Canagliflozin alleviates pulmonary hypertension by activating PPARγ and inhibiting its S225 phosphorylation.

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.

Mechanism Insights into the Enantioselective Bioactivity and Fumonisin Biosynthesis of Mefentrifluconazole to Fusarium verticillioides.

The occurrence of maize ear rot caused by Fusarium verticillioides (F. verticillioides) poses a threat to the yield and quality of maize. Mefentrifluconazole enantiomers appear to have strong stereoselective activity against F. verticillioides and cause differences in fumonisin production. We evaluated the stereoselective activity of mefentrifluconazole enantiomers by determining inhibition of the strain, hyphae, and conidia. Strain inhibition by R-(-)-mefentrifluconazole was 241 times higher than S-(+)-mefentrifluconazole and 376 times higher in conidia inhibition. For the mechanism of the enantioselective bioactivity, R-mefentrifluconazole had stronger binding to proteins than S-(+)-mefentrifluconazole. Under several concentration conditions, the fumonisin concentration was 1.3-24.9-fold higher in the R-(-)-mefentrifluconazole treatment than in the S-(+)-mefentrifluconazole treatment. The R-enantiomer stimulated fumonisin despite a higher bioactivity. As the incubation time increased, the stimulation of the enantiomers on fumonisin production decreased. R-(-)-Mefentrifluconazole stimulated higher fumonisin production in F. verticillioides at 25 °C compared to 30 °C. This study established a foundation for the development of high-efficiency and low-risk pesticides.

Clinical significance and potential pathogenesis of VCAN in adult non-cystic fibrosis bronchiectasis: a retrospective study.

BACKGROUND: The pathogenesis of adult non-cystic fibrosis (CF) bronchiectasis is complex, and the relevant molecular mechanism remains ambiguous. Versican (VCAN) is a key factor in inflammation through interactions with adhesion molecules. This study constructs a stable panoramic map of mRNA, reveals the possible pathogenesis of bronchiectasis, and provides new ideas and methods for bronchiectasis. METHODS: Peripheral blood and tissue gene expression data from patients with bronchiectasis and normal control were selected by bioinformatics analysis. The expression of VCAN in peripheral blood and bronchial tissues of bronchiectasis were obtained by transcriptome sequencing. The protein expression levels of VCAN in serums were verified by the enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of VCAN in co-culture of Pseudomonas aeruginosa and bronchial epithelial cells were verified by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the biological function of VCAN was detected by the transwell assay. RESULTS: The expression of VCAN was upregulated in the bronchiectasis group by sequencing analysis (P < 0.001). The expression of VCAN in the bronchial epithelial cell line BEAS-2B was increased in P. aeruginosa (P.a), which was co-cultured with BEAS-2B cells (P < 0.05). The concentration of VCAN protein in the serum of patients with bronchiectasis was higher than that in the normal control group (P < 0.05). Transwell experiments showed that exogenous VCAN protein induced the migration of neutrophils (P < 0.0001). CONCLUSIONS: Our findings indicate that VCAN may be involved in the development of bronchiectasis by increasing the migration of neutrophils and play an important role in bronchial pathogenesis.

Efficacy of Spleen-and-Stomach-Tonifying, Yin-Fire-Purging, and Yang-Raising Decoction Derived from the Trimethylamine N-Oxide Metabolic Pathway of Intestinal Microbiota on Macrovascular Lesions Caused by Type 2 Diabetes Mellitus.

Objective: We aimed to analyze the mechanisms underlying spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction derived from the trimethylamine N-oxide (TMAO) metabolic pathway of intestinal microbiota in the treatment of macrovascular lesions caused by type 2 diabetes mellitus (T2DM). Methods: Hartley-guinea pigs were randomly divided into 3 groups-the blank, model, and intervention groups. The T2DM combined with atherosclerosis guinea pig models were established in the model and intervention groups. After successful modeling, spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction were administered intragastrically to the intervention group, while the same volume of normal saline was administered via gavage to the blank and model groups. After 6 weeks of continuous gavage, guinea pigs were sacrificed in all groups, the colon contents were obtained, and the diversity and structural differences of intestinal microbiota were analyzed via bioinformatics. Serum was collected to detect differences in lipids, TMAO, oxidative stress, and inflammation markers between groups. Results: Compared to the blank group, the species diversity of the intestinal microbiota in the model and intervention groups was significantly reduced. Based on the results of Analysis of Similarities and Multiple Response Permutation Procedure, the microbiota structure of the intervention group was closer to that of the blank group. After modeling, the blood lipid levels of guinea pigs increased significantly, and drug intervention significantly reduced the levels of TC, TG, and LDL-C (P < 0.05). TMAO expression was significantly increased after modeling (P < 0.05), while drug intervention reduced TMAO expression (P < 0.05). Compared to the model group, drug intervention significantly increased the concentrations of SOD while decreasing the concentrations of MDA, ICAM-1, VCAM-1, IL-6, and hs-CRP. Conclusion: Spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction can reduce the risk of macrovascular lesions in T2DM, and its mechanism may be associated with its ability to regulate the TMAO metabolic pathway of intestinal microbiota.

DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

Mechanisms of adsorption and functionalization of biochar for pesticides: A review.

Agricultural production relies heavily on pesticides. However, factors like inefficient application, pesticide resistance, and environmental conditions reduce their effective utilization in agriculture. Subsequently, pesticides transfer into the soil, adversely affecting its physicochemical properties, microbial populations, and enzyme activities. Different pesticides interacting can lead to combined toxicity, posing risks to non-target organisms, biodiversity, and organism-environment interactions. Pesticide exposure may cause both acute and chronic effects on human health. Biochar, with its high specific surface area and porosity, offers numerous adsorption sites. Its stability, eco-friendliness, and superior adsorption capabilities render it an excellent choice. As a versatile material, biochar finds use in agriculture, environmental management, industry, energy, and medicine. Added to soil, biochar helps absorb or degrade pesticides in contaminated areas, enhancing soil microbial activity. Current research primarily focuses on biochar produced via direct pyrolysis for pesticide adsorption. Studies on functionalized biochar for this purpose are relatively scarce. This review examines biochar's pesticide absorption properties, its characteristics, formation mechanisms, environmental impact, and delves into adsorption mechanisms, functionalization methods, and their prospects and limitations.

Prognostic Value of Venous Outflow Profiles on Multiphase CT Angiography for the Patients with Acute Ischemic Stroke After Endovascular Thrombectomy.

To evaluate the prognostic value of venous outflow (VO) profiles evaluated on multiphase CTA (mCTA) for the patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). We retrospectively collected 150 patients with AIS who underwent pre-treatment CT perfusion (CTP) evaluation and subsequent EVT from April 2018 to April 2022. Three-phases (peak arterial phase, peak venous phase, late venous phase) CTA was reconstructed from CTP raw data, and VO was evaluated on three-phases CTA, respectively. Favorable VO was regarded as a cortical vein opacification score of 3-6, and unfavorable VO as a score of 0-2. Good outcome was defined as modified Rankin Scale score of 0-2 at 90 days after EVT. Multivariate logistic regression analysis was performed to explore the predictors of good outcome. Prognostic value was assessed and compared using receiver operating characteristic (ROC) curves and Delong test. We found that good outcome was achieved in 85 (56.7%) patients. Among the mCTA-derived VO profiles, only favorable peak venous phase VO was found to be independently associated with good outcome (P < 0.001). After integrating favorable peak venous phase VO with lower post-treatment National Institute of Health Stroke Scale score at 24 hours, successful recanalization and favorable hypoperfusion intensity ratio, the predictive ability for a good outcome was significantly improved than before (area under the ROC curve; 0.947 vs 0.881; P = 0.002). This study supports that favorable peak venous VO profiles on mCTA might be a promising biomarker in predicting the good outcome in patients with AIS after EVT.

Combustion of Al Nanoparticles Coated with Nitrocellulose/Ethanol/Ether Molecules by Equilibrium Molecular Dynamics Simulations.

Al nanoparticles (ANPs) have high reactivity, but they are easily inactivated by external oxidants. To improve their surface properties, we coat ANPs with a nitrocellulose (NC)/ethanol/ether solution. Comparative discussions are raised from the coating to the combustion process. Our results show that NC/ethanol/ether forms a dense coating layer on the surface of annealed ANPs and passivates ANPs through physical and chemical adsorption. The coating layer can block the contact between the active Al atoms and O2 molecules at low temperatures. In the ignition phase, the NC/ethanol/ether coating layer can increase the density of the O2 molecules around the ANPs and the surface temperature of ANPs. At the end of the ignition phase, the number of O atoms adsorbed on the surface of NC/ethanol/ether coating-passivated ANPs (csANPs) and NC/ethanol/ether coating-annealed ANPs (cANPs) increased by about 60 and 50%, respectively, compared with passivated ANPs (sANPs). Since the desorption and diffusion of the coating layer will expose more reaction sites, ANPs have a shorter ignition delay and a lower ignition temperature. According to the change in atomic displacement, the combustion stage can be divided into three stages: surface oxidation/core melting diffusion, combustion inward propagation, and uniform combustion. The decomposition of NC molecules can increase the combustion speed, combustion time, and efficiency of ANPs. Such improvement will enable ANPs to obtain better storage and combustion performance and play a stronger role in the field of energetic materials.

Provider-mother interactions are associated with birth outcome misclassifications in household surveys: A case-control study in Guinea-Bissau.

Background: Approximately 4.4 million children die peripartum annually, primarily in low- and middle-income countries. Accurate mortality tracking is essential to prioritising prevention efforts but is undermined by misclassification between stillbirths (SBs) and early neonatal deaths (ENNDs) in household surveys, which serve as key data sources. We explored and quantified associations between peripartum provider-mother interactions and misclassification of SBs and ENNDs in Guinea-Bissau. Methods: Using a case-control design, we followed up on women who had reported a SB or ENND in a retrospective household survey nested in the Bandim Health Project's Health and Demographic Surveillance Systems (HDSS). Using prospective HDSS registration as the reference standard, we linked the survey-reported deaths to the corresponding HDSS records and cross-tabulated SB/ENND classification to identify cases (discordant classification between survey and HDSS) and controls (concordant classification). We further interviewed cases and controls on peripartum provider-mother interactions and analysed data using descriptive statistics and logistic regressions. Results: We interviewed 278 women (cases: 63 (23%); controls: 215 (77%)). Most cases were SBs misclassified as ENNDs (n/N = 49/63 (78%)). Three-fourths of the interviewed women reported having received no updates on the progress of labour and baby's health intrapartum, and less than one-fourth inquired about this information. In comparison with births where women did inquire for information, misclassification was less likely when women did not inquire and recalled no doubts about progress of labour (odds ratio (OR) = 0.51; 95% confidence interval (CI) = 0.28-0.91), or baby's health (OR = 0.54; 95% CI = 0.30-0.97). Most women reported that service providers' death notifications lasted <5 minutes (cases: 23/27 (85%); controls: 61/71 (86%)), and most often encompassed neither events leading to the death (cases: 19/27 (70%); controls: 55/71 (77%)) nor causes of death (cases: 20/27 (74%); controls: 54/71 (76%)). Misclassification was more likely if communication lasted <1 compared to 1-4 minutes (OR = 1.83; 95% CI = 1.10-3.06) and if a formal service provider had informed the mother of the death compared to a family member (OR = 1.57; 95% CI = 1.04-2.36). Conclusions: Peripartum provider-mother interactions are limited in Guinea-Bissau and associated with birth outcome misclassifications in retrospective household surveys. In our study population, misclassification led to overestimated neonatal mortality.

Effects of wheat varieties, fungicides and application time on Fusarium head blight and deoxynivalenol contamination control in wheat.

BACKGROUND: Yield loss and toxin contamination caused by wheat Fusarium head blight (FHB) have always been a worldwide concern. Cultivating disease-resistant varieties and fungicide application are effective measures to control FHB. The comprehensive control technology system for FHB and toxin contamination of wheat in Anhui Province needs further improvement. This study compared the control efficacy of different wheat varieties, fungicides and application times on wheat FHB and deoxynivalenol (DON) contamination, and the dynamic change of DON accumulation after application. RESULTS: Among the 93 main wheat varieties in Anhui Province, the disease-resistant and low-toxic wheat variety "Ningmai 26" was more suitable for planting in the central part of Anhui Province. At the same time, "Yangmai 22" was used for subsequent experiments. The field efficacy trials of different fungicides showed that 30% prothioconazole oil dispersion (OD) had the highest control efficacy on FHB and DON contamination, reaching 94.33 and 77.49%, respectively. The study on the optimum application time of prothioconazole showed that the 0-20% flowering stage was the key point of DON control. The survey of the dynamic changes of DON accumulation showed that prothioconazole could significantly reduce the level of DON accumulation while inhibiting the accumulation rate of DON. At the same time, the control fungicide carbendazim increased the level of DON contamination. CONCLUSION: This study will provide excellent germplasm resources for cultivating disease-resistant and low-toxic wheat varieties, and provide a theoretical reference for establishing a collaborative prevention and control system of disease control and toxin reduction. © 2023 Society of Chemical Industry.

Antibiotic Resistance Patterns and Molecular Characterization of Streptococcus suis Isolates from Swine and Humans in China.

Streptococcus suis is a zoonotic pathogen that causes disease in humans after exposure to infected pigs or pig-derived food products. In this study, we examined the serotype distribution, antimicrobial resistance phenotypes and genotypes, integrative and conjugative elements (ICEs), and associated genomic environments of S. suis isolates from humans and pigs in China from 2008 to 2019. We identified isolates of 13 serotypes, predominated by serotype 2 (40/96; 41.7%), serotype 3 (10/96; 10.4%), and serotype 1 (6/96; 6.3%). Whole-genome sequencing analysis revealed that these isolates possessed 36 different sequence types (STs), and ST242 and ST117 were the most prevalent. Phylogenetic analysis revealed possible animal and human clonal transmission, while antimicrobial susceptibility testing indicated high-level resistance to macrolides, tetracyclines, and aminoglycosides. These isolates carried 24 antibiotic resistance genes (ARGs) that conferred resistance to 7 antibiotic classes. The antibiotic resistance genotypes were directly correlated with the observed phenotypes. We also identified ICEs in 10 isolates, which were present in 4 different genetic environments and possessed differing ARG combinations. We also predicted and confirmed by PCR analysis the existence of a translocatable unit (TU) in which the oxazolidinone resistance gene optrA was flanked by IS1216E elements. One-half (5/10) of the ICE-carrying strains could be mobilized by conjugation. A comparison of the parental recipient with an ICE-carrying transconjugant in a mouse in vivo thigh infection model indicated that the ICE strain could not be eliminated with tetracycline treatment. S. suis therefore poses a significant challenge to global public health and requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation. IMPORTANCE S. suis is a serious zoonotic pathogen. In this study, we investigated the epidemiological and molecular characteristics of 96 S. suis isolates from 10 different provinces of China from 2008 to 2019. A subset of these isolates (10) carried ICEs that were able to be horizontally transferred among isolates of different S. suis serotypes. A mouse thigh infection model revealed that ICE-facilitated ARG transfer promoted resistance development. S. suis requires continuous monitoring, especially for the presence of ICEs and associated ARGs that can be transferred via conjugation.

Pharmacological Mechanisms and Clinical Applications of Curcumin: Update.

Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin's druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification.

Degradation, adsorption, and bioaccumulation of novel triketone HPPD herbicide tembotrione.

Tembotrione is a new triketone HPPD herbicide widely used in Europe, USA, and other areas. However, tembotrione is moderately to highly toxic to algae and daphnia in aquatic ecosystems. In this study, hydrolysis, photolysis, soil degradation, soil adsorption, and bioaccumulation of tembotrione were systematically studied. Hydrolysis experiment revealed that tembotrione was stable in acidic, neutral, and alkaline conditions with half-lives of 231-289 days. The photolysis half-lives of tembotrione were 112-158 days and 76-107 days in pH 4, 7, 9 buffer solutions and on three soils surface, respectively, which demonstrated that tembotrione could be persisted in soil and water. Meanwhile, tembotrione Kfoc was 128-196 mL/g, indicating that tembotrione was not easily adsorbed to soil, and the adsorption capacity increased with the decrease in pH. The half-lives of tembotrione in the test soil were 32-48 days, and high organic matter soil is conducive to microbial activity and accelerates the degradation of tembotrione. Moreover, bioaccumulation experiment demonstrated that tembotrione with a BCF of 0.664 to 0.724 had a low risk of exposure to zebrafish. This study is very helpful for the evaluation environmental risk and safe use of tembotrione.

Effects of snow cover on urban light climate environment in the high latitudes of northeast China.

Light climate environment (LCE) has a significant impact on human health, behavioral characteristics, and the safety of life and property due to the high albedo of snow on the ground cover type, which in turn affects the regional climate and socio-economic development, but less relevant studies have been found. In this study, the effect of snow on daytime and nighttime light levels was quantified using comparative field observations and controlled experiments in artificial climate chambers, combined with analysis of variance and model fitting. The results of the study found that there was a significant difference between the presence and absence of snow on both daytime and nighttime light levels. During daytime, the ambient light level on the ground with snow is 5.68 times higher than without snow, an improvement of 12,711.06 Lux. At night, with moonlight, the nighttime illuminance with and without snow is 0.213 Lux and 0.01 Lux, respectively. When there is no moonlight, the snow has no significant effect on the light level. In addition, significant differences in LCE intensity with different snow depths, snow densities and black carbon (BC) pollution. At the same background light intensity, the LCE intensity varies significantly with increasing snow depth, snow density and BC pollution. The results reveals the quantitative impact of snow on LCE, providing scientific support for regional natural light energy use, human health and safety, urban environmental management and economic development.

Advances in holliday junction recognition protein (HJURP): Structure, molecular functions, and roles in cancer.

Oncogenes are increasingly recognized as important factors in the development and progression of cancer. Holliday Junction Recognition Protein (HJURP) is a highly specialized mitogenic protein that is a chaperone protein of histone H3. The HJURP gene is located on chromosome 2q37.1 and is involved in nucleosome composition in the mitotic region, forming a three-dimensional crystal structure with Centromere Protein A (CENP-A) and the histone 4 complex. HJURP is involved in the recruitment and assembly of centromere and kinetochore and plays a key role in stabilizing the chromosome structure of tumor cells, and its dysfunction may contribute to tumorigenesis. In the available studies HJURP is upregulated in a variety of cancer tissues and cancer cell lines and is involved in tumor proliferation, invasion, metastasis and immune response. In an in vivo model, overexpression of HJURP in most cancer cell lines promotes cell proliferation and invasiveness, reduces susceptibility to apoptosis, and promotes tumor growth. In addition, upregulation of HJURP was associated with poorer prognosis in a variety of cancers. These properties suggest that HJURP may be a possible target for the treatment of certain cancers. Various studies targeting HJURP as a prognostic and therapeutic target for cancer are gradually attracting interest and attention. This paper reviews the functional and molecular mechanisms of HJURP in a variety of tumor types with the aim of providing new targets for future cancer therapy.

Ecological threat caused by malathion and its chiral metabolite in a honey bee-rape system: Stereoselective exposure risk and the mechanism revealed by proteome.

Honey bees play an important role in the ecological environment. Regrettably, a decline in honey bee colonies caused by chemical insecticides has occurred throughout the world. Potential stereoselective toxicity of chiral insecticides may be a hidden source of danger to bee colonies. In this study, the stereoselective exposure risk and mechanism of malathion and its chiral metabolite malaoxon were investigated. The absolute configurations were identified using an electron circular dichroism (ECD) model. Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for chiral separation. In pollen, the initial residues of malathion and malaoxon enantiomers were 3571-3619 and 397-402 µg/kg, respectively, and R-malathion degraded relatively slowly. The oral LD50 values of R-malathion and S-malathion were 0.187 and 0.912 µg/bee with 5 times difference, respectively, and the malaoxon values were 0.633 and 0.766 µg/bee. The Pollen Hazard Quotient (PHQ) was used to evaluate exposure risk. R-malathion showed a higher risk. An analysis of the proteome, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and subcellular localization, indicated that energy metabolism and neurotransmitter transport were the main affected pathways. Our results provide a new scheme for the evaluation of the stereoselective exposure risk of chiral pesticides to honey bees.

The clinical significance and mechanism of microRNA-22-3p targeting TP53 in lung adenocarcinoma.

BACKGROUND: At present, studies on MircoRNA-22-3p (miR-22-3p) in lung adenocarcinoma use a single method, lack multi-center validation and multi-method validation, and there is no big data concept to predict and validate target genes. OBJECTIVE: To investigate the expression, potential targets and clinicopathological significance of miR-22-3p in lung adenocarcinoma (LUAD) tissues. METHODS: LUAD formalin-fixed paraffin-embedded (FFPE) tumors and adjacent normal lung tissues were collected for real-time quantitative polymerase chain reaction (RT-qPCR). Collect miR-22-3p in LUAD and non-cancer lung tissue from high-throughput datasets, standardized mean difference (SMD) and area under the curve (AUC) of the comprehensive receiver operating curve (summary receiver operating characteristic cure, sROC curve) were calculated. Cell function experiments on A549 cells transfected with LV-hsa-miR-22-3p. Target genes were predicted by the miRwalk2.0 website and the resulting target genes were subjected to Gene Ontology (GO) pathway enrichment analysis and constructed to protein-protein interaction network. Finally, the protein expression level of the key gene TP53 was validated by searching The Human Protein Atlas (THPA) database to incorporate TP53 immunohistochemical results in LUAD. RESULTS: RT-qPCR result from 41 pairs of LUAD and adjacent lung tissues showed that miR-22-3p was downregulated in LUAD (AUC = 0.6597, p= 0.0128). Globally, a total of 838 LUADs and 494 non-cancerous lung tissues were included, and were finally combined into 14 platforms. Compared with noncancerous tissue, miR-22-3p expression level was significantly reduced in LUAD tissue (SMD =-0.32, AUC = 0.72l); cell function experiments showed that miR-22-3p has inhibitory effects on cell proliferation, migration and invasion, and has promotion effect on apoptosis. Moreover, target genes prediction, GO pathway enrichment analysis and PPI network exhibited TP53 as a key gene of target gene of miR-22-3p; at last, a total of 114 high-throughput datasets were included, including 3897 LUADs and 2993 non-cancerous lung tissues, and were finally combined into 37 platforms. Compared with noncancerous tissue, TP53 expression level was significantly increased in LUAD (SMD = 0.39, p< 0.01) and it was verified by the protein expression data from THPA. CONCLUSION: Overexpression of miR-22-3p may inhibit LUAD cell proliferation, migration and invasion through TP53, and promote cell apoptosis.

Reconfiguring Hard Carbons with Emerging Sodium-Ion Batteries: A Perspective.

Hard carbons, an important category of amorphous carbons, are non-graphitizable and are widely accepted as the most promising anode materials for emerging sodium-ion batteries (SIBs)， because of their changeable low-potential charge/discharge plateaus. However, their microstructures are not fixed and are difficult to accurately demonstrate as graphites do. The successful use of hard carbons in SIBs revives the interest to clearly picture their complicated microstructures that are in close relevance to sodium storage. In this review, the past definitions and structural models of hard carbons are revisited first, and a renewed understanding of their sodium storage is presented. Three critical structural features are highlighted for hard carbons, namely crystallites, defects, and nanopores, which are directly responsible for the presence of the low-potential plateaus and their reversible extension. The impact of these structural features upon the sodium storage is then deeply discussed and sieving carbons is finally proposed as an ideal configuration of carbon anode for superhigh sodium storage. This review is expected to offer a clear picture of hard carbons, and help realize a truly rational design of high-capacity carbon anodes, driving the industrialization of SIBs, and more promisingly open up a window for exploring their possible new uses.