TRPV1 signaling of perirenal adipose tissue promotes DOCA-Salt-induced hypertension and kidney injury.

BACKGROUND: Denervation of renal or perirenal adipose tissue (PRAT) can reduce arterial blood pressure in various hypertensive experimental models. Trpv1 (transient receptor potential vanillin 1) channel is highly expressed in the renal sensory nerves and the dorsal root ganglias (DRGs) projected by PRAT. However, it is currently unclear whether Trpv1 in DRGs projected from PRAT can regulate renal hypertension. METHODS: We used resintoxin (RTX) to block the afferent sensory nerves of rat PRAT. We also constructed Trpv1-/- mice and Trpv1+/- mice or used the injection of AAV2-retro-shTrpv1 to detect the effects of Trpv1 knockout or knockdown of PRAT-projected DRGs on deoxycorticosterone acetate (DOCA)-Salt-induced hypertension and kidney injury. RESULTS: Blocking the afferent sensory nerves of PRAT with RTX can alleviate DOCA-Salt-induced hypertension and renal injury in rats. And this blockade reduces the expression of Trpv1 in the DRGs projected by PRAT. Injecting AAV2-retro-shTrpv1 into the PRAT of DOCA-Salt mice also achieved the same therapeutic effect. However, DOCA-Salt-induced hypertension and renal injury can be treated in Trpv1+/- mice but not alleviated or even worsened in Trpv1-/- mice, possibly because of compensatory increase of Trpv5 in DRG of Trpv1-/- mice. CONCLUSION: Reducing, rather than eliminating, Trpv1 in DRG from PRAT-projection can reduce blood pressure and kidney damage in DOCA-Salt in rats or mice. Trpv1 in PRAT-DRGs may serve as a therapeutic target for salt-sensitive hypertension and its renal complications.

Urea nitrogen-to-albumin ratio predicts ventricular aneurysm formation in ST-segment elevation myocardial infarction.

AIMS: Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. The aim of this study was to investigate the possible predictive value of blood urea nitrogen-to-albumin ratio (BAR) for the LVA formation in acute ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 1123 consecutive patients with STEMI were prospectively enrolled. The clinical and laboratory data were compared between LVA group and non-LVA group. Multivariable logistic regression analysis was performed to assess the independent risk factors of LVA formation. Predictive power of BAR and composite variable for LVA formation were assessed using receiver operating characteristic curve. LVA was detected in 162 patients (14.4%). The BAR was significantly higher in patients with LVA [0.16 (0.13-0.19) vs. 0.13 (0.10-0.17), P < 0.001]. Multivariable logistic regression analysis revealed that left ventricular ejection fraction (LVEF) [odds ratio (OR) = 0.865, P < 0.001], culprit vessel-left anterior descending artery (LAD) (OR = 4.705, P < 0.001), and BAR (OR = 2.208, P = 0.018) were all independent predictors for LVA formation. The predictive value of BAR remained significant even after cross-validation by splitting population into training set (OR = 1.957, P = 0.034) and validation set (OR = 1.982, P = 0.039). The maximal length and width of LVA were significantly increased in patients with BAR ≥ 0.15 when compared with BAR < 0.15 (3.37 ± 1.09 vs. 2.92 ± 0.93, P = 0.01, for maximal length, and 2.20 ± 0.55 vs. 1.85 ± 0.63, P = 0.001, for maximal width). The discriminant power of BAR for LVA is 0.723, which is superior to both blood urea nitrogen (C statistic = 0.586, P < 0.001) and albumin (C statistic = 0.64, P < 0.001). The combination of BAR, LVEF, and culprit vessel-LAD could significantly increase the predictive ability (C statistic = 0.874, P < 0.001, for vs. BAR). Subgroup analysis of age, sex, hypertension, diabetes, smoking, LVEF, serum albumin, multiple-vessel disease, and Gensini score had no effect on the association between BAR and risk of LVA formation (P < 0.05 for all subgroups). CONCLUSIONS: A higher BAR was an independent predictor for LVA formation in STEMI patients with primary PCI.

A novel experimental setup for axial-torsional coupled vibration impact-assisted PDC drill bit drilling.

The geological conditions of hot dry rock (HDR) reservoirs are complex. The geothermal mining of HDR faces major challenges in the drilling and construction of wells, fracturing to create storage, and flowing to extract heat. Vibration impacts help improve the rock-breaking efficiency, where the axial-torsional coupled vibration impact technology can increase the bit penetration depth and reduce the stick-slip effect. To study the feasibility and efficiency of the axial-torsional-coupled vibration impact-assisted Polycrystalline Diamond Compact (PDC) bit to break high-temperature and high-pressure rocks, a new experimental setup was designed. The system includes a drilling fluid circulation system, an axial-torsional coupled impact drilling system, a formation simulation system, and a data acquisition and control system. This setup can produce a rock-breaking torque of 2000 N·m, a drilling speed of 200 rpm, a weight on bit of 100 kN, an axial vibration frequency of 100 Hz, and a torsional vibration frequency of 50 Hz. It can simulate the formation pressure of 70 MPa and the rock temperature of 400 °C. A series of rock-breaking drilling experiments were successfully conducted using this setup. The results show that the axial-torsional coupled vibration-impact assisted PDC bit has a good performance in breaking high-temperature and hard rocks, which can accelerate the application of this new technology in deep formation drilling.

NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation.

BACKGROUND: Heart failure, characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects and mechanisms of NAT10 (N-acetyltransferase 10)-mediated N4-acetylcytidine (ac4C) acetylation during cardiac remodeling. METHODS: NAT10 and ac4C expression were detected in both human and mouse subjects with cardiac remodeling through multiple assays. Subsequently, acetylated RNA immunoprecipitation and sequencing, thiol-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), and ribosome sequencing (Ribo-seq) were employed to elucidate the role of ac4C-modified posttranscriptional regulation in cardiac remodeling. Additionally, functional experiments involving the overexpression or knockdown of NAT10 were conducted in mice models challenged with Ang II (angiotensin II) and transverse aortic constriction. RESULTS: NAT10 expression and RNA ac4C levels were increased in in vitro and in vivo cardiac remodeling models, as well as in patients with cardiac hypertrophy. Silencing and inhibiting NAT10 attenuated Ang II-induced cardiomyocyte hypertrophy and cardiofibroblast activation. Next-generation sequencing revealed ac4C changes in both mice and humans with cardiac hypertrophy were associated with changes in global mRNA abundance, stability, and translation efficiency. Mechanistically, NAT10 could enhance the stability and translation efficiency of CD47 and ROCK2 transcripts by upregulating their mRNA ac4C modification, thereby resulting in an increase in their protein expression during cardiac remodeling. Furthermore, the administration of Remodelin, a NAT10 inhibitor, has been shown to prevent cardiac functional impairments in mice subjected to transverse aortic constriction by suppressing cardiac fibrosis, hypertrophy, and inflammatory responses, while also regulating the expression levels of CD47 and ROCK2 (Rho associated coiled-coil containing protein kinase 2). CONCLUSIONS: Therefore, our data suggest that modulating epitranscriptomic processes, such as ac4C acetylation through NAT10, may be a promising therapeutic target against cardiac remodeling.

Association of Device-Measured Physical Activity With Cardiovascular Outcomes in Individuals With Hypertension.

BACKGROUND: There is insufficient evidence to show that the guidelines' recommendations of physical activity (PA) are associated with long-term benefits in individuals with hypertension. METHODS: This prospective cohort study included UK Biobank participants with hypertension. Time spent on vigorous-intensity PA (VPA), moderate-intensity PA (MPA), and light-intensity PA (LPA) measured by wrist-worn accelerometer were extracted. The primary outcomes were major adverse cardiovascular events (including cardiovascular death, stroke, and myocardial infarction) and all-cause mortality. The secondary outcomes were cardiovascular death, myocardial infarction, and stroke, respectively. The relationships of PA with outcomes were analyzed using Cox regression models. RESULTS: This study included 49 060 eligible participants with a median follow-up of 7.0 years. MPA was inversely associated with risks of major adverse cardiovascular events and all-cause mortality. Modest amounts of LPA or VPA were likely to be more beneficial than higher amounts of either in all-cause death or cardiovascular outcomes. Compared with the least active group, 150 to 300 min/wk of MPA or more was significantly associated with decreased risk of all-cause death (by 34%-54%) and major adverse cardiovascular events (by 23%-41%), but 75 to 150 min/wk of VPA or more was associated with few further benefits, even weakening the cardiovascular benefits. CONCLUSIONS: MPA had an inverse dose-response association with the risk of all-cause mortality and cardiovascular outcomes in individuals with hypertension. Modest amounts of LPA or VPA are also beneficial, but higher amounts may be not. MPA may be the optimal PA intensity for individuals with hypertension. Further researches are required to determine whether high levels of VPA should be recommended.

A torus source and its application for non-primary radiation evaluation.

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.

Circular Photogalvanic Current in Ni-Doped Cd3As2 Films Epitaxied on GaAs(111)B Substrate.

Magnetic element doped Cd3As2 Dirac semimetal has attracted great attention for revealing the novel quantum phenomena and infrared opto-electronic applications. In this work, the circular photogalvanic effect (CPGE) was investigated at various temperatures for the Ni-doped Cd3As2 films which were grown on GaAs(111)B substrate by molecular beam epitaxy. The CPGE current generation was found to originate from the structural symmetry breaking induced by the lattice strain and magnetic doping in the Ni-doped Cd3As2 films, similar to that in the undoped ones. However, the CPGE current generated in the Ni-doped Cd3As2 films was approximately two orders of magnitude smaller than that in the undoped one under the same experimental conditions and exhibited a complex temperature variation. While the CPGE current in the undoped film showed a general increase with rising temperature. The greatly reduced CPGE current generation efficiency and its complex variation with temperature in the Ni-doped Cd3As2 films was discussed to result from the efficient capture of photo-generated carriers by the deep-level magnetic impurity bands and enhanced momentum relaxation caused by additional strong impurity scattering when magnetic dopants were introduced.

Nuclear import of Mas-related G protein-coupled receptor member D induces pathological cardiac remodeling.

Alamandine (Ala), a ligand of Mas-related G protein-coupled receptor, member D (MrgD), alleviates angiotensin II (AngII)-induced cardiac hypertrophy. However, the specific physiological and pathological role of MrgD is not yet elucidated. Here, we found that MrgD expression increased under various pathological conditions. Then, MrgD knockdown prevented AngII-induced cardiac hypertrophy and fibrosis via inactivating Gαi-mediacted downstream signaling pathways, including the phosphorylation of p38 (p-P38), while MrgD overexpression induced pathological cardiac remodeling. Next, Ala, like silencing MrgD, exerted its cardioprotective effects by inhibiting Ang II-induced nuclear import of MrgD. MrgD interacted with p-P38 and promoted its entry into the nucleus under Ang II stimulation. Our results indicated that Ala was a blocking ligand of MrgD that inhibited downstream signaling pathway, which unveiled the promising cardioprotective effect of silencing MrgD expression on alleviating cardiac remodeling. Video Abstract.

Predictive value of ACEF II score for adverse prognosis in patients with coronary heart disease after percutaneous coronary intervention.

OBJECTIVE: To investigate the predictive value of age, creatinine and ejection fraction (ACEF) II score for the incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: A total of 445 patients with CHD who underwent PCI were consecutively enrolled. The receiver operating characteristic (ROC) curve was used to analyse the power of the ACEF II score in predicting MACCE. Kaplan-Meier survival curves and log-rank tests were chosen for survival analysis of adverse prognosis between groups. Finally, multivariate Cox proportional risk regression analysis was used to investigate independent risk factors for MACCEs in patients with CHD after PCI. RESULTS: There was a significantly higher incidence of MACCEs in patients with high ACEF II scores. The area under the ROC curve of ACEF II score was 0.718, suggesting it had ideal predictive value for MACCE risks. The ACEF II score had a best cut-off value of 1.461 (sensitivity 79.4%, specificity 53.7%). Survival analysis indicated that patients in the high-score group had a significantly lower cumulative MACCE-free survival rate. Multivariate Cox regression analysis showed that ACEF II scores ≥1.461, Gensini scores ≥61.5, age, cardiac troponin I and previous PCI were independent risk factors of MACCE in patients with CHD after PCI, while the utilisation of statins was an independent protective factor. CONCLUSIONS: The ACEF II score has an ideal capacity for risk stratification in patients with CHD undergoing PCI and offers good predictive value for MACCE in the long term.

Community Synergy of Lactic Acid Bacteria and Cleaner Fermentation of Oat Silage Prepared with a Multispecies Microbial Inoculant.

To investigate community synergy of lactic acid bacteria (LAB) and cleaner fermentation of oat silage, oat silages were prepared with or without (control) commercial LAB inoculants LI1 (containing Lactiplantibacillus plantarum, Lentilactobacillus buchneri, Lacticaseibacillus paracasei, and Pediococcus acidilactici) and LI2 (containing Lactiplantibacillus plantarum and Lentilactobacillus buchneri). The microbial community, LAB synergy, and cleaner fermentation were analyzed at 1, 3, 6, 15, 35, and 90 days of ensiling. The LAB inoculant improved fermentation quality, with significantly (P < 0.05) lower pH, ammonia nitrogen content, and gas production and higher lactic acid and acetic acid contents than those of the control. Enterobacteriaceae was the main bacterial community in early stage of fermentation, which utilizes sugar to produce CO2 gas, causing dry matter (DM) and energy loss. As fermentation progressed, the microbial diversity decreased, and the microbial community shifted from Gram-negative to Gram-positive bacteria. The inoculation of multispecies LAB displayed community synergy; Pediococcus acidilactici formed a dominant community in the early stage of fermentation, which produced an acid and anaerobic environment for the subsequent growth of Lentilactobacillus and Lacticaseibacillus species, thus forming a LAB-dominated microbial community. The predicted functional profile indicated that the silage inoculated with LI1 enhanced the carbohydrate metabolism pathway but inhibited the amino acid metabolism pathway, which played a role in promoting faster lactic acid production, reducing the decomposition of protein to ammonia nitrogen, and improving the fermentation quality of silage. Therefore, oat silage can be processed to high-quality and cleaner fermented feed by using an LAB inoculant, and LI1 showed better efficiency than LI2. IMPORTANCE Oat natural silage is rich in Enterobacteriaceae, increasing gas production and fermentation loss. Lactic acid bacteria interact synergistically to form a dominant community during ensiling. Pediococci grow vigorously in the early stage of fermentation and create an anaerobic environment. Lactobacilli inhibit the harmful microorganisms and result in cleaner fermentation of oat silage.

Gender differences in behavioral inhibitory control under evoked acute stress: An event-related potential study.

Purpose: This study investigated gender differences in behavioral inhibitory control among college students under acute stress state by using event-related potential technique. Methods: Acute stress was evoked in 41 college students (22 males and 19 females) using the Trier Social Stress paradigm, and the neutral state was matched using out-of-speech reading, with subjects completing a two-choice Oddball task in each of the two states. In combination with the ERP technique, the area under the stress curve, reaction time, number of errors, and the difference waves between the two stimulus conditions in the frontal-central region N2 wave amplitude and the parietal-central region P3 wave amplitude were compared between the two groups of subjects in the stressful and neutral state. Results: The results revealed that the area under the stress curve was larger under the stress condition compared to the neutral condition, and the area under the stress curve was larger in females than in males. Behavioral results showed no statistically significant differences in reaction time and number of errors between the two genders in the acute stress condition. The ERP results showed that the wave amplitudes of N2 and P3 decreased significantly in both genders in the acute stress state. The decrease in N2 amplitude was greater in females during the transition from neutral to stressful condition, while the difference in P3 amplitude was not statistically significant in both genders. Conclusion: The findings suggest that evoked acute stress can promote behavioral inhibitory control in both genders and that females are more sensitive to acute stress state.

Sense of hope affects secondary school students' mental health: A moderated mediation model.

Introduction: The study assesses the moderated mediation effect of sense of hope on the mental health of secondary school students. Methods: The Adult Dispositional Hope Scale (ADHS), Connor-Davidson Resilience Scale (CD-RISC), and the Symptom Check List 90 (SCL-90) were used to conduct a questionnaire survey on 1776 secondary school students. Results: The results showed that total mental health scores of secondary school students were significantly negatively correlated with sense of hope and psychological resilience; sense of hope was significantly positively correlated with psychological resilience; sense of hope significantly and positively predicted the level of mental health of secondary school students, and psychological resilience played a mediating role in it; gender plays a moderating role in the relationship between sense of hope and psychological resilience. Discussion: The study further revealed the mechanism of the effect of sense of hope on secondary school students' mental health, and provided suggestions for cultivating positive psychological qualities and promoting the mental health development of secondary school students.

Analysis of Clinical Treatment of Laryngeal Stenosis After Radiotherapy and Supracricoid Partial Laryngectomy with Cricohyoidoepiglottopexy of Mid-stage and Advanced Laryngeal Cancer.

OBJECTIVE: To investigate the possible causes and treatment methods of laryngeal stenosis after radiotherapy following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP). METHODS: The data of seven patients with laryngeal stenosis after radiotherapy following SCPL-CHEP were analysed retrospectively. All patients were diagnosed with mid-stage or advanced laryngeal carcinoma before surgery, and the pathological type was squamous cell carcinoma. All patients met the requirements for SCPL-CHEP surgery. When laryngeal stenosis was found during the post-surgical follow-up period, patients were immediately given the appropriate treatment according to their conditions. RESULTS: All seven patients had laryngeal stenosis. One patient underwent granulation resection using a laryngoscope, four patients underwent granulation removal + low-temperature plasma ablation using a laryngoscope, and two patients underwent laryngeal dehiscence surgery + laryngotracheal T-tube placement. All patients recovered well after surgery, with patent airways. CONCLUSION: Laryngeal stenosis in patients with mid- and late-stage laryngeal carcinoma is one of the rare complications of SCPL-CHEP. Second-stage laryngeal dilatation can be selected according to the patient's laryngeal stenosis. Most patients with laryngeal stenosis can be extubated completely.

In vivo antitumor efficacy of 17-AAG loaded PMMA in a human multiple myeloma xenograft mouse model.

Multiple myeloma (MM) is a monoclonal malignancy characterized by abnormal proliferation of plasma cells. The disease clinically manifests as anemia, hypercalcemia, renal insufficiencies, and osteolytic damage. Osteolytic damage goes with severe bone pain, spinal instability, and pathological fracture, symptoms that are collectively referred to as multiple myeloma bone disease (MMBD). Polymethylmethacrylate (PMMA) bone cement is widely used for bone repair after MMBD surgery, owing to its excellent biomechanical properties and fast curing. To date, however, efficacy of drug-loading PMMA in inhibition of tumor growth and angiogenesis remains unknown. Here, we report that 17-AAG-loaded PMMA bone cement inhibits MM growth in vivo and suppresses tumor diffusion to peripheral tissues. In addition, 17-AAG-loaded PMMA promotes MM apoptosis by downregulating Bax and active Caspase-3.

microRNA-181c-5p stimulates the development of coronary artery disease by targeting SIRT1.

OBJECTIVE: MicroRNA (miR) therapeutics is a promising approach to manage coronary artery disease (CAD). Herein, this research was aimed to explore miR-181c-5p-related mechanisms in CAD through regulating SIRT1. METHODS: A CAD mouse model was established by feeding a high-fat diet in 8-week-old ApoE-/- mice. miR-181c-5p, SIRT1, and acetylated p65 levels in mouse myocardial tissues were evaluated by RT-qPCR and Western blot. Hemodynamic parameters included the maximum rising rate of the left ventricular pressure (lv + dp/dtmax) and the time values from the onset of contraction to dp/dtmax (t-dp/dtmax), while hemorheological indices included whole blood viscosity (low shear, middle shear, or high shear), plasma viscosity, hematocrit, and platelet adhesion were measured. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected. Mouse pathological changes, degree of fibrosis, and cardiomyocyte apoptosis in myocardial tissues were assessed by HE, Masson, and TUNEL staining, respectively. The targeting relationship between miR-181c-5p and SIRT1 was verified by bioinformatics tools, dual luciferase reporter gene assay, and RNA pull-down assays. RESULTS: In myocardial tissue of CAD mice, miR-181c-5p and acetylated p65 were upregulated while SIRT1 was downregulated. Downregulating miR-181c-5p or upregulating SIRT1 effectively ameliorated CAD by improving hemodynamics and hemorheology and reducing inflammation, pathological changes, degree of fibrosis, and cardiomyocyte apoptosis in myocardial tissues of mice. miR-181c-5p targeted SIRT1, and overexpression of SIRT1 relieved upregulated miR-181c-5p-induced injuries in CAD mice. Regulating miR-181c-5p and SIRT1 affected the acetylation of p65. CONCLUSION: Downregulation of miR-181c-5p may ameliorate myocardial pathological changes and cardiomyocyte apoptosis in CAD by upregulating SIRT1 expression and decreasing acetylated p65 levels.

Evoked Acute Stress Alters Frontal Midline Neural Oscillations Affecting Behavioral Inhibition in College Students.

Purpose: The current research of the effect of acute stress on individual behavioral inhibition remains divergent. The present study aims to explore the effects of acute stress on behavioral inhibition in college students and to understand the neural oscillatory characteristics of their behavioral inhibition process. Patients and Methods: We invited 27 college students (12 males and 15 females) to participate in the study. The experiment was conducted using the Trier Social Stress paradigm to evoke an acute stress state and an out-of-speech reading to set a neutral state. Participants completed a two-choice Oddball task in the acute stress state and the neutral state, respectively. We used a 64-channel EEG cap to record EEG data from university students during the experimental task. In combination with the ERO technique, we compared the reaction time, the number of errors, and the power of the alpha (8-13 Hz) and theta (4-8 Hz) frequency bands at the midline of the frontal lobe for subjects in both states. The correlation between the area under the stress area line and the alpha as well as theta frequency bands was also analyzed. Results: We found that in the two-choice Oddball task, the response inhibition time was shorter, the number of response errors decreased, and the alpha-band power values decreased in the acute stress state compared to the neutral state. For the standard stimulus, the theta-band power increase in the acute stress state. Conclusion: Our results suggest that evoked acute stress promotes behavioral inhibition in college students by affecting their frontal midline neural oscillations.

Ultrafast Optical Probe of Coherent Acoustic Phonons in Dirac Semimetal Cd3As2 Film Epitaxied on GaAs(111)B Substrate.

Coherent longitudinal acoustic phonon (CAP) generation in epitaxial Dirac semimetal Cd3As2 films with different thicknesses was investigated by a time-resolved reflectance technique. The short-lived weak CAP oscillations can be observed only in the thicker Cd3As2 films, and their central frequency of 0.039 THz has no dependence on sample thickness, but is nearly inversely proportional to the probe wavelength. For the 20 nm thin film, the observed long-lived CAP with a central frequency of 0.049 THz is generated in the GaAs(111)B substrate underneath. A sound velocity of 3800 m/s for the Cd3As2 film and 5360 m/s for the GaAs(111)B substrate is thus deduced. In addition, the opposite CAP amplitude and lifetime dependence on temperature further confirms the electronic and thermal stress origination of CAP generated in GaAs(111)B and Cd3As2 film, respectively, based on the propagating strain pulse model. The central frequency of CAP is found to be stable with increasing pumping fluence and temperature, which makes Cd3As2 a potential material for thermoelectric device applications.

Case report: A 9-year systematic treatment failure of a pulmonary tuberculosis patient.

Objective: To explore the reasons of failure in a case of pulmonary tuberculosis (PTB) after 9 years systematic treatment. Methods: We extracted the patients' treatment history, drug susceptibility testing (DST), Computed tomography (CT) images, and sequenced the isolated strains by whole gene sequencing (WGS). Results: Although most results of the phenotypical DSTs were consistent with the genotype DST, the occurrence of gene resistance to amikacin (AMK), capreomycin (CAP), moxifloxacin (MFX) was earlier than the phenotypical DST. Based on the continuously reversed results of phenotypical DSTs, CT images in different stages and WGS, it can be confirmed that the patient was infected with two different strains of Mycobacterium tuberculosis (M.TB). Moreover, severe cavities may be another factor leading to treatment failure. Conclusion: Given the suggestive effect of genotype DST is earlier than the phenotypical DST, so genotype DST can play a better guiding role in patients with MDR-TB. Additionally, for patients who have not been cured for a long time, medication should be more cautious and the role of WGS in drug resistance surveillance should be fully utilized.

Alamandine alleviated heart failure and fibrosis in myocardial infarction mice.

Alamandine (Ala) is the newest identified peptide of the renin-angiotensin system and has protective effect on myocyte hypertrophy. However, it is still unclear whether Ala can alleviate heart failure (HF). The aim of this study was to explore the effects of Ala on HF and the related cardiac fibrosis, and to probe the mechanism. HF model was induced by myocardial infarction (MI) in mice. Four weeks after MI, Ala was administrated by intraperitoneal injection for two weeks. Ala injection significantly improved cardiac dysfunction of MI mice in vivo. The cardiac fibrosis and the related biomarkers were attenuated after Ala administration in HF mice in vivo. The increases of collagen I, alpha-smooth muscle actin and transforming growth factor-beta induced by oxygen-glucose deprivation (OGD) in neonatal rat cardiac fibroblasts (NRCFs) were inhibited by Ala treatment in vitro. The biomarkers of apoptosis were elevated in NRCFs induced by OGD, which were attenuated after treating with Ala in vitro. The enhancement of oxidative stress in the heart of MI mice or in the NRCFs treated with OGD was suppressed by treating with Ala in vivo and in vitro. These effects of Ala were reversed by tBHP, an exogenous inducer of oxidative stress in vitro. These results demonstrated that Ala could alleviate cardiac dysfunction and attenuate cardiac fibrosis via inhibition of oxidative stress.

Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction: A Meta-analysis.

Importance: In recent years, significant progress has been made in the pharmacologic treatment of heart failure (HF) with reduced ejection fraction (HFrEF), but there is still insufficient evidence for drug therapy for HF with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). Objective: To compare the outcomes associated with different drug combinations for the treatment of HFpEF and HFmrEF. Data Sources: A search of the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted for studies published from inception to October 9, 2021. Study Selection: Randomized clinical trials on the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), ß-blockers, and sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with HFpEF or HFmrEF. Data Extraction and Synthesis: Data extraction and bias assessment were independently performed by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All data for 3 outcomes were pooled with a fixed-effect model. Main Outcomes and Measures: The main outcomes were first hospitalization for HF, all-cause mortality, and cardiovascular mortality. Hazard ratios (HRs) and 95% credible intervals (CrIs) were evaluated using a bayesian network meta-analysis model. Results: In this analysis, 19 randomized clinical trials, including 20 633 patients with HF and an ejection fraction of 40% or more, without a remarkable risk of bias were included. Compared with placebo, no treatments were associated with a significant reduction in the risk of all-cause death or cardiovascular death. SGLT2 inhibitors, ARNIs, and MRAs were associated with a significant decrease in the risk of HF hospitalization compared with placebo (SGLT2 inhibitors: HR, 0.71 [95% CrI, 0.60-0.83]; ARNIs: HR, 0.76 [95% CrI, 0.61-0.95]; MRAs: HR, 0.83 [95% CrI, 0.69-0.99]), and SGLT2 inhibitors were the optimal drug class in terms of reducing the risk for HF admission. Sensitivity analysis results demonstrated a progressive decrease in the risk of HF admission and an advance in mean rank associated with the increasing use of drug classes. Conclusions and Relevance: The findings of this study suggest that SGLT2 inhibitors were the optimal drug class for HFpEF and HFmrEF, consistent with the most recent guideline recommendation. The incremental use of combinations of SGLT2 inhibitors, ACE inhibitors or ARBs, and ß-blockers may be associated with accumulative benefits in HF hospitalization rather than all-cause death among patients with HFpEF and HFmrEF.