Association between plasma metal exposure and health span in very elderly adults: a prospective cohort study with mixture statistical approach.

BACKGROUND: Metals have been linked to a diverse spectrum of age-related diseases; however, the effects of metal exposure on health span remains largely unknown. This cohort study aims to determine the association between plasma metal and health span in elder adults aged ≥ 90 years. METHODS: The plasma concentrations of seven metals were measured at baseline in 300 elder adults. The end of the health span (EHS) was identified as the occurrence of one of eight major morbidities or mortality events. We used Cox regression to assess hazard ratios (HR). The combined effects of multiple metal mixtures were estimated using grouped-weighted quantile sum (GWQS), quantile g-computation (Q-gcomp), and Bayesian kernel machine regression (BKMR) methods. RESULTS: The estimated HR for EHS with an inter-quartile range (IQR) increment for selenium (Se) was 0.826 (95% confidence interval [CI]: 0.737-0.926); magnesium (Mg), 0.806 (95% CI: 0.691-0.941); iron (Fe), 0.756 (95% CI: 0.623-0.917), and copper (Cu), 0.856 (95% CI: 0.750-0.976). The P for trend of Se, Mg, and Fe were all < 0.05. In the mixture analyses, Q-gcomp showed a negative correlation with EHS (P = 0.904), with the sum of the negative coefficients being -0.211. CONCLUSION: Higher plasma Se, Mg, and Fe reduced the risk of premature end of health span, suggesting that essential metal elements played a role in health maintenance in elder adults.

Design Principles and Routes for Calcium Alkoxyaluminate Electrolytes.

Multivalent-ion battery technologies are increasingly attractive options for meeting diverse energy storage needs. Calcium ion batteries (CIB) are particularly appealing candidates for their earthly abundance, high theoretical volumetric energy density, and relative safety advantages. At present, only a few Ca-ion electrolyte systems are reported to reversibly plate at room temperature: for example, aluminates and borates, including Ca[TPFA]2, where [TPFA]- = [Al(OC(CF3)3)4]- and Ca[B(hfip)4]2, [B(hfip)4]2- = [B(OCH(CF3)2)4]-. Analyzing the structure of these salts reveals a common theme: the prevalent use of a weakly coordinating anion (WCA) consisting of a tetracoordinate aluminum/boron (Al/B) center with fluorinated alkoxides. Leveraging the concept of theory-aided design, we report an innovative, one-pot synthesis of two new calcium-ion electrolyte salts (Ca[Al(tftb)4]2, Ca[Al(hftb)4]2) and two reported salts (Ca[Al(hfip)4]2 and Ca[TPFA]2) where hfip = (-OCH(CF3)2), tftb = (-OC(CF3)(Me)2), hftb = (-OC(CF3)2(Me)), [TPFA]- = [Al(OC(CF3)3)4]-. We also reveal the dependence of Coulombic efficiency on their inherent propensity for cation-anion coordination.

Association and mediation between educational attainment and respiratory diseases: a Mendelian randomization study.

BACKGROUND: Respiratory diseases are a major health burden, and educational inequalities may influence disease prevalence. We aim to evaluate the causal link between educational attainment and respiratory disease, and to determine the mediating influence of several known modifiable risk factors. METHODS: We conducted a two-step, two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) and single nucleotide polymorphisms (SNPs) as instrumental variables for educational attainment and respiratory diseases. Additionally, we performed a multivariable MR analysis to estimate the direct causal effect of each exposure variable included in the analysis on the outcome, conditional on the other exposure variables included in the model. The mediating roles of body mass index (BMI), physical activity, and smoking were also assessed. FINDINGS: MR analyses provide evidence of genetically predicted educational attainment on the risk of FEV1 (ß = 0.10, 95% CI 0.06, 0.14), FVC (ß = 0.12, 95% CI 0.07, 0.16), FEV1/FVC (ß = - 0.005, 95% CI - 0.05, 0.04), lung cancer (OR = 0.54, 95% CI 0.45, 0.65) and asthma (OR = 0.86, 95% CI 0.78, 0.94). Multivariable MR dicated the effect of educational attainment on FEV1 (ß = 0.10, 95% CI 0.04, 0.16), FVC (ß = 0.07, 95% CI 0.01, 0.12), FEV1/FVC (ß = 0.07, 95% CI 0.01, 0.01), lung cancer (OR = 0.55, 95% CI 0.42, 0.71) and asthma (OR = 0.88, 95% CI 0.78, 0.99) persisted after adjusting BMI and cigarettes per day. Of the 23 potential risk factors, BMI, smoking may partially mediate the relationship between education and lung disease. CONCLUSION: High levels of educational attainment have a potential causal protective effect on respiratory diseases. Reducing smoking and adiposity may be a target for the prevention of respiratory diseases attributable to low educational attainment.

Protein extraction from chlorella pyrenoidosa microalgae: Green methodologies, functional assessment, and waste stream valorization for bioenergy production.

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.

Fine simulation of PM2.5 combined with NPP-VIIRS night light remote sensing and mobile monitoring data.

Human activity plays a crucial role in influencing PM2.5 concentration and can be assessed through nighttime light remote sensing. Therefore, it is important to investigate whether the nighttime light brightness can enhance the accuracy of PM2.5 simulation in different stages. Utilizing PM2.5 mobile monitoring data, this study introduces nighttime lighting brightness as an additional factor in the PM2.5 simulation model across various time periods. It compares the differences in simulation accuracy, explores the impact of nocturnal human activities on PM2.5 concentrations at different periods of the following day, and analyzes the spatial and temporal pollution pattern of PM2.5 in urban functional areas. The results show that (1) the incorporation of nighttime lighting brightness effectively enhances the model's accuracy (R2), with an improvement ranging from 0.04 to 0.12 for different periods ranges. (2) the model's accuracy improves more prominently during 8:00-12:00 on the following day, and less so during 12:00-18:00, as the PM2.5 from human activities during the night experiences a strong aggregation effect in the morning of the next day, with the effect on PM2.5 concentration declining after diffusion until the afternoon. (3) PM2.5 is primarily concentrated in urban functional areas including construction sites, roads, and industrial areas during each period. But in the period of 8:00-12:00, there is a significant level of PM2.5 pollution observed in commercial and residential areas, due to the human activities that occurred the previous night.

Recent Advances in Mesoporous Silica Nanoparticles Delivering siRNA for Cancer Treatment.

Silencing genes using small interfering (si) RNA is a promising strategy for treating cancer. However, the curative effect of siRNA is severely constrained by low serum stability and cell membrane permeability. Therefore, improving the delivery efficiency of siRNA for cancer treatment is a research hotspot. Recently, mesoporous silica nanoparticles (MSNs) have emerged as bright delivery vehicles for nucleic acid drugs. A comprehensive understanding of the design of MSN-based vectors is crucial for the application of siRNA in cancer therapy. We discuss several surface-functionalized MSNs' advancements as effective siRNA delivery vehicles in this paper. The advantages of using MSNs for siRNA loading regarding considerations of different shapes, various options for surface functionalization, and customizable pore sizes are highlighted. We discuss the recent investigations into strategies that efficiently improve cellular uptake, facilitate endosomal escape, and promote cargo dissociation from the MSNs for enhanced intracellular siRNA delivery. Also, particular attention was paid to the exciting progress made by combining RNAi with other therapies to improve cancer therapeutic outcomes.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

BACKGROUND: Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. AIM: To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. METHODS: The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. RESULTS: The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. CONCLUSION: PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

Yulangsan polysaccharide inhibits epithelial-mesenchymal transition and invasion in NSCLC by attenuating the TGF-ß1/ERK signaling pathway.

Active polysaccharides have unique advantages in inhibiting cancer cell proliferation, invasion and metastasis and inducing apoptosis. Yulangsan polysaccharide (YLSPS) is derived from the root of Millettia pulchra var. laxior (Dunn) Z. Wei. Previous studies revealed that YLSPS exhibits bioactivities such as antibacterial, antidepressive, antitumor, hepatoprotective and immunomodulating activities. However, the anticancer effects of YLSPS on lung cancer have not yet been studied, and its mechanism of action remains unclear. The present study investigated the anti-migration/invasion effects of YLSPS and possible mechanisms in lung cancer cells (A549 and Lewis) in vitro and in vivo. The data suggested that YLSPS reversed epithelial-mesenchymal transition (EMT) and inhibited the invasion and migration of lung cancer cells by inhibiting the TGF-ß1-induced ERK signaling pathway. Furthermore, YLSPS reduced the levels of proteins associated with EMT, including vimentin, but increased those of E-cadherin, as determined by Western blotting. In vivo, YLSPS significantly inhibited the growth of xenograft tumors, and decreased the levels of TGF-ß1 and protein markers associated with EMT. Importantly, YLSPS had fewer toxic side effects than cisplatin. Overall, YLSPS significantly delayed non-small cell lung cancer (NSCLC) progression by modulating EMT and TGF-ß1/ERK signaling pathway. The present findings suggest that YLSPS may be a potential adjuvant therapy and drug for improving the tumor microenvironment of lung cancer.

Association between maternal postpartum depression and children's physical growth in early childhood: a birth cohort study.

Background: Untreated maternal postpartum depression (PPD) has consequences for children's physical growth, but no published study has evaluated changes in this effect over time. Here we therefore aimed to evaluate the dynamic effects of PPD on the physical growth of children in a prospective birth cohort. Methods: Between 2015 and 2019, 960 mother-child pairs in Changsha, China were followed up when the child was aged 1-48 months. Data were obtained through household surveys. The mothers' depressive symptoms were measured using the Edinburgh Postpartum Depression Scale (EPDS) at 1 month postpartum. Linear mixed models were used to examine the changes in the association of PPD and EPDS scores with physical growth in six different age groups of children between 1 and 48 months. Results: A total of 604 mother-child pairs completed the follow-up, and 3.3% of mothers reported PPD. No associations were found between PPD and weight or height growth at any age. While EPDS scores were associated with weight gain (ß = -0.014, 95% CI (-0.025, -0.002), P = 0.024) and height growth (ß = -0.044, 95% CI (-0.084, -0.004), P = 0.030) rates at 1-3 months, no associations were found in older children. Limitations: The number of mothers who reported PPD was relatively small, and the measurement of PPD was not continuously taken. Conclusions: After adjustments for confounders, no dynamic association was found between PPD and children's weight and height growth. EPDS scores, in contrast, did negatively affect children's weight and height growth at age 1-3 months, but this effect was not long-lasting.

Association of ambient PM10 and PM2.5 with coronary stenosis measured using selective coronary angiography.

BACKGROUND: Long-term ambient particulate matter (PM) exposure exerts detrimental effects on cardiovascular health. Evidence on the relation of chronically exposed ambient PM10 and PM2.5 with coronary stenosis remains lacking. Our aim was to investigate the association of PM10 and PM2.5 with coronary stenosis in patients undergoing coronary angiography. METHODS: We performed a retrospective cohort study consisting of 7513 individuals who underwent coronary angiography in Fujian Province, China, from January 2019 to December 2021. We calculated a modified Gensini score (GS) to represent the degree of stenosis in coronary arteries by selective coronary angiography. We fitted linear regressions and logistic models to assess the association of PM10 and PM2.5 with coronary stenosis. We employed restricted cubic splines to describe the exposure-response curves. We performed mediation analyses to assess the potential mediators. RESULTS: Long-term ambient PM10 and PM2.5 (prior three years average) exposure was significantly associated with the GS, with a breakpoint concentration of 47.5 µg/m3 and 25.8 µg/m3 for PM10 and PM2.5, respectively, above which we found a linear positive exposure-response relationship of ambient PM with GS. Each 10 µg /m3 increase in PM10 exposure (ß: 4.81, 95 % CI: 0.44-9.19) and PM2.5 exposure [ß: 10.50, 95 % CI: 3.14-17.86] were positively related to the GS. The adjusted odds ratio (OR) for each 10 µg/m3 increment in PM10 exposure on severe coronary stenosis was 1.33 (95 % CI: 1.04-1.76). Correspondingly, the adjusted OR for PM2.5 was 1.87 (95 % CI: 1.24-2.99). The mediation analysis indicated that the effect of PM10 on coronary stenosis may be partially mediated through total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, serum creatinine and blood urea nitrogen, and the effect of PM2.5 may be mediated in part by hemoglobin A1c. CONCLUSION: Our study provides the first evidence that chronic ambient PM10 and PM2.5 exposure was associated with coronary stenosis assessed by GS in patients with suspected coronary artery disease and reveals its potential mediators.

Synthetic bone grafting with preserved cartilage flap via a medial malleolus osteotomy approach to treat osteochondral lesion of the talus: technical note and preliminary clinical results.

PURPOSE: Although various surgical procedures are available for osteochondral lesion of the talus (OLT), there is still no consensus on its best treatment. The purposes of this study were to describe a new surgical technique to treat OLT and to analyze its preliminary clinical results. METHODS: Eight patients were enrolled in this retrospective study between March 2019 and May 2022 in the Second Affiliated Hospital of Chongqing Medical University. All patients were treated by synthetic bone grafting with preserved cartilage flap via a medial malleolus osteotomy approach. The patients' characteristics, operative time, and estimated blood loss were evaluated. Intraoperative photos, preoperative and postoperative X-ray and MRI imaging were recorded. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analog scale (VAS) score were also recorded before surgery and at each follow-up. RESULTS: At six months after the operation, all patients showed bone ingrowth and remodeling according to X-ray and MRI. No obvious defects or ladder was found on the cartilage surface of all patients according to MRI. The AOFAS score improved from 61.63 ± 8.85 (range, 49-74) to 91.13 ± 4.49 (range, 83-97) (p < 0.001) and VAS score improved from 5.50 ± 1.60 (range, 4-8) before surgery to 1.88 ± 0.83 (range, 1-3) (p < 0.001) at latest follow-up. In all eight patients, no wound infection, skin necrosis, or delayed healing of osteotomy was found. CONCLUSION: We proposed a simple and effective technique that restored the shape of the cartilage surface by preserving the cartilage flap and restoring the natural congruency of the subchondral bone by synthetic bone grafting. We found satisfying clinical outcomes in short-term follow-up. Our new technique might be a new surgical option for the treatment of OLT and its effectiveness should be further evaluated.

Effects of N and P addition on nutrient and stoichiometry of rhizosphere and non-rhizosphere soils of alfalfa in alkaline soil.

Nitrogen (N) and phosphorus (P) are important nutrients for plant growth and development. Soil alkalization is one of the main obstacles limiting the sustainable development of agriculture. Northern Ningxia is located in the arid and semi-arid region, with serious soil alkalinization. Alfalfa has the advantages of strong saline-alkali tolerance, high yield, high quality, and wide adaptability. It is an important forage for the comprehensive improvement and rational utilization of saline-alkali land and has great significance for solving land resource shortages, improving the ecological environment, and ensuring food security. It is important to study soil organic carbon (SOC), total N (TN), total P (TP), and stoichiometry of the rhizosphere and non-rhizosphere of alfalfa in alkaline soils. Therefore, N and P were added to the alkaline alfalfa field in the Yinchuan Plain of Hetao Basin in our experiment. Six treatments were set up, i.e., N-free (WN), medium N (MN) for 90 kg/hm2, high N (HN) for 180 kg/hm2, P-free (WP), medium P (MP) for 135 kg/hm2, and high P (HP) for 270 kg/hm2. The results are as follows: The N addition promotes SOC and TN but inhibits TP, and P addition promotes SOC and TP but inhibits TN of three soil layers. The N addition decreases C/N but increases C/P and N/P, while the P addition increases C/N but decreases C/P and N/P of three soil layers. The SOC, TN, TP, C/N, C/P, and N/P under HN and HP treatment reach the significance level (P < 0.05). Appropriate additions of N and P can improve rhizosphere and non-rhizosphere nutrients and stoichiometric structure, facilitating absorption and utilization by alfalfa and improve the production potential of alfalfa in alkaline soil.

Combining conventional ultrasound and ultrasound elastography to predict HER2 status in patients with breast cancer.

Introduction: Identifying the HER2 status of breast cancer patients is important for treatment options. Previous studies have shown that ultrasound features are closely related to the subtype of breast cancer. Methods: In this study, we used features of conventional ultrasound and ultrasound elastography to predict HER2 status. Results and Discussion: The performance of model (AUROC) with features of conventional ultrasound and ultrasound elastography is higher than that of the model with features of conventional ultrasound (0.82 vs. 0.53). The SHAP method was used to explore the interpretability of the models. Compared with HER2- tumors, HER2+ tumors usually have greater elastic modulus parameters and microcalcifications. Therefore, we concluded that the features of conventional ultrasound combined with ultrasound elastography could improve the accuracy for predicting HER2 status.

Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2-5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection.

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

Retraction: Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold.

Retraction of 'Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold' by Donghai Li et al., Biomater. Sci., 2018, 6, 519-537, https://doi.org/10.1039/C7BM00975E.

A Gγ protein regulates alkaline sensitivity in crops.

The use of alkaline salt lands for crop production is hindered by a scarcity of knowledge and breeding efforts for plant alkaline tolerance. Through genome association analysis of sorghum, a naturally high-alkaline-tolerant crop, we detected a major locus, Alkaline Tolerance 1 (AT1), specifically related to alkaline-salinity sensitivity. An at1 allele with a carboxyl-terminal truncation increased sensitivity, whereas knockout of AT1 increased tolerance to alkalinity in sorghum, millet, rice, and maize. AT1 encodes an atypical G protein γ subunit that affects the phosphorylation of aquaporins to modulate the distribution of hydrogen peroxide (H2O2). These processes appear to protect plants against oxidative stress by alkali. Designing knockouts of AT1 homologs or selecting its natural nonfunctional alleles could improve crop productivity in sodic lands.

Bone marrow mesenchymal stem cell-derived exosomal lncRNA KLF3-AS1 stabilizes Sirt1 protein to improve cerebral ischemia/reperfusion injury via miR-206/USP22 axis.

BACKGROUND: Cerebral ischemia/reperfusion (I/R) is a pathological process that occurs in ischemic stroke. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been verified to relieve cerebral I/R-induced inflammatory injury. Hence, we intended to clarify the function of BMSC-Exos-delivered lncRNA KLF3-AS1 (BMSC-Exos KLF3-AS1) in neuroprotection and investigated its potential mechanism. METHODS: To mimic cerebral I/R injury in vivo and in vitro, middle cerebral artery occlusion (MCAO) mice model and oxygen-glucose deprivation (OGD) BV-2 cell model were established. BMSC-Exos KLF3-AS1 were administered in MCAO mice or OGD-exposed cells. The modified neurological severity score (mNSS), shuttle box test, and cresyl violet staining were performed to measure the neuroprotective functions, while cell injury was evaluated with MTT, TUNEL and reactive oxygen species (ROS) assays. Targeted genes and proteins were detected using western blot, qRT-PCR, and immunohistochemistry. The molecular interactions were assessed using RNA immunoprecipitation, co-immunoprecipitation and luciferase assays. RESULTS: BMSC-Exos KLF3-AS1 reduced cerebral infarction and improved neurological function in MCAO mice. Similarly, it also promoted cell viability, suppressed apoptosis, inflammatory injury and ROS production in cells exposed to OGD. BMSC-Exos KLF3-AS1 upregulated the decreased Sirt1 induced by cerebral I/R. Mechanistically, KLF3-AS1 inhibited the ubiquitination of Sirt1 protein through inducing USP22. Additionally, KLF3-AS1 sponged miR-206 to upregulate USP22 expression. Overexpression of miR-206 or silencing of Sirt1 abolished KLF3-AS1-mediated protective effects. CONCLUSION: BMSC-Exos KLF3-AS1 promoted the Sirt1 deubiquitinating to ameliorate cerebral I/R-induced inflammatory injury via KLF3-AS1/miR-206/USP22 network.

The Effects of Nine Compounds on Aldehyde-Oxidase-Related Genes in Bactrocera dorsalis (Hendel).

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) (B. dorsalis) is an important agricultural, major invasive, and quarantine pest that can cause significant damage to the economic value of the fruit and vegetable industry. Male bait is one of the most effective methods of surveying, monitoring, and controlling B. dorsalis. In our study, we constructed cDNA libraries using total RNA extracted independently from the antennae, mouthparts, and thoracic legs of male and female adults and the ovipositors of female adults and screened out four aldehyde-oxidase-related genes (AOX-related), C58800, C66700, C67485, and C67698. Molecular docking predictions showed that eight compounds, including 3,4-dimethoxycinnamyl alcohol, 3,4-dimethoxy-cinnamaldehyde, deet, ethyl N-acetyl-N-butyl-ß-alaninate, n-butyl butyrate, n-butyl butyrate, ethyl butyrate, methyl eugenol, and ethyl acetate, could combine with proteins encoded by the four B. dorsalis AOX-related genes. Furthermore, QPCR was performed to confirm that four compounds, including 3,4-dimethoxy cinnamic aldehyde, butyl levulinic acid ethyl ester (mosquito repellent), butyl butyrate, and methyl eugenol, induced significant changes in the AOX-related genes of B. dorsalis. These results provide useful information and guidance for the batch screening of potentially useful compounds and the search for effective attractants of B. dorsalis.

Temporal molecular program of human hematopoietic stem and progenitor cells after birth.

Hematopoietic stem and progenitor cells (HSPCs) give rise to the blood system and maintain hematopoiesis throughout the human lifespan. Here, we report a transcriptional census of human bone-marrow-derived HSPCs from the neonate, infant, child, adult, and aging stages, showing two subpopulations of multipotent progenitors separated by CD52 expression. From birth to the adult stage, stem and multipotent progenitors shared similar transcriptional alterations, and erythroid potential was enhanced after the infant stage. By integrating transcriptome, chromatin accessibility, and functional data, we further showed that aging hematopoietic stem cells (HSCs) exhibited a bias toward megakaryocytic differentiation. Finally, in comparison with the HSCs from the cord blood, neonate bone-marrow-derived HSCs were more quiescent and had higher long-term regeneration capability and durable self-renewal. Taken together, this work provides an integral transcriptome landscape of HSPCs and identifies their dynamics in post-natal steady-state hemopoiesis, thereby helping explore hematopoiesis in development and diseases.