US Population Eligibility and Estimated Impact of Tirzepatide Treatment on Obesity Prevalence and Cardiovascular Disease Events.

PURPOSE: Tirzepatide promotes weight loss and reduces risk factors for cardiovascular disease (CVD) in adults with overweight and obesity. We examined the number of US adults eligible for tirzepatide and its impact on obesity and CVD events. METHODS: We identified US adults aged ≥ 18 years from the cross-sectional US National Health and Nutrition Examination Survey (NHANES) 2015-2018 eligible for tirzepatide based on SURMOUNT-1 trial eligibility criteria. Weight changes in SURMOUNT-1 from tirzepatide 15 mg treatment were used to project the impact on weight change and obesity prevalence in the population assuming titration to this dosage. We estimated 10-year CVD risks from BMI-based Framingham CVD risk scores before and after applying tirzepatide 15 mg treatment BMI and risk factor effects from SURMOUNT-1, the differences in estimated risks multiplied by the eligible NHANES weighted population representing the estimated "preventable" CVD events. RESULTS: We identified 4015 US adults (estimated population size of 93.4 million [M]) to fit SURMOUNT-1 eligibility criteria, representing 38% of US adults. When the effects of 15 mg tirzepatide were applied, we estimated 70.6% (65.9 M) and 56.7% (53.0 M) of adults to show ≥ 15% and ≥ 20% reductions in weight, respectively, translating to 58.8% (55.0 M) fewer persons with obesity. Among those without CVD, estimated 10-year CVD risks were 10.1% "before" and 7.7% "after" tirzepatide "treatment" reflecting a 2.4% absolute (and 23.6% relative) risk reduction translating to 2.0 million preventable CVD events over 10 years. CONCLUSION: Tirzepatide treatment in appropriate US adults may substantially reduce obesity prevalence and CVD events, impacting beneficially on associated healthcare costs.

Large-Scale Synthesis of High-Loading Single Metallic Atom Catalysts by a Metal Coordination Route.

Single atom catalyst (SAC) is one of the most efficient and versatile catalysts with well-defined active sites. However, its facile and large-scale preparation, the prerequisite of industrial applications, has been very challenging. This dilemma originates from the Gibbs-Thomson effect, which renders it rather difficult to achieve high single atom loading (< 3 mol%). Further, most synthesizing procedures are quite complex, resulting in significant mass loss and thus low yields. Herein, a novel metal coordination route is developed to address these issues simultaneously, which is realized owing to the rapid complexation between ligands (e.g., biuret) and metal ions in aqueous solutions and subsequent in situ polymerization of the formed complexes to yield SACs. The whole preparation process involves only one heating step operated in air without any special protecting atmospheres, showing general applicability for diverse transition metals. Take Cu SAC for an example, a record yield of up to 3.565 kg in one pot and an ultrahigh metal loading 16.03 mol% on carbon nitride (Cu/CN) are approached. The as-prepared SACs are demonstrated to possess high activity, outstanding selectivity, and robust cyclicity for CO2 photoreduction to HCOOH. This research explores a robust route toward cost-effective, massive production of SACs for potential industrial applications.

PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice.

Airborne fine particulate matter (PM2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment.

Prevalence and molecular characterization of Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis in dairy cattle in Ningxia, northwestern China.

Cryptosporidium spp., Enterocytozoon bieneusi, and Giardia duodenalis are common intestinal pathogens that infect humans and animals. To date, research regarding these three protozoa in the Ningxia Hui Autonomous Region (Ningxia) has mostly been limited to a single pathogen, and comprehensive data on mixed infections are unavailable. This study aimed to evaluate the zoonotic potential of these three protozoa. In this study, small subunit ribosomal RNA (SSU rRNA) and 60 kDa glycoprotein (gp60) genes of Cryptosporidium; internal transcribed spacer (ITS) gene of E. bieneusi; and SSU rRNA, glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis were examined. DNA extraction, polymerase chain reaction, and sequence analysis were performed on fecal samples collected from 320 dairy cattle at three intensive dairy farms in Ningxia in 2021 to determine the prevalence and genetic characteristics of these three protozoa. The findings revealed that 61.56% (197/320) of the samples were infected with at least one protozoan. The overall prevalence of Cryptosporidium was 19.38% (62/320), E. bieneusi was 41.56% (133/320), and G. duodenalis was 29.38% (94/320). This study identified four Cryptosporidium species (C. bovis, C. andersoni, C. ryanae, and C. parvum) and the presence of mixed infections with two or three Cryptosporidium species. C. bovis was the dominant species in this study, while the dominant C. parvum subtypes were IIdA15G1 and IIdA20G1. The genotypes of E. bieneusis were J, BEB4, and I alongside the novel genotypes NX1-NX8, all belonging to group 2, with genotype J being dominant. G. duodenalis assemblages were identified as assemblages E, A, and B, and a mixed infection involving assemblages A + E was identified, with assemblage E being the dominant one. Concurrently, 11 isolates formed 10 different assemblage E multilocus genotypes (MLGs) and 1 assemblage A MLG and assemblage E MLGs formed 5 subgroups. To the best of our knowledge, this is the first report on mixed infection with two or three Cryptosporidium species in cattle in Ningxia and on the presence of the C. parvum subtype IIdA20G1 in this part of China. This study also discovered nine genotypes of E. bieneusis and novel features of G. duodenalis assemblages in Ningxia. This study indicates that dairy cattle in this region may play a significant role in the zoonotic transmission of Cryptosporidium spp., E. bieneusi, and G. duodenalis.

Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort.

BACKGROUND: Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts. OBJECTIVES: This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S. METHODS: The study included data on Lp(a) and ASCVD outcomes from 5 U.S. PROSPECTIVE STUDIES: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities). Lp(a) levels were classified on the basis of cohort-specific percentiles. Multivariable Cox regression related Lp(a) with composite incident ASCVD events by risk group and diabetes status. RESULTS: The study included 27,756 persons without previous ASCVD who were aged 20 to 79 years, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with mean follow-up of 21.1 years. Compared with Lp(a) levels <50th percentile, Lp(a) levels in the 50th to <75th, 75th to <90th, and ≥90th percentiles had adjusted HRs of 1.06 (95% CI: 0.99-1.14), 1.18 (95% CI: 1.09-1.28), and 1.46 (95% CI: 1.33-1.59), respectively for ASCVD events. Elevated Lp(a) predicted incident ASCVD events similarly by risk group, sex, and race or ethnic groups, but more strongly in patients with vs without diabetes (interaction P = 0.0056), with HRs for Lp(a) levels ≥90th percentile of 1.92 (95% CI: 1.50-2.45) and 1.41 (95% CI: 1.28-1.55), respectively. Lp(a) also individually predicted myocardial infarction, revascularization, stroke, and coronary heart disease death, but not total mortality. CONCLUSIONS: The study shows, in a large U.S. pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk, including in patients with diabetes.

Electrosynthesis of H2 O2 Promoted by π-π Interaction on a Metal-Free Carbon Catalyst.

The synthesis of hydrogen peroxide (H2 O2 ) through electrocatalytic oxygen reduction reaction is an ideal alternative to the current energy-intensive anthraquinone process, but developing cost-effective and high-efficiency electrocatalysts is still challenging. Herein, a metal-free graphitic carbon nitride/carbon nanotube (g-C3 N4 /CNT) hybrid catalyst can enhance H2 O2 production via π-π interaction is reported, achieving almost unity (97%) H2 O2 production at 0.57 V with high selectivity of over 92% across the wide potential range from 0.6 to 0 V. Other carbon materials with weak interaction with g-C3 N4 , such as acetylene black and super P, show markedly weakened H2 O2 production, indicating the importance of π-π interaction. Electron transfer kinetic analysis combined with density functional theory calculations indicates that the synergistic effect between g-C3 N4 and CNT enhances electron transfer and O2 activation between g-C3 N4 and CNT, leading to enhanced H2 O2 production performance. This work provides a complementary approach for H2 O2 production from oxygen reduction besides introducing oxygenated groups or heteroatom doping into carbon materials.

LRRK2 is involved in heat exposure-induced acute lung injury and alveolar type II epithelial cell dysfunction.

Heat exposure induces excessive hyperthermia associated with systemic inflammatory response that leads to multiple organ dysfunction including acute lung injury. However, how heat impairs the lung remains elusive so far. We aimed to explore the underlying mechanism by focusing on leucine-rich repeat kinase 2 (LRRK2), which was associated with lung homeostasis. Both in vivo and in vitro models were induced by heat exposure. Firstly, heat exposure exerted core temperature (Tc) disturbance, pulmonary dysfunction, atelectasis, inflammation, impaired energy metabolism, and reduced surfactant proteins in the lung of mice. In addition, decreased LRRK2 expression and increased heat shock proteins (HSPs) 70 were observed with heat exposure in both the lung of mice and alveolar type II epithelial cells (AT2). Furthermore, LRRK2 inhibition aggravated heat exposure-initiated Tc dysregulation, injury in the lung and AT2 cells, and enhanced HSP70 expression. In conclusion, LRRK2 is involved in heat-induced acute lung injury and AT2 cell dysfunction.

Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence.

It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-ß1 (TGF-ß1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated ß-galactosidase (SA-ß-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.

Biomimetic Design of a Dynamic M-O-V Pyramid Electron Bridge for Enhanced Nitrogen Electroreduction.

Electrochemical nitrogen reduction reaction (eNRR) offers a sustainable route for ammonia synthesis; however, current electrocatalysts are limited in achieving optimal performance within narrow potential windows. Herein, inspired by the heliotropism of sunflowers, we present a biomimetic design of Ru-VOH electrocatalyst, featuring a dynamic Ru-O-V pyramid electron bridge for eNRR within a wide potential range. In situ spectroscopy and theoretical investigations unravel the fact that the electrons are donated from Ru to V at lower overpotentials and retrieved at higher overpotentials, maintaining a delicate balance between N2 activation and proton hydrogenation. Moreover, N2 adsorption and activation were found to be enhanced by the Ru-O-V moiety. The catalyst showcases an outstanding Faradaic efficiency of 51.48% at -0.2 V (vs RHE) with an NH3 yield rate exceeding 115 µg h-1 mg-1 across the range of -0.2 to -0.4 V (vs RHE), along with impressive durability of over 100 cycles. This dynamic M-O-V pyramid electron bridge is also applicable to other metals (M = Pt, Rh, and Pd).

First report of Giardia duodenalis in dairy cattle and beef cattle in Shanxi, China.

BACKGROUND: Giardia duodenalis is an important intestinal parasitic protozoan that infects several vertebrates, including humans. Cattle are considered the major source of giardiasis outbreak in humans. This study aimed to investigate the prevalence and multilocus genotype (MLG) of G. duodenalis in Shanxi, and lay the foundation for the prevention and control of Giardiosis. METHODS AND RESULTS: DNA extraction, nested polymerase chain reaction, sequence analysis, MLG analysis, and statistical analysis were performed using 858 bovine fecal samples from Shanxi based on three gene loci: ß-giardin (bg), glutamate dehydrogenase (gdh), and triosephosphate isomerase (tpi). The overall prevalence of G. duodenalis was 28.3%, while its prevalence in Yingxian and Lingqiu was 28.1% and 28.5%, respectively. The overall prevalence of G. duodenalis in dairy cattle and beef cattle was 28.0% and 28.5%, respectively. G. duodenalis infection was detected in all age groups evaluated in this study. The overall prevalence of G. duodenalis in diarrhea and nondiarrhea samples was 32.4% and 27.5%, respectively, whereas that in intensively farmed and free-range cattle was 35.0% and 19.9%, respectively. We obtained 83, 53, and 59 sequences of bg, gdh, and tpi in G. duodenalis, respectively. Moreover, assemblage A (n = 2) and assemblage E (n = 81) by bg, assemblage A (n = 1) and assemblage E (n = 52) by gdh, and assemblage A (n = 2) and assemblage E (n = 57) by tpi were identified. Multilocus genotyping yielded 29 assemblage E MLGs, which formed 10 subgroups. CONCLUSIONS: To the best of our knowledge, this is the first study to report cattle infected with G. duodenalis in Shanxi, China. Livestock-specific G. duodenalis assemblage E was the dominant assemblage genotype, and zoonotic sub-assemblage AI was also detected in this region.

Nanoreactor Confined and Enriched Intermediates for Electroreduction of CO2 to C2+ Products.

In the process of electroreduction of carbon dioxide (eCO2RR) to multi-carbon (C2+) products, it is imperative to enhance the concentration of key intermediate species on the catalyst surface. The utilization of micro-nano reactors to achieve confinement effects has been widely observed in various catalytic reactions, yet it has seldom been employed in eCO2RR. Here, we present a novel nanoreactor composed of stacked CuS nanosheets for eCO2RR to C2+ products. In comparison to catalyst comprising of nanosheet with open space, the C-C coupling within this confined nanospace is significantly enhanced, resulting in the increase of Faraday efficiency (FE) of C2+ products to 53 %. In situ infrared (IR) spectroscopy reveals the confinement and enrichment of key intermediate by the nanoreactor. Our research findings demonstrate that a meticulously designed nanoreactor can elevate the selectivity of C2+ products, thereby aiding in the design of eCO2RR catalysts.

Albumin combined with neutrophil-to-lymphocyte ratio score and outcomes in patients with acute coronary syndrome treated with percutaneous coronary intervention.

BACKGROUND: Evidence about the association between albumin combined with neutrophil-to-lymphocyte ratio score (ANS) and survival outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is rare. This study aimed to evaluate the prognostic value of ANS in patients with ACS undergoing PCI by propensity score matching (PSM) analysis. PATIENTS AND METHODS: Patients with ACS undergoing PCI were consecutively enrolled in this prospective cohort study from January 2016 to December 2018. The albumin and neutrophil-to-lymphocyte ratio cutoff values for predicting major adverse cardiovascular events (MACEs) were calculated using receiver operating characteristic curves. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazard regression models and PSM. The study endpoint was the occurrence of a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. RESULTS: Overall, 1549 patients with adequate specimens were identified and assigned into different groups for comparison. Before and after PSM, the Kaplan-Meier curves showed that a higher ANS value was associated with a higher risk of MACEs (all P  < 0.001). The multivariate Cox proportional hazard regression model showed that the ANS (per 1 score increase) [hazard ratio (HR), 2.016; 95% confidence interval (CI), 1.329-3.057; P  = 0.001 vs. HR, 2.166; 95% CI, 1.344-3.492; P  = 0.002] was an independent predictor for MACEs. CONCLUSION: This study tentatively confirms that ANS may be a valuable clinical indicator to identify high-risk ACS patients after PCI. More high-quality prospective studies are needed in the future.

Tuning Coordination Structures of Zn Sites Through Symmetry-Breaking Accelerates Electrocatalysis.

Manipulating the coordination environment of individual active sites in a precise manner remains an important challenge in electrocatalytic reactions. Herein, inspired by theoretical predictions, a facile procedure to synthesize a series of symmetry-breaking zinc metal-organic framework (Zn-MOF) catalysts with well-defined structures is presented. Benefiting from the optimized coordination microenvironment regulated by symmetry-breaking, Zn-N2 S2 -MOF exhibits the best performance of nitrogen (N2 ) reduction reaction (NRR) with NH3 yield rate of 25.07 ± 1.57 µg h-1  cm-2 and Faradaic efficiency of 44.57 ± 2.79% compared with reported Zn-based NRR catalysts. X-ray absorption near-edge structure shows that the symmetry-breaking distorts the coordination environment and modulates the delocalized electrons around the Zn sites, which favors the formation of unpaired low-valence Znδ+ , thereby facilitating the adsorption/activation of N2 . Theoretical calculations elucidate that low-valence Znδ+ in Zn-N2 S2 -MOF can effectively lower the energy barrier of potential determining step, promoting the kinetics and boosting the NRR activity. This work highlights the relationship between the precise coordination environment of metal sites and the catalytic activity, which offers insightful guidance for rationally designing high-efficiency electrocatalysts.

Effect of endoscopic mucosal resection and endoscopic submucosal dissection on postoperative wound complications in patients with gastric cancer: A meta-analysis.

Endoscopic submucosa dissection (ESD) allows complete excision of the whole lesion, which results in a higher percentage of complete excision and an improved quality of life by minimizing the amount of excision as opposed to an endoscopic mucosal resection (EMR). Although ESD is now being carried out in the majority of hospitals, ESD's possible complications (such as trauma and perforation) have given rise to doubts about ESD practices in patients with early-stage stomach cancer when deciding on therapy and reimbursement. This study was designed to evaluate the effectiveness and safety of ESD over EMR in treating early-stage stomach cancer. Four main databases have been searched, including EMBASE and published. The ROBINS-I tool suggested in the Cochrane Handbook has been applied to evaluate the quality of the chosen trials. It may better reflect the risk of bias in the included studies. The meta-analyses were carried out with ReMan 5.3, and the results were treated with endote. Seven cohort studies have been completed. Meta analysis indicated that EMR and ESD surgery did not differ significantly from each other in terms of postoperative haemorrhage (OR, 0.76; 95%CI, 0.56,1.04 p = 0.09); EMR, however, was associated with a lower rate of postoperative perforation than ESD surgery (OR, 0.36; 95%CI, 0.24,0.54 p < 0.0001). Taking into account that ESD and EMR did not differ significantly in the risk of wound bleeding, even though the risk of perforation is not likely to result in life-threatening illness. In the analysis of these data, however, the potential advantages of EMR might be greater than ESD.

Prevalence and molecular characterization of Cryptosporidium spp. in dairy and beef cattle in Shanxi, China.

Cryptosporidium spp. are key gastrointestinal protists in humans and animals worldwide. Infected cattle are considered the main source of cryptosporidiosis outbreaks in humans. However, little is known about the genetic makeup of Cryptosporidium populations in Shanxi province, China. We analyzed 858 fecal samples collected from farms in Shanxi. The presence of Cryptosporidium spp. was determined via polymerase chain reaction and subsequent sequence analysis of the small subunit rRNA gene as well as restriction fragment length polymorphism analysis. Cryptosporidium parvum was subtyped following sequence analysis of the 60 kDa glycoprotein gene (gp60). The overall prevalence of Cryptosporidium in cattle was 11.19%, with a prevalence of 13.30% and 8.67% in Lingqiu and Yingxian, respectively. The overall prevalence of Cryptosporidium in dairy and beef cattle was 10.78% and 11.50%, respectively. Cryptosporidium infection was detected across all analyzed age groups. The overall prevalence of Cryptosporidium in diarrhea and nondiarrhea samples was 18.24% and 9.72%, respectively, whereas that in intensively farmed and free-range cattle was 17.40% and 3.41%, respectively. We identified five Cryptosporidium species, with C. andersoni being the dominant species. Further, two cases of mixed infections of Cryptosporidium species were detected. All identified C. parvum isolates belonged to the subtype IIdA17G1.

The impact of submandibular glands protection on xerostomia as monitored by diffusion-weighted imaging in nasopharyngeal carcinoma patients.

PURPOSE: To determine the impact of sparing submandibular glands (SMGs) on alleviating xerostomia and the functional dynamics of the irradiated parotid glands (PGs) and sublingual glands (SLGs) by diffusion-weighted imaging. METHODS: 97 participants underwent 9 rounds of DWI scans before IC (pre-IC), pre-radiation (pre-RT), the midpoint of radiation (mid-RT), the end of radiation (post-RT), 1, 3, 6, 9, 12 (12m-RT) months following radiation. Apparent diffusion coefficient of SMGs (ADCSMG), PGs (ADCPG), and SLGs (ADCSLG), xerostomia questionnaire scores (XQ), and saliva flow rate measures under unstimulated (uSFR) and stimulated condition (sSFR) were documented. RESULTS: ADCPG, ADCSMG, ADCSLG, and XQ showed a rapid increase with a top at 3m-RT followed by regression, whereas uSFR and sSFR had the reverse trend. The change rate of ADC correlated with the dose to PGs, SMGs, and SLGs, as well as uSFR, sSFR, and XQ scores (p < 0.05 for all, except for uSFR with ADCPG (p = 0.063)). Maingroup for ADCPG, uSFR, and sSFR were significant (p values were 0.028, 0.000, 0.000 respectively); ADCPG in SMG sparing group was lower while uSFR, and sSFR were higher than those in the SMG-unsparing group. Simplegroup for ADCSMG, ADCSLG (all p < 0.05 from mid-RT to 12m-RT), and XQ (all p < 0.001 at mid-, 6m-, 9m-, and 12m-RT) were significant; ADCSMG, ADCSLG, and XQ were lower in the SMG-sparing group. CONCLUSIONS: SMG protection has a great impact on the functional retention of PGs and SLGs, resulting in alleviating xerostomia and improving quality of life. TRIAL REGISTRATION: The clinical trial was also registered with the Chinese Clinical Study Registry (registered number: ChiCTR1900024328, Date: July 6, 2019; URL: https://www.chictr.org.cn/showproj.aspx?proj=40726 ).

Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism.

BACKGROUND: The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation. METHODS: To focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myocardial structure and function were examined using echocardiography, histology, and biochemical assays. We further investigated the underlying effects of mitochondrial AKT1 on mitochondrial structure and function, its interaction with ATP synthase, and explored in vivo metabolism beyond the heart. RESULTS: Upon induction of dominant negative mitochondrial AKT1, CAMDAKT mice developed cardiac fibrosis accompanied by left ventricular hypertrophy and dysfunction. Cardiac mitochondrial oxidative phosphorylation efficiency and ATP content were reduced, mitochondrial cristae structure was lost, and ATP synthase structure was compromised. Conversely, CAMCAKT mice were protected against development of diabetic cardiomyopathy when challenged with a high calorie diet. Activation of mitochondrial AKT1 protected cardiac function and increased fatty acid uptake in myocardium. In addition, total energy expenditure was increased in CAMCAKT mice, accompanied by reduced adiposity and reduced development of fatty liver. CONCLUSION: CAMDAKT mice modeled the effects of impaired mitochondrial signaling which occurs in the diabetic myocardium. Disruption of this pathway is a key step in the development of cardiomyopathy. Activation of mitochondrial AKT1 in CAMCAKT had a protective role against diabetic cardiomyopathy as well as improved metabolism beyond the heart.

Association of diabetes with coronary artery calcium in South Asian adults and other race/ethnic groups: The multi-ethnic study of atherosclerosis and the mediators of atherosclerosis in South Asians living in America study.

PURPOSE: South Asian (SA) persons have increased risks for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). We examined whether the association of DM with subclinical atherosclerosis assessed by coronary artery calcium (CAC) differs in SA versus other ethnic groups. METHODS: We studied adults from the Multi-Ethnic Study of Atherosclerosis and the Mediators of Atherosclerosis in South Asians Living in America studies without ASCVD. CAC was examined among those normoglycemic, pre-DM and DM. Logistic regression examined pre-DM and DM with the odds of any CAC > 0 and CAC ≥ 100. RESULTS: Among 7562 participants, CAC > 0 and CAC ≥ 100 in those with DM was highest in non-Hispanic White (NHW) (80% and 48%) and SA (72% and 41%) persons. Adjusted Ln (CAC + 1) was highest in NHW (3.68 ± 0.21) and SA (3.60 ± 0.23) (p < .01) DM patients. SA and NHW adults with DM (vs normoglycemic) had highest odds of CAC > 0 (2.13 and 2.27, respectively, p < .01). For CAC ≥ 100, SA and Chinese adults had the highest odds (2.28 and 2.27, respectively, p < .01). Fasting glucose and glycated hemoglobin were most strongly associated with CAC among SA. CONCLUSIONS: Diabetes mellitus most strongly relates to any CAC in SA and NHW adults and CAC ≥ 100 in SA and Chinese adults, helping to explain the relation of DM with ASCVD in these populations.

Multimetallic Single-Atom Catalysts for Bifunctional Oxygen Electrocatalysis.

Multimetallic alloys have demonstrated promising performance for the application of metal-air batteries, while it remains a challenge to design multimetallic single-atom catalysts (MM-SACs). Herein, metal-C3N4 and nitrogen-doped carbon are employed as cornerstones to synthesize MM-SACs by a general two-step method, and the inherent features of atomic dispersion and the strong electronic reciprocity between the multimetallic sites have been verified. The trimetallic FeCoZn-SACs and quatermetallic FeCoCuZn-SACs are both found to deliver superior oxygen evolution reaction and oxygen reduction reaction activity, respectively, as well as outstanding bifunctional durability. Density functional theory calculations elucidate the crucial contribution of Co sites of FeCoCuZn-SACs to the efficient catalysis of both the ORR and the OER. More importantly, Zn-air batteries with FeCoCuZn-SACs as cathodic catalysts exhibit a high power density (252 mW cm-2), high specific capacity (817 mAh gZn-1), and considerable stability (over 225 h) for charging-discharging processes. This work provides a visual perspective for the advantages of MM-SACs toward oxygen electrocatalysis.

Advanced Lung Cancer Inflammation Index for Predicting Prognostic Risk for Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Purpose: The decreased advanced lung cancer inflammation index (ALI), defined as body mass index (BMI) * albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR), is an independent prognostic risk factor for overall survival in gastric, lung, and colorectal cancers. This study aimed to investigate the value of ALI in predicting the risk of major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Patients and Methods: A total of 1624 patients with ACS undergoing percutaneous coronary intervention (PCI) were consecutively enrolled between January 2016 and December 2018. Follow-up data were collected at 1, 3, 6, and 12 months and annually thereafter. The primary endpoints were MACEs. All endpoints were defined as all-cause mortality, recurrent angina pectoris, restenosis/intra stent thrombosis, stroke, heart failure, and all-cause bleeding. Results: The MACEs group and non-MACEs group showed significant differences in patients with age >65 years (28 [50.0%] vs 319 [23.7%]), history of heart failure (16 [28.6%] vs 127 [9.4%]), history of ischemic stroke (14 [25.0%] vs 186 [13.8%]), history of cardiogenic shock (6 [10.71%] vs 16 [1.19%]), left ventricular ejection fraction <40% (8 [14.29%] vs 33 [2.46%]), and ALI <343.96 (44 [78.65%] vs 680 [50.60%]) (all p<0.001). The optimal cut-off value for ALI was 334.96. The area under the curve (AUC) of the 1-, 2-, 3-, and 5-year was 0.560, 0.577, 0.665, and 0.749, respectively. The survival rate was significantly lower in the low ALI group than in the high ALI group (log-rank p<0.001). Low ALI was an independent risk factor for the long-term prognosis of patients with ACS after PCI, univariate HR: 3.671, 95% CI: 1.938-6.953, p<0.001; multivariate HR: 3.009, 95% CI: 1.57-5.769, p=0.001. Conclusion: ALI score less than 334.96 is an independent prognostic risk factor for patients with ACS undergoing PCI and may be a novel marker for clinical practice.