without cancer, 2005-2020.

BACKGROUND: Understanding trend characteristics of depression among cancer survivors is essential for healthcare policies and planning. This study estimates longitudinal trends in the prevalence and treatment of depression among adults in the United States with and without cancer. METHODS: This cross-sectional study focused on adults aged 20 years or older based on nationally representative data from the National Health and Nutrition Examination Surveys 2005-2020. Weighted logistic regression model was established to assess association between depression and cancer status after adjusting various covariates potentially related to depression. RESULTS: Among the 37,283 participants (weighted mean age, 47.5; women, 50.9 %), 3648 (9.8 %) were diagnosed with cancer and 3343 (9.0 %) were screened positive for depression. The age-standardized prevalence of depression showed a U-shaped trend in cancer survivors, decreasing from 11.8 % (95 % confidence interval, 8.4 %-15.2 %) in 2005-2008 to 8.3 % (5.6 %-11.0 %) in 2013-2016, then increasing to 11.7 % (6.3 %-17.2 %) in 2017-2020. These trends varied by population subgroup. Among depressive patients with cancer, antidepressant use increased from 38.6 % (28.7 %-48.5 %) in 2005-2008 to 62.9 % (40.6 %-85.2 %) in 2017-2020, whereas mental health consultation increased slightly. LIMITATIONS: Using a screening questionnaire instead of diagnostic criteria to identify depression; small sample size of patients with cancer; and cross-sectional analysis without prospective outcomes. CONCLUSIONS: From 2005 to 2020, the depression disease burden in patients with cancer eased in 2009-2015, but deteriorated recently. A healthy lifestyle and reasonable treatment for depression, based on an objective examination of depression characteristics, would improve long-term cancer outcomes and quality of life.

Disentangling the effects of vapor pressure deficit on northern terrestrial vegetation productivity.

The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity's response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle's response to global warming.