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.

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.

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.

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.

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.

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.

Systematic review of the nuclear factor erythroid 2-related factor 2 (NRF2) system in human chronic kidney disease: alterations, interventions and relation to morbidity.

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NRF2) and its effectors NAD(P)H:quinoneoxidoreductase 1 (NQO1) and haem oxygenase 1 (HO-1) are of interest in kidney disease. We therefore reviewed studies about their status in patients with chronic kidney disease (CKD). METHODS: We undertook systematic searches of PubMed and Excerpta Medica dataBASE (EMBASE) databases. Alterations of NRF2, NQO1 and HO-1 in CKD, their responses to interventions and their relation to clinically relevant parameters were reported. RESULTS: We identified 1373 articles, of which 32 studies met the inclusion criteria. NRF2 levels were decreased in the majority of analyses of CKD patients. Half of the analyses showed a similar or increased NQO1 level versus control, whereas in half of the analyses NQO1 was decreased. Most of the studies reported either an increased or similar HO-1 level in CKD patients compared with controls. For patients with CKD Stages 1-4, studies reported positive correlations to markers of kidney disease severity. Also, positive associations of NQO1/HO-1 levels to inflammation and comorbidities were reported. One-third of the studies showed discordant changes between gene expression and protein level of NRF2 system components. Two-thirds of intervention studies (50% dietary, such as using resistant starch) reported an increase of NRF2, NQO1 or HO-1. CONCLUSIONS: In patients with CKD, NRF2 expression was downregulated, while NQO1 and HO-1 showed varying alterations related to inflammation, comorbidities and severity of kidney damage. Interventions that increased NRF2 system components were described, but their effectiveness and clinical relevance require further clinical studies of high quality. Research on gene expression together with protein analyses is indispensable to understand NRF2 system alterations in CKD.

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.

T4-like Phages Reveal the Potential Role of Viruses in Soil Organic Matter Mineralization.

Viruses are the most abundant biological entities in the world, but their ecological functions in soil are virtually unknown. We hypothesized that greater abundance of T4-like phages will increase bacterial death and thereby suppress soil organic carbon (SOC) mineralization. A range of phage and bacterial abundances were established in sterilized soil by reinoculation with 10-3 and 10-6 dilutions of suspensions of unsterilized soil. The total and viable 16S rRNA gene abundance (a universal marker for bacteria) was measured by qPCR to determine bacterial abundance, with propidium monoazide (PMA) preapplication to eliminate DNA from non-viable cells. Abundance of the g23 marker gene was used to quantify T4-like phages. A close negative correlation between g23 abundance and viable 16S rRNA gene abundance was observed. High abundance of g23 led to lower viable ratios for bacteria, which suggested that phages drove microbial necromass production. The CO2 efflux from soil increased with bacterial abundance but decreased with higher abundance of T4-like phages. Elimination of extracellular DNA by PMA strengthened the relationship between CO2 efflux and bacterial abundance, suggesting that SOC mineralization by bacteria is strongly reduced by the T4-like phages. A random forest model revealed that abundance of T4-like phages and the abundance ratio of T4-like phages to bacteria are better predictors of SOC mineralization (measured as CO2 efflux) than bacterial abundance. Our study provides experimental evidence of phages' role in organic matter turnover in soil: they can retard SOC decomposition but accelerate bacterial turnover.

Flooding and straw returning regulates the partitioning of soil phosphorus fractions and phoD-harboring bacterial community in paddy soils.

Flooding and straw returning are effective agricultural practices in promoting phosphorus (P) availability in paddy soils. However, little is known about the effects of these practices and their interaction on the soil P pools and functional microbes responsible for soil P mobilization. Our 4-year paddy field experiment aimed to analyze the responses of soil P fractions and phoD-harboring bacterial communities in a double-rice cropping system to intermittent flooding (IF) and continuous flooding (CF), in plots with (+ S) and without (-S) straw return. Compared to IF, CF significantly increased soil citrate-P and marginally decreased the HCl-P fractions, suggesting that the stable inorganic P pools are transferred to labile inorganic P at lower redox potentials. Compared to the -S treatments, + S treatments significantly increased the labile organic fractions (enzyme-P). Correspondingly, a decreased soil total organic P concentration was observed in + S treatment. Additionally, + S treatment significantly increased the activity of acid phosphomonoesterase and alkaline phosphomonoesterase and the abundance of phoD-harboring bacteria. These results indicated that straw promoted organic P minimization to release orthophosphate. The diversity of the phoD-harboring bacteria and complexity of the co-occurrence network decreased under the CF + S treatment; however, all keystone species of the phoD-harboring bacteria were retained in this oxygen-deficient environment. This study highlights that irrigation regimes mediate the processes of inorganic P mobilization, while straw returns regulate the processes of organic P mineralization. Additionally, flooding could be a more effective agricultural practice than straw returning to promote soil P availability in paddy soils. KEY POINTS: •Soil P pools and phoD-harboring bacteria communities were assessed. •Straw return mainly affects the mineralization of organic P. •Continuous flooding mainly affects the mobilization of inorganic P.

Mitochondrial Pyruvate Carriers Prevent Cadmium Toxicity by Sustaining the TCA Cycle and Glutathione Synthesis.

Cadmium (Cd) is a major heavy metal pollutant, and Cd toxicity is a serious cause of abiotic stress in the environment. Plants protect themselves against Cd stress through a variety of pathways. In a recent study, we found that mitochondrial pyruvate carriers (MPCs) are involved in Cd tolerance in Arabidopsis (Arabidopsis thaliana). Following the identification of MPCs in yeast (Saccharomyces cerevisiae) in 2012, most studies have focused on the function of MPCs in animals, as a possible approach to reduce the risk of cancer developing. The results of this study show that AtMPC protein complexes are required for Cd tolerance and prevention of Cd accumulation in Arabidopsis. AtMPC complexes are composed of two elements, AtMPC1 and AtMPC2 (AtNRGA1 or AtMPC3). When the formation of AtMPCs was interrupted by the loss of AtMPC1, glutamate could supplement the synthesis of acetyl-coenzyme A and sustain the TCA cycle. With the up-regulation of glutathione synthesis following exposure to Cd stress, the supplementary pathway could not efficiently drive the tricarboxylic acid cycle without AtMPC. The ATP content decreased concomitantly with the deletion of tricarboxylic acid activity, which led to Cd accumulation in Arabidopsis. More importantly, ScMPCs were also required for Cd tolerance in yeast. Our results suggest that the mechanism of Cd tolerance may be similar in other species.

Enhanced nitrogen deposition over China.

China is experiencing intense air pollution caused in large part by anthropogenic emissions of reactive nitrogen. These emissions result in the deposition of atmospheric nitrogen (N) in terrestrial and aquatic ecosystems, with implications for human and ecosystem health, greenhouse gas balances and biological diversity. However, information on the magnitude and environmental impact of N deposition in China is limited. Here we use nationwide data sets on bulk N deposition, plant foliar N and crop N uptake (from long-term unfertilized soils) to evaluate N deposition dynamics and their effect on ecosystems across China between 1980 and 2010. We find that the average annual bulk deposition of N increased by approximately 8 kilograms of nitrogen per hectare (P < 0.001) between the 1980s (13.2 kilograms of nitrogen per hectare) and the 2000s (21.1 kilograms of nitrogen per hectare). Nitrogen deposition rates in the industrialized and agriculturally intensified regions of China are as high as the peak levels of deposition in northwestern Europe in the 1980s, before the introduction of mitigation measures. Nitrogen from ammonium (NH4(+)) is the dominant form of N in bulk deposition, but the rate of increase is largest for deposition of N from nitrate (NO3(-)), in agreement with decreased ratios of NH3 to NOx emissions since 1980. We also find that the impact of N deposition on Chinese ecosystems includes significantly increased plant foliar N concentrations in natural and semi-natural (that is, non-agricultural) ecosystems and increased crop N uptake from long-term-unfertilized croplands. China and other economies are facing a continuing challenge to reduce emissions of reactive nitrogen, N deposition and their negative effects on human health and the environment.

ZmOST1 mediates abscisic acid regulation of guard cell ion channels and drought stress responses.

The phytohormone abscisic acid (ABA) is an important mediator in the drought response, participating in, among other processes, stomatal movements. In Arabidopsis thaliana, the serine/threonine protein kinase, OST1, regulates this response, but the function of its maize homolog has yet to be established. Here, we isolated ZmOST1 and show that its encoded protein indeed acts to regulate guard cell movement. ZmOST1 was ubiquitously expressed throughout the plant, being highly expressed in guard cells, and inducible both by exogenous ABA and water stress. Transient expression of a ZmOST1-GFP fusion protein, in maize mesophyll protoplasts, indicated its subcellular localization in the cytoplasm and nucleus. A Zmost1 loss-of-function mutant exhibited reduced sensitivity to ABA-activated slow anion channels in maize guard cells, and reduced drought tolerance. Constitutive expression of ZmOST1, in an A. thaliana ost1-1 mutant rescued the phenotype with respect both to the sensitivity of guard cell slow anion currents to ABA treatment and stomatal closure. Our findings indicate a positive regulatory role for ZmOST1 in guard cell ABA signaling and drought response in maize plants.

Mitochondrial pyruvate carrier 1 mediates abscisic acid-regulated stomatal closure and the drought response by affecting cellular pyruvate content in Arabidopsis thaliana.

BACKGROUND: Stomata are micropores surrounded by pairs of guard cells, and their opening is finely controlled to balance water vapor loss as transpiration and CO2 absorption for photosynthesis. The regulatory signaling network for stomatal movement is complicated, and increasing numbers of new genes have been shown to be involved in this process. Our previous study indicated that a member of the plant putative mitochondrial pyruvate carrier (MPC) family, NRGA1, is a negative regulator of guard cell abscisic acid (ABA) signaling. In this study, we identified novel physiological roles of pyruvate and MPC1, another member of the MPC family, in the regulation of stomatal closure in Arabidopsis. RESULTS: Loss-of-function mutants of MPC1 (mpc1) were hypersensitive to ABA-induced stomatal closure and ABA-activated guard cell slow-type anion currents, and showed a reduced rate of water loss upon drought treatment compared with wild-type plants. In contrast, plants overexpressing MPC1 showed a hyposensitive ABA response and increased sensitivity to drought stress. In addition, mpc1 mutants accumulated more pyruvate after drought or ABA treatment. The increased pyruvate content also induced stomatal closure and activated the slow-type anion channels of guard cells, and this process was dependent on the function of RbohD/F NADPH oxidases and reactive oxygen species concentrations in guard cells. CONCLUSIONS: Our findings revealed the essential roles of MPC1 and pyruvate in stomatal movement and plant drought resistance.

THI1, a Thiamine Thiazole Synthase, Interacts with Ca2+-Dependent Protein Kinase CPK33 and Modulates the S-Type Anion Channels and Stomatal Closure in Arabidopsis.

Thiamine is required for both plant growth and development. Here, the involvement of a thiamine thiazole synthase, THI1, has been demonstrated in both guard cell abscisic acid (ABA) signaling and the drought response in Arabidopsis (Arabidopsis thaliana). THI1 overexpressors proved to be more sensitive to ABA than the wild type with respect to both the activation of guard cell slow type anion channels and stomatal closure; this effectively reduced the rate of water loss from the plant and thereby enhanced its level of drought tolerance. A yeast two-hybrid strategy was used to screen a cDNA library from epidermal strips of leaves for THI1 regulatory factors, and identified CPK33, a Ca(2+)-dependent protein kinase, as interactor with THI1 in a plasma membrane-delimited manner. Loss-of-function cpk33 mutants were hypersensitive to ABA activation of slow type anion channels and ABA-induced stomatal closure, while the CPK33 overexpression lines showed opposite phenotypes. CPK33 kinase activity was essential for ABA-induced stomatal closure. Consistent with their contrasting regulatory role over stomatal closure, THI1 suppressed CPK33 kinase activity in vitro. Together, our data reveal a novel regulatory role of thiamine thiazole synthase to kinase activity in guard cell signaling.

Evidence for the Importance of Atmospheric Nitrogen Deposition to Eutrophic Lake Dianchi, China.

Elevated atmospheric nitrogen (N) deposition has significantly influenced aquatic ecosystems, especially with regard to their N budgets and phytoplankton growth potentials. Compared to a considerable number of studies on oligotrophic lakes and oceanic waters, little evidence for the importance of N deposition has been generated for eutrophic lakes, even though emphasis has been placed on reducing external N inputs to control eutrophication in these lakes. Our high-resolution observations of atmospheric depositions and riverine inputs of biologically reactive N species into eutrophic Lake Dianchi (the sixth largest freshwater lake in China) shed new light onto the contribution of N deposition to total N loads. Annual N deposition accounted for 15.7% to 16.6% of total N loads under variable precipitation conditions, 2-fold higher than previous estimates (7.6%) for the Lake Dianchi. The proportion of N deposition to total N loads further increased to 27-48% in May and June when toxic blooms of the ubiquitous non-N2 fixing cyanobacteria Microcystis spp. are initiated and proliferate. Our observations reveal that reduced N (59%) contributes a greater amount than oxidized N to total N deposition, reaching 56-83% from late spring to summer. Progress toward mitigating eutrophication in Lake Dianchi and other bloom-impacted eutrophic lakes will be difficult without reductions in ammonia emissions and subsequent N deposition.

Contribution of atmospheric nitrogen deposition to diffuse pollution in a typical hilly red soil catchment in southern China.

Atmospheric nitrogen (N) deposition is currently high and meanwhile diffuse N pollution is also serious in China. The correlation between N deposition and riverine N export and the contribution of N deposition to riverine N export were investigated in a typical hilly red soil catchment in southern China over a two-year period. N deposition was as high as 26.1 to 55.8kgN/(ha·yr) across different land uses in the studied catchment, while the riverine N exports ranged from 7.2 to 9.6kgN/(ha·yr) in the forest sub-catchment and 27.4 to 30.3kgN/(ha·yr) in the agricultural sub-catchment. The correlations between both wet N deposition and riverine N export and precipitation were highly positive, and so were the correlations between NH4(+)-N or NO3(-)-N wet deposition and riverine NH4(+)-N or NO3(-)-N exports except for NH4(+)-N in the agricultural sub-catchment, indicating that N deposition contributed to riverine N export. The monthly export coefficients of atmospheric deposited N from land to river in the forest sub-catchment (with a mean of 14%) presented a significant positive correlation with precipitation, while the monthly contributions of atmospheric deposition to riverine N export (with a mean of 18.7% in the agricultural sub-catchment and a mean of 21.0% in the whole catchment) were significantly and negatively correlated with precipitation. The relatively high contribution of N deposition to diffuse N pollution in the catchment suggests that efforts should be done to control anthropogenic reactive N emissions to the atmosphere in hilly red soil regions in southern China.

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.

One-Step Synthesis of Chitosan Hydrogel as Electrochemical Chemosensor for Hydrogen Sulfide Detection in Pregnancy-Induced Hypertension Syndrome Serum Sample.

Oxidative stress caused by pregnancy-induced hypertension syndrome significantly affects the health of pregnant women. Hydrogen sulfide is a typical gaseous signal molecule against oxidative stress, and it is of profound significance to develop a detection method. In this study, a stimuli-responsive hydrogel was constructed based on the coordination and bonding principle of metal ions and chitosan (CS) to realize the quantitative detection of hydrogen sulfide (H2S). The chain of CS contains a large number of amino groups and hydroxyl groups, which can form the coordination structure with Cu2+, triggering CS to form a stable hydrogel. The hydrogel can be formed within about 5 s, which has the characteristics of rapid preparation. In the presence of target H2S, the cross-linking agent Cu2+ in the hydrogel can compete out, resulting in the collapse of the hydrogel and the release of the electrochemical probe. By detecting the concentration of the released electrochemical probe, the quantitative detection of H2S can be achieved. The prepared hydrogel has a good linear relationship with the concentration of H2S from 1 µM to 60 µm. At the same time, the hydrogel has good specificity and stability, and it can be applied to the detection of H2S in serum samples.

Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3.

Extracellular matrix (ECM) stiffening is a typical characteristic of cartilage aging, which is a quintessential feature of knee osteoarthritis (KOA). However, little is known about how ECM stiffening affects chondrocytes and other molecules downstream. This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane (PDMS) substrates. It demonstrated that epigenetic Parkin regulation by histone deacetylase 3 (HDAC3) represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology. We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro, while the stiffness ECM downregulated HDAC3, prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis (OA) in mice. Contrarily, intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice. The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals, promoted the Parkin acetylation and hyperactivated mitophagy, and damaged chondrocyte health. These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM, suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.