Mechanistic insights into phosphoactivation of SLAC1 in guard cell signaling.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.

Microglia aggravate white matter injury via C3/C3aR pathway after experimental subarachnoid hemorrhage.

The activation of glial cells is intimately associated with the pathophysiology of neuroinflammation and white matter injury (WMI) during both acute and chronic phases following subarachnoid hemorrhage (SAH). The complement C3a receptor (C3aR) has a dual role in modulating inflammation and contributes to neurodevelopment, neuroplasticity, and neurodegeneration. However, its impact on WMI in the context of SAH remains unclear. In this study, 175 male C57BL/6J mice underwent SAH through endovascular perforation. Oxyhemoglobin (oxy-Hb) was employed to simulate SAH in vitro. A suite of techniques, including immunohistochemistry, transcriptomic sequencing, and a range of molecular biotechnologies, were utilized to evaluate the activation of the C3-C3aR pathway on microglial polarization and WMI. Results revealed that post-SAH abnormal activation of microglia was accompanied by upregulation of complement C3 and C3aR. The inhibition of C3aR decreased abnormal microglial activation, attenuated neuroinflammation, and ameliorated WMI and cognitive deficits following SAH. RNA-Seq indicated that C3aR inhibition downregulated several immune and inflammatory pathways and mitigated cellular injury by reducing p53-induced death domain protein 1 (Pidd1) and Protein kinase RNA-like ER kinase (Perk) expression, two factors mainly function in sensing and responding to cellular stress and endoplasmic reticulum (ER) stress. The deleterious effects of the C3-C3aR axis in the context of SAH may be related to endoplasmic reticulum (ER) stress-dependent cellular injury and inflammasome formation. Agonists of Perk can exacerbate the cellular injury and neuroinflammation, which was attenuated by C3aR inhibition after SAH. Additionally, intranasal administration of C3a during the subacute phase of SAH was found to decrease astrocyte reactivity and alleviate cognitive deficits post-SAH. This research deepens our understanding of the complex pathophysiology of WMI following SAH and underscores the therapeutic potential of C3a treatment in promoting white matter repair and enhancing functional recovery prognosis. These insights pave the way for future clinical application of C3a-based therapies, promising significant benefits in the treatment of SAH and its related complications.

Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation.

Low-density lipoprotein receptor-related protein-1 (LRP1) is an endocytic/signaling cell-surface receptor that regulates diverse cellular functions, including cell survival, differentiation, and proliferation. LRP1 has been previously implicated in the pathogenesis of neurodegenerative disorders, but there are inconsistencies in its functions. Therefore, whether and how LRP1 maintains brain homeostasis remains to be clarified. Here, we report that astrocytic LRP1 promotes astrocyte-to-neuron mitochondria transfer by reducing lactate production and ADP-ribosylation factor 1 (ARF1) lactylation. In astrocytes, LRP1 suppressed glucose uptake, glycolysis, and lactate production, leading to reduced lactylation of ARF1. Suppression of astrocytic LRP1 reduced mitochondria transfer into damaged neurons and worsened ischemia-reperfusion injury in a mouse model of ischemic stroke. Furthermore, we examined lactate levels in human patients with stroke. Cerebrospinal fluid (CSF) lactate was elevated in stroke patients and inversely correlated with astrocytic mitochondria. These findings reveal a protective role of LRP1 in brain ischemic stroke by enabling mitochondria-mediated astrocyte-neuron crosstalk.

Thiol-ene Click Chemistry Synthesis of L-Cysteine-Grafted Graphene Oxide As a New Corrosion Inhibitor for Q235 Steel in Acidic Environment.

l-cysteine, as an eco-friendly and nontoxic corrosion inhibitor, was directly covalently linked to the carbon/carbon double bonds of the GO flakes by a thiol-ene click reaction to avoid decreasing the number of hydrophilic oxygen-containing polar functionalities. The corrosion inhibition performances of Cys-GO toward Q235 steel (QS) in diluted hydrochloric acid were studied by electrochemical methods. The corrosion was a charge transfer-controlled process, and Cys-GO manifested as a mixed-type corrosion inhibitor. The corrosion inhibition efficiency (η) for QS showed a first-increase-and-then-decrease trend with increasing Cys-GO concentrations. The optimum concentration of Cys-GO was 15 mg L-1, and the according η value was up to 90%. The Cys-GO adsorbed on the QS surface to form a protective barrier was responsible for the efficient corrosion inhibition. Langmuir adsorption isotherm model was fitted well with the experiment data, indicating a monolayer adsorption. Furthermore, the coordinate covalent bonds, π-back-donation effect, and electrostatic attraction were responsible for the Cys-GO adsorption on the QS surface.

Advanced Diffusion Tensor Imaging in White Matter Injury After Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is recognized as an especially severe stroke variant, notorious for its high mortality and long-term disability rates, in addition to a range of both immediate and enduring neurologic impacts. Over half of the SAH survivors experience varying degrees of neurologic disorders, with many enduring chronic neuropsychiatric conditions. Due to the limitations of traditional imaging techniques in depicting subtle changes within brain tissues posthemorrhage, the accurate detection and diagnosis of white matter (WM) injuries are complicated. Against this backdrop, diffusion tensor imaging (DTI) has emerged as a promising biomarker for structural imaging, renowned for its enhanced sensitivity in identifying axonal damage. This capability positions DTI as an invaluable tool for forming precise and expedient prognoses for SAH survivors. This study synthesizes an assessment of DTI for the diagnosis and prognosis of neurologic dysfunctions in patients with SAH, emphasizing the notable changes observed in DTI metrics and their association with potential pathophysiological processes. Despite challenges associated with scanning technology differences and data processing, DTI demonstrates significant clinical potential for early diagnosis of cognitive impairments following SAH and monitoring therapeutic effects. Future research requires the development of highly standardized imaging paradigms to enhance diagnostic accuracy and devise targeted therapeutic strategies for SAH patients. In sum, DTI technology not only augments our understanding of the impact of SAH but also may offer new avenues for improving patient prognoses.

Neglected Spleen Transcriptional Profile Reveals Inflammatory Disorder Conferred by Rabbit Hemorrhagic Disease Virus 2 Infection.

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the rabbit hemorrhagic disease virus (RHDV). Since the first outbreaks of type 2 RHDV (RHDV2) in April 2020 in China, the persistence of this virus in the rabbit population has caused substantial economic losses in rabbit husbandry. Previous failures in preventing RHDV2 prompted us to further investigate the immune mechanisms underlying the virus's pathogenicity, particularly concerning the spleen, a vital component of the mononuclear phagocyte system (MPS). For this, a previous RHDV2 isolate, CHN/SC2020, was utilized to challenge naive adult rabbits. Then, the splenic transcriptome was determined by RNA-Seq. This study showed that the infected adult rabbits had 3148 differentially expressed genes (DEGs), which were associated with disease, signal transduction, cellular processes, and cytokine signaling categories. Of these, 100 upregulated DEGs were involved in inflammatory factors such as IL1α, IL-6, and IL-8. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were significantly enriched in the cytokine-cytokine receptor interaction signaling pathway, which may play a vital role in CHN/SC2020 infection. At the same time, proinflammatory cytokines and chemokines were significantly increased in the spleen at the late stages of infection. These findings suggested that RHDV2 (CHN/SC2020) might induce dysregulation of the cytokine network and compromise splenic immunity against viral infection, which expanded our understanding of RHDV2 pathogenicity.

Observational retrospective clinical study on clinical features of macrolide-resistant Mycoplasma pneumoniae pneumonia in Chinese pediatric cases.

This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P < 0.001), and higher MP DNA loads than MSMP patients (P = 0.037). Based on clinical symptoms, MRMP was divided into RMPP (n = 56) and OMPP (n = 70), with RMPP demonstrating significantly increased IL-18, community-acquired respiratory distress syndrome (CARDS) toxins in nasopharyngeal aspirate, and serum CRP levels (P < 0.001; P = 0.006; P < 0.001). In conclusion, timely recognition of RMPP is crucial for enhancing prognosis. The identification of MRMP, coupled with proinflammatory cytokines such as IL-18, CARDS toxins, and CRP, emerges as promising markers with the potential to contribute significantly to diagnostic accuracy and prognosis assessment.

The threaten of typhoons to the health of residents in inland areas: a study on the vulnerability of residents to death risk during typhoon "Lekima" : In Jinan, China.

BACKGROUND: Studies had suggested increased risk of death of residents was associated with typhoons, particularly coastal regions. However, these findings ignored the impact of inland typhoons on the health of residents, especially the indirect death risk caused by typhoons. This study aimed to investigate the acute death risk of residents during inland typhoon Lekima in Jinan, further identify vulnerable populations and areas. METHODS: We selected the daily death from 11 to 27th August 2019 in Jinan as case period, and conducted a time-stratified case-crossover design to match the contemporaneous data from 2016 to 2018 as control period. We used the generalized linear Poisson models to estimate the related effects of death risk during typhoon Lekima and lag days. RESULTS: During the Lekima typhoon month, there were 3,366 deaths occurred in Jinan. Compared to unexposed periods, the acute death risk of non-accidental diseases (especially circulatory diseases), female and the older adults increased significantly in the second week after the typhoon. The maximum significant effect of circulatory disease deaths, female and older adult deaths were appeared on lag9, lag9, and lag13 respectively. And the typhoon-associated RR were 1.19 (95%CI:1.05,1.34), 1.28 (95%CI:1.08,1.52), and 1.22 (95%CI:1.06,1.42) respectively. The acute death risk of residents living in TQ and CQ increased significantly on Lag2 and Lag6 after the typhoon, respectively, while those living in LX, LC, HY, JY, and SH occurred from Lag 8 to Lag 13 after the typhoon. LC lasted the longest days. CONCLUSIONS: Typhoons would increase the vulnerability of residents living in Jinan which mainly occurred from the seventh day after the typhoon. Residents suffering from non-accidental diseases (circulatory diseases), female and the older adults were more vulnerable. The vulnerability of TQ and CQ occurred on Lag2 and Lag6 after typhoon Lekima, respectively, and the other areas except ZQ and PY occurred from Lag 8 to Lag 13. LC lasted the longest duration. Our findings emphasized the importance of the emergency response, which would help policymakers to identify vulnerable regions and populations accurately during typhoons and formulate the emergency response plan.

QiDiTangShen granules alleviates diabetic nephropathy podocyte injury: A network pharmacology study and experimental validation in vivo and vitro.

Background: QiDiTangShen granules (QDTS), a traditional Chinese medicine (TCM) compound prescription, have remarkable efficacy in diabetic nephropathy (DN) patients, and their pharmacological mechanism needs further exploration. Methods: According to the active ingredients and targets of the QDTS in the TCMSP database, the network pharmacology of QDTS was investigated. The potential active ingredients were chosen based on the oral bioavailability and the drug similarity index. At the same time, targets for DN-related disease were obtained from GeneCards, OMIM, PharmGKB, TTD, and DrugBank. The TCM-component-target network and the protein-protein interaction (PPI) network were constructed with the Cytoscape and STRING platforms, respectively, and then the core targets of DN were selected with CytoNCA. GO and KEGG enrichment analysis using R software. Molecular docking to identify the core targets of QDTS for DN. In vivo, db/db mice were treated as DN models, and the urine microalbuminuria, the pathological changes in the kidney and the protein expression levels of p-PI3K, p-Akt, JUN, nephrin and synaptopodin were detected by immunohistochemistry, immunofluorescence method and Western blotting. After QDTS was used in vitro, the protein expression of mouse podocyte clone-5 (MPC5) cells was detected by immunohistochemistry, immunofluorescence and Western blot. Results: Through network pharmacology analysis, 153 potential targets for DN in QDTS were identified, 19 of which were significant. The KEGG enrichment analysis indicated that QDTS might have therapeutic effects on IL-17, TNF, AGE-RAGE, PI3K-Akt, HIF-1, and EGFR through interfering with Akt1 and JUN. The main active ingredients in QDTS are quercetin, ß-sitosterol, stigmasterol and kaempferol. Both in vivo and in vitro studies showed that QDTS could decrease the urine microalbuminuria and renal pathology of db/db mice, and alleviate podocyte injuries through the PI3K/Akt signaling pathway. Conclusion: Through network pharmacology, in vivo and in vitro experiments, QDTS has been shown to improve the urine microalbuminuria and renal pathology in DN, and to reduce podocyte damage via the PI3K/Akt pathway.

Modulating Smart Mechanoluminescent Phosphors for Multistimuli Responsive Optical Wood.

Mechanoluminescence is a smart light-emitting phenomenon in which applied mechanical energy is directly converted into photon emissions. In particular, mechanoluminescent materials have shown considerable potential for applications in the fields of energy and sensing. This study thoroughly investigates the mechanoluminescence and long afterglow properties of singly doped and codoped Sr2 MgSi2 O7 (SMSO) with varying concentrations of Eu2+ and Dy3+ ions. Subsequently, a comprehensive analysis of its multimode luminescence properties, including photoluminescence, mechanoluminescence, long afterglow, and X-ray-induced luminescence, is conducted. In addition, the density of states mapping is acquired through first-principles calculations, confirming that the enhanced mechanoluminescence properties of SMSO primarily stem from the deep trap introduced by Dy3+ . In contrast to traditional mixing with Polydimethylsiloxane, in this study, the powders are incorporated into optically transparent wood to produce a multiresponse with mechanoluminescence, long afterglow, and X-ray-excited luminescence. This structure is achieved by pretreating natural wood, eliminating lignin, and subsequently modifying the wood to overall modification using various smart phosphors and epoxy resin composites. After natural drying, a multifunctional composite wood structure with diverse luminescence properties is obtained. Owing to its environmental friendliness, sustainability, self-power, and cost-effectiveness, this smart mechanoluminescence wood is anticipated to find extensive applications in construction materials and energy-efficient displays.

Different doses of methimazole treatment of children and adolescents with graves' disease: a clinical study based on 161 cases of outpatients.

OBJECTIVE: This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD. METHODS: One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3-0.5 mg/kg/day, n = 78), Group B (moderate, 0.6-0.8 mg/kg/day, n = 37), Group C (severe, 0.6-0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed. RESULTS: After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P < 0.01). Remission was achieved in 38 patients (23.6%). CONCLUSIONS: Lower doses of MMI (0.3-0.5 mg/kg/day) are suitable for mild GD, and higher doses of MMI (0.6-0.8 mg/kg/day) are advisable for moderate or severe GD. Much higher doses of MMI (0.8-1.0 mg/kg/day) are harmful for initial use in children and adolescents with GD patients.

Identification of endoplasmic reticulum stress-related biomarkers of diabetes nephropathy based on bioinformatics and machine learning.

Backgrounds: Diabetes nephropathy (DN) is a growing public health concern worldwide. Renal dysfunction impairment in DN is intimately linked to ER stress and its related signaling pathways. Nonetheless, the underlying mechanism and biomarkers for this function of ER stress in the DN remain unknown. Methods: Microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database, and ER stress-related genes (ERSRGs) were downloaded from the MSigDB and GeneCards database. We identified hub ERSRGs for DN progression by intersecting ERSRGs with differentially expressed genes and significant genes in WGCNA, followed by a functional analysis. After analyzing hub ERSRGs with three machine learning techniques and taking the intersection, we did external validation as well as developed a DN diagnostic model based on the characteristic genes. Immune infiltration was performed using CIBERSORT. Moreover, patients with DN were then categorized using a consensus clustering approach. Eventually, the candidate ERSRGs-specific small-molecule compounds were defined by CMap. Results: Several biological pathways driving pathological injury of DN and disordered levels of immune infiltration were revealed in the DN microarray datasets and strongly related to deregulated ERSRGs by bioinformatics multi-chip integration. Moreover, CDKN1B, EGR1, FKBP5, GDF15, and MARCKS were identified as ER stress signature genes associated with DN by machine learning algorithms, demonstrating their potential as DN biomarkers. Conclusions: Our research sheds fresh light on the function of ER stress in DN pathophysiology and the development of early diagnostic and ER stress-related treatment targets in patients with DN.

Corrigendum: High follicle-stimulating hormone level associated with risk of rheumatoid arthritis and disease activity.

[This corrects the article DOI: 10.3389/fendo.2022.862849.].

Predictors of female sexual problems in Shanxi, China: a population-based cross-sectional epidemiologic survey.

Background: Large studies on female sexual function have been conducted globally. Nonetheless, whether the state of female sexual function in China is significantly different from that in the rest of the world is largely unknown. Aim: In this study, we aimed to investigate the associated risk factors for sexual problems in women in Shanxi, China, by conducting a population-based cross-sectional epidemiological survey. Methods: Using the Chinese version of the Female Sexual Function Index (CV-FSFI), we surveyed women aged 20-70 years to diagnose the sexual problems. We used multiple linear regression models to estimate the risk factors for sexual problems. Outcomes: We used the CV-FSFI for investigating the female sexual function. Results: Our results included 6720 women, of whom 1205 were the sexually inactive and 5515 were sexually active. The mean FSFI score for sexually active women was 25.38 ± 4.20 (99% CI 25.27-25.49). Negative numerical coefficients were found for model predictors of age (B = -0.134, P < 0.001), postmenopausal status (B = -2.250, P < 0.001), chronic diseases (B = -0.512, P < 0.001), and gynecologic diseases (B = -0.767, P < 0.001). In contrast, positive numerical coefficients were found for education (B = 0.466, P < 0.001) and cesarean section (B = 0.312, P = 0.009). Clinical Implications: It is important to pay attention to the sexual health of women and explore the factors influencing the sexual problems of women in China. Strengths and Limitations: The present study is to our knowledge the first to evaluate the sexual function of women in Shanxi, China. Answers to questions asked in the CV-FSFI survey may be somewhat subjective, and thus additional tools and documentation are probably needed for accurate assessment. Conclusion: Similarly to other worldwide studies, our study found that increasing age, postmenopausal status, chronic diseases, and gynecological diseases were risk factors for sexual problems, whereas high education levels and cesarean section childbirth were protective factors for sexual problems.

Corrigendum: Neutrophil extracellular traps in autoimmune diseases: Analysis of the knowledge map.

[This corrects the article DOI: 10.3389/fimmu.2023.1095421.].

Neutrophil extracellular traps in autoimmune diseases: Analysis of the knowledge map.

Introduction: Recent studies have shown much progress in the research of exosomes in AIDs. However, there is no bibliometric analysis in this research field. This study aimed to provide a bibliometrics review of the knowledge structure and research hotspots of neutrophil extracellular traps (NETs) in autoimmune diseases (AIDs). Methods: Articles relevant to NETs in AIDs from 2010 to 2022 were retrieved through the Web of Science Core Collection (WoSCC) database. This bibliometric analysis was performed by VOSview, CiteSpace, and Scimago Graphica. Results: A total of 289 papers analyzed in this research were from 493 organizations in 47 countries by 1537 authors. They were published in 133 journals and cited 20,180 citations from 2,465 journals. The number of annual publications in this field is growing steadily and rapidly, with the United States, China and Germany leading the research effort. Frontiers in Immunology and Journal of Immunology have significantly impacted research in this field. Kaplan, Mariana J, from the National Institutes of Health (The United States), has the most published articles, and Brinkmann, v, from Max Planck Institute for Infection Biology (Germany), is the most co-cited author. Systemic lupus erythematosus and rheumatoid arthritis are the leading topics in this field. The trend of clinical application in the future is the development of new therapies by controlling NETs in the progression of AIDs. Conclusions: Our study summarized the research trends and developments of NETs in AIDs in recent years and would provide a reference for scholars in this field.

Strontium and simvastatin dual loaded hydroxyapatite microsphere reinforced poly(ε-caprolactone) scaffolds promote vascularized bone regeneration.

The promotion of vascular network formation in the early stages of implantation is considered a prerequisite for successful functional bone regeneration. In this study, we successfully constructed 3D printed scaffolds with strong mechanical strength and a controllable pore structure that can sustainably release strontium (Sr) ions and simvastatin (SIM) for up to 28 days by incorporation of Sr2+ and SIM-loaded hydroxyapatite microspheres (MHA) into a poly(ε-caprolactone) (PCL) matrix. In vitro cell experiments showed that Sr-doped scaffolds were beneficial to the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs), an appropriate dose of SIM was beneficial to cell proliferation and angiogenesis, and a high dose of SIM was cytotoxic. The Sr- and SIM-dual-loaded scaffolds with an appropriate dose significantly induced osteogenic differentiation of BMSCs and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and promoted vascular network and functional bone formation in vivo. Ribose nucleic acid (RNA) sequencing analysis suggested that the mechanism of promotion of vascularized bone regeneration by fabricated scaffolds is that dual-loaded Sr2+ and SIM can upregulate osteogenic and vasculogenic-related genes and downregulate osteoclast-related genes, which is beneficial for vascular and new bone regeneration. The 3D printed composite scaffolds loaded with high-stability and low-cost inorganic Sr2+ ions and SIM small-molecule drugs hold great promise in the field of promoting vascularized bone regeneration.

Flocking dynamics and pattern motion for the Cucker-Smale system with distributed delays.

In this paper, a new class of Cucker-Smale systems with distributed delays are developed from the measurement perspective. By combining dissipative differential inequalities with a continuity argument, some new sufficient criteria for the flocking dynamics of the proposed model with general communication rate, especially the non-normalized rate, are established. In order to achieve the prescribed pattern motion, the driving force term is incorporated into the delayed collective system. Lastly, some examples and simulations are provided to illustrate the validity of the theoretical results.