IGF2BP2 regulates the inflammation of fibroblast-like synoviocytes via GSTM5 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

Efficacy and Safety of Kuoxin Formula in the Treatment of Dilated Cardiomyopathy-Related Heart Failure: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial.

Background: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients' quality of life. This trial aims to further evaluate KXF's safety and efficacy in managing DCM-related heart failure. Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee's heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded. Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients. Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.

The impact of grandparenting on mental health among rural middle-aged and older adults in China: exploring the role of children's support.

Objectives: In the rural regions of China, characterized by a pronounced aging demographic and limited resources, a substantial proportion of middle-aged and older adults engage in grandparenting roles. Yet, the literature lacks consistent evidence regarding the effects of grandparenting on the mental health of this cohort. Accordingly, this study aimed to explore the impact of grandparenting on the mental health of rural middle-aged and older adults, as well as the underlying mechanisms. Methods: This analysis encompassed 10,881 middle-aged and older adults, utilizing data from the 2018 Harmonized China Health and Retirement Longitudinal Study (CHARLS). The mental health of participants was assessed using the Center for Epidemiological Studies Depression-10 (CESD-10) scale, while support from children was categorized into financial and emotional types. The study employed logistic and OLS regression models to identify the mediating role of child support and utilized the Karlson-Holm-Breen (KHB) method for decomposing this mediating effect. Results: The findings demonstrated that grandparenting had a significant negative impact on depression among rural middle-aged and older adults. Furthermore, children's support played a vital role in mediating this relationship, accounting for approximately one-third of the overall influence. Moreover, the decomposition analysis revealed that both emotional and economic support from adult children equally contributed to the declination of depression among rural middle-aged and older adults. Conclusion: Grandparenting significantly enhances mental well-being in rural middle-aged and older adults, with the support from adult children serving as a vital pathway for this positive impact. Both economic and emotional assistance from children hold equal importance in this dynamic. It underscores the necessity of fortifying the family support system to amplify the support provided by children, which in turn could significantly enhance the mental health of rural middle-aged and older adults.

Cartilage stem/progenitor cells-derived exosomes facilitate knee cartilage repair in a subacute osteoarthritis rat model.

Cartilage defects in the knee are often associated with the progression of degenerative osteoarthritis (OA), and cartilage repair is a useful strategy for managing this disease. However, cartilage repair is challenging because of the unique environment within the tissue. Recently, stem cell-based therapies have shed new light on this issue. In this study, we prepared exosomes (EXOs) from cartilage stem/progenitor cells (CSPCs) and found that treatment with EXOs increased the viability, migration, and proliferation of cultured primary chondrocytes. In a subacute OA rat model, the application of EXOs facilitated cartilage regeneration as evidenced by histological staining. Exosomal protein analysis together with bioinformatics suggested that cyclin-dependent kinase 9 (CDK9) is a key factor for chondrocyte growth and migration. Functional studies confirmed this prediction, that is, inhibiting CDK9 reduced the beneficial effects induced by EXOs in primary chondrocytes; while overexpression of CDK9 recapitulated the EXOs-induced phenotypes. RNA-Seq data showed that a set of genes involved in cell growth and migration were up-regulated by EXOs in chondrocytes. These changes could be partially reproduced by CDK9 overexpression. Overall, our data suggest that EXOs derived from primary CSPCs hold great therapeutic potential for treating cartilage defect-associated disorders such as degenerative OA, and that CDK9 is a key factor in this process.

Revisiting the association between grandparenting and mental health in China: New evidence from the harmonized CHARLS.

BACKGROUND: In the context of the global aging challenge, an increasing number of middle-aged and older adults (MAOAs) are engaging in grandparenting. However, the effect of grandparenting on the mental health of caregivers has shown inconsistent findings. To effectively promote healthy aging, it is imperative to adopt a comprehensive perspective and employ a rigorous approach to further investigate the relationship between these two social phenomena. METHODS: The data from the Harmonized China Health and Retirement Longitudinal Study were analyzed, focusing on MAOAs with at least one grandchild. Mental health assessments used the center for epidemiologic studies depression scale scale. The study employed a series of difference-in-differences (DID) models, especially complemented by propensity score matching, to evaluate the average treatment effect for the treated (ATT) on mental health of caregivers, considering covariates like personal and family characteristics. The intervention perspective includes both the provision and cessation of grandparenting. RESULTS: The study found that providing grandchildren care does not have a significant effect on the mental health of grandparents, in comparison to those who have never engaged in such care (ATT = -0.172, T = 0.65, p = 0.517 in the PSM-DID model). Furthermore, ceasing this care also appears to have no substantial effect on the mental health of the caregivers, relative to individuals who have consistently offered grandchildren care (ATT = 0.060, T = 0.26, p = 0.795 in the PSM-DID model). Furthermore, subsequent robustness analyses consistently supported these findings, even when considering data from different survey waves. CONCLUSIONS: In contrast to many prior studies that have reported either positive or negative effects, our research reveals that grandparenting exerts no significant effect on the mental health of MAOAs. Consequently, health practitioners and policymakers should carefully consider the diverse cultural context when tailoring interventions and support strategies.

Enhancing Older Household Consumption: The Impact of Long-term Care Insurance in China.

OBJECTIVES: Household consumption significantly impacts the quality of life and successful aging of older adults. However, prior research has often overlooked the connection between household consumption and long-term care insurance (LTCI). This study aims to investigate the influence of LTCI on consumption patterns within older Chinese households. METHODS: We used harmonized data from the China Health and Retirement Longitudinal Study (CHARLS) and merged it with data from cities that implemented LTCI in China. We analyzed a total of 6,494 households consisting of individuals who were 60 years of age or older. To ensure accurate and stable research findings, we employed a series of difference-in-differences (DID) models. RESULTS: We found that LTCI has a significant impact on consumption levels, including total and per capita consumption within older households. Furthermore, our research demonstrates that LTCI significantly enhances enjoyable consumption across the consumption types. Through a heterogeneous analysis, it is shown that LTCI has a unique effect on both the total and enjoyable consumption of urban older households, and also promotes comprehensive consumption improvements in older rural and disabled households. DISCUSSION: These findings highlight the crucial role of LTCI in improving the financial security and well-being of older households. They also have considerable policy implications for dealing with the challenges of an aging population.

Drought decreases cotton fiber strength by altering sucrose flow route.

The potential mechanisms by which drought restricts cotton fiber cell wall synthesis and fiber strength formation are still not fully understood. Herein, drought experiments were conducted using two upland cotton cultivars of Dexiamian 1 (drought-tolerant) and Yuzaomian 9110 (drought-sensitive). Results showed that drought notably reduced sucrose efflux from cottonseed coats to fibers by down-regulating the expression of GhSWEET10 and GhSWEET15 in outer cottonseed coats, leading to promoted sucrose accumulation in cottonseed coats but decreased sucrose accumulation in fibers. Within cotton fibers, drought restricted the hydrolysis from sucrose to UDPG by suppressing sucrose synthase activity, and drought favored the conversion of UDPG to ß-1, 3-glucan rather than cellulose by up-regulating GhCALS5. Hence, cellulose content was reduced, which was the main reason for the decreased fiber strength under drought. Moreover, drought promoted lignin synthesis by up-regulating the expression of Gh4CL4, GhPAL9, GhCCR5, GhCAD11, and GhOMT6, which partly offset the negative influence of reduced cellulose content on fiber strength. Compared with Yuzaomian 9110, the drought-tolerance of Dexiamian 1 was evidenced in the following ways: (1) slighter blocked sucrose flow from seedcoat to fiber, (2) less ß-1, 3-glucan accumulation, and (3) more lignin biosynthesis under drought. Overall, this study provides new insights into the mechanism of drought impacting cotton fiber strength formation.

Changes in carbohydrate distribution of cotton and increase in boll weight reduced yield loss under high temperature.

Cotton yield is sometimes unresponsive to high temperature (HT) that induce significant reductions in fruit retention. To investigate the underlying mechanisms, a greenhouse experiment was conducted with two temperature regimes (control, control treatment, 28 °C; HT, 34 °C) for 7 days. Results showed HT did not significantly influence cotton yield, but remarkably reduce boll number and increase boll weight. 13C distribution ratio of the leaf subtending to cotton boll (LSCB) decreased while that of cotton boll increased under HT. Transcriptomic and proteomic analyses of LSCB revealed up-regulated genes involved in cytokinin and jasmonic acid synthesis, as well as SWEET15 (GH_D01G0218), which positively regulated photosynthesis and transport photosynthate, ultimately leading to increased boll weight. After 7 days recovering from HT, 13C distribution ratio of LSCB increased while that of cotton boll decreased. However, the boll weight still increased, which was related to the increased amylase and sucrose phosphate synthase activities and up-regulated sucrose transport genes in main-stem leaf and capsule wall. Thus, both the accelerated sucrose synthesis and transport in LSCB under HT and the increased sucrose supply ability in main-stem leaf and capsule wall after recovering from HT contributed to an increased boll weight, which finally maintained cotton yield.

ALOX5 drives the pyroptosis of CD4+ T cells and tissue inflammation in rheumatoid arthritis.

Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A4 (LTA4), were increased in CD4+ T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4+ T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4+ T cells enhanced the production of the LTA4 derivative LTB4, which stimulated Ca2+ influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA.

Filial piety and older adult caregiving among Chinese and Chinese-American families in the United States: a concept analysis.

BACKGROUND: The culturally sensitive nursing practice has not embedded filial piety as a cultural value and stance pertaining to caregiving among aging Chinese and Chinese-American (CCA) families in the United States, yet it is critical for healthy aging among CCAs. PURPOSE: To understand filial piety when caring for aging CCAs and conceptualize an operational definition and framework. METHODS: A systematic search was conducted in CINAHL, PubMed, Scopus, and PsycINFO databases. Analysis of the concept of filial piety among CCAs used Walker and Avant's methods. Twenty-six studies were selected in the final full-text analysis. FINDINGS: Synthesis of evidence identified four antecedents: (a) filial obligation as a 'cultural gene', (b) sense of altruism, (c) familial solidarity, and (d) societal expectation of 'birth right'. Attributes included familial material and emotional support, obedience, pious reverence, and societal norms. Consequences were related to caregiver burden, psychological and physical well-being, quality of life, and health equity. CONCLUSION: Filial piety is an intrinsic desire to support aging parents and an extrinsic desire to adhere to Chinese societal moral tenets. The proposed operational framework "Caregiving for aging CCAs in the United States" merits further study.

Endoplasmic reticulum aminopeptidase 2 regulates CD4+ T cells pyroptosis in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease with a complex pathogenesis that has not yet been fully elucidated, and T-cell pyroptosis is an important pathogenetic factor in RA. This study aimed to investigate the role of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the pyroptosis of CD4+ T cells in RA and the specific molecular mechanism. METHODS: Peripheral venous blood was collected from human subjects, and CD4+ T cells were isolated and activated to measure the level of pyroptosis and ERAP2 expression. Pyroptosis levels were assessed using immunofluorescence, flow cytometry, qRT-PCR, and Western blotting. Changes in pyroptosis levels were observed upon knockdown or overexpression of ERAP2. To detect activated Caspase-1 in tissues, chimeric mice were engrafted with human synovial tissue and reconstituted with human CD4+ T cells. CD4 + T cells were treated with GLI1 antagonists and SMO receptor agonists to detect changes in pyroptosis levels. RESULTS: CD4+ T cell levels undergoing pyroptosis were found to be elevated in the blood and synovium of RA patients. The gene and protein expression of ERAP2 were significantly higher in CD4+ T cells from RA patients. Deletion of ERAP2 suppressed pyroptosis of these cells, attenuated the activation of Caspase-1 in tissue T cells, and reduced tissue inflammatory responses. Reciprocally, overexpression of ERAP2 triggered inflammasome assembly, activated Caspase-1, and induced pyroptosis in CD4+ T cells. Mechanistically, ERAP2 inhibits the Hedgehog signaling pathway and upregulates the expression of nucleotide-binding oligomerization segment-like receptor family 3(NLRP3), cleaved Caspase-1, and Gasdermin D to promote pyroptosis in CD4+ T cells. CONCLUSIONS: Taken together, our results identify a novel mechanism by which ERAP2 regulates RA development and document the effect of the ERAP2/Hedgehog signaling axis on pyroptosis of CD4+ T cells from RA patients.

Exercise Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating Endoplasmic Reticulum Stress and Mitophagy Through M2 Acetylcholine Receptor.

Aims: Adaptive changes in the heart by exercise have been shown to reduce the risk of cardiovascular disease, and M2 Acetylcholine receptor (M2AChR), a receptor abundantly present on cardiac parasympathetic nerves, is closely associated with the development of cardiovascular disease. The present study intends to investigate whether exercise can regulate endoplasmic reticulum stress (ERS) and mitophagy through M2AChR to resist myocardial ischemia-reperfusion (I/R) injury and to elucidate its mechanism of action. Results: Exercise enhanced parasympathetic nerve function and increased myocardial M2AChR protein expression in I/R rats. In addition, it promoted the protein expression of MFN2 and inhibited the expression of Drp1, Chop, PINK1/Parkin, and PERK/eIF2α/ATF4 signaling pathways, effectively reducing mitophagy, ERS, and apoptosis. At the cellular level, 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) reduced hypoxia/reoxygenation (H/R)-induced ERS through the downregulated expression of PERK/eIF2α/ATF4 pathway proteins in H9C2 cardiomyocytes. When intervened with M2AChR inhibitors, the levels of ERS and phosphorylation levels of the PERK/eIF2α/ATF4 pathway were increased in H/R cells. Innovation and Conclusion: Exercise intervention activated the parasympathetic state in rats. It inhibited myocardial mitophagy and ERS levels, and reduced myocardial apoptosis through M2AChR, thereby resisting I/R-induced myocardial injury and improving cardiac function. Antioxid. Redox Signal. 40, 209-221.

Correlation analysis of hypertension, traditional Chinese medicine constitution, and LPL gene polymorphism in the elderly in communities in Shanghai.

BACKGROUND: Research on the genetic mechanisms of hypertension has been a hot topic in the cardiovascular field. OBJECTIVE: To study the correlation between senile hypertension and traditional Chinese medicine (TCM) constitution and lipoprotein lipase (LPL) gene polymorphism and to provide the theoretical basis for TCM prevention and treatment of hypertension. METHODS: The elderly population in communities in Shanghai (hypertensive: 264 cases; non-hypertensive: 159 cases) was taken as the research object. Essential data and information on TCM constitution were collected. The LPL gene mutation was detected using the second-generation sequencing method. Statistical analysis was performed to clarify the relationship between hypertension and senile hypertension. The correlation of TCM constitution with risk factors and LPL gene polymorphisms was studied. RESULTS: The primary TCM constitutions in the hypertension group were phlegm-dampness constitution (51.52%), yin-deficiency constitution (17.42%), balanced constitution (15.53%), and yin-deficiency (9.43%). Logistic regression analysis showed that the phlegm-dampness constitution (P< 0.05, OR = 2.587) and yin-deficiency constitution (P< 0.01, OR = 2.693) were the risk constitutions of hypertension in the elderly. A total of 37 LPL gene mutation loci (SNP: 22; new discovery: 15) were detected in the LPL gene, and the mutation rates of rs254, rs255, rs3208305, rs316, rs11570891, rs328, rs11570893, and rs13702 were relatively high, which were 26.24%, 26.24%, 16.08%, 14.66%, 13.24%, 12.06%, and 10.64%. In the phlegm-dampness group, the proportion of rs254 CC type, rs255 TT type, and rs13702 TT type in the hypertensive group (77.21%, 77.21%, and 93.38%) was higher than that in the non-hypertensive group (56.41%, 56.41%, and 82.05%), The difference was statistically significant (P< 0.05). CONCLUSION: The phlegm-dampness constitution and yin-deficiency constitution are the risk factors of hypertension in the elderly; in the phlegm-dampness population, rs254 CC type, rs255 TT type, and rs13702 TT type are the risk factors for elderly hypertension.

Effects of bone mineral density at the lateral sclerotic boundary on the femoral head collapse onset in osteonecrosis of the femoral head: A preliminary study.

BACKGROUND: In the natural course of osteonecrosis of the femoral head, sclerotic changes at the boundary of necrotic lesion gradually occur until femoral head collapse. This study aims to examine the effects of bone mineral density at the lateral boundary of necrotic lesion on a subsequent femoral head collapse. METHODS: We developed patient-specific finite element models of 9 hips with subsequent collapse and 10 hips without subsequent collapse. Cubic regions of interest were selected at both subchondral areas of the lateral boundary and the adjacent necrotic lesion. Bone mineral density values of the regions of interest were quantitatively measured, and a ratio of bone mineral density values (lateral boundary/necrotic lesion) was calculated. Stress values at the lateral boundary were also evaluated. FINDINGS: The ratio of bone mineral density values was significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0016). The median equivalent stress and shear stress were significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0071, and p = 0.0143, respectively). The ratio of bone mineral density values showed a promising value in predicting the occurrence of subsequent femoral head collapse (AUC = 0.97). INTERPRETATION: Our results indicated that bone mineral density value at the lateral boundary of necrotic lesion may be associated with the occurrence of subsequent femoral head collapse in pre-collapse stage osteonecrosis of the femoral head.

Upregulation of miR-21-5p rescues the inhibition of cardiomyocyte proliferation induced by high glucose through negative regulation of Rhob.

Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.

Evaluation of the serum tRNA-derived fragment tRF-5022B as a potential biomarker for the diagnosis of osteoarthritis.

Osteoarthritis (OA) is a degenerative disease. It is common in middle-aged and elderly people and is one of the main causes of disability. Currently, the etiology of OA is unclear, and no specific biomarkers for the diagnosis of OA have been identified. Therefore, finding a highly sensitive biomarker is essential for a proper diagnosis.TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are newly discovered classes of noncoding RNAs. tRF has been proven in several studies to have significant associations with tumor diagnosis, making it a promising biomarker in cancer research. However, the diagnostic utility of tRF in OA patients and the correlation between OA progression and trf differential expression have yet to be elaborated. The purpose of this research was to identify tRFs with differential expression in OA to assess their potential as OA biomarkers. To determine the tRF-5022B expression level in this research, real-time fluorescence quantitative PCR has been employed. Agarose gel electrophoresis, Sanger sequencing, and other investigations have been employed for evaluating tRF-5022B's molecular properties. Receiver operating characteristic curve analysis has been utilized for assessing the diagnostic effectiveness of the tRF-5022B. The findings demonstrated that tRF-5022B expression was considerably lower in OA serum. The Kellgren-Lawrence grading scale was shown to correspond with serum expression levels. The ROC curve confirmed that tRF-5022B serum expression levels might differentiate OA cases from healthy individuals and RA patients. According to the aforementioned findings, tRF-5022B may be employed as a novel biomarker for OA diagnosis due to its excellent diagnostic value.

Auxin and abscisic acid play important roles in promoting glucose metabolism of reactivated young kernels of maize (Zea mays L.).

In maize, young kernels that are less competitive and have poor sink activity often abort. Studies have indicated that such poor competitiveness depends, in part, on the regulation by auxin (IAA) and abscisic acid (ABA). However, the mechanisms for such effects remain unclear. We used pollination-blocking and hand-pollination treatments accompanied by multi-omics and physiological tests, to identify underlying mechanism by which IAA and ABA, along with sugar signaling affect kernel development. Results showed that preventing pollination of the primary ears reactivated kernels in the secondary ears and altered both sugar metabolism and hormone signaling pathways. This was accompanied by increased enzyme activities in carbon metabolism and concentrations of glucose and starch, as well as increased levels of IAA and decreased levels of ABA in the reactivated kernels. Positive and negative correlations were observed between IAA, ABA contents and cell wall invertase (CWIN) activity, and glucose contents, respectively. In vitro culture revealed that the expression of genes involved in glucose utilization was upregulated by IAA, but downregulated by ABA. IAA could promote the expression of ABA signaling genes ZmPP2C9 and ZmPP2C13 but downregulated the expression of Zmnced5, an ABA biosynthesis gene, and ZmSnRK2.10, which is involved in ABA signal transduction. However, these genes showed opposite trends when IAA transport was inhibited. To summarize, we suggest a regulatory model for how IAA inhibits ABA metabolism by promoting the smooth utilization of glucose in reactivated young kernels. Our findings highlight the importance of IAA in ABA signaling by regulating glucose production and transport in maize.

Foliar melatonin ameliorates drought-induced alterations in enzyme activities of sugar and nitrogen metabolisms in cotton leaves.

Sugar and nitrogen metabolisms help plants maintain cellular homeostasis, stress tolerance, and sustainable growth in drought conditions. Melatonin, a potent antioxidant and signaling molecule, appears to mitigate the negative impacts of drought on plants. This study aimed to investigate the potential role of foliar-applied melatonin in ameliorating drought-induced alterations in leaf sugar and nitrogen metabolisms' enzyme activities during cotton flowering and boll formation. To date, no study has examined drought-induced sugar and nitrogen metabolisms' enzyme activity changes in cotton treated with foliar melatonin. Drought levels (FC1 = 75 ± 5%, FC2 = 60 ± 5%, and FC3 = 45 ± 5%) were maintained between 3 and 35 days after flowering (DAF), and melatonin (M) concentrations (0, 25, 50, and 100 µmol L-1 ) were applied at 3 and 21 DAF in a completely randomized design. M100 concentrations at low FC levels significantly enhanced leaf sugar and N-metabolic enzyme activities, such as sucrose synthase (65.56%) and glutamine synthetase (55.24%), compared to plants not treated with melatonin; peaking between 7 and 21 DAF and declining gradually with crop growth. Moreover, the M100 concentrations at all FC levels, particularly FC3, significantly increased the relative expression of GhSusB, GhSusC, SPS1, and SPS3 genes, indicating that melatonin improves leaf sugar and N-metabolism enzymatic activities under drought stress. Therefore, applying M100 concentrations to cotton foliage under FC3 conditions during reproductive stages improves leaf water status, sugar, and N-metabolism enzyme activities, demonstrating melatonin's potent anti-stress, osmoregulatory, and growth-promoting properties in overcoming drought stress in cotton crops. Future research into the molecular mechanisms of melatonin-mediated sugar and nitrogen metabolism enzyme activities in cotton leaves may lead to biotechnological methods to improve drought resilience in cotton and other crops.

Cinnamaldehyde alleviates doxorubicin-induced cardiotoxicity by decreasing oxidative stress and ferroptosis in cardiomyocytes.

Although doxorubicin (DOX) is an efficient chemotherapeutic drug for human tumors, severe cardiotoxicity restricts its clinical use. Cinnamaldehyde (CA), a bioactive component isolated from Cinnamonum cassia, possesses potent anti-oxidative and anti-apoptotic potentials. The major aim of this study was to evaluate the protective role of CA against DOX-induced cardiotoxicity. To this end, cardiomyocyte injury models were developed using DOX-treated H9c2 cells and DOX-treated rats, respectively. Herein, we found that CA treatment increased cardiomyocyte viability and attenuated DOX-induced cardiomyocyte death in vitro. CA further protected rats against DOX-induced cardiotoxicity, as indicated by elevated creatine kinase (CK) and lactate dehydrogenase (LDH) levels, myocardium injury, and myocardial fibrosis. CA alleviated DOX-induced myocardial oxidative stress by regulating reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels. Mechanistically, CA markedly accelerated nuclear translocation of nuclear erythroid factor 2-related factor 2 (Nrf2) and increased heme oxygenase-1 (HO-1) expression. Consequently, CA decreased DOX-induced cardiomyocyte ferroptosis, while Erastin (a ferroptosis agonist) treatment destroyed the effect of CA on increasing cardiomyocyte viability. Taken together, the current results demonstrate that CA alleviates DOX-induced cardiotoxicity, providing a promising opportunity to increase the clinical application of DOX.