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Ganoderma has received much attention for its medicinal value, but the manipulation of multiple genes remains a challenge, hindering the genetic engineering of this species for the development of cell factories. Here, we first showed that the presence of an intron is necessary for the efficient expression of the endogenous cDNA of carboxin-resistant gene (cbx) in G. lucidum. Then, the self-cleaving function of 2â¯A peptide was investigated in G. lucidum by linking cbx cDNA to the codon-optimized hygromycin B-resistant gene (ophph) using the 2A-peptide sequence. The results showed that cbx cDNA and ophph can be successfully expressed in G. lucidum in a bicistronic manner from a single transcript. Moreover, the expression of both genes was not affected by the order within the 2â¯A cassette. In addition, simultaneous expression of cbx cDNA, ophph, and codon-optimized yellow fluorescent protein gene (opyfp) was conducted for the first time in G. lucidum using the 2â¯A peptide-based approach. The developed method was successfully applied to express both cDNA of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgr) and squalene epoxidase gene (se) for enhanced production of ganoderic acids (GAs) in G. lucidum. The engineered strain produced the maximum content of GA-Mk, GA-T, GA-S, and GA-Me were 26.56±3.53,39.58±3.75, 16.54±2.16, and 19.1±1.87 µg/100â¯mg dry weight, respectively. These values were 3.85-, 4.74-, 3.65-, and 3.23-fold higher than those produced by the control strain. The developed method will be useful for the manipulation of complex metabolic or regulatory pathways involving multiple genes in Ganoderma.
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BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.
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Glicemia , Resistência à Insulina , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/metabolismo , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Glicemia/metabolismo , Glicemia/análise , China/epidemiologia , Modelos de Riscos Proporcionais , Idoso , Povo Asiático , População do Leste AsiáticoRESUMO
In this study, we developed a method for determining cotinine and 3-hydroxycotinine in human serum and established a methodology for an in-depth study of tobacco exposure and health. After the proteins in the human serum samples were precipitated with acetonitrile, they were separated on a ZORBAX SB-Phenyl column with a mobile phase of methanol encompassing 0.3% formic acid-water encompassing 0.15% formic acid. The measurement was performed on an API5500 triple quadrupole mass spectrometer in the multiple reaction monitoring mode. Cotinine, 3-hydroxycotinine, and cotinine-d3 isotope internal standards were held for 2.56 minutes, 1.58 minutes, and 2.56 minutes, respectively. In serum, the linear range was 0.05 to 500 ng·mL-1 for cotinine and 0.50 to 1250 ng·mL-1 for 3-hydroxycotinine. The lower limit of quantification (LLOQ) was 0.05 ng·mL-1 and 0.5 ng·mL-1 for cotinine and 3-hydroxycotinine, respectively. The intra-day and inter-day relative standard deviations were <11%, and the relative errors were withinâ ±â 7%. Moreover, the mean extraction recoveries of cotinine and 3-hydroxycotinine were 98.54% and 100.24%, respectively. This method is suitable for the rapid determination of cotinine and 3-hydroxycotinine in human serum because of its rapidity, sensitivity, strong specificity, and high reproducibility. The detection of cotinine levels in human serum allows for the identification of the cutoff value, providing a basis for differentiation between smoking and nonsmoking populations.
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Cotinina , Espectrometria de Massas em Tandem , Humanos , Cotinina/sangue , Cotinina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Reprodutibilidade dos Testes , Limite de DetecçãoRESUMO
BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16,189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.
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Compost-based organic fertilizers often contain high levels of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). Previous studies focused on quantification of total ARGs and MGEs. For a more accurate risk assessment of the dissemination risk of antibiotic resistance, it is necessary to quantify the intracellular and extracellular distribution of ARGs and MGEs. In the present study, extracellular ARGs and MGEs (eARGs and eMGEs) and intracellular ARGs and MGEs (iARGs and iMGEs) were separately analyzed in 51 commercial composts derived from different raw materials by quantitative polymerase chain reaction (qPCR) and metagenomic sequencing. Results showed that eARGs and eMGEs accounted for 11-56% and 4-45% of the total absolute abundance of ARGs and MGEs, respectively. Comparable diversity, host composition and association with MGEs were observed between eARGs and iARGs. Contents of high-risk ARGs were similar between eARGs and iARGs, with high-risk ARGs in the two forms accounting for 6.7% and 8.2% of the total abundances, respectively. Twenty-four percent of the overall ARGs were present in plasmids, while 56.7% of potentially mobile ARGs were found to be associated with plasmids. Variation partitioning analysis, null model and neutral community model indicated that the compositions of both eARGs and iARGs were largely driven by deterministic mechanisms. These results provide important insights into the cellular distribution of ARGs in manure composts that should be paid with specific attention in risk assessment and management.
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Resistência Microbiana a Medicamentos , Fertilizantes , Resistência Microbiana a Medicamentos/genética , Microbiologia do Solo , Compostagem , Genes BacterianosRESUMO
Reported herein is a photochemical strategy for C(sp3)-H azolation of ethers via a hydrogen-atom transfer and radical-polar crossover process, offering efficient access to valuable N-alkylated azoles under visible-light irradiation. The protocol is metal-free and photocatalyst-free, and exhibits good to excellent yields and broad substrate scope with regard to azoles. EPR experiments provide evidence for the formation of intermediates formed in situ.
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Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.
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HLA-C*04:01:152 differs from HLA-C*04:01:01:01 by one nucleotide in exon 1.
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População do Leste Asiático , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Sequência de Bases , Nucleotídeos , Análise de Sequência de DNARESUMO
Acute coronary syndrome (ACS),with increasing mortality year by year,has become a major public health problem in China.Exercise rehabilitation as an important part of the out-of-hospital rehabilitation for the patients with heart diseases can further reduce the mortality of patients on the basis of drug treatment.The available studies have proved that high-intensity interval training (HIIT) is more effective and efficient than moderate-intensity continuous training (MICT) such as walking and jogging on chronic cardiovascular diseases such as heart failure,stable coronary heart disease,and hypertension and has high security.According to the latest research,HIIT can reduce the platelet response,mitigate myocardial ischemia-reperfusion injury,and increase the exercise compliance of ACS patients more significantly than MICT.Moreover,it does not increase the risk of thrombotic adverse events or malignant arrhythmia.Therefore,HIIT is expected to become an important part of exercise prescription in out-of-hospital cardiac rehabilitation strategy for the patients with ACS.
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Síndrome Coronariana Aguda , Reabilitação Cardíaca , Insuficiência Cardíaca , Treinamento Intervalado de Alta Intensidade , Humanos , PlaquetasRESUMO
An analytical method is proposed in this paper to achieve complete energy conversion in sum frequency generation based on the Lewis-Riesenfeld invariants theory. In the proposed scheme, a quasi-adiabatic single control parameter model is established, and the value of single control parameter is selected to make the initial eigenstate perfectly converted to the final eigenstate as needed. Corresponding to the nonlinear frequency conversion process, a nonlinear crystal structure is designed by inverse engineering using the optimal control theory. It is robust against perturbations of the coupling coefficient and phase mismatch, including variations in the pump intensity and crystal polarization period, and achieves almost 100% conversion efficiency at any crystal length. Theoretical simulations show that frequency conversion can be achieved in the wavelength range of 2.6â µm-3.6â µm, and the spectral bandwidth of conversion efficiency exceeds 50% and approaches 400â nm when the crystal length L = 1 mm.
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Constructing efficient artificial solid electrolyte interface (SEI) film is extremely vital for the practical application of lithium metal batteries. Herein, a dense artificial SEI film, in which lithiophilic Zn/Lix Zny are uniformly but nonconsecutively dispersed in the consecutive Li+ -conductors of Lix SiOy , Li2 O and LiOH, is constructed via the in situ reaction of layered zinc silicate nanosheets and Li. The consecutive Li+ -conductors can promote the desolvation process of solvated-Li+ and regulate the transfer of lithium ions. The nonconsecutive lithiophilic metals are polarized by the internal electric field to boost the transfer of lithium ions, and lower the nucleation barrier. Therefore, a low polarization of ≈50â mV for 750â h at 2.0â mA cm-2 in symmetric cells, and a high capacity retention of 99.2 % in full cells with a high lithium iron phosphate areal loading of ≈13â mg cm-2 are achieved. This work offers new sights to develop advanced alkali metal anodes for efficient energy storage.
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Background: Sacubitril/valsartan therapy reduced the risks of death and of hospitalization for heart failure (HF). HF and cardiac arrhythmias have shared physiological mechanisems. Therefore, sacubitril/valsartan may exhibit anti-arrhythmic properties in HF. The purpose of this study was to evaluate the effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of sudden cardiac death (SCD) in HF. Methods: This meta-analysis was performed according to PRISMA guidelines. We searched PubMed and Embase (from inception up to 6 February 2022) to identify randomized control trials (RCTs) on the effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of SCD in HF. Primary outcomes were the occurrence of atrial arrhythmias, ventricular arrhythmias, and SCD. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis. Results: We included 9 RCTs (published between 2012 and 2021) with 18,500 patients (9,244 sacubitril/valsartan vs. 9,256 active control). Enalapril and valsartan were used as active control in six and two studies, respectively. Follow-up ranged from 2 to 35 months. The cumulative occurrence of events was 76, 13, and 48 per 1,000 patient-years for atrial arrhythmias, ventricular arrhythmias and SCD, respectively. There was no significant association between sacubitril/valsartan therapy and the occurrence of atrial arrhythmias (RR 1.06; 95% CI: 0.97-1.17; P = 0.19) and ventricular arrhythmias (RR 0.86; 95% CI 0.68-1.10; P = 0.24). However, sacubitril/valsartan therapy significantly reduced the risk of SCD (RR 0.79; 95% CI 0.70-0.90; P = 0.03) compared with control. Conclusion: No association between sacubitril/valsartan therapy and the occurrence of atrial and ventricular arrhythmias was found, but sacubitril/valsartan therapy significantly reduced the risk of SCD.
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As competitive next-generation rechargeable batteries, lithium-sulfur batteries (LSBs) suffer from the shuttle effect and the sluggish kinetics of intermediate polysulfides during charge and discharge processes, adversely affecting their electrochemical performances and actual applications. Herein, we demonstrate a polymer encapsulation strategy to synthesize atomic Fe and N co-doped hollow carbon nanospheres (Fe-NHC) with Fe-Nx sites for modifying commercial PP separator of LSBs to suppress the shuttle effect and promote the kinetics of intermediate polysulfides. Benefiting from the excellent structural design, the doped-N with positive charges could effectively adsorb negatively charged soluble polysulfides, help attract the soluble polysulfides to the Fe atoms and boost the catalytic transformation of the soluble polysulfides. Additionally, such a thin carbon shell could provide a short mass diffusion pathway and hence promote the adsorption and the catalytic conversion. Therefore, the battery with the Fe-NHC/PP separator delivers outstanding cycling and rate performances. At the large current density of 1â C, the specific capacity is 1079â mA h g-1 and maintains a low loss of 0.076 % per cycle within 500â cycles. Even at a harsh current density of 4â C, a high capacity of 824â mA h g-1 is still achieved, indicating the advantage of the Fe-NHC/PP separator in LSBs.
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BACKGROUND: Increased homocysteine levels are associated with the risk of cardiovascular disease (CVD) and death. However, their prevention has not been effective in decreasing CVD risk. This study investigated the individual and combined associations of hyperhomocysteinemia and hypertension with incident CVD events and all-cause death in the Chinese elderly population without a history of CVD. METHODS: This prospective study was conducted among 1,257 elderly participants (mean age: 69 years). A questionnaire survey, physical examinations, and laboratory tests were conducted to collect baseline data. Hyperhomocysteinemia was defined as homocysteine level ≥ 15 µmol/L. H-type hypertension was defined as concomitant hypertension and hyperhomocysteinemia. Multivariate Cox regression analysis was used to evaluate individual and combined associations of hyperhomocysteinemia and hypertension with the risks of incident CVD events and all-cause death. RESULTS: Over a median of 4.84-year follow-up, hyperhomocysteinemia was independently associated with incident CVD events and all-cause death. The hazard ratios (HRs) were 1.45 (95% CI: 1.01-2.08) for incident CVD events and 1.55 (95% CI: 1.04-2.30) for all-cause death. After adjustment for confounding factors, H-type hypertension had the highest HRs for incident CVD events and all-cause death. The fully adjusted HRs were 2.44 for incident CVD events (95% CI: 1.28-4.65), 2.07 for stroke events (95% CI: 1.01-4.29), 8.33 for coronary events (95% CI: 1.10-63.11), and 2.31 for all-cause death (95% CI: 1.15-4.62). CONCLUSIONS: Hyperhomocysteinemia was an independent risk factor, and when accompanied by hypertension, it contributed to incident CVD events and all-cause death in the Chinese elderly population without a history of CVD.
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Although organosulfur compounds can protect lithium anodes, participate in the redox reaction, and suppress the shuttle effect, the sluggish electrochemical dynamics of their bulk structure and the notorious shuttle effect of covalent long-chain sulfurs largely impede their actual applications. Herein, sulfurized carbon nanotube@aminophenol-formaldehyde (SC@A) with covalently linked short-chain sulfurs is firstly synthesized by in situ polymerization of aminophenol-formaldehyde (AF) on the surface of carbon nanotubes (CNTs) followed by acetone etching and inverse sulfurization processes, forming mesoporous yolk-shell organosulfur nanotubes with abundant internal joints between the yolk of CNTs and the shell of sulfurized AF for the first time. In situ Raman spectra, in situ XRD patterns, and ex situ XPS spectra verify that the covalent short-chain sulfurs bring about a reversible solid-solid conversion process of sulfur, thoroughly avoiding the shuttle effect. The mesoporous yolk-shell structure with abundant internal joints can effectively accommodate the volume change, fully expose active sites and efficiently improve the transport of electrons and lithium ions, thus highly promoting the solid-solid electrochemical reaction kinetics. Therefore, the SC@A cathode exhibits a superior specific capacity of 841 mAh g-1 and a capacity decay of 0.06% per cycle within 500 cycles at a large current density of 5.0 C.
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BACKGROUND: The safety of discontinuing oral anticoagulant (OAC) therapy after atrial fibrillation (AF) ablation remains controversial. A meta-analysis was performed to assess the safety and feasibility of discontinuing OAC therapy after successful AF ablation. METHODS: PubMed and Embase were searched up to October 2020 for prospective cohort studies that reported the risk of thromboembolism (TE) after successful AF ablation in off-OAC and on-OAC groups. The primary outcome was the incidence of TE events. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 11,148 patients (7,160 in the off-OAC group and 3,988 in the on-OAC group) from 10 studies were included to meta-analysis. No significant difference in TE between both groups was observed (OR, 0.73; 95%CI, 0.51-1.05; I2 = 0.0%). The risk of major bleeding in off-OAC group was significantly lower compared to the on-OAC group (OR, 0.18; 95%CI, 0.07-0.51; I2 = 51.7%). CONCLUSIONS: Our study suggests that it may be safe to discontinue OAC therapy in patients after successful AF ablation. Additionally, an increased risk of major bleeding was observed in patients on OAC. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among the included study designs. Large-scale and adequately powered randomized controlled trials are warranted to confirm these findings.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter , Administração Oral , Fibrilação Atrial/epidemiologia , Humanos , Incidência , Estudos ProspectivosAssuntos
Traumatismos dos Dedos , Dedos , Traumatismos dos Dedos/cirurgia , Dedos/cirurgia , HumanosRESUMO
BACKGROUND: Chronic pulmonary aspergillosis (CPA) is a rare syndrome that is often accompanied by gradual lung tissue destruction. Voriconazole is usually employed as the first-line agent for CPA treatment. However, some patients can develop hepatotoxicity and often were forced to stop voriconazole treatment. AIM: To record the improving trend of liver function and the therapeutic effects in patients after lowering the trough concentration of voriconazole. METHODS: This study retrospectively analyzed 12 adult CPA patients who developed hepatotoxicity during the voriconazole treatment. In these patients, the oral dose was reduced to 3/4 or 1/2 of the standard dose (4 mg/kg, twice daily), and the lower limit of voriconazole trough concentration was maintained more than 0.5 µg/mL. The trend of remission of liver toxicity after drug reduction in 12 patients was recorded. During the same period, 25 patients who received standard doses served as the control group. Data from the two groups were collected and analyzed for different parameters such as demographic characteristics, underlying pulmonary disorders, laboratory tests, and therapeutic effect. The differences between the two groups were statistically compared. RESULTS: Hepatotoxicity occurred in 12 patients within 28-65 d after oral voriconazole treatment. Hepatotoxicity was mainly manifested by the significantly increased level of gamma-glutamyltransferase and a slight increase of alanine aminotransferase and aspartate aminotransferase. The oral dose of voriconazole was reduced to approximately 3 mg/kg in seven patients and approximately 2 mg/kg in five patients. The average trough concentrations for the 12 patients before and after voriconazole oral dose reduction were 3.17 ± 1.47 µg/mL (1.5-6.0 µg/mL) and 1.70 ± 0.78 µg/mL (0.6-3.3 µg/mL), respectively (P = 0.02). After lowering the trough concentrations, the hepatotoxicity was alleviated in all the patients. However, gamma-glutamyltransferase levels declined slowly. After 4 mo of treatment, 7 of the 12 patients were successfully treated in the low trough concentrations group (41.7%). Similarly, 8 of the 25 patients in the standard treatment dose group (32.0%) were effectively treated. There was no statistical difference between the groups (P = 0.72). CONCLUSION: Reducing the lower limit of the voriconazole trough concentration to 0.5 µg/mL can alleviate the hepatotoxicity and maintained certain clinical efficacy in CPA patients; however, patients should be closely monitored.