Intestinal microbiota by angiotensin receptor blocker therapy exerts protective effects against hypertensive damages.

Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB-treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.

Examining public private partnership investment in energy towards achieving sustainable development goal 7 for ASEAN region.

The gradual progress in aligning financial flows with the adoption of clean technologies reveals a persistent funding gap, signaling a global misallocation of capital. Addressing this challenge necessitates political leadership and robust policies to counteract the insecurities impeding the redirection of financial flows. This study investigates into the impact of energy-related public-private partnership investments (PPPIE) and macro-environmental variables on the attainment of Sustainable Development Goal 7 (SDG7) across Association of Southeast Asian Nations (ASEAN) member countries from 1999 to 2021. Employing the Dynamac command technique, we conduct autoregressive distribution lag analysis and the Bounds Cointegration Test to evaluate ASEAN's efforts in achieving SDG7. Results indicate that a ten-year exogenous shock to the GDP growth rate initially causes a temporary decline in both GDP and PPPIE, albeit not statistically significant. However, in the long run, the shock becomes statistically significant, correlating with a negative decline in the GDP growth rate. This underscores the negative impact of external factors like the COVID-19 pandemic on the economic growth of ASEAN member countries. Specifically, a percentage increase in PPPIE leads to an 8.3% reduction in the GDP growth rate, revealing a detrimental and unsustainable impact on the economy. This signifies that energy investments in the ASEAN region, are predominantly unsustainable and adversely impact economic growth. Moreover, these energy investments contribute to a significant 52.6% increase in greenhouse gas emissions, indicating a substantial setback in the region's progress towards meeting SDG7's clean energy objectives by 2030. This suggests the present state of PPPIE does not align with sustainable clean energy goals of the region. Therefore, recommendations should include diversifying energy sources and investment strategies to enhance sustainable clean energy. Also, policymakers and researchers should reassess the terms and conditions of PPPIE, refining frameworks for private sector involvement to align with long-term economic sustainability goals.

Predicting bowel function after diverting stoma closure in patients with rectal cancer.

Background: Patients with rectal cancer undergoing laparoscopic anterior resection and diverting stomas often suffer from bowel dysfunction after stoma closure, impairing their quality of life. This study aims to develop a machine learning tool to predict bowel function after diverting stoma closure. Methods: Clinicopathological data and post-operative follow-up information from patients with mid-low rectal cancer after diverting stoma closure were collected and analyzed. Patients were randomly divided into training and test sets in a 7:3 ratio. A machine learning model was developed in the training set to predict major low anterior resection syndrome (LARS) and evaluated in the test set. Decision curve analysis (DCA) was used to assess clinical utility. Results: The study included 396 eligible patients who underwent laparoscopic anterior resection and diverting stoma in Tongji Hospital affiliated with Huazhong University of Science and Technology from 1 January 2012 to 31 December 2020. The interval between stoma creation and closure, neoadjuvant therapy, and body mass index were identified as the three most crucial characteristics associated with patients experiencing major LARS in our cohort. The machine learning model achieved an area under the receiver operating characteristic curve (AUC) of 0.78 [95% confidence interval (CI): 0.74-0.83] in the training set (n=277) and 0.74 (95% CI: 0.70-0.79) in the test set (n=119), and area under the precision-recall curve (AUPRC) of 0.73 and 0.69, respectively, with sensitivity of 0.67 and specificity of 0.66 for the test set. DCA confirmed clinical applicability. Conclusions: This study developed a machine learning model to predict major LARS in rectal cancer patients after diverting stoma closure, aiding their decision-making and counseling.

The silent information regulator 1 agonist SRT1720 reduces experimental intracerebral hemorrhagic brain injury by regulating the blood-brain barrier integrity.

Intracerebral hemorrhage (ICH) is a significant public health matter that has no effective treatment. ICH-induced destruction of the blood-brain barrier (BBB) leads to neurological deterioration. Astrocytic sonic hedgehog (SHH) alleviates brain injury by maintaining the integrity of the BBB after ICH. Silent information regulator 1 (SIRT1) is neuroprotective in several central nervous system diseases via BBB regulation. It is also a possible influential factor of the SHH signaling pathway. Nevertheless, the role of SIRT1 on BBB and the underlying pathological process associated with the SHH signaling pathway after ICH remain unclear. We established an intracerebral hemorrhagic mouse model by collagenase injection. SRT1720 (a selective agonist of SIRT1) was used to evaluate the effect of SIRT1 on BBB integrity after ICH. SIRT1 expression was reduced in the mouse brain after ICH. SRT1720 attenuated neurobehavioral impairments and brain edema of ICH mouse. After ICH induction, SRT1720 improved BBB integrity and tight junction expressions in the mouse brain. The SHH signaling pathway-related factors smoothened and glioma-associated oncogene homolog-1 were increased with the intervention of SRT1720, while cyclopamine (a specific inhibitor of the SHH signaling pathway) reversed these effects. These findings suggest that SIRT1 protects from ICH by altering BBB permeability and tight junction expression levels. This process is associated with the SHH signaling pathway, suggesting that SIRT1 may be a potential therapeutic target for ICH.

Golgi dispersal in cancer stem cells promotes chemoresistance of colorectal cancer via the Golgi stress response.

Chemotherapy is a crucial treatment for colorectal tumors. However, its efficacy is restricted by chemoresistance. Recently, Golgi dispersal has been suggested to be a potential response to chemotherapy, particularly to drugs that induce DNA damage. However, the underlying mechanisms by which Golgi dispersal enhances the capacity to resist DNA-damaging agents remain unclear. Here, we demonstrated that DNA-damaging agents triggered Golgi dispersal in colorectal cancer (CRC), and cancer stem cells (CSCs) possessed a greater degree of Golgi dispersal compared with differentiated cancer cells (non-CSCs). We further revealed that Golgi dispersal conferred resistance against the lethal effects of DNA-damaging agents. Momentously, Golgi dispersal activated the Golgi stress response via the PKCα/GSK3α/TFE3 axis, resulting in enhanced protein and vesicle trafficking, which facilitated drug efflux through ABCG2. Identification of Golgi dispersal indicated an unexpected pathway regulating chemoresistance in CRC.

Nuclear Softness Promotes the Metastatic Potential of Large-Nucleated Colorectal Cancer Cells via the ErbB4-Akt1-Lamin A/C Signaling Pathway.

Abnormal nuclear enlargement is a diagnostic and physical hallmark of malignant tumors. Large nuclei are positively associated with an increased risk of developing metastasis; however, a large nucleus is inevitably more resistant to cell migration due to its size. The present study demonstrated that the nuclear size of primary colorectal cancer (CRC) cells at an advanced stage was larger than cells at an early stage. In addition, the nuclei of CRC liver metastases were larger than those of the corresponding primary CRC tissues. CRC cells were sorted into large-nucleated cells (LNCs) and small-nucleated cells (SNCs). Purified LNCs exhibited greater constricted migratory and metastatic capacity than SNCs in vitro and in vivo. Mechanistically, ErbB4 was highly expressed in LNCs, which phosphorylated lamin A/C at serine 22 via the ErbB4-Akt1 signaling pathway. Furthermore, the level of phosphorylated lamin A/C was a negative determinant of nuclear stiffness. Taken together, CRC LNCs possessed greater constricted migratory and metastatic potential than SNCs due to ErbB4-Akt1-mediated lamin A/C phosphorylation and nuclear softening. These results may provide a potential treatment strategy for tumor metastasis by targeting nuclear stiffness in patients with cancer, particularly CRC.

Tunable anisotropic van der Waals films of 2M-WS2 for plasmon canalization.

In-plane anisotropic van der Waals materials have emerged as a natural platform for anisotropic polaritons. Extreme anisotropic polaritons with in-situ broadband tunability are of great significance for on-chip photonics, yet their application remains challenging. In this work, we experimentally characterize through Fourier transform infrared spectroscopy measurements a van der Waals plasmonic material, 2M-WS2, capable of supporting intrinsic room-temperature in-plane anisotropic plasmons in the far and mid-infrared regimes. In contrast to the recently revealed natural hyperbolic plasmons in other anisotropic materials, 2M-WS2 supports canalized plasmons with flat isofrequency contours in the frequency range of ~ 3000-5000 cm-1. Furthermore, the anisotropic plasmons and the corresponding isofrequency contours can be reversibly tuned via in-situ ion-intercalation. The tunable anisotropic and canalization plasmons may open up further application perspectives in the field of uniaxial plasmonics, such as serving as active components in directional sensing, radiation manipulation, and polarization-dependent optical modulators.

Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps.

Purpose: This study identified subtypes and prognostic signature of stage I and stage II gastric cancer based on neutrophil extracellular trap (NET)-related genes. Methods: The gene expression data associated with stage I and stage II gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. NET-related genes were obtained from previous reference. Differentially expressed NET-related genes were selected by consensus cluster analysis. The differences in immune infiltration between two subtypes were analyzed. Prognosis-related genes were further screened by univariate Cox regression analysis. Gene Set Enrichment Analysis (GSEA) of prognostic signatures was conducted with clusterprofiler. Finally, a miRNA-mRNA-transcription factor (TF) network was constructed. Results: Total 43 differential NET-related genes were obtained and two subtypes were obtained based on these genes. Patients of cluster 2 had a better prognosis compared to cluster 1. Eight types of immune cells were differential in infiltration level between two subtypes. Following univariate Cox regression analysis, two genes of CXC chemokine receptor 4 (CXCR4) and nuclear factor, erythroid 2-like 2 (NFE2L2) significantly related to patient survival were selected. GSEA of single gene revealed that CXCR4 was associated with allograft rejection and NFE2L2 was associated with drug metabolism-cytochrome P450. A network with 421 miRNA-mRNA-TF regulatory pairs was constructed. Conclusion: The present study identified two subtypes and a prognostic signature for stage I and stage II gastric cancer based on NET-related genes.

Injectable Antiswelling and High-Strength Bioactive Hydrogels with a Wet Adhesion and Rapid Gelling Process to Promote Sutureless Wound Closure and Scar-free Repair of Infectious Wounds.

Developing injectable antiswelling and high-strength bioactive hydrogels with wet tissue adhesiveness and a rapid gelling process to meet the requirements for rapid hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds continues to have ongoing challenges. Herein, injectable, antibacterial, and antioxidant hydrogel adhesives based on poly(citric acid-co-polyethylene glycol)-g-dopamine and amino-terminated Pluronic F127 (APF) micelles loaded with astragaloside IV (AS) are prepared. The H2O2/horseradish peroxidase (HRP) system is used to cause cross-linking of the hydrogel network through oxidative coupling between catechol groups and chemical cross-linking between the catechol group and the amino group. The hydrogels exhibit a rapid gelling process, high mechanical strength, an antiswelling effect, good antioxidant property, H2O2 release behavior, and degradability. In addition, the hydrogels present good wet tissue adhesiveness, high bursting pressure, excellent antibacterial activity, long-term sustained release of AS, and good biocompatibility. The hydrogels perform good hemostasis on mouse liver, rat liver, and rabbit femoral vein bleeding models and achieve much better closure and healing of skin incisions than biomedical glue and surgical sutures. Furthermore, the hydrogel dressing significantly improved the scar-free repair of MRSA-infected full thickness skin defect wounds by modulating inflammation, regulating the ratio of collagen I/III, and improving the vascularization and granulation tissue formation. Thus, AS-loaded hydrogels show huge potential as multifunctional dressings for in vivo hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction.

BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.

Comparing Long-Term survival benefits of hepatocellular carcinoma between thermal ablation monotherapy and combined therapy with transarterial Chemoembolization: A propensity score matched study.

PURPOSE: To compare the long-term survival benefits of hepatocellular carcinoma (HCC) in thermal ablation (TA) monotherapy and TA combined with transarterial chemoembolization (TACE) using propensity score matching (PSM). MATERIALS AND METHODS: Between 1 January 2015 and 28 February 2021, 432 consecutive patients (357 men, 75 women; age range, 20-87 years) with HCC (Barcelona Clinic Liver Cancer stage 0-B) underwent ultrasonography-guided percutaneous TA, which included radiofrequency ablation (n = 340) and microwave ablation (n = 92). The association between combined treatment of TACE prior to TA versus TA monotherapy and survival prognosis was evaluated, including (a) local tumor progression (LTP) by using a logistic regression model, and (b) disease-free survival (DFS) and (c) overall survival (OS) by using a Cox proportional hazards model according to propensity score matched data. RESULTS: After PSM, the final matched cohort consisted of 146 patients, with 73 receiving TA monotherapy and 73 receiving TA combined with TACE. The cumulative LTP rates did not show a significant difference between the two groups (P = 0.960). Neither the DFS nor OS rate was significantly different between the two groups (P = 0.070 and P = 0.680, respectively). The multivariate analysis identified two significant findings. Firstly, ultrasound echo, minimal ablative margin, and high risk of tumor burden score were found to be associated with LTP. Secondly, the type of TA, Child-Turcotte-Pugh grade, ablation time, and lymphocyte-monocyte ratio were identified as independent prognostic factors for OS. CONCLUSION: The differences in LTP, DFS, and OS rates of HCC patients were found to be statistically non-significant between TA monotherapy and TACE + TA groups. For HCC patients with BCLC stage 0-B, the combination treatment of TACE prior to TA may be not associated with long-term survival benefits relative to TA monotherapy.

Layer-dependent exciton polarizability and the brightening of dark excitons in few-layer black phosphorus.

The evolution of excitons from 2D to 3D is of great importance in photo-physics, yet the layer-dependent exciton polarizability hasn't been investigated in 2D semiconductors. Here, we determine the exciton polarizabilities for 3- to 11-layer black phosphorus-a direct bandgap semiconductor regardless of the thickness-through frequency-resolved photocurrent measurements on dual-gate devices and unveil the carrier screening effect in relatively thicker samples. By taking advantage of the broadband photocurrent spectra, we are also able to reveal the exciton response for higher-index subbands under the gate electrical field. Surprisingly, dark excitons are brightened with intensity even stronger than the allowed transitions above certain electrical field. Our study not only sheds light on the exciton evolution with sample thickness, but also paves a way for optoelectronic applications of few-layer BP in modulators, tunable photodetectors, emitters and lasers.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS: Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Tunable optical topological transitions of plasmon polaritons in WTe2 van der Waals films.

Naturally existing in-plane hyperbolic polaritons and the associated optical topological transitions, which avoid the nano-structuring to achieve hyperbolicity, can outperform their counterparts in artificial metasurfaces. Such plasmon polaritons are rare, but experimentally revealed recently in WTe2 van der Waals thin films. Different from phonon polaritons, hyperbolic plasmon polaritons originate from the interplay of free carrier Drude response and interband transitions, which promise good intrinsic tunability. However, tunable in-plane hyperbolic plasmon polariton and its optical topological transition of the isofrequency contours to the elliptic topology in a natural material have not been realized. Here we demonstrate the tuning of the optical topological transition through Mo doping and temperature. The optical topological transition energy is tuned over a wide range, with frequencies ranging from 429 cm-1 (23.3 microns) for pure WTe2 to 270 cm-1 (37.0 microns) at the 50% Mo-doping level at 10 K. Moreover, the temperature-induced blueshift of the optical topological transition energy is also revealed, enabling active and reversible tuning. Surprisingly, the localized surface plasmon resonance in skew ribbons shows unusual polarization dependence, accurately manifesting its topology, which renders a reliable means to track the topology with far-field techniques. Our results open an avenue for reconfigurable photonic devices capable of plasmon polariton steering, such as canaling, focusing, and routing, and pave the way for low-symmetry plasmonic nanophotonics based on anisotropic natural materials.

Twist-Angle and Thickness-Ratio Tuning of Plasmon Polaritons in Twisted Bilayer van der Waals Films.

Stacking bilayer structures is an efficient way to tune the topology of polaritons in in-plane anisotropic films, e.g., by leveraging the twist angle (TA). However, the effect of another geometric parameter, the film thickness ratio (TR), on manipulating the plasmon topology in bilayers is elusive. Here, we fabricate bilayer structures of WTe2 films, which naturally host in-plane hyperbolic plasmons in the terahertz range. Plasmon topology is successfully modified by changing the TR and TA synergistically, manifested by the extinction spectra of unpatterned films and the polarization dependence of the plasmon intensity measured in skew ribbon arrays. Such TR- and TA-tunable topological transitions can be well explained based on the effective sheet optical conductivity by adding up those of the two films. Our study demonstrates TR as another degree of freedom for the manipulation of plasmonic topology in nanophotonics, exhibiting promising applications in biosensing, heat transfer, and the enhancement of spontaneous emission.

Machine learning model for prediction of low anterior resection syndrome following laparoscopic anterior resection of rectal cancer: A multicenter study.

BACKGROUND: Low anterior resection syndrome (LARS) severely impairs patient postoperative quality of life, especially major LARS. However, there are few tools that can accurately predict major LARS in clinical practice. AIM: To develop a machine learning model using preoperative and intraoperative factors for predicting major LARS following laparoscopic surgery of rectal cancer in Chinese populations. METHODS: Clinical data and follow-up information of patients who received laparoscopic anterior resection for rectal cancer from two medical centers (one discovery cohort and one external validation cohort) were included in this retrospective study. For the discovery cohort, the machine learning prediction algorithms were developed and internally validated. In the external validation cohort, we evaluated the trained model using various performance metrics. Further, the clinical utility of the model was tested by decision curve analysis. RESULTS: Overall, 1651 patients were included in the present study. Anastomotic height, neoadjuvant therapy, diverting stoma, body mass index, clinical stage, specimen length, tumor size, and age were the risk factors associated with major LARS. They were used to construct the machine learning model to predict major LARS. The trained random forest (RF) model performed with an area under the curve of 0.852 and a sensitivity of 0.795 (95%CI: 0.681-0.877), a specificity of 0.758 (95%CI: 0.671-0.828), and Brier score of 0.166 in the external validation set. Compared to the previous preoperative LARS score model, the current model exhibited superior predictive performance in predicting major LARS in our cohort (accuracy of 0.772 for the RF model vs 0.355 for the preoperative LARS score model). CONCLUSION: We developed and validated a robust tool for predicting major LARS. This model could potentially be used in the clinic to identify patients with a high risk of developing major LARS and then improve the quality of life.

Comparisons of different new-generation transcatheter aortic valve implantation devices for patients with severe aortic stenosis: a systematic review and network meta-analysis.

BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.

Changes in the gut microbiota structure and function in rats with doxorubicin-induced heart failure.

Objectives: The rat model of heart failure (HF) induced by doxorubicin (DOX), a broad spectrum and highly effective chemotherapeutic anthracycline with high-affinity to myocardial tissue that causes severe dose-dependent irreversible cardiotoxicity has been widely recognized and applied in HF pathogenesis and drug therapy studies. The gut microbiota (GM) has attracted significant attention due to its potential role in HF, and research in this area may provide beneficial therapeutic strategies for HF. Considering the differences in the route, mode, and total cumulative dose of DOX administration used to establish HF models, the optimal scheme for studying the correlation between GM and HF pathogenesis remains to be determined. Therefore, focusing on establishing the optimal scheme, we evaluated the correlation between GM composition/function and DOX-induced cardiotoxicity (DIC). Methods: Three schemes were investigated: DOX (at total cumulative doses of 12, 15 or 18 mg/kg using a fixed or alternating dose via a tail vein or intraperitoneal injection) was administered to Sprague Dawley (SD) for six consecutive weeks. The M-mode echocardiograms performed cardiac function evaluation. Pathological changes in the intestine were observed by H&E staining and in the heart by Masson staining. The serum levels of N-terminal pre-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured by ELISA. The GM was analysed by 16S rRNA gene sequencing. Key findings: Strikingly, based on the severity of cardiac dysfunction, there were marked differences in the abundance and grouping of GM under different schemes. The HF model established by tail vein injection of DOX (18 mg/kg, alternating doses) was more stable; moreover, the degree of myocardial injury and microbial composition were more consistent with the clinical manifestations of HF. Conclusions: The model of HF established by tail vein injection of doxorubicin, administered at 4mg/kg body weight (2mL/kg) at weeks 1, 3 and 5, and at 2mg/kg body weight (1mL/kg) at weeks 2, 4 and 6, with a cumulative total dose of 18mg/kg, is a better protocol to study the correlation between HF and GM.

Structure and bonding properties of the platinum-mediated tetrametallic endohedral fullerene La3Pt@C98.

Nowadays, focus is on encapsulating a greater variety and amount of metal species into fullerene cages due to their diverse structures and fascinating properties. Nevertheless, the encapsulation of more positively charged metal atoms inside one cage means more Coulomb repulsion, which makes the formation of such endohedral metallofullerenes (EMFs) difficult. In general, non-metallic atoms such as N and O should be introduced as mediators for the formation of trimetallic or tetrametallic endohedral fullerenes. However, it is still unknown whether metal atoms can serve as mediators themselves to form such EMFs. In this paper, the endohedral tetrametallic fullerene La3Pt@C98 with the platinum atom as a metallic mediator is reported. The EMFs of La3Pt@C2n (2n = 98-300) were generated by the method of laser ablation in the gas phase and verified by mass spectrometry. Among them, the EMF of La3Pt@C98 was selected and studied by theoretical calculations. Results show that the two most stable isomers are La3Pt@C2(231010)-C98 and La3Pt@C1(231005)-C98. For both of them, the inner La3Pt metallic cluster appears in a pyramidal shape, different from the planar triangular pattern of La3N clusters previously reported. Further calculations prove the existence of encaged La-Pt bonds in the La3Pt cluster. It was also revealed that the negatively charged Pt atom is situated near the center of the four-center two-electron (4c-2e) metal bond with the highest occupancy number. The platinum-mediated cluster stabilizes the EMFs greatly, promising the possibility of synthesizing new species of Pt-containing EMFs.