Chemical inertness conversion of carbon fraction in coal gangue via N-doping for efficient benzo(a)pyrene degradation.

Efficient degradation of organic pollutants in complex media via advanced oxidation processes (AOPs) is still critical and challenging. Herein, nitrogen (N)-doped coal gangue (CG) catalysts (N-CG) with economic competitiveness and environmental friendliness were successfully synthesized to activate peroxymonosulfate (PMS), exhibiting ultrafast degradation performance toward benzo(a)pyrene (BaP) with 100.00 % and 93.21 % in contaminated solution and soil under optimized condition, respectively. In addition, 0.4 N-CG possessed excellent reusability toward BaP degradation with over 80.00 % after five cycles. However, BaP removal efficiency was significantly affected by some co-existing anions (HCO3- and SO42-) and humic acid (HA) in solution and soil, as well as inhibited under alkaline conditions, especially pH ≥ 9. According to the characterizations, N-doping could promote the generation of pyridinic N and graphitic N in N-CG via high-temperature calcination, which was conducive to produce hydroxyl radical (•OH), sulfate radical (SO4•-), superoxide radical (•O2-) and single oxygen (1O2). In 0.4 N-CG/PMS system, 1O2 and •O2- were proved to be the predominant reactive oxygen species (ROSs) in BaP degradation, as well as •OH and SO4•- made certain contributions. To sum up, this work provided a promising strategy for synthesis of CG-based catalysts by chemical inertness conversion of carbon fracture via N-doping for PMS activation and opened a novel perspective for environmental remediation of hydrophobic and hydrophilic contaminants pollution.

Macrophage senescence in health and diseases.

Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. Persistent senescence of macrophages may lead to maladaptation, immune dysfunction, and finally the development of age-related diseases, infections, autoimmune diseases, and malignancies. However, it is a ubiquitous, multi-factorial, and dynamic complex phenomenon that also plays roles in remodeled processes, including wound repair and embryogenesis. In this review, we summarize some general molecular changes and several specific biomarkers during macrophage senescence, which may bring new sight to recognize senescent macrophages in different conditions. Also, we take an in-depth look at the functional changes in senescent macrophages, including metabolism, autophagy, polarization, phagocytosis, antigen presentation, and infiltration or recruitment. Furthermore, some degenerations and diseases associated with senescent macrophages as well as the mechanisms or relevant genetic regulations of senescent macrophages are integrated, not only emphasizing the possibility of regulating macrophage senescence to benefit age-associated diseases but also has an implication on the finding of potential targets or drugs clinically.

Single-cell RNA sequencing reveals cell-cell communication and potential biomarker in sepsis and septic shock patients.

BACKGROUND: Sepsis is a disease characterized by infection-induced multiorgan dysfunction, which can progress to septic shock if not promptly treated. Early identification of sepsis is crucial for its treatment. However, there are currently limited specific biomarkers for sepsis or septic shock. This study aims to identify potential biomarkers for sepsis and septic shock. METHODS: We analyzed single-cell transcriptomic data of peripheral blood mononuclear cells (PBMCs) from healthy individuals, sepsis and septic shock patients, identified differences in gene expression and cell-cell communication between different cell types during disease progression. Moreover, our analyses were further validated with flow cytometry and bulk RNA-seq data. RESULTS: Our study elucidates the alterations in cellular proportions and cell-cell communication among healthy controls, sepsis, and septic shock patients. We identified a specific augmentation in the Resistin signaling within sepsis monocytes, mediated via RETN-CAP1 ligand-receptor pairs. Additionally, we observed enhanced IL16 signaling within monocytes from septic shock patients, mediated through IL16-CD4 ligand-receptor pairs. Subsequently, we confirmed our findings by validating the increase in CAP-1+ monocytes in sepsis and IL16+ monocytes in septic shock in mouse models. And a significant upregulation of CAP-1 and IL16 was also observed in the bulk RNA-seq data from patients with sepsis and septic shock. Furthermore, we identified four distinct clusters of CD14+ monocytes, highlighting the heterogeneity of monocytes in the progress of sepsis. CONCLUSIONS: In summary, our work demonstrates changes in cell-cell communication of healthy controls, sepsis and septic shock, confirming that the molecules CAP-1 and IL16 on monocytes may serve as potential diagnostic markers for sepsis and septic shock, respectively. These findings provide new insights for early diagnosis and stratified treatment of the disease.

Sandwich-like CuNPs@AgNPs@PSB SERS substrates for sensitive detection of R6G and Forchlorfenuron.

The development of a highly sensitive, synthetically simple and economical SERS substrate is technically very important. A fast, economical, sensitive and reproducible CuNPs@AgNPs@ Porous silicon Bragg reflector (PSB) SERS substrate was prepared by electrochemical etching and in situ reduction method. The developed CuNPs@AgNPs@PSB has a large specific surface area and abundant "hot spot" region, which makes the SERS performance excellent. Meanwhile, the successful synthesis of CuNPs@AgNPs can not only modulate the plasmon resonance properties of nanoparticles, but also effectively prolong the time stability of Cu nanoparticles. The basic performance of the substrate was evaluated using rhodamine 6G (R6G). (Detection limit reached 10-15 M, R2 = 0.9882, RSD = 5.3 %) The detection limit of Forchlorfenuron was 10 µg/L. The standard curve with a regression coefficient of 0.979 was established in the low concentration range of 10 µg/L -100 µg/L. This indicates that the prepared substrates can accomplish the detection of pesticide residues in the low concentration range. The prepared high-performance and high-sensitivity SERS substrate have a very promising application in detection technology.

Relationship between benefit finding and volunteer motivation among nursing students: The mediating role of perceived social support.

BACKGROUND: Volunteer motivation is essential to advancing community service, education, and career development of nursing students. However, few studies have been conducted on nursing students' volunteer motivation. OBJECTIVES: To investigate the relationship between social support benefit finding and volunteer motivation among nursing students and the role of social support in these relationships. METHOD: This study adopted a descriptive cross-sectional design. A total of 2166 nursing students were recruited from eighteen medical schools in Henan Province, China. Participants completed a sociodemographic questionnaire, the Social Support Scale, the Benefit Finding Scale, and the Volunteer Motivation Scale online between March and May 2022. Correlation and mediation analyses were used to explore the mediating role of social support in the relationships among social support, benefit finding, and volunteer motivation. RESULTS: A total of 2166 valid questionnaires were collected in this study. Benefit finding positively affected volunteer motivation (ß = 0.422, p < 0.01), and perceived social support positively affected volunteer motivation (ß = 0.407, p < 0.01). Perceived social support played a mediating role between benefit finding and volunteer motivation (ß = 0.112, 95 % confidence interval 0.076, 0.148). CONCLUSIONS: The study provides evidence on the mechanisms of action between benefit finding and volunteer motivation among nursing students. Professionals in schools and voluntary organizations should prioritize guiding nursing students to explore the motivations behind volunteering while also fostering a supportive environment for student volunteers in nursing.

Biomarker-Driven DNA-Functionalized Colloidal Programmed Simultaneous Assembly and Disassembly in Cells.

Complex structures and devices, both natural and artificial, can often undergo assembly and disassembly. Assembly and disassembly allow multiple stimuli to initiate, for example, the assembly and disassembly of primary cilia under the control of E3 ubiquitin ligases and deubiquitinases. Although biology relies on such schemes, they are rarely available in materials science. Here, we demonstrate a DNA-functionalized colloidal Au response to endogenous biomarkers to trigger simultaneous assembly and disassembly techniques. Colloidal Au is initially inert because the starting DNA strands are paired and prehybridized. TK1 mRNA competes to bind one of the paired strands and release its complement. The released complement binds to the next colloidal Au to initiate assembly, and APE1 can shear the colloidal Au assembly binding site to initiate disassembly. Our strategy provides temporal and spatial logic control during colloidal Au assembly and disassembly, and this simultaneous assembly and disassembly process can be used for sequential detection and cellular imaging of two biomarkers, effectively reducing signal false-positive results and shortening detection time. This work highlights biomarker-controlled colloidal Au simultaneous assembly and disassembly in ways that are simple and versatile, with the potential to enrich the application scope of DNA nanotechnology and provide an idea for the application of precision medicine testing.

[Analysis of clinical research features and outcome indexes of traditional Chinese medicine intervention in septic kidney injury].

This study aims to systematically review the clinical features and outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) intervention in septic kidney injury and provide a reference for optimizing clinical study design and building the core outcome set(COS) of TCM treatment of septic kidney injury. Computer searches were conducted on PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed to find published RCT of TCM intervention in septic kidney injury in the past five years, extract the basic characteristics, intervention measures, outcome indicators, and other data of included studies, and conduct descriptive analysis. 53 RCTs were included, and the sample size was mostly concentrated in 60-80 cases, with abdominal infection being the most common(15 articles, 83.3%) and the TCM syndrome of blood stasis being the most frequent(9 articles, 50.0%). The frequency of intervention methods from high to low were TCM decoction(28 articles, 52.8%), Chinese patent medicine(22 articles, 41.5%), and combined TCM therapy(3 articles, 7.5%); the intervention time of the trial was more than 7 d(34 articles, 69.4%). The risk of bias in included studies was unclear. A total of 84 outcome indicators were involved, which were divided into 9 fields, including 63 physical and chemical tests(305 times, 72.2%), 4 kinds of disease degree(48 times, 11.6%), 4 kinds of clinical effective rate(15 times, 3.6%), 1 kind of quality of life(1 time, 0.2%), 2 kinds of economic evaluation(14 times, 3.3%), 1 kind of TCM disease(9 times, 2.1%), 2 kinds of long-term prognosis(16 times, 3.8%), 2 kinds of safety events(6 times, 1.4%), and 5 other indicators(8 times, 0.7%). The cumulative frequency was 422 times, among which the outcome indicators with higher frequency were inflammatory factors(42 articles, 79.2%) and markers of renal function and kidney injury(40 articles, 75.5%). Only 1(1.9%) of the included articles mentioned primary and secondary outcome indicators, and 6 articles(11.3%) mentioned safety events, 13 articles(24.5%) mentioned economic assessment. The RCT quality of TCM intervention in septic renal injury was generally low, and the reference standards for sepsis, kidney injury, and TCM syndrome diagnosis were not uniform. There are some problems in outcome indicators, such as unclear distinction between primary and secondary indicators, neglect of endpoint indicators, lack of application of TCM characteristic indicators, and insufficient attention to safety events and economic assessment. It is suggested that the quality of clinical research methodology should be improved in the future, and the COS should be constructed to provide high-level evidence-based evidence for TCM intervention in septic kidney injury.

NET-related gene signature for predicting AML prognosis.

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan-Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs-CFTR, ENO1, PARVB, DDIT4, MPO, LDLR-were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p < 0.001), which was validated in two external datasets (GSE71014 and GSE106291). The 6-NRG signature and corresponding nomograms exhibit superior predictive accuracy, offering insights for pre-immune response evaluation and guiding future immuno-oncology treatments and drug selection for AML patients.

In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice.

Despite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.

XBP1s activates METTL3/METTL14 for ER-phagy and paclitaxel sensitivity regulation in breast cancer.

Cancer cells employ the unfolded protein response (UPR) or induce autophagy, especially selective removal of certain ER domains via reticulophagy (termed ER-phagy), to mitigate endoplasmic reticulum (ER) stress for ER homeostasis when encountering microenvironmental stress. N6-methyladenosine (m6A) is one of the most abundant epitranscriptional modifications and plays important roles in various biological processes. However, the molecular mechanism of m6A modification in the ER stress response is poorly understood. In this study, we first found that ER stress could dramatically elevate m6A methylation levels through XBP1s-dependent transcriptional upregulation of METTL3/METTL14 in breast cancer (BC) cells. Further MeRIP sequencing and relevant validation results confirmed that ER stress caused m6A methylation enrichment on target genes for ER-phagy. Mechanistically, METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and p62, thus enhancing their mRNA stability. Of note, we further confirmed that the chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase m6A methylation for ER-phagy. Furthermore, the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice. Thus, our data built a novel bridge on the crosstalk between ER stress, m6A methylation and ER-phagy. Most importantly, our work provides novel evidence of METTL3 and METTL14 as potential therapeutic targets for PTX sensitization in breast cancer.

FAM83B regulates mitochondrial metabolism and anti-apoptotic activity in pulmonary adenocarcinoma.

Chemotherapy is an effective therapeutic modality; nevertheless, a significant proportion of patients diagnosed with lung adenocarcinoma (LUAD) demonstrate resistance to chemotherapy. Therefore, it is crucial to understand the potential regulatory mechanisms to develop novel treatment strategies. This study aims to understand how increased FAM83B expression impacts mitochondrial activity, cell apoptosis, and chemotherapy effectiveness in LUAD. Multiple assays, such as CCK8, wound healing, EdU, and transwell assays, were employed to confirm the augmented chemotherapy resistance, heightened cell proliferation, migration, and invasion caused by FAM83B overexpression in LUAD cells. Furthermore, MIMP, MTG, and ATP assays were utilized to quantify changes in mitochondrial metabolism. In vitro functional assays were performed to evaluate the influence of FAM83B overexpression on the malignant progression and resistance mechanisms to chemotherapy in LUAD. In the context of this study, it was determined that LUAD patients with increased FAM83B expression had shorter survival times, and tissue samples with FAM83B overexpression were more prone to metastasis compared to primary samples. As a result, FAM83B is identified as an adverse prognostic marker. The mechanistic analysis demonstrated that FAM83B impedes the translocation of calbindin 2 (CALB2) from the cytoplasm to the mitochondria, resulting in the inhibition of apoptosis and the promotion of mitochondrial activity. Consequently, this ultimately confers resistance to chemotherapy in LUAD. Furthermore, the administration of metformin, which blocks mitochondrial oxidative phosphorylation (OXPHOS), can restore sensitivity to drug resistance in LUAD. Taken together, these findings provide substantial evidence supporting the notion that FAM83B enhances chemotherapy resistance in LUAD through the upregulation of mitochondrial metabolism and the inhibition of apoptosis.

Review on mechanism and remediation strategies of dissolved oxygen abnormal in surface water.

Dissolved oxygen (DO) is an important index to evaluate the quality of surface water environments. In recent years, anomalies in DO level have emerged as a major contributor to the decline of surface water quality. These anomalies have triggered several ecological and environmental challenges such as biodiversity loss, the degradation of water environmental quality, intensification of eutrophication, and an exacerbation of the greenhouse effect. Understanding the mechanisms underlying DO anomalies and devising targeted remediation strategies holds paramount importance in the scientific pursuit of water pollution control and aquatic ecosystem restoration. We explored and summarized the fluctuations and abnormal mechanism of DO concentration in surface water, focusing on factors like oxygen solubility, reoxygenation rates, and oxygen consumption by water bodies. We compiled a range of approaches for addressing DO anomalies, including pollution source management, artificial oxygenation, and the reconfiguration of aquatic ecosystems. Ultimately, we underscored the emerging significance of monitoring and regulating DO level in surface waters. Future research in this realm should encompass the establishment of distinct quality standards for surface water, the development of a comprehensive real-time spatial monitoring system for DO levels across watersheds, and the formulation of standardized procedures and technical norms.

Insights into the Mechanism of Selective Removal of Heavy Metal Ions by the Pulsed/Direct Current Electrochemical Method.

Heavy metal pollution treatment in industrial wastewater is crucial for protecting biological and environmental safety. However, the highly efficient and selective removal of heavy metal ions from multiple cations in wastewater is a significant challenge. This work proposed a pulse electrochemical method with a low-/high-voltage periodic appearance to selectively recover heavy metal ions from complex wastewater. It exhibited a higher recovery efficiency for heavy metal ions (100% for Pb2+ and Cd2+, >98% for Mn2+) than other alkali and alkaline earth metal ions (Na+, Ca2+, and Mg2+ were kept below 3.6, 1.3, and 2.6%, respectively) in the multicomponent solution. The energy consumption was only 34-77% of that of the direct current electrodeposition method. The results of characterization and experiment unveil the mechanism that the low-/high-voltage periodic appearance can significantly suppress the water-splitting reaction and break the mass-transfer limitation between heavy metal ions and electrodes. In addition, the plant study demonstrates the feasibility of treated wastewater for agricultural use, further proving the high sustainability of the method. Therefore, it provides new insights into the selective recovery of heavy metals from industrial wastewater.

RNF126-mediated ubiquitination of FSP1 affects its subcellular localization and ferroptosis.

Medulloblastoma (MB) is a prevalent malignant brain tumor among children, which can be classified into four primary molecular subgroups. Group 3 MB (G3-MB) is known to be highly aggressive and associated with a poor prognosis, necessitating the development of novel and effective therapeutic interventions. Ferroptosis, a regulated form of cell death induced by lipid peroxidation, has been identified as a natural tumor suppression mechanism in various cancers. Nevertheless, the potential role of ferroptosis in the treatment of G3-MB remains unexplored. In this study, we demonstrate that RNF126 acts as an anti-ferroptotic gene by interacting with ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) and ubiquitinating FSP1 at the 4KR-2 sites. Additionally, the deletion of RNF126 reduces the subcellular localization of FSP1 in the plasma membrane, resulting in an increase in the CoQ/CoQH2 ratio in G3-MB. The RNF126-FSP1-CoQ10 pathway plays a pivotal role in suppressing phospholipid peroxidation and ferroptosis both in vivo and in vitro. Clinically, RNF126 exhibited elevated expression in G3-MB and its overexpression was significantly associated with reduced patient survival. Our findings indicate that RNF126 regulates G3-MB sensitivity to ferroptosis by ubiquitinating FSP1, which provides new evidence for the potential G3-MB therapy.

Warming enhances the negative effects of shrub removal on phosphorus mineralization potential.

Shrubs have developed various mechanisms for soil phosphorus utilization. Shrub encroachment caused by climate warming alters organic phosphorus mineralization capability by promoting available phosphorus absorption and mediating root exudates. However, few studies have explored how warming regulates the effects of dominant shrubs on soil organic phosphorus mineralization capability. We provide insights into warming, dominant shrub removal, and their interactive effects on the soil organic phosphorus mineralization potential in the Qinghai-Tibetan Plateau. Real-time polymerase chain reaction was used to quantify the soil microbial phosphatase genes (phoC and phoD), which can characterize the soil organic phosphate mineralization potential. We found that warming had no significant effect on the soil organic phosphate-mineralized components (total phosphate, organic phosphate, and available phosphate), genes (phoC and phoD), or enzymes (acid and alkaline phosphatases). Shrub removal negatively influenced the organic phosphate-mineralized components and genes. It significantly decreased soil organic phosphate mineralization gene copy numbers only under warming conditions. Warming increased fungal richness and buffered the effects of shrub removal on bacterial richness and gene copy numbers. However, the change in the microbial community was not the main factor affecting organic phosphate mineralization. We found only phoC copy number had significant correlation to AP. Structural equation modelling revealed that shrub removal and the interaction between warming and shrub removal had a negative direct effect on phoC copy numbers. We concluded that warming increases the negative effect of shrub removal on phosphorus mineralization potential, providing a theoretical basis for shrub encroachment on soil phosphate mineralization under warming conditions.

Preliminary application of real-time shear wave elastography to evaluate endometrial receptivity and predict pregnancy outcome.

BACKGROUND: Endometrial receptivity is crucial for the establishment of a healthy pregnancy outcome. Previous research on endometrial receptivity primarily examined endometrial thickness, endometrial echo types, and endometrial blood supply. OBJECTIVE: To explore the differences in the elastic modulus of the endometrium in women with various pregnancy outcomes by real-time shear wave elastography (SWE) and to investigate its application value in evaluation of endometrial receptivity. METHODS: A total of 205 pregnant women who were admitted at Wenzhou People's Hospital between January 2021 and December 2022 were selected. Three-dimensional transvaginal sonography and real-time shear wave elastography were performed in the proliferative phase and receptive phase of the endometrium, and the average elastic modulus of the endometrium in the two phases was obtained and compared. According to whether the pregnancy was successful or not, the participants were divided into the pregnancy group (n= 72) and non-pregnancy group (n= 133), and the differences in intimal thickness, 3D blood flow parameters, and average elastic modulus of intima were compared between the two groups. RESULTS: The average elastic modulus of the endometrium in the proliferative phase and receptive phase was (23.92 ± 2.31) kPa and (11.82 ± 2.24) kPa, respectively, and the difference was statistically significant P< 0.05. The average elastic modulus of the endometrium in the pregnancy group and non-pregnancy group was (9.97 ± 1.08) kPa and (12.82 ± 2.06) kPa, respectively, and the difference was statistically significant P< 0.05. The area under the curve of predicting pregnancy by the average elastic modulus of the endometrium in the receptive phase was 0.888 (0.841∼0.934), with corresponding P value < 0.05. The critical value was 11.15, with a corresponding sensitivity of 81.7% and specificity of 78.2%. CONCLUSION: Real-time shear wave elastography can quantitatively evaluate endometrial elasticity, indirectly reflect the endometrial phase, and provide a new diagnostic concept for evaluating endometrial receptivity and predicting pregnancy outcome in infertile patients.

Genetic screen identified PRMT5 as a neuroprotection target against cerebral ischemia.

Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remain largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. PRMT5 was identified as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. PRMT5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that PRMT5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, mice were treated with middle cerebral artery occlusion with the PRMT5 inhibitor EPZ015666 and found that PRMT5 inhibition sustains protection against neuronal death in vivo. Together, these findings revealed a novel epigenetic mechanism of PRMT5 in cerebral ischemia and uncovered a potential target for neuroprotection.

Estrogen receptor GPR30 in the anterior cingulate cortex mediates exacerbated neuropathic pain in ovariectomized mice.

Menopausal women experience neuropathic pain 63% more frequently than men do, which may attribute to the estrogen withdrawal. However, the underlying mechanisms remain unclear. Here, the role of estrogen receptors (ERs) in ovariectomized (OVX) female mice following chronic constriction injury (CCI) was investigated. With 17ß-estradiol (E2) supplemented, aggravated mechanical allodynia in OVX mice could be significantly alleviated, particularly after intra-anterior cingulate cortex (ACC) E2 delivery. Pharmacological interventions further demonstrated that the agonist of G-protein-coupled estrogen receptor 30 (GPR30), rather than ERα or ERß in the ACC, exhibited the similar analgesic effect as E2, whereas antagonist of GPR30 exacerbated allodynia. Furthermore, OVX surgery reduced GPR30 expression in the ACC, which could be restored with estrogen supplementation. Selective downregulation of GPR30 in the ACC of naïve female mice induces mechanical allodynia, whereas GPR30 overexpression in the ACC remarkedly alleviated OVX-exacerbated allodynia. Collectively, estrogen withdrawal could downregulate the ACC GPR30 expression, resulting in exacerbated neuropathic pain. Our findings highlight the importance of GPR30 in the ACC in aggravated neuropathic pain during menopause, and offer a potential therapeutic candidate for neuropathic pain management in menopausal women.

Effect of electroacupuncture on global cerebral ischemia-reperfusion injury in rats: A urine proteome analysis.

BACKGROUND: This study aimed to investigate dynamic urinary proteome changes of electroacupuncture (EP) on cerebral ischemia-reperfusion (CI/R) injured rats and to explore the therapeutic biological mechanisms of EP. METHODS: First, changed urinary proteins were found in EP stimulation in healthy rats. Then, we used a CI/R injury rat model induced by Pulsinelli's four-vessel occlusion (4-VO) method to explore the function of EP on urinary proteome in CI/R injury. Urine samples were collected for proteome analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis. RESULTS: In total, 384 proteins were identified, among which 47 proteins (23 upregulated, 24 downregulated) were differentially expressed with 0.6-log FC and p < .05. Gene ontology analysis revealed that the cell redox homeostasis, acute-phase response, response to lipopolysaccharide, and cellular response to glucocorticoid stimulus were significantly enriched. The partially biologically connected differential proteins were found by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in the EP group. With the CI/R rat model, 80 proteins (27 upregulated, 53 downregulated) were significantly changed in the CI/R rats compared to the controls. Among these differentially expressed proteins (DEPs), 23 proteins (17 upregulated, six downregulated) showed significant changes after EP treatment (0.6-log FC change, p < .05). The main related biological processes were aging, immune response, acute-phase response, liver regeneration, protein catabolic process, and response to oxidative stress. Many metabolic pathways were enriched by KEGG analysis. CONCLUSION: Our results indicate that the EP could alleviate cerebral damage induced by ischemia-reperfusion through an anti-inflammatory and metabolism regulation mechanism. The urinary proteome might reflect the pathophysiological changes in EP pretreatment in the treatment and prevention of CI/R injury.

The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients' orthodontic treatment.