Mechanism of the apoptosis of bone marrow erythroblasts in rats under hypobaric hypoxia.

This study aimed to investigate the mechanism of the apoptosis of erythroblasts in rat bone marrow after the exposure to hypobaric hypoxia. Male SD rats were randomly divided into three groups. The hypoxic group was kept in a hypobaric hypoxia chamber at a simulated altitude of 5000 m for 7 and 28 days, respectively. The control group was kept at an altitude of 2260 m. We found that myeloid: erythroid (M:E) ratio was significantly lower after hypoxia exposure and the proportions of polychromatic erythroblasts and orthochromatic erythroblasts significantly increased compared to control group, along with significant increase in the proportion of CD71+ cells and apoptosis rate. The expression levels of caspase-3, Bax, and Cyt-C in CD71+ cells were higher after hypoxia exposure than those in control group, while there was no significant difference in the expression levels of TNFR and Fas. In conclusion, after exposure to hypobaric hypoxia the proliferation of peripheral blood and bone marrow erythroblasts in rats increased, and apoptosis also increased, indicating that bone marrow erythroblasts in rats is regulated by both proliferation and apoptosis, and the mitochondrial pathway is one of the important pathways for apoptosis.

Anisotropic growth of gold anchors on CdSe semiconductor quantum platelets for self-assembled architectures with well-connected electronic circuits for the electrochemical detection of enrofloxacin.

Anisotropic growth of nanomaterials enables advances in building diverse and complex architectures, which exhibit unique properties and enrich the choice of nano-building modules for electrochemical sensor devices. Herein, an anisotropic growth method was proposed to anchor gold nanoparticles (AuNPs) onto both ends of quasi-two-dimensional CdSe semiconductor quantum nanoplatelets (NPLs), appearing with a monodisperse and uniform nano-dumbbell shape. Then, these AuNPs were exploited as natural anchor points and further initiated self-assembly to create complex architectures via dithiol bridges. Detailed studies illustrated that the covalent Se-Au bonds facilitate effective charge transfer in the internal metal-semiconductor (M-S) electric field. The narrowed energy gap and up-shifted highest occupied molecular orbital were favored for electron removal during the electro-oxidation process. The ultrathin CdSe NPLs supplied a large specific surface area, carrying remaining holes and abundant active sites for target electro-catalysis. As a result, using the assembled complex as the electrode matrix with well-connected electronic circuits, a reliable electrochemical sensor was achieved for enrofloxacin detection. Under the optimal conditions, the current response exhibits two linear dynamic ranges, 0.01-10.0 µM and 10.0-250 µM, and the detection limit was calculated as 0.0026 µM. This work not only opens up broad application prospects for heterogeneous M-S combinations as effective electrochemical matrixes but also develops reliable antibiotic assays for food and environmental safety.

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models.

BACKGROUND: Gold nanoparticles (GNPs) have been extensively recognized as an active candidate for a large variety of biomedical applications. However, the clinical conversion of specific types of GNPs has been hindered due to their potential liver toxicity. The origin of their hepatotoxicity and the underlying key factors are still ambiguous. Because the size, shape, and surfactant of GNPs all affect their properties and cytotoxicity. An effective and sensitive platform that can provide deep insights into the cause of GNPs' hepatotoxicity in vitro is therefore highly desired. METHODS: Here, hepatocyte organoid models (Hep-orgs) were constructed to evaluate the shape-dependent hepatotoxicity of GNPs. Two types of GNPs with different nanomorphology, gold nanospheres (GNSs) and spiny gold nanobranches (GNBs), were synthesized as the representative samples. Their shape-dependent effects on mice Hep-orgs' morphology, cellular cytoskeletal structure, mitochondrial structure, oxidative stress, and metabolism were carefully investigated. RESULTS: The results showed that GNBs with higher spikiness and tip curvature exhibited more significant cytotoxicity compared to the rounded GNSs. The spike structure of GNBs leads to a mitochondrial damage, oxidative stress, and metabolic disorder in Hep-orgs. Meanwhile, similar trends can be observed in HepG2 cells and mice models, demonstrating the reliability of the Hep-orgs. CONCLUSIONS: Hep-orgs can serve as an effective platform for exploring the interactions between GNPs and liver cells in a 3D perspective, filling the gap between 2D cell models and animal models. This work further revealed that organoids can be used as an indispensable tool to rapidly screen and explore the toxic mechanism of nanomaterials before considering their biomedical functionalities.

Plasma exosomal microRNA expression profiles in patients with high-altitude polycythemia.

High-altitude polycythemia (HAPC) is a chronic mountain sickness characterized by multiple severe ill-effects. Its pathogenesis is still unclear, and till date, no study has been conducted to investigate the plasma exome profile of Tibetan patients with HAPC. In this study, we aimed to elucidate the pathogenesis of HAPC by determining the microRNA (miRNA) signatures. We compared the plasma exosome miRNA expression profiles of eight patients with HAPC and eight healthy controls using next-generation miRNA sequencing. Further, we extracted and identified plasma exosomes using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to validate differentially expressed plasma exosomal miRNAs. Finally, we analyzed the diagnostic values of the differentially expressed miRNAs for HAPC using receiver operating characteristic (ROC) curves. We detected 2007 miRNAs from confirmed plasma exosomes, including 1342 known miRNAs and 665 newly predicted miRNAs. We verified the expression of the top 10 differentially expressed miRNAs via qRT-PCR. Patients with HAPC showed significantly upregulated hsa-miR-122-5p, hsa-miR-423-5p, hsa-miR-4433b-3p, hsa-miR-1291, and hsa-miR-106b-5p expression levels, while hsa-miR-200c-3p expression was downregulated. This study may provide background knowledge for future studies on HAPC studies, which may further facilitate the development of novel therapies against this common disease.

Metal-Based Aerogels Catalysts for Electrocatalytic CO2 Reduction.

General strategies for metal aerogel synthesis, including single-metal, transition-metal doped, multi-metal-doped, and nano-metal-doped carbon aerogel are described. In addition, the latest applications of several of the above-mentioned metal aerogels in electrocatalytic CO2 reduction are discussed. Finally, considering the possibility of future applications of electrocatalytic CO2 reduction technology, a vision for industrialization and directions that can be optimized are proposed.

Pharmacokinetics and tissue distribution of trans-ferulic acid-4-ß-glucoside in rats using UPLC-MS/MS.

Trans-ferulic acid-4-ß-glucoside (FAG) is a monomer extracted from Radix Aconiti Lateralis Preparata, which is a potential candidate for the prevention and treatment of cold injury. To determine the concentration of FAG in rats, it is essential to develop an ultra-performance liquid chromatography coupled with MS/MS method. Chromatographic separation was achieved by an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm). A Xevo triple quadrupole tandem mass spectrometer was used to quantitatively determine FAG in the negative-ion mode. The standard calibration curve was linear over the concentration range of 0.1-100 µg/mL and 0.0626-31.28 µg/g for rat plasma and liver tissue homogenate samples, respectively. The inter- and intra-batch precision (% relative standard deviation) of the assay was ≤8.29%, and accuracy (% relative error) ranged from -7.41 to 10.99%. The matrix effect was between 92.99 and 102.39%. The oral absolute bioavailability of FAG was obtained as 1.80%. The results of tissue distribution suggested that FAG spread rarely in the liver and brown adipose, which was not propitious to exert its ability to treat cold injury. In general, these studies were significant to provide necessary information for further study.

Isolation and evaluation of strong endogenous promoters for the heterologous expression of proteins in Pichia pastoris.

BACKGROUND: The heterologous expression of biosynthetic pathway genes for pharmaceutical or fine chemical production usually requires to express more than one gene in the host cells. In eukaryotes, the pathway flux is typically balanced by controlling the transcript levels of the genes involved. It is difficult to balance the stoichiometric fine-tuning of the reaction steps of the pathway by acting on one or two promoters. Furthermore, the promoter used should not be identical to avoid loss of inserted genes by recombination or dilute its transcription factors. RESULTS: Based on RNA-seq data, 18 candidate genes with the highest transcription levels at three carbon sources (glucose, glycerol and methanol) were selected and their promoter regions were isolated from GS115 genome. The performance of these promoters on the level of protein production was evaluated using LacZ and EGFP genes as the reporters, respectively. These isolated promoters all exhibited activity to express LacZ gene. Using LacZ as a reporter, of the 18 promoter candidates, 9 promoters showed higher expression levels for the reporter compare to pGAP, a strong promoter widely used for constitutive expression of heterologous proteins in Pichia pastoris. These promoters with high expression levels were further employed to evaluate secreted expression using EGFP as a reporter. 6 promoters exhibited stronger protein expression compare to pGAP. Interestingly, the protein expression driven by pFDH1 was slightly higher than that of commonly used pAOX1 at methanol, and methanol-induced expression of pFDH1 was not repressed by glycerol. CONCLUSION: The various promoters identified in this study could be used for heterologous expression of biosynthetic pathway genes for pharmaceutical or fine chemical production. the methanol-induced pFDH1 that is not repressed by glycerol is an attractive alternative to pAOX1 and may provide a novel way to produce heterologous proteins in Pichia pastoris.

Water-Induced Formation of Ni2 P-Ni12 P5 Interfaces with Superior Electrocatalytic Activity toward Hydrogen Evolution Reaction.

The interface between two material phases typically exhibits unique electronic states distinct from their pure phases, thus, providing a very promising channel to construct catalysts with excellent activity and stability. Here, water-induced formation of Ni2 P-Ni12 P5 through a one-step phosphorization of nickel foam (NF) is demonstrated for the first time. The abundant interfaces endow Ni2 P-Ni12 P5 /NF with excellent electrocatalytic hydrogen evolution reaction (HER) activity in alkaline condition, with an overpotential of 76 mV at a current density of 10 mA cm-2 and of 147 mV at a current density of 100 mA cm-2 , and a Tafel slope of 68.0 mV dec-1 . The Ni2 P-Ni12 P5 /NF also exhibits better durability than Pt/C/NF during HER at relatively large overpotential. Density functional theory calculations show that the electronic states at the Ni2 P-Ni12 P5 interface are greatly altered, which enables optimal hydrogen adsorption, accelerates the charge transfer kinetics, and thus enhances the HER electrocatalytic activity. Superior overall water-splitting performance is also obtained by combining Ni2 P-Ni12 P5 /NF with NiFe-layered double hydroxide (LDH) oxygen evolution reaction (OER) catalyst. Overpotentials of the cell for achieving 10 mA cm-2 are only 324 mV. This work provides a facile method for the preparation of interfaces between different nickel phosphide polymorphs toward HER.

Physicochemical Characterization and Biopharmaceutical Evaluation of ZWF: A Novel Anticancer Drug for the Treatment of Non-small Cell Lung Cancer.

The orally available novel small molecule drug ZWF is under preclinical development for an anticancer purpose. The present study aimed to assess the viability of developing ZWF as a form of oral formulation for clinical application based on the principles of biopharmaceutics and pharmacokinetics. The crucial physicochemical properties of ZWF were determined by in vitro assays. The in situ gastrointestinal absorption characteristics and in vivo pharmacokinetic behaviors of ZWF in rats were characterized. The solubility of ZWF showed a highly pH-dependent profile, decreasing from 25,392.89 to 20.48 µg/mL as the solution pH increased from 1.0 to 5.8. In PBS with a pH of 1.0 to 5.8, the LogP value of ZWF ranged from -2.35 to 2.20 and was gradually increased as the pH value increased. ZWF was partially absorbed in the stomach, and the favorable absorption sites were the duodenum, jejunum, and ileum. Pharmacokinetic studies showed that the AUC(0-t) and Cmax values of ZWF after its oral administration as a suspension prepared with 0.5% CMC-Na were increased by 18.97% and 40% than that with normal saline, providing a model oral formulation of ZWF with ideal bioavailability and system exposure in rats. From the perspective of oral absorption, ZWF possessed appealing qualities as a drug candidate and could be prepared as an oral preparation for clinical application. The present study has established a fundamental foundation for the development and quality evaluation of the ZWF oral formulations.

EPAS1 regulates proliferation of erythroblasts in chronic mountain sickness.

Excessive erythrocytosis (EE) is a characteristic of chronic mountain sickness (CMS). Currently, the pathogenesis of CMS remains unclear. This study was intended to investigate the role of EPAS1 in the proliferation of erythroblasts in CMS. Changes of HIF-1α and EPAS1/HIF-2α in the bone marrow erythroblasts of 21 patients with CMS and 14 control subjects residing at the same altitudes were determined by RT-qPCR and western blotting. We also developed a lentiviral vector, Lv-EPAS1/sh-EPAS1, to over-express/silence EPAS1 in K562 cells. Cells cycle and proliferation were detected by flow cytometry. Transcriptome analyses were carried out on Illumina. CMS patients showed a higher expression of EPAS1/HIF-2α in the bone marrow erythroblasts than those of controls. Variations in EPAS1 expression in CMS patients were positively correlated with RBC levels, and negatively correlated with SaO2. Over-expressing of EPAS1 in K562 cells accelerated the erythroid cells cycle progression and promoted the erythroid cells proliferation-and vice versa. Transcriptome data indicated that proliferation-related DEGs were significantly enriched in EPAS1 overexpression/silencing K562 cells. Our results suggest that EPAS1 might participate in the pathogenesis of EE by regulating the proliferation of erythroblasts.

Downregulation of intrinsic apoptosis pathway in erythroblasts contributes to excessive erythrocytosis of chronic mountain sickness.

Chronic mountain sickness (CMS) has a higher incidence in the plateau region and is characterized by excessive erythrocytosis and hypoxemia. Bcl-2 family plays an important role in the process of erythropoiesis and the regulation of apoptosis. This study aimed to examine the change in apoptosis of erythroblasts in CMS patients and explore the involvement of Bcl-2 family. Bone marrow mononuclear cells (BMMNCs) were isolated by density gradient centrifugation from 18 CMS patients and 17 control participants. The apoptotic rate, mitochondrial membrane potential (MMP), the protein expression of caspase-3, TNFR, Fas, Bcl-2, Bax and Cyt-C were examined by flow cytometry, and mRNA expression was determined by real-time PCR. The results showed that apoptotic rate of erythroblasts was lower and MMP was higher in CMS group than in control group. The mRNA and protein expression levels of Bcl-2 were higher while Bax level was lower in CMS group than in control group. In CMS group, the apoptosis rate of CD71+ erythroblasts was negatively correlated with the ratio of CD71+ cells in BMMNCs and positively correlated with hemoglobin level. In conclusion, erythroblasts apoptosis is decreased due to the regulation of the expression of Bcl-2 family members in the erythroblasts of CMS patients.

Nanoscaled porphyrinic metal-organic framework for photodynamic/photothermal therapy of tumor.

Nanoagents achieving photodynamic therapy (PDT) and photothermal therapy (PTT) combination treatment with improved therapeutic effect are highly desirable. However, the incorporation of both PDT and PTT into a single nanoagent often requires multistep fabrication process. Herein, we report that photoactive porphyrin ligands have been successfully introduced into Zn-TCPP structure to construct the nanoagents that possesses photodynamic performance and photothermal performance simultaneously. Such a nanoagent enables the generation of single oxygen and heat under laser irradiation. Additionally, it exhibits satisfactory biocompatibility and high light toxicity against cancer cells. The current work provides a feasible approach to introduce both PDT and PTT into a single nanoplatform.

Time-Dependent Hormetic Response of Soil Alkaline Phosphatase Induced by Cd and the Association with Bacterial Community Composition.

Hormetic dose-response that involved Cd in soils is increasingly paid attentions for risk assessment of Cd toxicity, but insufficient studies were conducted to define the temporary modification of soil enzyme and the potential microbial responses. The present study chooses soil alkaline phosphatase (ALP) as endpoint to uncover the time-dependent hormetic responses to low doses of Cd and its association with bacterial community composition. The results showed that addition of 0.01-3.0 mg kg-1 Cd significantly increased ALP's activities with maximum stimulatory magnitude of 11.4-27.2%, indicating a typical hormesis. The response started at 12 h after Cd addition and maintained about 24 h. This demonstrated that the hormetic response is time-dependent and transient. Changes of soil bacterial community composition showed that, at 6 h, relative abundances (RAs) of Proteobacteria and Firmicutes at phylum and Pontibacter, Bacillaceae-Bacillus, Bacillaceae1-Bacillus, and Paenisporosarcina at genus significantly correlated with ALP's activities at 12-36 h (P < 0.05). This suggests that soil bacteria likely showed an earlier response to Cd and potentially contributes to the subsequent soil enzyme's hormesis. In addition, it was found that Gram-negative bacteria other than Gram-positive bacteria are prone to exhibiting a hormetic response under Cd stress. Our findings provide much insight into ecotoxicological risk assessment for soil Cd pollution.

Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes: A cross-sectional study.

BACKGROUND: Dietary fiber (DF) intake may have a protective effect against type 2 diabetes (T2D); however, its relationship with diabetic kidney disease (DKD) remains unclear. AIM: To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018. DF intake was assessed through 24-h dietary recall interviews, and DKD diagnosis in individuals with T2D was based on predefined criteria, including albuminuria, impaired glomerular filtration rate, or a combination of both. Logistic regression analysis was used to assess the association between DF intake and DKD, and comprehensive subgroup and sensitivity analyses were performed. RESULTS: Among the 6032 participants, 38.4% had DKD. With lower DF intake-T1 (≤ 6.4 g/1000 kcal/day)-as a reference, the adjusted odds ratio for DF and DKD for levels T2 (6.5-10.0 g/1000 kcal/day) and T3 (≥ 10.1 g/1000 kcal/day) were 0.97 (95%CI: 0.84-1.12, P = 0.674) and 0.79 (95%CI: 0.68-0.92, P = 0.002), respectively. The subgroup analysis yielded consistent results across various demographic and health-related subgroups, with no statistically significant interactions (all P > 0.05). CONCLUSION: In United States adults with T2D, increased DF intake may be related to reduced DKD incidence. Further research is required to confirm these findings.

Development and validation of a nomogram for predicting difficult radial artery cannulation in adult surgical patients.

Background: Radial artery cannulation is an invasive procedure commonly performed in patients in the perioperative time, in the intensive care unit, and in other critical care settings. The current study aimed to explore the preoperative risk factors associated with difficult radial artery cannulation and develop a nomogram model for adult patients undergoing major surgery. This nomogram may optimize preoperative clinical decision-making, thereby reducing the number of puncture attempts and preventing associated complications. Methods: This was a single-center prospective cohort study. Between December 2021 and May 2022, 530 adult surgical patients were enrolled. The patients were randomized into the training and validation cohorts at a ratio of 8:2. Radial artery cannulation was performed before the induction of anesthesia. Univariate and multivariate logistic regression analyses were performed to identify variables that were significantly associated with difficult radial artery cannulation. These variables were then incorporated into the nomogram. The discrimination and calibration abilities of the nomogram were assessed. Results: One hundred and seventy-three (41.7 %) patients in the training cohort had difficult radial artery cannulation. Based on multivariate analysis, the independent risk factors were wrist circumference, anatomical abnormalities, BMI <18.5 kg/m2, grade II hypertension, hypotension, and history of chemotherapy and stroke. The concordance indices were 0.765 (95 % confidence interval [CI]: 0.719-0.812) and 0.808 (95 % CI: 0.725-0.890) in the training and validation cohorts, respectively. The calibration curve showed good agreement between the actual and predicted risks. Conclusions: A preoperative predictive model for difficult radial artery cannulation in adult patients undergoing surgery was developed and validated. This model can provide reliable data for optimizing preoperative clinical decision-making.

Polydopamine-based plasmonic nanocomposites: rational designs and applications.

Taking advantage of its adhesive nature and chemical reactivity, polydopamine (PDA) has recently been integrated with plasmonic nanoparticles to yield unprecedented hybrid nanostructures. With advanced architectures and optical properties, PDA-based plasmonic nanocomposites have showcased their potential in a wide spectrum of plasmon-driven applications, ranging from catalysis and chemical sensing, to drug delivery and photothermal therapy. The rational design of PDA-based plasmonic nanocomposites entails different material features of PDA and necessitates a thorough understanding of the sophisticated PDA chemistry; yet, there is still a lack of a systematic review on their fabrication strategies, plasmonic properties, and applications. In this Highlight review, five representative types of PDA-based plasmonic nanocomposites will be featured. Specifically, their design principles, synthetic strategies, and optical behaviors will be elucidated with an emphasis on the irreplaceable roles of PDA in the synthetic mechanisms. Together, their essential functions in diverse applications will be outlined. Lastly, existing challenges and outlooks on the rational design and assembly of next-generation PDA-based plasmonic nanocomposites will be presented. This Highlight review aims to provide synthetic insights and hints to inspire and aid researchers to innovate PDA-based plasmonic nanocomposites.

Yolk-shelled silver nanowire@amorphous metal-organic framework for controlled drug delivery and light-promoting infected wound healing.

Bacteria-infected wounds healing has been greatly hindered by antibiotic resistance and persistent inflammation. It is crucial to develop multifunctional nanocomposites that possess effective antibacterial properties and can simultaneously accelerate the wound healing process to overcome the above challenges. Herein, we prepared a yolk-shell structured Ag nanowires (NWs)@amorphous hollow ZIF-67 by etching ZIF-67 onto the Ag NWs for infected wound healing for the first time. The etched hollow structure of amorphous ZIF-67 in the nanocomposite makes it a promising platform for loading healing-promoting drugs. We extensively studied the antibacterial and healing-promoting properties of the curcumin (CCM)-loaded nanocomposite (Ag NWs@C-HZ67). Ag NWs, being noble metal materials with plasmonic effects, can absorb a broad range of natural light and convert it to thermal energy. This photothermal conversion further improves the release of antibacterial components and wound healing drugs when exposed to light. During the healing process of an infected wound, Ag and Co ions were released from Ag NWs@C-HZ67 upon direct contact with the wound exudate and under the influence of light irradiation. Simultaneously, the loaded CCM leaked out to repair the infected wound. The minimum inhibitory concentrations of the Ag NWs@C-HZ67 groups against Escherichia coli and Staphylococcus aureus bacteria decreased to 3 and 3 µg ml-1 when exposed to white light. Furthermore, an in vivo assessment of infected wound healing demonstrated that combining Ag NWs@C-HZ67 with light significantly accelerated the wound healing process, achieving 70% healing by the 6th day and almost complete healing by the 8th day. This advanced nanocomposite, consisting of components that possess antibacterial and growth-promoting properties, offers a safe, effective and clinically-translatable solution for accelerating the healing process of infected wounds.

China's carbon emissions peaking pathway in the post-COVID-19 era.

Several countries have weakened the carbon emission objectives to immediately revive the economy in the post-COVID-19 era. Therefore, it is a challenge worth addressing to readjust the economic development and carbon emissions after the COVID-19 pandemic. From the perspective of China's carbon emissions, this study shapes a multi-objective dynamic optimization model based on the material capital input and R&D support aspects. The proposed model imitates China's economic development, energy consumption, and carbon dioxide (CO2) emissions. The model provides theoretical suggestion for the government to revive economic development and reduce carbon emissions. In addition, this research paper compares the evolutionary path of carbon peak under the two scenarios. The first scenario requires maintaining the pre-epidemic development state and pace of carbon emission reduction, referred to as the baseline scenario (BS). The second scenario is termed the optimal scenario (OS) based on the model calculation. The study findings exhibit that China is not able to accomplish the 2030 CO2 emission peak objective, under the BS. However, China under the OS shall expectedly accomplish the 2030 carbon peak objective ahead of schedule, while the peak CO2 emissions shall be around 11.28 billion tons. Reportedly, at least 788 million tons of CO2 reduction contrasted with the BS. Furthermore, there is an 80.35% decline in energy intensity as compared to 2005. Consequently, the study results contribute theoretical guidance for the "green recovery" of China's economy and the adjustment of carbon emission reduction's path after the COVID-19 epidemic. Consistent with this, the research method also contributes to the theoretical research on carbon emissions at the national level while extending a new research perspective for the economic and environmental fields.

Weighted gene co-expression network analysis reveals the hub genes associated with pulmonary hypertension.

Pulmonary hypertension (PH) is a cardiopulmonary vascular disease that acutely endangers human health and can be fatal. It progresses rapidly and has a high mortality rate. Its pathophysiology is complicated and still not completely elucidated; therefore, achieving treatment breakthroughs are difficult. In this study, data from 58 normal controls and 135 patients with PH were extracted from the GSE24988, GSE113439, and GSE117261 datasets in the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs). In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Weighted gene co-expression network analysis (WGCNA) was used to identify the key modules and hub genes associated with PH. Eight PH-associated hub genes were identified. Furthermore, correlation analysis between immune cell infiltration and hub genes was performed, and the receiver operating characteristic (ROC) curves showed that TARDBP had the best diagnostic efficacy. Moreover, a rat hypoxic pulmonary hypertension (HPH) model was generated, and the expression of hub genes in the lungs and pulmonary arteries of HPH rats was verified using western blotting assays. Our results showed that mTOR, PSMD2, RBM8A, SMARCA4, TARDBP, and UBXN7 were highly expressed in the lungs. In addition, EFTUD2, mTOR, RBM8A, SMARCA4, TARDBP, and UBXN7 were significantly upregulated, whereas DDB1 was significantly downregulated in the pulmonary arteries of HPH rats compared with those of controls. In conclusion, we identified PH hub genes with diagnostic and predictive value by performing WGCNA on data from the GEO database. Furthermore, we provided novel insights of PH that might be utilized to evaluate potential biomarker genes and therapeutic targets.

New insights into the role of soil properties in driving cadmium-induced hormesis in soil alkaline phosphatase under vegetation cover change.

This study investigated the hormetic responses of soil alkaline phosphatase (ALP) to exogenous Cd under five different vegetation cover types in a typical coastal wetland, including mudflat (Mud), Phragmites australis (PA), Spartina alterniflora (SA), Metasequoia glyptostroboides (MG), and Cinnamomum camphora (CC). The results showed that the activity of soil ALP was significantly enhanced by exogenous 0.3-1.0, 0.2-0.8, 0.05-0.3, 0.05-0.6, and 0.05-0.60 mg Cd /kg in Mud, PA, SA, MG, and CC, respectively. Moreover, the Horzone (an integrated indicator of the stimulation phase) of Mud and PA was significantly higher than that of SA, MG, and CC. Multiple factor analysis revealed that soil chemical properties and soil bacteria community play an important role in the hormetic effect of soil ALP to Cd stress. Soil electric conductivity (EC) and the relative abundance of Gammaproteobacteria were also identified as key drivers of the hormetic effects of Cd on soil ALP under five vegetation cover types. These findings suggest that the soil ecosystem had better resistance to exogenous Cd stress under mudflat and native species (PA) than invasive species (SA), and artificial forests (MG and CC) when soil ALP activity was the test endpoint. Consequently, this study is beneficial for future ecological risk assessment of soil Cd contamination under divergent vegetation covers.