Dysregulated microRNAs and long non-coding RNAs associated with extracellular matrix stiffness.

Extracellular matrix (ECM) stiffness regulates development and homeostasis in vivo and affects both physiological and pathological processes. A variety of studies have demonstrated that mRNAs, such as Piezo1, integrin ß1, and Yes-associated protein (YAP)/tafazzin (TAZ), can sense the mechanical signals induced by ECM stiffness and transmit them from the extracellular space into the cytoplasm. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been reported to play important roles in various cellular processes. Therefore, the interactions between ncRNAs and ECM stiffness, as well as the underlying molecular mechanisms, have become intriguing. In this review, we summarize recent findings on miRNAs and lncRNAs that interact with ECM stiffness. Several miRNAs and lncRNAs are involved in the progression of liver cancer, breast cancer, osteosarcoma, and cardiovascular diseases under the regulation of ECM stiffness. Through these ncRNAs, cellular behaviors including cell differentiation, proliferation, adhesion, migration, invasion, and epithelial-mesenchymal transition (EMT) are affected by ECM stiffness. We also integrate the ncRNA signaling pathways associated with ECM stiffness, in which typical signaling pathways like integrin ß1/TGFß1, phosphatidylinositol-3 kinase (PI3K)/AKT, and EMT are involved. Although our understanding of the relationships between ncRNAs and ECM stiffness is still limited, further investigations may provide new insights for disease treatment. ECM-associated ncRNAs may serve as disease biomarkers or be targeted by drugs.

Size-Switchable Ru Nanoaggregates for Enhancing Phototherapy: Hyaluronidase-Triggered Disassembly to Alleviate Deep Tumor Hypoxia.

Hypoxia is a critical factor for restricting photodynamic therapy (PDT) of tumor, and it becomes increasingly severe with increasing tissue depth. Thus, the relief of deep tumor hypoxia is extremely important to improve the PDT efficacy. Herein, tumor microenvironment (TME)-responsive size-switchable hyaluronic acid-hybridized Ru nanoaggregates (HA@Ru NAs) were developed via screening reaction temperature to alleviate deep tumor hypoxia for improving the tumor-specific PDT by the artful integration multiple bioactivated chemical reactions in situ and receptor-mediated targeting (RMT). In this nanosystem, Ru NPs not only enabled HA@Ru NAs to have near infrared (NIR)-mediated photothermal/photodynamic functions, but also could catalyze endogenous H2O2 to produce O2 in situ. More importantly, hyaluronidase (HAase) overexpressed in the TME could trigger disassembly of HA@Ru NAs via the hydrolysis of HA, offering the smart size switch capability from 60 to 15 nm for enhancing tumor penetration. Moreover, the RMT characteristics of HA ensured that HA@Ru NAs could specially enter CD44-overexpressed tumor cells, enhancing tumor-specific precision of phototherapy. Taken together these distinguishing characteristics, smart HA@Ru NAs successfully realized the relief of deep tumor hypoxia to improve the tumor-specific PDT.

Combining a machine-learning derived 4-lncRNA signature with AFP and TNM stages in predicting early recurrence of hepatocellular carcinoma.

BACKGROUND: Near 70% of hepatocellular carcinoma (HCC) recurrence is early recurrence within 2-year post surgery. Long non-coding RNAs (lncRNAs) are intensively involved in HCC progression and serve as biomarkers for HCC prognosis. The aim of this study is to construct a lncRNA-based signature for predicting HCC early recurrence. METHODS: Data of RNA expression and associated clinical information were accessed from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Recurrence associated differentially expressed lncRNAs (DELncs) were determined by three DEG methods and two survival analyses methods. DELncs involved in the signature were selected by three machine learning methods and multivariate Cox analysis. Additionally, the signature was validated in a cohort of HCC patients from an external source. In order to gain insight into the biological functions of this signature, gene sets enrichment analyses, immune infiltration analyses, as well as immune and drug therapy prediction analyses were conducted. RESULTS: A 4-lncRNA signature consisting of AC108463.1, AF131217.1, CMB9-22P13.1, TMCC1-AS1 was constructed. Patients in the high-risk group showed significantly higher early recurrence rate compared to those in the low-risk group. Combination of the signature, AFP and TNM further improved the early HCC recurrence predictive performance. Several molecular pathways and gene sets associated with HCC pathogenesis are enriched in the high-risk group. Antitumor immune cells, such as activated B cell, type 1 T helper cell, natural killer cell and effective memory CD8 T cell are enriched in patients with low-risk HCCs. HCC patients in the low- and high-risk group had differential sensitivities to various antitumor drugs. Finally, predictive performance of this signature was validated in an external cohort of patients with HCC. CONCLUSION: Combined with TNM and AFP, the 4-lncRNA signature presents excellent predictability of HCC early recurrence.

A Method to Evaluate Spectral Analysis by Spectroscopy.

Visible and near infrared spectroscopy has been widely used to develop a method for rapidly determining organic carbon in soils or sediments (SOC). Most of these studies concentrated on how to establish a good spectral model but ignored how to evaluate the method, such as the use of detection range (max and min), resolution and error for SOC spectral analysis. Here, we proposed a method to evaluate the spectral analysis of SOC. Using 96 sediments sampled in the Yellow Sea and Bohai Sea, China, we established three spectral models of SOC after collecting their spectral reflectance by Agilent Cary 5000, ASD FieldSpec 4 and Ocean Optics QEPro, respectively. For both the calibration set and validation set in each spectrometer, the predicted SOC concentrations followed a distribution curve (function), in which the x-axis was the SOC concentrations. Using these curves, we developed these four technical parameters. The detection ranges were the SOC concentrations where the curve was near to or crossing with the lateral axis, while the detection resolution was the average difference between the two neighboring SOC concentrations. The detection errors were the differences between the predicted SOC and the measured SOC. Results showed that these technical parameters were better in the bench-top spectrometer (Cary 5000) than those in the portable spectrometers when analyzing the same samples. For the portable spectrometers, QEPro had a broader detection range and more consistent detection error than FieldSpec 4, suggesting that the low-cost QEPro performed as well as the high-cost FieldSpec 4. This study provides a good example for evaluating spectral analysis by spectroscopy, which can support the development of the spectral method.

Analysis and Model Comparison of Carbon and Nitrogen Concentrations in Sediments of the Yellow Sea and Bohai Sea by Visible-Near Infrared Spectroscopy.

Visible-near infrared spectroscopy is considered an effective method for rapidly determining total carbon (TC) and total nitrogen (TN) in terrestrial soils. However, reports on measuring them by VNIR in marine sediments are limited. This article provides an analysis and spectral model comparison of TC and TN in marine sediments using VNIR. The best TC and TN spectral models were established when using the least square support vector machine algorithm with a wavelength, which extended from 226 nm to 975 nm. The prediction results of TN have a high coefficient of determination and residual predictive deviation, providing accurate quantitative predictions. The TC spectral model comes with a disadvantage might due to its usual high concentrations of organic carbon. Characteristic wavelength extraction may lead to the loss of identification information for the characteristics of TC and TN, and full wavelength spectrum contains more information helps more to the quantification.

Electrochemical degradation of DCF by boron-doped diamond anode: degradation mechanism, pathways and influencing factors.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely detected in wastewater and surface water, indicating that the removal of NSAIDs by wastewater treatment plants was not efficient. Electrochemical advanced oxidation technology is considered to be an effective process. This study presents an investigation of the kinetics, mechanism, and influencing factors of diclofenac (DCF) degradation by an electrochemical process with boron-doped diamond anodes. Relative operating parameters and water quality parameters are examined. It appears that the degradation follows the pseudo-first-order degradation kinetics. DCF degradation was accelerated with the increase of pH from 6 to 10. The degradation was promoted by the addition of electrolyte concentrations and current density. Humic acid and bicarbonate significantly inhibited the degradation, whereas chloride accelerated it. According to the quenching tests, hydroxyl radicals (•OH) and sulfate radicals contributed 76.5% and 6.5%, respectively, to the degradation. Sodium sulfate remains a more effective electrolyte, compared to sodium nitrate and sodium phosphate, suggesting the quenching effect of nitrate and phosphate on •OH. Major DCF transformation products were identified. According to the degradation products detected by liquid chromatography-mass spectrometry, hydroxylation and decarboxylation are the main pathways of DCF degradation; while dechlorination, chlorination, and nitro substitution are also included in this electrochemical degradation process.

TPH2 gene polymorphisms and bipolar disorder: A meta-analysis.

BACKGROUND: Disturbance of the serotonergic system contributes to the etiology of bipolar disorder (BD). Tryptophan hydroxylase-2 (TPH2) is an important rate-limiting enzyme in the synthetic pathway for brain serotonin and has been suggested to play a role in BD. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of all studies to date investigating the association studies between TPH2 and BD published before Aug 2014. All studies were abstracted from PubMed, Embase, HuGNet, and China National Knowledge Infrastructure (CNKI). Manuscripts and the supplementary documents of published genome-wide association studies in the field were also included. Effect sizes of independent loci that have been studied in more than three articles were synthesized using fixed and random effects models. RESULTS: Eight eligible studies addressed association between 63 TPH2 gene single nucleotide polymorphisms (SNPs) with BD, after linkage disequilibrium analysis, 12 independent SNPs were identified. Finally, three SNPs (rs4760820, rs11178998, and rs7954758) were found associated with BD using fixed effects models, and rs4760820 and rs11178998 were still associated with BD even with the more conservative random effects models. CONCLUSIONS: rs4760820 and rs11178998 were identified to have strong genetic association with BD in present study though confirmation will require larger sample sizes and in additional populations.

Beck Hopelessness Scale: Psychometric Properties Among Rural Chinese Suicide Attempters and Non-Attempters.

The authors recruited 401 suicide attempters from general hospitals and 409 matched non-attempters to evaluate the psychometric properties of the Beck Hopelessness Scale (BHS) in rural China. All participants completed the BHS, Center for Epidemiologic Studies Depression Scale (CES-D), and Trait Anxiety Inventory (TAI). Suicide attempters had higher BHS scores than non-attempters. Cronbach's alpha coefficients were satisfactory and BHS scores significantly correlated to CES-D and TAI scores. Confirmatory factor analysis supported a four-factor model for suicide attempters and a five-factor model for non-attempters. The BHS is satisfactory in assessing hopelessness among suicide attempters in rural China.

Effects of antipsychotics on bone mineral density and prolactin levels in patients with schizophrenia: a 12-month prospective study.

OBJECTIVE: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia. METHODS: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole) was prescribed for 12 months as appropriate. BMD and PRL were tested before and after treatment. Same measures were conducted in 90 matched healthy controls. RESULTS: Baseline BMD of postero-anterior L1-L4 range from 1.04 ± 0.17 to 1.42 ± 1.23, and there was no significant difference between the patients group and healthy control group. However, post-treatment BMD values in patients (ranging from 1.02 ± 0.15 to 1.23 ± 0.10) were significantly lower than that in healthy controls (ranging from 1.15 ± 0.12 to 1.42 ± 1.36). The BMD values after conventional antipsychotics were significantly lower than that after atypical antipsychotics. The PRL level after conventional antipsychotics (53.05 ± 30.25 ng/ml) was significantly higher than that after atypical antipsychotics (32.81 ± 17.42 ng/ml). Conditioned relevance analysis revealed significant negative correlations between the PRL level and the BMD values after conventional antipsychotics. CONCLUSION: The increase of PRL might be an important risk factor leading to a high prevalence of osteoporosis in patients with schizophrenia on long-term conventional antipsychotic medication.

Portable hydrogel kit driven by bimetallic carbon dots nanozyme for H2O2-self-supplying dual-modal monitoring of atmospheric CH3SH.

Due to the typical volatility of gaseous pollutant methyl mercaptan (CH3SH), the development of a facile, reliable, and accurate onsite environmental surveillance of highly toxic CH3SH faces many challenges, but it is critical to environmental atmosphere assessment and safeguarding public health. Here, we prepared a novel bimetallic carbon dots (Fe&Cu@CDs) nanozyme with high peroxidase-mimicking activity to design a portable hydrogel kit for onsite visual H2O2-self-supplying enzymatic cascade catalytic colorimetric and photothermal signal synergistic amplification dual-modal monitoring of CH3SH in atmospheric environment. Assisted by alcohol oxidase (AOX), CH3SH could be specifically converted into H2O2 for oxidizing chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by Fe&Cu@CDs to produce dark blue ox-TMB with absorption at 652 nm and photothermal characters. Consequently, a CH3SH concentration-dependent change both in naked-eye color and photothermal effect-triggered temperature were observed. By hybridizing AOX-assisted Fe&Cu@CDs + TMB with agarose, a H2O2-self-supplying colorimetric and photothermal signal synergistic amplification sensory hydrogel kit integrated with Color Picker APP-installed smartphone and 660 nm laser-equipped handheld thermal imager for CH3SH was proposed with acceptable results in atmospheric environment around wastepile (e.g., solid waste and food waste piles), which exhibited great potentials to further develop commercial onsite monitoring platforms in warning-early abnormal atmospheric CH3SH for safeguarding environmental health.

Fish-mussel-algae-bacteria model remedied eutrophication pollution: Application in Dongxiang district reservoir.

Eutrophication pollution has become an important ecological problem in China. Biological treatment is a common means to repair eutrophication pollution. Therefore, based on the biological manipulation technology, we put forward a fishing scheme for the Xiaoxiangshan and Shizishan reservoirs in Dongxiang District, which have been in a serious eutrophication pollution level for a long time, that is, to improve the quality and control water by operating fish, mussel, algae, and bacteria. The monitoring results in the middle stage of treatment showed that the structure of phytoplankton changed, and the degree of eutrophication pollution improved. In the later stage of treatment, the plankton diversity and richness of the two reservoirs increased significantly, the density and biomass of Cyanobacteria decreased significantly, and the degree of eutrophication pollution decreased to mesotrophic type. Overall, our research puts forward new ideas for the prevention and control of water eutrophication pollution and provides a reference for other kinds of water body treatment.

Intelligent onsite dual-modal assay based on oxidase-like fluorescence carbon dots-driven competitive effect for ethyl carbamate detection.

Intelligent onsite accurate monitoring ethyl carbamate (EC, a group 2 A carcinogen) in environment is of great significance to safeguard environmental health and public safety. Herein, we reported an intelligent dual-modal point-of-care (POC) assay based on the bimetallic Mn and Ce co-doped oxidase-like fluorescence carbon dots (Ce&MnCDs) nanozyme-driven competitive effect. In brief, the oxidase-like activity of Ce&MnCDs was inhibited by thiocholine (TCh, originating from the hydrolysis of acetylcholinesterase (AChE) to acetylthiocholine (ATCh)), preventing the oxidation of o-phenylenediamine (OPD) to 2,3-diaminophenothiazine (DAP). However, with the aid of Br2 + NaOH, EC inactivated AChE to prevent TCh generation for re-launching the oxidase-like activity of Ce&MnCDs to trigger the oxidation of OPD into DAP, thereby outputting an EC concentration-dependent ratiometric fluorescence and colorimetric readouts by employing Ce&MnCDs and OPD as the optical signal reporters. Interestingly, these dual-modal optical signals could be transduced into the gray values that was linearly proportional to the residual levels of EC on a smartphone-based portable platform, with a detection limit down to 1.66 µg/mL, qualifying the requirements of analysis of EC residues in real samples. This opened up a new avenue for onsite assessment of the risk of residues of EC, safeguarding environmental health and public safety.

Acidity-responsive polyphenol-coordinated nanovaccines for improving tumor immunotherapy via bidirectional reshaping of the immunosuppressive microenvironment and controllable release of antigens.

The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI). Therefore, it is necessary to develop a new strategy for TIME reshaping and controllable release of antigens to improve the NBI efficacy. Herein, an acidity-responsive Schiff base-conjugated polyphenol-coordinated nanovaccine was constructed for the first time to realize bidirectional TIME reshaping and controllable release of antigens for activating T cells. In particular, an acidity-responsive tannic acid-ovalbumin (TA-OVA) nanoconjugate was prepared via a Schiff base reaction. FeIII was coordinated with TA-OVA to produce a FeIII-TA-OVA nanosystem, and 1-methyltryptophan (1-MT) as an indoleamine 2,3-dioxygenase inhibitor was loaded to form a polyphenol-coordinated nanovaccine. The coordination between FeIII and TA could cause photothermal ablation of primary tumors, and the acidity-triggered Schiff base dissociation of TA-OVA could controllably release OVA to realize lysosome escape, initiating the body's immune response. More importantly, oxidative stress generated by a tumor-specific Fenton reaction of Fe ions could promote the polarization of tumor-associated macrophages from the M2 to M1 phenotype, resulting in the upregulation of cytotoxic T cells and helper T cells. Meanwhile, 1-MT could downregulate immunosuppressive regulatory T cells. Overall, such skillful combination of bidirectional TIME reshaping and controllable antigen release into one coordination nanosystem could effectively enhance the NBI efficacy of tumors.

Vaginal microbiota are associated with in vitro fertilization during female infertility.

The vaginal microbiome plays an essential role in the reproductive health of human females. As infertility increases worldwide, understanding the roles that the vaginal microbiome may have in infertility and in vitro fertilization (IVF) treatment outcomes is critical. To determine the vaginal microbiome composition of 1411 individuals (1255 undergoing embryo transplantation) and their associations with reproductive outcomes, clinical and biochemical features are measured, and vaginal samples are 16S rRNA sequenced. Our results suggest that both too high and too low abundance of Lactobacillus is not beneficial for pregnancy; a moderate abundance is more beneficial. A moderate abundance of Lactobacillus crispatus and Lactobacillus iners (~80%) (with a pregnancy rate of I-B: 54.35% and III-B: 57.73%) is found beneficial for pregnancy outcomes compared with a higher abundance (>90%) of Lactobacillus (I-A: 44.81% and III-A: 51.06%, respectively). The community state type (CST) IV-B (contains a high to moderate relative abundance of Gardnerella vaginalis) shows a similar pregnant ratio (48.09%) with I-A and III-A, and the pregnant women in this CST have a higher abundance of Lactobacillus species. Metagenome analysis of 71 samples shows that nonpregnant women are detected with more antibiotic-resistance genes, and Proteobacteria and Firmicutes are the main hosts. The inherent differences within and between women in different infertility groups suggest that vaginal microbes might be used to detect infertility and potentially improve IVF outcomes.

Soil carbon content prediction using multi-source data feature fusion of deep learning based on spectral and hyperspectral images.

Visible near-infrared reflectance spectroscopy (VNIR) and hyperspectral images (HSI) have their respective advantages in soil carbon content prediction, and the effective fusion of VNIR and HSI is of great significance for improving the prediction accuracy. But the contribution difference analysis of multiple features in the multi-source data is inadequate, and there is a lack of in-depth research on the contribution difference analysis of artificial feature and deep learning feature. In order to solve the problem, soil carbon content prediction methods based on VNIR and HSI multi-source data feature fusion are proposed. The multi-source data fusion network under the attention mechanism and the multi-source data fusion network with artificial feature are designed. For the multi-source data fusion network based on the attention mechanism, the information are fused through the attention mechanism according to the contribution difference of each feature. For the other network, artificial feature are introduced to fuse multi-source data. The results show that multi-source data fusion network based on the attention mechanism can improve the prediction accuracy of soil carbon content, and multi-source data fusion network combined with artificial feature has better prediction effect. Compared with two single-source data from the VNIR and HSI, the relative percent deviation of Neilu, Aoshan Bay and Jiaozhou Bay based on multi-source data fusion network combined with artificial feature are increased by 56.81% and 149.18%, 24.28% and 43.96%, 31.16% and 28.73% respectively. This study can effectively solve the problem of the deep fusion of multiple features in the soil carbon content prediction by VNIR and HSI, so as to improve the accuracy and stability of soil carbon content prediction, promote the application and development of soil carbon content prediction in spectral and hyperspectral image, and provide technical support for the study of carbon cycle and the carbon sink.

In Situ Polymerization of Aniline Derivative in Vivo for NIR-II Phototheranostics of Tumor.

Natural biopolymers can be controllably in situ synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of in situ biosynthesis of functional polymers in vivo will be an important way to obtain materials for meeting biological requirements. Herein, in situ biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (H2O2) overexpressed in TME to produce hydroxyl radical (•OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the in situ polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, in situ polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated in situ biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.

The impact of culture systems on the gut microbiota and gut metabolome of bighead carp (Hypophthalmichthys nobilis).

BACKGROUND: The gut microbiota of fish confers various effects on the host, including health, nutrition, metabolism, feeding behaviour, and immune response. Environment significantly impacts the community structure of fish gut microbiota. However, there is a lack of comprehensive research on the gut microbiota of bighead carp in culture systems. To demonstrate the impact of culture systems on the gut microbiome and metabolome in bighead carp and investigate a potential relationship between fish muscle quality and gut microbiota, we conducted a study using 16S ribosomal ribonucleic acid sequencing, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry techniques on bighead carp in three culture systems. RESULTS: Our study revealed significant differences in gut microbial communities and metabolic profiles among the three culture systems. We also observed conspicuous changes in muscle structure. The reservoir had higher gut microbiota diversity indices than the pond and lake. We detected significant differences in phyla and genera, such as Fusobacteria, Firmicutes, and Cyanobacteria at the phylum level, Clostridium sensu stricto 1, Macellibacteroides, Blvii28 wastewater sludge group at the genus level. Multivariate statistical models, including principal component analysis and orthogonal projections to latent structures-discriminant analysis, indicated significant differences in the metabolic profiles. Key metabolites were significantly enriched in metabolic pathways involved in "arginine biosynthesis" and "glycine, serine, and threonine metabolism". Variation partitioning analysis revealed that environmental factors, such as pH, ammonium nitrogen, and dissolved oxygen, were the primary drivers of differences in microbial communities. CONCLUSIONS: Our findings demonstrate that the culture system significantly impacted the gut microbiota of bighead carp, resulting in differences in community structure, abundance, and potential metabolic functions, and altered the host's gut metabolism, especially in pathways related to amino acid metabolism. These differences were influenced substantially by environmental factors. Based on our study, we discussed the potential mechanisms by which gut microbes affect muscle quality. Overall, our study contributes to our understanding of the gut microbiota of bighead carp under different culture systems.

Co-activation of NMDAR and mGluRs controls protein nanoparticle-induced osmotic pressure in neurotoxic edema.

BACKGROUND: Glutamate stimuli and hyperactivation of its receptor are predominant determinants of ischemia-induced cytotoxic cerebral edema, which is closely associated with protein nanoparticle (PN)-induced increases in osmotic pressure. Herein, we investigated the electrochemical and mechanical mechanisms underlying the neuron swelling induced by PNs via the co-activation of N-methyl-D-aspartate receptor subunit (NMDAR) and excitatory metabotropic glutamate receptors (mGluRs). RESULTS: We observed that co-activation of ionic glutamate receptor NMDAR and Group I metabotropic mGluRs promoted alteration of PN-induced membrane potential and increased intracellular osmosis, which was closely associated with calcium and voltage-dependent ion channels. In addition, activation of NMDAR-induced calmodulin (CaM) and mGluR downstream diacylglycerol (DAG)/protein kinase C α (PKCα) were observed to play crucial roles in cytotoxic hyperosmosis. The crosstalk between CaM and PKCα could upregulate the sensitivity and sustained opening of sulfonylurea receptor 1 (SUR1)-transient receptor potential cation channel subfamily M member 4 (TRPM4) and transmembrane protein 16 A (TMEM16A) channels, respectively, maintaining the massive Na+/Cl- influx, and the resultant neuron hyperosmosis and swelling. Intracellular PNs and Na+/Cl- influx were found to be as potential targets for cerebral edema treatment, using the neurocyte osmosis system and a cerebral ischemic rat model. CONCLUSIONS: This study highlights PNs as a key factor in "electrochemistry-tension" signal transduction controlling Na+/Cl- ion channels and increased osmotic pressure in ischemia-induced cytotoxic edema. Moreover, enhanced sensitivity in both Na+ and Cl- ion channels also has a crucial role in cerebral edema.

Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis.

Cell swelling and membrane blebbing are characteristic of pyroptosis. In the present study, we explored the role of intracellular tension activity in the deformation of pyroptotic astrocytes. Protein nanoparticle-induced osmotic pressure (PN-OP) was found to be involved in cell swelling and membrane blebbing in pyroptotic astrocytes, and was associated closely with inflammasome production and cytoskeleton depolymerization. However, accumulation of protein nanoparticles seemed not to be absolutely required for pyroptotic permeabilization in response to cytoskeleton depolymerization. Gasdermin D activation was observed to be involved in modification of typical pyroptotic features through inflammasome-induced OP upregulation and calcium increment. Blockage of nonselective ion pores can inhibit permeabilization, but not inflammasome production and ion influx in pyroptotic astrocytes. The results suggested that the inflammasomes, as protein nanoparticles, are involved in PN-OP upregulation and control the typical features of pyroptotic astrocytes.

Effects of vitamin D-related gene polymorphisms on attempted suicide.

OBJECTIVE: Emerging evidence suggests that vitamin D might protect from attempted suicide. The study aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) related to vitamin D levels identified in a large genome-wide association study and attempted suicide in rural China. METHODS: This 1:1 matched case-control study included altogether 510 suicide attempters and 510 community controls. Genotypes of four target SNPs (DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679, and CYP24A1-rs6013897) were determined, and a genetic risk score (GRS) was constructed to evaluate the combined effect of them. Demographic and psychological information was acquired through face-to-face interviews. RESULTS: The A allele of CYP24A1-rs6013897 was significantly associated with attempted suicide (OR = 1.27, 95% CI, 1.03-1.58, P = 0.029), even after adjusting for demographic and psychological confounders (adjusted OR = 1.53, 95% CI, 1.01-2.30, P = 0.043). The GRS analyses revealed a significantly higher risk of attempted suicide with a greater number of low vitamin D alleles (adjusted OR = 1.33, 95% CI, 1.13-1.58, P < 0.001). Subgroup analyses stratified by sex indicated that the genetic associations were only significant among males with adjusted ORs of 3.77 (95% CI, 1.56-9.10) for the A allele of rs6013897 and 2.04 (95% CI, 1.32-3.17) for GRS. CONCLUSIONS: Our findings identity CYP24A1-rs6013897 as a potential biomarker for attempted suicide and indicate that a genetic predisposition to lower vitamin D levels may contribute to attempted suicide. It suggests the possibility that vitamin D may have the preventive potential for attempted suicide.