An analysis of AURKB's prognostic and immunological roles across various cancers.

Aurora kinase B (AURKB), an essential regulator in the process of mitosis, has been revealed through various studies to have a significant role in cancer development and progression. However, the specific mechanisms remain poorly understood. This study, therefore, seeks to elucidate the multifaceted role of AURKB in diverse cancer types. This study utilized bioinformatics techniques to examine the transcript, protein, promoter methylation and mutation levels of AURKB. The study further analysed associations between AURKB and factors such as prognosis, pathological stage, biological function, immune infiltration, tumour mutational burden (TMB) and microsatellite instability (MSI). In addition, immunohistochemical staining data of 50 cases of renal clear cell carcinoma and its adjacent normal tissues were collected to verify the difference in protein expression of AURKB in the two tissues. The results show that AURKB is highly expressed in most cancers, and the protein level of AURKB and the methylation level of its promoter vary among cancer types. Survival analysis showed that AURKB was associated with overall survival in 12 cancer types and progression-free survival in 11 cancer types. Elevated levels of AURKB were detected in the advanced stages of 10 different cancers. AURKB has a potential impact on cancer progression through its effects on cell cycle regulation as well as inflammatory and immune-related pathways. We observed a strong association between AURKB and immune cell infiltration, immunomodulatory factors, TMB and MSI. Importantly, we confirmed that the AURKB protein is highly expressed in kidney renal clear cell carcinoma (KIRC). Our study reveals that AURKB may be a potential biomarker for pan-cancer and KIRC.

Autoimmune diseases and the risk of bladder cancer: A Mendelian randomization analysis.

OBJECTIVE: To investigate the association between autoimmune diseases (AIDs) and bladder cancer (BC) at the genetic level using Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms (SNPs) associated with the seven AIDs were extracted from the IEU GWAS database, and the SNPs were quality-controlled using strict screening criteria. The association between AIDs and BC risk was assessed by inverse-variance weighted (IVW), MR-Egger regression and Weighted median method. The heterogeneity of SNPs was evaluated by Cochran Q test. MR-Egger intercept test and MR-PRESSO global test were used to test the horizontal pleiotropy of SNPs. Both sides with potential causal associations were validated using the validation set. RESULTS: Our result showed that genetically predicted RA was significantly associated with an increased risk of BC (IVW OR = 1.214, 95 % CI = 1.062-1.388, P = 0.005). MS nominally increased the risk of BC (IVW OR = 1.095, 95 % CI = 1.005-1.193, P = 0.037), consistent with the results of the MR analysis of the BC validation cohort. However SLE, T1D, UC, CD, and MG were not causally associated with BC risk (P > 0.05). The sensitivity analyses showed that there was no heterogeneity or horizontal pleiotropy in our findings. CONCLUSION: This study provides evidence of a causal relationship between AIDs and BC risk at the genetic level, confirming a causal relationship between RA and MS in increasing the risk of BC.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Rapid Thermochromic and Highly Thermally Conductive Nanocomposite Based on Silicone Rubber for Temperature Visualization Thermal Management in Electronic Devices.

Effective heat dissipation and real-time temperature monitoring are crucial for ensuring the long-term stable operation of modern, high-performance electronic products. This study proposes a silicon rubber polydimethylsiloxane (PDMS)-based nanocomposite with a rapid thermal response and high thermal conductivity. This nanocomposite enables both rapid heat dissipation and real-time temperature monitoring for high-performance electronic products. The reported material primarily consists of a thermally conductive layer (Al2O3/PDMS composites) and a reversible thermochromic layer (organic thermochromic material, graphene oxide, and PDMS nanocoating; OTM-GO/PDMS). The thermal conductivity of OTM-GO/Al2O3/PDMS nanocomposites reached 4.14 W m-1 K-1, reflecting an increase of 2200% relative to that of pure PDMS. When the operating temperature reached 35, 45, and 65 °C, the surface of OTM-GO/Al2O3/PDMS nanocomposites turned green, yellow, and red, respectively, and the thermal response time was only 30 s. The OTM-GO/Al2O3/PDMS nanocomposites also exhibited outstanding repeatability and maintained excellent color stability over 20 repeated applications.

Clinical diagnostic biomarker "circulating tumor cells" in breast cancer - a meta-analysis.

Objective: Using meta-analysis, we evaluate circulating tumor cells(CTCs) as a potential diagnostic tool for breast cancer. Methods: A document search was conducted using publicly available databases up to May 2021. Specific inclusion and exclusion criteria were formulated and summarize relevant data through literature types, research types, case populations, samples, etc. Subgroup analysis of documents based on regions, enrichment methods, and detection methods. The included research projects were evaluated using DeeKs' bias, and evaluation indicators such as specificity (SPE), sensitivity (SEN), diagnosis odds ratio (DOR) were used as evaluation indicators. Results: 16 studies on the use of circulating tumor cells to diagnose breast cancer were included in our meta-analysis. Overall sensitivity value was 0.50 (95%CI:0.48-0.52), specificity value was 0.93 (95%CI:0.92- 0.95), DOR value was 33.41 (95%CI:12.47-89.51), and AUC value was 0.8129. Conclusion: In meta-regressions and subgroup analysis, potential heterogeneity factors were analyzed, but the source of heterogeneity is still unclear. CTCs, as a novel tumor marker, have a good diagnostic value, but its enrichment and detection methods still need to continue to be developed to improve detection accuracy. Therefore, CTCs can be used as an auxiliary means of early detection, which is helpful to the diagnosis and screening of breast cancer.

Dual Targeted Nanoparticles for the Codelivery of Doxorubicin and siRNA Cocktails to Overcome Ovarian Cancer Stem Cells.

Most anticancer treatments only induce the death of ordinary cancer cells, while cancer stem cells (CSCs) in the quiescent phase of cell division are difficult to kill, which eventually leads to cancer drug resistance, metastasis, and relapse. Therefore, CSCs are also important in targeted cancer therapy. Herein, we developed dual-targeted and glutathione (GSH)-responsive novel nanoparticles (SSBPEI-DOX@siRNAs/iRGD-PEG-HA) to efficiently and specifically deliver both doxorubicin and small interfering RNA cocktails (siRNAs) (survivin siRNA, Bcl-2 siRNA and ABCG2 siRNA) to ovarian CSCs. They are fabricated via electrostatic assembly of anionic siRNAs and cationic disulfide bond crosslinking-branched polyethyleneimine-doxorubicin (SSBPEI-DOX) as a core. Interestingly, the SSBPEI-DOX could be degraded into low-cytotoxic polyethyleneimine (PEI). Because of the enrichment of glutathione reductase in the tumor microenvironment, the disulfide bond (-SS-) in SSBPEI-DOX can be specifically reduced to promote the controlled release of siRNA and doxorubicin (DOX) in the CSCs. siRNA cocktails could specifically silence three key genes in CSCs, which, in combination with the traditional chemotherapy drug DOX, induces apoptosis or necrosis of CSCs. iRGD peptides and "sheddable" hyaluronic acid (HA) wrapped around the core could mediate CSC targeting by binding with neuropilin-1 (NRP1) and CD44 to enhance delivery. In summary, the multifunctional delivery system SSBPEI-DOX@siRNAs/iRGD-PEG-HA nanoparticles displays excellent biocompatibility, accurate CSC-targeting ability, and powerful anti-CSC ability, which demonstrates its potential value in future treatments to overcome ovarian cancer metastasis and relapse. To support this work, as exhaustive search was conducted for the literature on nanoparticle drug delivery research conducted in the last 17 years (2007-2023) using PubMed, Web of Science, and Google Scholar.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Analysis of white-light imaging-based features predictive for determination of lesion depths of superficial flat esophageal squamous cell carcinoma: a retrospective multicenter study from China.

OBJECTIVES: Endoscopic diagnosis of invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by white-light imaging (WLI) modality remains difficult. This study aims to clarify WLI-based features which are predictive for invasion depth of SESCC. METHODS: A two-phase study was performed by enrolling 1288 patients with 1396 SESCC lesions. Endoscopic appearances, clinical characteristics and post-operative pathological outcomes were collected and reviewed. The association between lesion features and invasion depth were analyzed. A predictive nomogram was constructed for prediction of invasion depth. RESULTS: Among 1396 lesions in derivation and validation cohort, 1139 (81.6%), 194 (13.9%) and 63 (4.5%) lesions were diagnosed as lesions confined into the intraepithelium or the lamina propria mucosa (T1a-EP/LPM), lesions invading the muscularis mucosa (T1a-MM) or superficial submucosa (T1b-SM1) and tumor with moderate invasion into the submucosa or deeper submucosal invasion (≥ T1b-SM2), respectively. Lesion length > 2 cm (p < 0.001), wider circumferential extension (p < 0.001, 0.002 and 0.048 for > 3/4, 1/2-3/4 and 1/4-1/2 circumferential extension, respectively), surface unevenness (p < 0.001 for both type 0-IIa/0-IIc lesions and mixed type lesions), spontaneous bleeding (p < 0.001), granularity (p < 0.001) and nodules (p < 0.001) were identified as significant factors predictive for lesion depth. A nomogram based on these factors was constructed and the values of area under the Receiver Operating Characteristics curve were 0.89 and 0.90 in the internal and external patient cohort. CONCLUSIONS: Our study provides six WLI-based morphological features predicting for lesion depth of SESCC. Our findings will make endoscopic evaluation of invasion depth for SESCC more convenient by assessing these profiles.

Artificial intelligence assisted detection of superficial esophageal squamous cell carcinoma in white-light endoscopic images by using a generalized system.

BACKGROUND: The use of artificial intelligence (AI) assisted white light imaging (WLI) detection systems for superficial esophageal squamous cell carcinoma (SESCC) is limited by training with images from one specific endoscopy platform. METHODS: In this study, we developed an AI system with a convolutional neural network (CNN) model using WLI images from Olympus and Fujifilm endoscopy platforms. The training dataset consisted of 5892 WLI images from 1283 patients, and the validation dataset included 4529 images from 1224 patients. We assessed the diagnostic performance of the AI system and compared it with that of endoscopists. We analyzed the system's ability to identify cancerous imaging characteristics and investigated the efficacy of the AI system as an assistant in diagnosis. RESULTS: In the internal validation set, the AI system's per-image analysis had a sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 96.64%, 95.35%, 91.75%, 90.91%, and 98.33%, respectively. In patient-based analysis, these values were 90.17%, 94.34%, 88.38%, 89.50%, and 94.72%, respectively. The diagnostic results in the external validation set were also favorable. The CNN model's diagnostic performance in recognizing cancerous imaging characteristics was comparable to that of expert endoscopists and significantly higher than that of mid-level and junior endoscopists. This model was competent in localizing SESCC lesions. Manual diagnostic performances were significantly improved with the assistance by AI system, especially in terms of accuracy (75.12% vs. 84.95%, p = 0.008), specificity (63.29% vs. 76.59%, p = 0.017) and PPV (64.95% vs. 75.23%, p = 0.006). CONCLUSIONS: The results of this study demonstrate that the developed AI system is highly effective in automatically recognizing SESCC, displaying impressive diagnostic performance, and exhibiting strong generalizability. Furthermore, when used as an assistant in the diagnosis process, the system improved manual diagnostic performance.

Inspired by game theory: Multi-signal output photoelectrochemical point-of-care immunoassay based on target-triggered organic electronic barriers.

This work presents an integrated photoelectrochemical, impedance and colorimetric biosensing platform for flexible detection of cancer markers based on the targeted response by combining liposome amplification strategies and target-induced non-in situ formation of electronic barriers as the signal transduction modality on carbon-modified CdS photoanodes. Inspired by game theory, the carbon layer modified CdS hyperbranched structure with low impedance and high photocurrent response was firstly obtained by surface modification of CdS nanomaterials. Through a liposome-mediated enzymatic reaction amplification strategy, a large number of organic electron barriers were formed by a biocatalytic precipitation (BCP) reaction triggered by horseradish peroxidase released from cleaved liposomes after the introduction of the target molecule, thereby increasing the impedance characteristics of the photoanode as well as attenuating the photocurrent. The BCP reaction in the microplate was accompanied by a significant color change, which opened up a new window for point-of-care testing. Taking carcinoembryonic antigen (CEA) as a proof of concept, the multi-signal output sensing platform showed a satisfactory sensitive response to CEA with an optimal linear range of 20 pg mL-1-100 ng mL-1. The detection limit was as low as 8.4 pg mL-1. Meanwhile, with the assistance of a portable smartphone and a miniature electrochemical workstation, the electrical signal obtained was synchronized with the colorimetric signal to correct the actual target concentration in the sample, further reducing the occurrence of false reports. Importantly, this protocol provides a new idea for the sensitive detection of cancer markers and the construction of a multi-signal output platform.

QTL mapping and identification of candidate genes for cold tolerance at the germination stage in wild rice.

BACKGROUND: Cold damage stress significantly affects rice growth (germination and seedling) and causes serious losses in yield in temperate and high-altitude areas around the globe. OBJECTIVE: This study aimed to explore the cold tolerance (CT) locus of rice and create new cold-tolerant germplasm. We constructed a chromosome segment substitution line (CSSL) with strong CT and fine mapped quantitative trait loci (QTLs) associated with CT by performing the whole-genome resequencing of CSSL with phenotypes under cold treatment. METHODS: A chromosome CSSL, including 271 lines from a cross between the cold-tolerant wild rice Y11 (Oryza rufipogon Griff.) and the cold-sensitive rice variety GH998, was developed to map QTLs conferring CT at the germination stage. The whole-genome resequencing was performed on CSSL for mapping QTLs of associated with CT at the germination stage. RESULTS: A high-density linkage map of the CSSLs was developed using the whole-genome resequencing of 1484 bins. The QTL analysis using 615,466 single-nucleotide polymorphisms (SNPs) led to the identification of 2 QTLs related to germination rate at low-temperature on chromosome 8 (qCTG-8) and chromosome 11 (qCTG-11). The qCTG-8 and qCTG-11 explained 14.55% and 14.31% of the total phenotypic variation, respectively. We narrowed down qCTG-8 and qCTG-11 to 195.5 and 78.83-kb regions, respectively. The expression patterns of important candidate genes in different tissues, and of RNA-sequencing (RNA-seq) in CSSLs, were identified based on gene sequences in qCTG-8 and qCTG-11 cold-induced expression analysis. LOC_Os08g01120 and LOC_Os08g01390 were identified as candidate genes in qCTG-8, and LOC_Os11g32880 was identified as a candidate gene in qCTG-11. CONCLUSIONS: This study demonstrated a general method that could be used to identify useful loci and genes in wild rice and aid in the future cloning of candidate genes of qCTG-8 and qCTG-11. The CSSLs with strong CT were supported for breeding cold-tolerant rice varieties.

Multifunctional chondroitin sulfate based hydrogels for promoting infected diabetic wounds healing by chemo-photothermal antibacterial and cytokine modulation.

Diabetic foot (DF) is difficult to heal due to the formation of drug-resistant bacterial biofilms and dysregulation of the wound microenvironment. To solve this problem, multifunctional hydrogels were prepared by in situ or spraying with 3-aminophenylboronic acid modified oxidized chondroitin sulfate (APBA-g-OCS), polyvinyl alcohol (PVA) and black phosphorus/bismuth oxide/ε-polylysine (BP/Bi2O3/ε-PL) as precursors for promoting infected diabetic wounds healing. The hydrogels display multiple stimulus responsiveness, strong adhesion and rapid self-healing ability owing to the dynamic borate ester bonds, hydrogen bonds and π-π conjugation cross-link points, remain synergistic chemo-photothermal antibacterial effect and anti-biofilm formation ability due to the doping of BP/ Bi2O3/ε-PL into the hydrogel by dynamic imine bonds crosslinking and possess anti-oxidation and inflammatory chemokine adsorption ability attributing to the presence of APBA-g-OCS. Most importantly, as a result of the above functions, the hydrogels can not only respond to the wound microenvironment to conduct combined PTT and chemotherapy for efficient anti-inflammation, but also improve the wound microenvironment by scavenging ROS and regulating the expression of cytokines, thus further accelerating collagen deposition, promoting granulation tissue formation and angiogenesis, finally promoting the healing of infected wounds in diabetic rats.

OrMKK3 Influences Morphology and Grain Size in Rice.

Although morphology and grain size are important to rice growth and yield, the identity of abundant natural allelic variations that determine agronomically important differences in crops is unknown. Here, we characterized the function of mitogen-activated protein kinase 3 from Oryza officinalis Wall. ex Watt encoded by OrMKK3. Different alternative splicing variants occurred in OrMKK3. Green fluorescent protein (GFP)-OrMKK3 fusion proteins localized to the cell membrane and nuclei of rice protoplasts. Overexpression of OrMKK3 influenced the expression levels of the grain size-related genes SMG1, GW8, GL3, GW2, and DEP3. Phylogenetic analysis showed that OrMKK3 is well conserved in plants while showing large amounts of variation between indica, japonica, and wild rice. In addition, OrMKK3 slightly influenced brassinosteroid (BR) responses and the expression levels of BR-related genes. Our findings thus identify a new gene, OrMKK3, influencing morphology and grain size and that represents a possible link between mitogen-activated protein kinase and BR response pathways in grain growth. Supplementary Information: The online version contains supplementary material available at 10.1007/s12374-020-09290-2.

Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases.

Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 µM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1ß secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.

Study protocol for artificial intelligence-assisted sponge cytology as pre-endoscopy screening for early esophegeal squmaous epithelial lesions in China.

BACKGROUND: Endoscopic screening is the widely accepted screening strategy for esophageal squmaous cell carcinoma (ESCC). However, massive endoscopic screening is expensive and not cost-efficient, and novel pre-endoscopy detection used as a preliminary screening method arouses new concerns. We are planning to launch an artificial intelligence (AI) assisted sponge cytology for detecting esophageal squmaous high-grade intraepithelial neoplasia (HGIN) and above lesions. The aim of this trail is to investigate the efficiency of AI-assisted sponge cytology in population-based screening of early esophageal squmaous epithelial lesions. METHODS: The study will be prospectively conducted in five regions with a high prevalence of ESCC. AI-assisted sponge cytology and endoscopic examination will be sequentially performed. Based on our previous data, at least 864 patients with esophageal HGIN and above lesions are needed to achieve enough statistical power. And, a calculated 112,500 individuals with high risks of ESCC will be recruited. In the first stage, each 24,000 participants who meet the inclusion criteria will be recruited on a voluntary basis. Setting pathological results as standard reference, diagnostic threshold and according performance of AI-assisted detection will be evaluated. A prediction model will be constructed by co-analyzing cytological results and relevant risk factors. Then, an external validation cohort will be used for validation of the model efficiency. Also, cost-efficiency analysis will be performed. This study protocol was registered on chineseclinicaltrial.gov (ChiCTR1900028524). DISCUSSION: Our study will determine whether this AI-assisted sponge cytology can be used as an effective pre-endoscopy detection tool for large-scale screening for ESCC in high-risk areas.

Association between variants of MTHFR genes and psychiatric disorders: A meta-analysis.

Background: Psychiatric disorders have seriously affected human life, one of the risk genes related to psychosis is the methylenetetrahydrofolatereductase (MTHFR) gene. This gene has a potential role in psychiatric disorders. Therefore, a meta-analysis is conducted to investigate the correlations between two prevalent MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T, A1298C, severe psychological disorders (schizophrenia, major depression, bipolar disorder). Methods: A total of 81 published studies were screened and selected by a search of electronic databases up to April 2022. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR polymorphism and psychiatric disorders susceptibility by using random effect models. Results: We found that MTHFR C677T polymorphism is significantly related to schizophrenia and major depression in the overall population. MTHFR C677T has been linked to an increased risk of bipolar disorder in the recessive model (TT vs. CT + CC). Ethnic subgroup analysis shows that schizophrenia and major depression significantly correlate with MTHFR C677T and A1298C in Asian populations but not Caucasians. Besides, schizophrenia is correlated substantially with MTHFR C677T in the African population. However, the MTHFR A1298C polymorphism is only marginally linked to major depression. Conclusion: Findings of the current study revealed that MTHFR may contribute to the common pathogenesis of psychiatric diseases and that its variants may be essential in controlling the expression of psychosis-related genes. This study could help the researchers and health specialists in the early diagnosis and treatment of psychiatric disorders.

Systematic Analysis of NB-ARC Gene Family in Rice and Functional Characterization of GNP12.

The NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4) gene family plays a critical role in plant development. However, our understanding of the mechanisms of how NB-ARC genes regulate plant development in the plant panicle is still limited. Here, we subjected 258 NB-ARC genes in rice to genome-wide analysis to characterize their structure, function, and expression patterns. The NB-ARC genes were classified into three major groups, and group II included nine subgroups. Evolutionary analysis of NB-ARC genes in a dicotyledon plant (Arabidopsis thaliana) and two monocotyledonous plants (Oryza sativa L. and Triticum aestivum) indicated that homologous genome segments were conserved in monocotyledons and subjected to weak positive selective pressure during evolution. Dispersed and proximal replication events were detected. Expression analysis showed expression of most NB-ARC genes in roots, panicles, and leaves, and regulation at the panicle development stage in rice Ce253. The GNP12 gene encodes RGH1A protein, which regulates rice yield according to panicle length, grain number of panicle, and grain length, with eight major haplotypes. Most members of NB-ARC protein family are predicted to contain P-loop conserved domains and localize on the membrane. The results of this study will provide insight into the characteristics and evolution of NB-ARC family and suggest that GNP12 positively regulates panicle development.

Bacterial responsive hydrogels based on quaternized chitosan and GQDs-ε-PL for chemo-photothermal synergistic anti-infection in diabetic wounds.

Clinically, systemic antibiotic therapy and traditional dressings care are not satisfactory in treating chronic diabetic ulcers (DU). Therefore, we presented sprayable antibacterial hydrogel for effective treatment of DU by using antibacterial macromolecules (quaternized chitosan, QCS, Mn ≈ 1.5 × 105), photothermal antibacterial nanoparticles (ε-poly-l-lysine grafted graphene quantum dots, GQDs-ε-PL) and miocompatible macromolecules (benzaldehyde-terminated four-arm poly(ethylene glycol), 4 arm PEG-BA) as materials. The results revealed that the hydrogel could be in situ formed in 70-89 s through dynamic imine bonds crosslinking and exhibited a pH-dependent swelling ability and degradability. The hydrogel could respond to bacterial triggered acidic environment to play a synergistic effect of chemotherapy and xenon light irradiated PTT, leading to the rupture of the bacterial membrane and the inactivation of bacteria, promoting the migration and proliferation of fibroblast cell, enhancing the adhesion of platelet endothelial cell, and finally accelerating the healing of infected diabetic wound. Moreover, the hydrogel displayed self-healing, hemostatic, and biocompatible abilities, which could provide a better healing environment for wound and further promote wound healing. Hence, the multifunctional hydrogel is expected to be a potential dressing for the clinical treatment of DU.

Expression characteristics of polymeric immunoglobulin receptor in Bactrian camel (Camelus bactrianus) lungs.

Polymeric immunoglobulin receptor (pIgR), the transmembrane transporter of polymeric immunoglobulin A and M, has multiple immune functions. To explore the characteristics of pIgR expression in Bactrian camel lungs, twelve healthy adult (2-7 years old) Bactrian camels were systematically studied. The results showed that pIgR was mainly expressed in the cytoplasm and membrane of ciliated cells, as well as in the cytoplasm and membrane of basal cells, serous cells of bronchial glands, club cells and alveolar type 2 cells in Bactrian camel lungs. Specially, as the bronchial branches extended, the pIgR expression level in ciliated cells significantly declined (p<0.05), and the corresponding bronchial luminal areas obviously decreased (p<0.05). However, pIgR was not expressed in goblet cells, endocrine cells, alveolar type 1 cells and mucous cells of bronchial glands. The results demonstrated that ciliated cells continuously distributed throughout the whole bronchial tree mucosa were the major expression sites of pIgR, and pIgR was also expressed in basal cells, serous cells of bronchial glands, club cells and alveolar type 2 cells, which would facilitate secretory immunoglobulin A (SIgA) transmembrane transport by pIgR and form an intact protective barrier. Moreover, the pIgR expression level in ciliated cells was positively correlated with the bronchial luminal areas; but negatively correlated with the cleanliness of airflow through the bronchial cross-sections, showing that the pIgR expression level in the bronchial epithelium was inhomogeneous. Our study provided a foundation for further exploring the regulatory functions of immunoglobulins (i.e., SIgA) after transport across the membrane by pIgR in Bactrian camel lungs.

Low Chloride-Regulated ClC-5 Contributes to Arterial Smooth Muscle Cell Proliferation and Cerebrovascular Remodeling.

BACKGROUND: Low serum chloride (Cl-) level is considered an independent predictor of cardiovascular mortality associated with chronic hypertension. However, the underlying mechanisms are unknown. ClC-5, a member of the Cl- channel family, is sensitive to changes in intracellular and extracellular Cl- concentration and conducts outwardly rectifying Cl- currents. The aims of this study were to determine if ClC-5 is regulated by low extracellular Cl-, clarify its putative roles in hypertension-induced cerebrovascular remodeling, and elucidate the associated underlying mechanisms. METHODS: Whole-cell patch technique, intracellular Cl- concentration measurements, flow cytometry, Western blot, Clcn5 knockdown (Clcn5-/y), and adenovirus-mediated ClC-5 overexpression mice, 2-kidney, 2-clip, and angiotensin II infusion-induced hypertensive models were used. RESULTS: We found that low extracellular Cl- evoked a ClC-5-dependent Cl- current that was abolished by ClC-5 depletion in basilar artery smooth muscle cells (BASMCs). ClC-5 was upregulated in the arterial tissues of rats and patients with hypertension. Low Cl--induced current and ClC-5 protein expression positively correlated with basilar artery remodeling during hypertension. ClC-5 knockdown ameliorated hypertension-induced cerebrovascular remodeling and smooth muscle cell proliferation, whereas ClC-5 overexpression mice exhibited the opposite phenotype. ClC-5-dependent Cl- efflux induced by low extracellular Cl- activated WNK1 (lysine-deficient protein kinase 1) which, in turn, activated AKT (protein kinase B), and culminated in BASMC proliferation and vascular remodeling. CONCLUSIONS: ClC-5 mediates low extracellular Cl-induced Cl- currents in BASMCs and regulates hypertension-induced cerebrovascular remodeling by promoting BASMC proliferation via the WNK1/AKT signaling pathway.