BackgroundPast studies have found a strong relationship between alcohol drinking and human health.MethodsIn this study, we first tested the association of rs671 with alcohol use in 2349 participants ...in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis.ResultsWe found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship.ConclusionsCompared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.
Three hypothetical complexes were designed using diimides (PMDI, NTCDI, and PTCDI) as the acceptor unit and B(III)‐submonoazaporphyrin (1) as the donor unit. These complexes have smaller HOMO‐LUMO ...energy gaps (3.39–3.96 eV) than pristine 1 (6.61 eV). Further, the energy gap can be tuned by changing the number of benzene rings of these diimides. Remarkably, these proposed complexes possess considerable first hyperpolarizabilities (β0) (4865–6921 a.u.), and the regularity of the β0 values remained the same in the gas phase and toluene solvent conditions. There is an inverse relationship between the energy gap and the polarizability/first hyperpolarizability. In addition, absorption spectra, frontier molecular orbitals, and hole electron distributions were obtained using time‐dependent density functional theory calculations to emphasize the relationship between structure and properties. Ultraviolet‐Visible absorption spectra reveals that all complexes show satisfying IR working regions. Further analysis of the first hyperpolarizability density reveals the nature of the excellent NLO properties of the studied systems. This study can provide valuable insights for the development of potential high‐performance NLO molecules.
Three hypothetical complexes were theoretically designed using diimides (PMDI, NTCDI, and PTCDI) as the acceptor unit and B(III)‐submonoazaporphyrin (1) as the donor unit. Theoretical calculations show that the first hyperpolarizabilities of these complexes can increase significantly with increasing size of the diimide unit.
This article is concerned with event‐triggered adaptive tracking control design of strict‐feedback nonlinear systems, which are subject to input saturation and unknown control directions. In the ...design procedure, a smooth nonlinear function is employed to approximate the saturation function so that the controller can be designed under the framework of backstepping. The Nussbaum gain technique is employed to address the issue of the unknown control directions. A predetermined time convergent performance function and a nonlinear mapping technique are introduced to guarantee that the tracking error can converge in the predetermined time with a fast convergence rate and a high accuracy. Then the event‐triggered adaptive prescribed performance tracking control strategy is proposed, which not only ensures the boundedness of all the closed‐loop signals and the convergence of tracking error but also reduces the communication burden from the controller to the actuator. At last, the simulation study further tests the availability of the proposed control strategy.
Summary
Heterotrophic nitrifiers are able to oxidize and remove ammonia from nitrogen‐rich wastewaters but the genetic elements of heterotrophic ammonia oxidation are poorly understood. Here, we ...isolated and identified a novel heterotrophic nitrifier, Alcaligenes ammonioxydans sp. nov. strain HO‐1, oxidizing ammonia to hydroxylamine and ending in the production of N2 gas. Genome analysis revealed that strain HO‐1 encoded a complete denitrification pathway but lacks any genes coding for homologous to known ammonia monooxygenases or hydroxylamine oxidoreductases. Our results demonstrated strain HO‐1 denitrified nitrite (not nitrate) to N2 and N2O at anaerobic and aerobic conditions respectively. Further experiments demonstrated that inhibition of aerobic denitrification did not stop ammonia oxidation and N2 production. A gene cluster (dnfT1RT2ABCD) was cloned from strain HO‐1 and enabled E. coli accumulated hydroxylamine. Sub‐cloning showed that genetic cluster dnfAB or dnfABC already enabled E. coli cells to produce hydroxylamine and further to 15N2 from (15NH4)2SO4. Transcriptome analysis revealed these three genes dnfA, dnfB and dnfC were significantly upregulated in response to ammonia stimulation. Taken together, we concluded that strain HO‐1 has a novel dnf genetic cluster for ammonia oxidation and this dnf genetic cluster encoded a previously unknown pathway of direct ammonia oxidation (Dirammox) to N2.
Dysbiosis of gut microbiota are commonly reported in autism spectrum disorder (ASD) and may contribute to behavioral impairment. Vitamin A (VA) plays a role in regulation of gut microbiota. This ...study was performed to investigate the role of VA in the changes of gut microbiota and changes of autism functions in children with ASD.
Sixty four, aged 1 to 8 years old children with ASD completed a 6-month follow-up study with VA intervention. High-performance liquid chromatography was used to assess plasma retinol levels. The Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess autism symptoms. CD38 and acid-related orphan receptor alpha (RORA) mRNA levels were used to assess autism-related biochemical indicators' changes. Evaluations of plasma retinol, ABC, CARS, SRS, CD38 and RORA mRNA levels were performed before and after 6 months of intervention in the 64 children. Illumina MiSeq for 16S rRNA genes was used to compare the differences in gut microbiota before and after 6 months of treatment in the subset 20 of the 64 children. After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased (all P < 0.05); the scores of ABC, CARS and SRS scales showed no significant differences (all P > 0.05) in the 64 children. Meanwhile, the proportion of Bacteroidetes/Bacteroidales significantly increased and the proportion of Bifidobacterium significantly decreased in the subgroup of 20 (all false discovery rate (FDR) q < 0.05).
Bacteroidetes/Bacteroidales were the key taxa related to VA. Moreover, VA played a role in the changes in autism biomarkers. It remains unclear whether the VA concentration is associated with autism symptoms.
The study protocol was peer reviewed and approved by the institutional review board of Children's Hospital, Chongqing Medical University in 2013 and retrospectively registered in Chinese Clinical Trial Registry (ChiCTR) on November 6, 2014 (TRN: ChiCTR-ROC-14005442 ).
Soybean (Glycine max (L.) Merr.) is a typical short-day and warm season plant, and the interval between emergence and flowering has long been known to be regulated by environmental factors, primarily ...photoperiod and temperature. While the effects of photoperiod and temperature on soybean flowering have been extensively studied, a dissection of the component photo-thermal effects has not been documented for Chinese germplasm. Our objective of the current study was to evaluate the independent- and interactive-photo-thermal responses of 71 cultivars from 6 ecotypes spanning the soybean production regions in China. These cultivars were subjected in pot experiments to different temperature regimes by planting in spring (low temperature (LT)) and summer (high temperature (HT)), and integrating with short day (SD, 12 h), natural day (ND, variable day-length), and long day (LD, 16 h) treatments over two years. The duration of the vegetative phase from emergence to first bloom (R1) was recorded, and the photo-thermal response was calculated. The outcome of this characterization led to the following conclusions: (1) There were significant differences in photo-thermal response among the different ecotypes. High-latitude ecotypes were less sensitive to the independent- and interactive-photo-thermal effects than low-latitude ecotypes; and (2) there was an interaction between photoperiod and temperature, with the effect of photoperiod on thermal sensitivity being greater under the LD than the SD condition, and with the effect of temperature on photoperiodic sensitivity being greater under the LT than the HT condition. The strengths and limitations of this study are discussed in terms of implications for current knowledge and future research directions. The study provides better understanding of photo-thermal effects on flowering in soybean genotypes from different ecotypes throughout China and of the implications for their adaptation more broadly.
Timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value ...of the antibody test to RNA test need to be demonstrated.
Serial sera of 80 patients with PCR-confirmed coronavirus disease 2019 (COVID-19) were collected at the First Affiliated Hospital of Zhejiang University, Hangzhou, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described.
The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e.) or 9, 10 and 12 days post onset (d.p.o.), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared with IgM and IgG (33.3% for both; p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3%, respectively, 2 weeks later. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays.
A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic-specific diagnosis and helpful information to evaluate the adapted immunity status of patients.
Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with advancing age ...in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown.
In this study, we investigated the role of SIRT1 (Sirtuin 1), a class III histone deacetylase, in AAA formation and the underlying mechanisms linking vascular senescence and inflammation.
The expression and activity of SIRT1 were significantly decreased in human AAA samples. SIRT1 in vascular smooth muscle cells was remarkably downregulated in the suprarenal aortas of aged mice, in which AAAs induced by angiotensin II infusion were significantly elevated. Moreover, vascular smooth muscle cell-specific knockout of SIRT1 accelerated angiotensin II-induced formation and rupture of AAAs and AAA-related pathological changes, whereas vascular smooth muscle cell-specific overexpression of SIRT1 suppressed angiotensin II-induced AAA formation and progression in Apoe
mice. Furthermore, the inhibitory effect of SIRT1 on AAA formation was also proved in a calcium chloride (CaCl
)-induced AAA model. Mechanistically, the reduction of SIRT1 was shown to increase vascular cell senescence and upregulate p21 expression, as well as enhance vascular inflammation. Notably, inhibition of p21-dependent vascular cell senescence by SIRT1 blocked angiotensin II-induced nuclear factor-κB binding on the promoter of monocyte chemoattractant protein-1 and inhibited its expression.
These findings provide evidence that SIRT1 reduction links vascular senescence and inflammation to AAAs and that SIRT1 in vascular smooth muscle cells provides a therapeutic target for the prevention of AAA formation.
Ultrasound (US)‐mediated sonodynamic therapy (SDT) has the advantages of non‐invasiveness and deep tissue penetration. Nanosystems are prominently used in sonosensitization; however, most ...nano‐sonosensitizers have a low reactive oxygen species (ROS) yield, thus restraining the application of SDT. Sodium molybdenum bronze nanoparticles (SMB NPs) with rich oxygen vacancies are developed and interlayer gaps of molybdenum trioxide nanobelts are expanded. Owing to the increased oxygen vacancy density and wide interlayer gap‐induced narrower band gap of SMB NPs, the electrons (e–) and holes (h+) generated by US are separated more rapidly, and oxygen vacancies prevent electrons–holes recombination under US irradiation. SMB NPs exhibit a second near‐infrared (NIR‐II) photothermal effect to promote the generation of ROS by the sonosensitizer. The SMB NPs system is successfully realized to eliminate Staphylococcus aureus (S. aureus) and dissipate biofilm. Therefore, multimodal therapy using SMB NPs serves as an effective and promising regimen for deep‐seated bacterial infections. The newly developed Mo‐based sonosensitizer is presented for the first time to demonstrate excellent antimicrobial activity through hyperthermia‐promoting SDT therapeutics. This work proposes a novel strategy in the field of NIR‐II photo‐amplified SDT with Mo‐based materials for bacterial eradication and other important biomedical applications.
The newly developed Mo‐based sonosensitizer is presented for the first time to demonstrate excellent eradicate bacteria in deep‐seated infected tissues in vivo through photothermal‐amplified sonodynamic therapy (SDT) to accelerate abscess healing, which can open a new window in the field of NIR‐II photo‐amplified SDT with Mo‐based materials for bacterial eradication and other biomedical applications.
Background
This is a sub‐analysis of the Personalized Antithrombotic Therapy for Coronary Heart Disease after PCI (PATH‐PCI) trial in China to explore the relationship between smoking and outcomes ...following personalized antiplatelet therapy (PAT) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI).
Methods
As a single‐center, prospective, randomized controlled and open‐label trial, the PATH‐PCI trial randomized CCS patients undergoing PCI into standard group or personalized group guided by a novel platelet function test (PFT), from December 2016 to February 2018. All patients were divided into smokers and nonsmokers according to their smoking status. Subsequently, we underwent a 180‐day follow‐up evaluation. The primary endpoint was the net adverse clinical events (NACE).
Results
Regardless of smoking status, in the incidence of NACE, there was a reduction with PAT but that the reductions are not statistically significant. In the incidence of bleeding events, we found no statistically significant difference between two groups (smokers: 2.0% vs. 1.4%, HR = 1.455, 95% confidence interval CI: 0.595−3.559, p = .412; nonsmokers: 2.2% vs. 1.8%, HR = 1.228, 95% CI: 0.530−2.842, p = .632). In smokers, PAT reduced major adverse cardiac and cerebrovascular events (MACCE) by 48.7% (3.0% vs. 5.9%, HR = 0.513, 95% CI: 0.290−0.908, p = .022), compared with standard antiplatelet therapy (SAT). PAT also reduced the major adverse cardiovascular events (MACE) but there was no statistically difference in the reductions (p > .05). In nonsmokers, PAT reduced MACCE and MACE by 51.5% (3.3% vs. 6.7%, HR = 0.485, 95% CI: 0.277−0.849, p = .011) and 63.5% (1.8% vs. 4.9%, HR = 0.365, 95% CI: 0.178−0.752, p = .006), respectively. When testing p‐values for interaction, we found there was no significant interaction of smoking status with treatment effects of PAT (pint‐NACE = .184, pint‐bleeding = .660).
Conclusion
Regardless of smoking, PAT reduced the MACE and MACCE, with no significant difference in bleeding. This suggests that PAT was an recommendable regimen to CCS patients after PCI, taking into consideration both ischemic and bleeding risk.
PL‐12 is a new platelet function analyzer testing the platelet maximum aggregation rate. The Personalized Antithrombotic Therapy for Coronary Heart Disease after PCI trial established that personalized antiplatelet therapy (PAT) guided by PL‐12 greatly improved the prognosis of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention. We explored the efficacy and safety of PAT in CCS patients under different smoking status.
PDF
