The First Discovery of Spherical Carborane Molecular Ferroelectric Crystals.

Carborane compounds, known for their exceptional thermal stability and non-toxic attributes, have garnered widespread utility in medicine, supramolecular design, coordination/organometallic chemistry, and others. Although there is considerable interest among chemists, the integration of suitable carborane molecules into ferroelectric materials remains a formidable challenge. In this study, we employ the quasi-spherical design strategy to introduce functional groups at the boron vertices of the o-carborane cage, aiming to reduce molecular symmetry. This approach led to the successful synthesis of the pioneering ferroelectric crystals composed of cage-like carboranes: 9-OH-o-carborane (1) and 9-SH-o-carborane (2), which undergo above-room ferroelectric phase transitions (Tc) at approximately 367 K and 347 K. Interestingly, 1 and 2 represent uniaxial and multiaxial ferroelectrics respectively, with 2 exhibiting six polar axes and as many as twelve equivalent polarization directions. As the pioneering instance of carborane ferroelectric crystals, this study introduces a novel structural archetype for molecular ferroelectrics, thereby providing fresh insights into the exploration of molecular ferroelectric crystals with promising applications.

Structure and dynamics of microbial communities associated with the resurrection plant Boea hygrometrica in response to drought stress.

MAIN CONCLUSION: The resurrection plant Boea hygrometrica selectively recruits and assembles drought-specific microbial communities across the plant-soil compartments, which may benefit plant growth and fitness under extreme drought conditions. Plant-associated microbes are essential for facilitating plant growth and fitness under drought stress. The resurrection plant Boea hygrometrica in natural habitats with seasonal rainfall can survive rapid desiccation, yet their interaction with microbiomes under drought conditions remains unexplored. This study examined the bacterial and fungal microbiome structure and drought response across plant-soil compartments of B. hygrometrica by high-throughput amplicon sequencing of 16S rRNA gene and internal transcribed spacer. Our results demonstrated that the diversity, composition, and functional profile of the microbial community varied considerably across the plant-soil compartments and were strongly affected by drought stress. Bacterial and fungal diversity was significantly reduced from soil to endosphere and belowground to aboveground compartments. The compartment-specific enrichment of the dominant bacteria phylum Cyanobacteriota and genus Methylorubrum in leaf endosphere, genera Pseudonocardia in rhizosphere soil and Actinoplanes in root endosphere, and fungal phylum Ascomycota in the aboveground compartments and genera Knufia in root endosphere and Cladosporium in leaf endosphere composed part of the core microbiota with corresponding enrichment of beneficial functions for plant growth and fitness. Moreover, the recruitment of dominant microbial genera Sphingosinicella and Plectosphaerella, Ceratobasidiaceae mycorrhizal fungi, and numerous plant growth-promoting bacteria involving nutrient supply and auxin regulation was observed in desiccated B. hygrometrica plants. Our results suggest that the stable assembled drought-specific microbial community of B. hygrometrica may contribute to plant survival under extreme environments and provide valuable microbial resources for the microbe-mediated drought tolerance enhancement in crops.

Regioselective 1,4-/1,3-Difunctionalization of 1,3-Enynes with Selenosulfonates in Water.

1,4-/1,3-Regioselective bifunctionalization of 1,3-enynes with selenosulfonates in water under catalyst-free conditions for the construction of sulfonyl allene and 1,3-disulfonyl-conjugated dienes respectively have been developed. The reactions feature mild reaction conditions in aqueous solution and remarkable regioselectivity controlled by substrates.

Single-cell analysis defines LGALS1 + fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma.

The incidence rate of intrahepatic cholangiocarcinoma (ICC), which has a poor prognosis, is rapidly increasing. To investigate the intratumor heterogeneity of ICC, we analyzed single-cell RNA sequencing data from the primary tumor and adjacent normal tissues of 14 treatment-naïve patients. We identified ten major cell types, along with 45 subclusters of cells. Notably, we identified a fibroblast cluster, Fibroblast_LUM+, which was preferably enriched in tumor tissues and actively interacted with cholangiocytes. LGALS1 was verified as a marker gene of Fibroblast_LUM+, contributing to the malignant phenotype of ICC. The higher amount of LGALS1 + fibroblasts were associated with poorer overall survival in ICC patients. LGALS1 + fibroblasts activated the proliferation and migration of tumor cells by upregulating the expression levels of CCR2, ADAM15, and ß-integrin. Silencing LGALS1 in cancer-associated fibroblasts (CAFs) suppressed CAF-augmented tumor cell migration and invasion in vitro as well as tumor formation in vivo, suggesting that blockade of LGALS1 serves as a potential therapeutic approach for ICC. Taken together, our single-cell analysis provides insight into the interaction between malignant cells and specific subtypes of fibroblasts. Our work will further the understanding of the intratumor heterogeneity of ICC and provide novel strategies for the treatment of ICC by targeting fibroblasts in the tumor microenvironment.

Using ozone nanobubbles, and microalgae to promote the removal of nutrients from aquaculture wastewater: Insights from the changes of microbiomes.

Integrated aquaculture wastewater treatment systems (IAWTSs) are widely used in treating aquaculture wastewater with the aeration-microalgae unit serving as an important component. In this study, we artificially constructed an IAWTS and applied two aeration-microalgae methods: ordinary aeration or ozone nanobubbles (ONBs) with microalgae (Nannochloropsis oculata). The impact of N.oculata and ONBs on the removal performance of nutrients and the underlying micro-ecological mechanisms were investigated using 16S rRNA gene amplicon sequencing. The results demonstrated that the combined use of ONBs and N.oculata exhibited superior purification effects with 78.25%, 76.59% and 86.71% removal of CODMn, TN and TP. N.oculata played a pivotal role as the primary element in wastewater purification, while ONBs influenced nutrient dynamics by affecting both N.oculata and bacterial communities. N.oculata actively shaped bacterial communities, with a specific focus on nitrogen and phosphorus cycling in the micro-environment remodeled by ONBs. Rare bacterial communities displayed heightened activity in response to the changes in N.oculata, ONBs, and nutrient levels. These findings provide a novel approach to improve the technological processes the IAWTS, contributing to the advancement of sustainable aquaculture practices by offering valuable insights into wastewater purification efficiency and micro-ecological mechanisms.

Peimenine unleashes therapeutic promise in urothelial bladder cancer: inhibition of proliferation, induction of cell death and modulation of key pathways.

Peimenine (PEI) is a steroid alkaloid substance isolated from Fritillaria thunbergii bulbs. It has various pharmacological activities, such as relief from coughs and asthma, expectorant properties, antibacterial effects, sedative qualities, and anti-inflammatory properties. Notably, PEI can effectively inhibit the proliferation and tumor formation of liver cancer and osteosarcoma cells by inducing autophagic cell death. However, the precise effect and mechanisms of PEI on urothelial bladder cancer (UBC) cells remain uncertain. Thus, this study aims to investigate the impact of PEI on UBC cells both in vivo and in vitro. The IC50 values of BIU-87 and EJ-1 cells after 48 h were 710.3 and 651.1 µg/mL, respectively. Additionally, PEI blocked the cell cycle in BIU-87 and EJ-1 cells during the G1 phase. Furthermore, it hindered the migration of BIU-87 and EJ-1 cells substantially. PEI significantly inhibited the tumor development of EJ-1 cells within the xenograft tumor model in vivo. Mechanically, PEI augmented the protein and mRNA expression of BIM, BAK1, and Cytochrome C (CYCS) in UBC cells. Taken together, PEI suppressed the proliferation of UBC cells both in vitro and in vivo by inducing cell death and cell cycle arrest, suggesting that PEI could be applied in the treatment of UBC.

Study on Mudcake disintegration in clayey strata during shield tunneling: Effects of dispersants and bentonite slurry.

While tunnel boring machines (TBMs) tunneling in clayey strata, the adhered excavated soil on the cutterhead and cutting tools tends to form mudcake after compaction and consolidation. Mudcake can obstruct the cutterhead openings and rendering the cutting tools ineffective, leads to a substantial reduction in advance rate. Dispersants are recognized as an effective method for the disintegration of mudcakes. A novel set of equipment, comprising a mudcake compression device and a mudcake disintegration apparatus, is developed for assessing mudcake disintegration properties. The results showed that mudcakes underwent a tripartite disintegration process in water, including an initial stage, a rapid disintegration stage, and a stable stage. In the initial stage, the mudcakes absorbed water before disintegration, resulting in marginal changes in the weight of the disintegrated mudcakes. In the rapid disintegration stage, the weight of the disintegrated mudcakes increased quickly. During the stable stage, the weight of the disintegrated mudcakes remained relatively constant. The submersion of mudcakes in a dispersant solution substantially increased the rate of disintegration. Greater dispersant concentration corresponded to an increase in the disintegration rate. No weight gain was observed in mudcakes during the initial disintegration stage. When mudcakes disintegrated in a bentonite slurry, the weight of the disintegrated mudcakes initially decreased and then stabilized. The weight of the disintegrated mudcakes turned negative, indicating an increase in the weight of mudcakes. This suggested that bentonite significantly hindered mudcake disintegration.

Characterizing the Dynamic Expression of C1q/TNF-α-Related Protein 6 (CTRP6) during Pregnancy in Humans and Mice with Gestational Diabetes Mellitus.

AIM: C1q/TNF-related protein 6 (CTRP6) is a novel adipokine involved in insulin resistance. Thus, we aim to investigate the expression profile of CTRP6 in the plasma, adipose tissue and placenta of GDM patients and mice. METHODS: Chinese Han pregnant women (GDM n = 9, control n = 10) with a scheduled caesarean section delivery were recruited. A number of high-fat diet (HFD) induced-pregnancy C57BL/6 mice were chosen as an animal model of GDM. Circulating levels of CTRP6 and adiponectin were examined by ELISA. CTRP6 expression in adipose tissue and placenta were detected by real-time qPCR and WB. RESULT: Plasma CTRP6 levels were decreased during the first and second trimesters in mice, as well as the second and third trimesters in patients, while they were increased at delivery in GDM patients and mice. Plasma CTRP6 levels were significantly correlated with WBC, systolic pressure, diastolic pressure and fasting blood glucose. Moreover, CTRP6 mRNA expression in the subcutaneous (sWAT) and omental white adipose tissue (oWAT), as well as in the placenta, was significantly higher in GDM human patients at cesarean delivery. Furthermore, the mRNA expression of Ctrp6 was increased in the sWAT and visceral WAT (vWAT), whilst decreased in the interscapular brown adipose tissue (iBAT), of GDM mice at cesarean delivery. CONCLUSION: Dynamically expressed CTRP6 may be served as a candidate target for treatment of GDM.

Study on the Mechanism of Action of the Traditional Chinese Medical Prescription Gushukang in Treating Osteoporosis Based on Network Pharmacology and Experimental Verification.

BACKGROUND: Gushukang (GSK), a traditional Chinese medical prescription, has made a great and extensive contribution to the treatment of different forms of osteoporosis, but polypharmacology studies of its mechanism of action are lacking. This study investigates the pharmacological mechanism of osteoporosis using network pharmacology and molecular docking. Experimental verification was carried out to confirm the efficacy of GSK on RANKLinduced osteoclast differentiation in RAW264.7 cells to verify the network pharmacology studies. METHODS: The effective chemical components and corresponding targets of osteoporosis with oral bioavailability of more than 30% and drug-like properties greater than 0.18 were searched in the TCMSP and TCM-ID databases. DrugBank, GeneCards, OMIM, TTD, and other databases were examined for targets related to osteoporosis. Using Cytoscape software, a network of possible TCM-active ingredient-osteoporosis targets was created. STRING software was used to create the networks of protein-protein interactions. The DAVID program was carried out to conduct GO and KEGG pathway enrichment analyses of the targets. Molecular docking and pattern of action analysis were carried out using software like AutoDock Vina and Discovery Studio Visualizer. The growth media for RAW264.7 cells contained varying doses of GSK serum and 50 ng/mL RANKL. The activity of TRAP was altered. Additionally, genes related to osteoclasts were examined using an RT-PCR assay. RESULTS: Network pharmacological analysis revealed that the primary efficacy targets of osteoporosis were PTGS2, PTGS1, HSP90AA1, NCOA2, ADRB2, ESR1, NCOA1, and AR. The pharmacological targets of osteoporosis may be mediated by substances including quercetin, kaempferol, luteolin, naringenin, icariin, anthocyanin, tanshinone IIA, and cryptotanshinone. GSK markedly inhibited RANKL-induced TRAP activity. qRT-PCR results revealed decreased expression of the PTGS2 and ADRB2 genes upon GSK treatment. CONCLUSION: The findings of network pharmacology, molecular docking, as well as experimental verification provide a new further study for elucidating the pharmacodynamic substance basis and polypharmacology mechanism of GSK in treating osteoporosis.

Development of an atmospheric pressure plasma-based OES device for in-situ mapping of Cd and related elements in plants.

We have developed an innovative optical emission spectrometry imaging device integrating a diode laser for sample introduction and an atmospheric pressure plasma based on dielectric barrier discharge for atomization and excitation. By optimizing the device parameters and ensuring appropriate leaf moisture, we achieved effective imaging with a lateral resolution as low as 50 µm. This device allows for tracking the accumulation of Cd and related species such as K, Zn, and O2+∙, in plant leaves exposed to different Cd levels and culture times. The results obtained are comparable to established in-lab imaging and quantitative methods. With its features of compact construction, minimal sample preparation, ease of operation, and low limit of detection (0.04 µg/g for Cd), this novel methodology shows promise as an in-situ elemental imaging tool for interdisciplinary applications.

Study on the Alkali-Free Three-Component Flooding System in the Daqing Oilfield.

ASP flooding is an important method to further improve oil recovery by a large margin. At present, it has entered the stage of industrial application, but there are still problems of scaling in the injection production system and high production maintenance costs. Based on the industrialized mature technology of weak alkali ASP flooding, sodium chloride is used to replace sodium carbonate, and the alkali-free three-component flooding (TC) system in the Daqing Oilfield is developed by mixing with petroleum sulfonate and partially hydrolyzed polyacrylamide. Based on the experiments of viscosity increasing, interface performance, stability, adsorption, and oil displacement effect, the differences between the alkali-free TC system and the weak alkali ASP system are compared and analyzed. The laboratory research results show that both systems are basically the same in terms of viscosity, viscoelasticity, shear resistance, interfacial activity, stability, and flowability. Due to the lack of alkaline water, the adsorption, emulsification, and oil displacement performance of the alkali-free TC system is slightly lower than that of the weak alkali ASP system. The recovery factor of core flooding can be increased by 27.31% over water flooding, which is 2.56 percentage points lower than that of the weak alkali ASP system. On the premise of the same 1% EOR effect, the agent cost of the alkali-free system is 17.02% lower than that of the alkali ASP system. This article innovatively verifies the feasibility of using NaCl instead of Na2CO3 and explains the mechanism of significantly improving oil recovery in composite systems under alkali-free conditions from the ion level. However, the emulsification effect of the alkali-free TC system is relatively weak. The next step of research would be to consider adding an E-surfactant to enhance the emulsification performance of the composite system. By improving the system composition, technical references are provided for the efficient development of other terrestrial sandstone oilfields.

Novel CDK19-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake.

Cyclin-dependent kinase 19 (CDK19) is overexpressed in prostate cancer, making it an attractive target for both imaging and therapy. Since little is known about the optimized approach for radioligands of nuclear proteins, linker optimization strategies were used to improve pharmacokinetics and tumor absorption, including the adjustment of the length, flexibility/rigidity, and hydrophilicity/lipophilicity of linkers. Molecular docking was conducted for virtual screening and followed by IC50 determination. Both BALB/c mice and P-16 xenografts were used for tissue distribution and PET/CT imaging. The ligand 68Ga-10c demonstrated high absorption in tumor 5 min after injection and sustains long-term imaging within 3 h. Furthermore, 68Ga-10c exhibited slow clearance within the tumor and was predominantly metabolized in both the liver and kidneys, showing the potential to alleviate metabolic pressure and enhance tissue safety. Therefore, the linker optimization strategy is well suited for CDK19 and provides a reference for the radioactive ligands of other nuclear targets.

Robotic-assisted laparoscopic versus abdominal and laparoscopic myomectomy: A systematic review and meta-analysis.

BACKGROUND: Myomectomy is the preferred treatment for women with uterine fibroids and fertility requirements. There are three modalities are used in clinical practice for myomectomy: abdominal myomectomy (AM), laparoscopic myomectomy (LM), and robot-assisted laparoscopic myomectomy (RLM). OBJECTIVES: To compare the perioperative and postoperative outcomes of RLM, AM, and LM. SEARCH STRATEGY: We searched PubMed, Web of Science, Embase, and Clinical Trials for relevant literature published between January 2000 and January 2023. SELECTION CRITERIA: We included all studies reporting peri- and postoperative outcomes of myomectomy in patients with uterine myomas. Surgical treatments were classified as RLM, LM, or AM. DATA COLLECTION AND ANALYSIS: Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the patient characteristics and myoma characteristics. We used the I2 statistic to quantify heterogeneity and the random-effects model for meta-analysis when appropriate. We used the funnel plot to assess the publication bias. MAIN RESULTS: A total of 32 studies with 6357 patients were included, of which 1982 women had undergone RLM. The operating time was significantly longer (MD = 43.58, 95% confidence interval [CI]: 25.22-61.93, P < 0.001), and the incidence of cesarean section after myomectomy was significantly lower (OR = 0.27, 95% CI: 0.10-0.78, P = 0.02) in RLM than in LM. Compared with AM, the operation time, blood loss, blood transfusion rate, complication rate, total cost, length of hospital stay, and pregnancy rate of patients with RLM were significantly different. CONCLUSIONS: The safety and effectiveness of RLM are superior to those of AM but inferior to those of LM.

METTL3-mediated m6A methylation of DNMT1 promotes the progression of non-small cell lung cancer by regulating the DNA methylation of FOXO3a.

Background: The aim of this study was to investigate the effect of DNA methylation of Fork Head Box O3 (FOXO3a) on the process of epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Methods: The expressions of FOXO3a, DNA methyltransferase 1 (DNMT1), METTL3, and EMT-related proteins (E-cadherin and N-cadherin) were measured. The influence of 5-Aza-dC and DNMT1 on the methylation level in the promoter region of FOXO3a was examined through the application of methylation-specific PCR (MSP). Chromatin immunoprecipitation (ChIP) was employed to detect binding between DNMT1 and the FOXO3a promoter. Methylated RNA immunoprecipitation (MeRIP) was utilized to evaluate the level of DNMT1 N6-methyladenosine (m6A) methylation. The assessment of cell viability and invasion abilities of A549 cells was performed using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. NSCLC xenograft mouse models were established by subcutaneously injected treated A549 cells into nude mice. Results: The expression levels of DNMT1 and DNA methylation level FOXO3a were found to be significantly increased, whereas FOXO3a expression was considerably decreased in NSCLC cell lines and NSCLC tumor tissues. Both 5-Aza-dC treatment and DNMT1 knockdown resulted in the down-regulation of DNA methylation levels of FOXO3a while simultaneously up-regulating the expression of FOXO3a. A ChIP assay demonstrated that DNMT1 has the ability to bind to the promoter region of FOXO3a. Furthermore, the knockdown of DNMT1 promoted E-cadherin expression, but inhibited expression of N-cadherin, cell viability, and invasion ability. However, the knockdown of FOXO3a hindered the effect of DNMT1 knockdown on EMT, cell viability, and invasion ability of A549 cells. This was evidenced by decreased E-cadherin expression and increased N-cadherin expression, as well as increased cell viability and invasion ability. Increased expression of DNMT1 resulted from m6A methylation of DNMT1, which was mediated by METTL3. Overexpression of DNMT1 decreased of E-cadherin expression while increased N-cadherin expression, cell viability, and invasion ability in METTL3-shRNA treated A549 cells. In xenograft mouse models, DNMT1 knockdown significantly reduced tumor volumes and tumor weight. DNMT1 knockdown upregulated the expression of FOXO3a and E-cadherin, while downregulated N-cadherin expression in vivo. Conclusion: METTL3-mediated m6A methylation of DNMT1 up-regulates FOXO3a promoter methylation, thereby promoting the progression of NSCLC.

A Strong, Tough, and Stable Composite with Nacre-Inspired Sandwich Structure.

Improving the fracture resistance of nacre-inspired composites is crucial in addressing the strength-toughness trade-off. However, most previously proposed strategies for enhancing fracture resistance in these composites have been limited to interfacial modification by polymer, which restricts mechanical enhancement. Here, a composite material consisting of graphene oxide (GO) lamellae and nanocrystalline reinforced amorphous alumina nanowires (NAANs) has been developed. The structure of the composite is inspired by nacre and is composed of stacked GO nanosheets with NAANs in between, forming a sandwich-like structure. This design enhances the fracture resistance of the composite through the pull-out of GO nanosheets at the nanoscale and GO/NAANs sandwich-like coupling at the micro-scale, while also providing stiff ceramic support. This composite simultaneously possesses high strength (887.8 MPa), toughness (31.6 MJ m-3), superior cyclic stability (1600 cycles), and long-term (2 years) immersion stability, which outperform previously reported GO-based lamellar composites. The hierarchical fracture design provides a new path to design next-generation strong, tough, and stable materials for advanced engineering applications.

Targeted Knockdown of Hepatic Δ-5 Fatty Acid Desaturase FADS1 Aggravates Atherosclerosis in ApoE-/- Mice.

BACKGROUND: The endogenous metabolism of polyunsaturated fatty acids is regulated by the fatty acid desaturase (FADS) gene cluster and is strongly associated with diseases such as atherosclerosis, dyslipidemia, and type 2 diabetes. However, the association between FADS and atherosclerosis remains a subject of debate. METHODS: In this study, we specifically investigated the physiological role of Δ-5 fatty acid desaturase (FADS1) in aortic and peripheral vessel (namely, the femoral artery) atherosclerosis by targeting the selective knockdown of hepatic Fads1 in apolipoprotein E-null (ApoE-⁣/-) mice with antisense oligonucleotides (ASOs). RESULTS: Knockdown of hepatic Fads1 in ApoE-⁣/- mice exacerbated aortic atherosclerosis and non-alcoholic fatty liver disease (NAFLD), resulting in weight loss. Upregulation of FADS1 mRNA expression in more severe atherosclerosis vascular tissues potentially caused the upregulation of angiopoietin-like 4 expression. CONCLUSIONS: Our study demonstrated that knockdown of hepatic Fads1 in ApoE-⁣/- mice aggravates spontaneous atherosclerosis and NAFLD but does not affect peripheral atherosclerosis (femoral artery) induced by vascular cuff combined with tandem stenosis.

COVID-19 vaccination affects short-term anti-coagulation levels in warfarin treatment.

Vaccines against SARS-CoV-2 have been recommended across the world, yet no study has investigated whether COVID-19 vaccination influences short-term warfarin anti-coagulation levels. Patients on stable warfarin treatment who received anti-SARS-CoV-2 vaccination were prospectively enrolled and followed up for three months. INR values less than 10 days before vaccination (baseline), 3-5 days (short-term) and 6-14 days (medium-term) after vaccination were recorded as INR0, INR1, and INR2, respectively. The variations of INR values within individuals were compared, and the linear mixed effect model was used to evaluate the variations of INR values at different time points. Logistic regression analysis was performed to determine covariates related to INR variations after COVID-19 vaccination. Vaccination safety was also monitored. There was a significant difference in INR values between INR0 and INR1 (2.15 vs. 2.26, p = 0.003), yet no marked difference was found between INR0 and INR2. The linear mixed effect model also demonstrated that INR variation was significant in short-term but not in medium-term or long-term period after vaccination. Logistic regression analysis showed that no investigated covariates, including age, vaccine dose, genetic polymorphisms of VKORC1 and CYP2C9 etc., were associated with short-term INR variations. Two patients (2.11%) reported gingival hemorrhage in the short-term due to increased INR values. The overall safety of COVID-19 vaccines for patients on warfarin was satisfying. COVID-19 vaccines may significantly influence warfarin anticoagulation levels 3-5 days after vaccination. We recommend patients on warfarin to perform at least one INR monitoring within the first week after COVID-19 vaccination.

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

Medicarpin suppresses lung cancer cell growth in vitro and in vivo by inducing cell apoptosis.

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

The impact of arbuscular mycorrhizal fungi and endophytic bacteria on peanuts under the combined pollution of cadmium and microplastics.

It remains unclear how symbiotic microbes impact the growth of peanuts when they are exposed to the pollutants cadmium (Cd) and microplastics (MPs) simultaneously. This study aimed to investigate the effects of endophytic bacteria Bacillus velezens SC60 and arbuscular mycorrhizal fungus Rhizophagus irregularis on peanut growth and rhizosphere microbial communities in the presence of Cd at 40 (Cd40) or 80 (Cd80) mg kg-1 combined without MP or the presence of low-density polyethylene (LDPE) and poly butyleneadipate-co-terephthalate (PBAT). This study assessed soil indicators, plant parameters, and Cd accumulation indicators. Results showed that the application of R. irregularis and B. velezens significantly enhanced soil organic carbon and increased Cd content under the conditions of Cd80 and MPs co-pollution. R. irregularis and B. velezens treatment increased peanut absorption and the enrichment coefficient for Cd, with predominate concentrations localized in the peanut roots, especially under combined pollution by Cd and MPs. Under treatments with Cd40 and Cd80 combined with PBAT pollution, soil microbes Proteobacteria exhibited a higher relative abundance, while Actinobacteria showed a higher relative abundance under treatments with Cd40 and Cd80 combined with LDPE pollution. In conclusion, under the combined pollution conditions of MPs and Cd, the co-treatment of R. irregularis and B. velezens effectively immobilized Cd in peanut roots, impeding its translocation to the shoot.