ABSTRACT
OBJECTIVE: Low cardiac output syndrome (LCOS) is a dangerous postoperative complication in patients with acute type A aortic dissection (ATAAD). This study aims to develop and evaluate a nomogram model that can reliably identify risk variables for postoperative LCOS in elderly patients suffering from ATAAD. PATIENTS AND METHODS: In this retrospective study, a total of 310 elderly patients with ATAAD admitted to Fujian Medical University Union Hospital were included and categorized into the LCOS and non-LCOS groups. Stepwise logistic regression was used to analyze independent predictors of LCOS, and a nomogram was constructed. The best clinical decision points were found using decision analysis and a clinical impact curve. RESULTS: Postoperative LCOS occurred in 22 (7.1%) of elderly patients with ATAAD. Independent risk factors for postoperative LCOS were age, smoking history, aortic cross-clamp (ACC), coronary heart disease (CHD), and preoperative shock. The nomogram constructed based on the identified risk factors showed good performance. CONCLUSIONS: Our results suggest that preventive treatment can be administered when needed when the risk of LCOS in older patients with ATAAD after surgery is >60%. This study contributes to developing a methodology that may improve therapeutic decision-making in older patients and provides insights for assessing the risk of LCOS.
Subject(s)
Aortic Dissection , Cardiac Output, Low , Nomograms , Humans , Aged , Aortic Dissection/surgery , Female , Male , Retrospective Studies , Cardiac Output, Low/diagnosis , Cardiac Output, Low/etiology , Risk Factors , Postoperative Complications/epidemiology , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Middle Aged , Aged, 80 and overABSTRACT
We report the pressure (P) effect on the superconducting transition temperatureTcand the upper critical fieldµ0Hc2of infinite-layer Nd0.8Sr0.2NiO2thin films by measuring the electrical transport properties under various hydrostatic pressures to 4.6 GPa. At ambient pressure, it shows the clear superconducting transition withTcâ¼ 10 K. Based on the evolution of resistanceR(T), we found that theTcis monotonically enhanced to â¼14 K upon increasing pressure to 2.9 GPa. The constructed temperature-pressure phase diagram indicates that the calculated slope dTc/dPis about 1.14 K GPa-1and the superconductingTcshows no signatures of saturation with pressure. It thus gives the possibility to further enhanceTcby employing higher pressures or heterostructure engineering. In addition, the normalized slope of upper critical fieldµ0Hc2(0) implies that the electron correlations are gradually decreasing with pressure, which exhibits an opposite evolution with superconductingTc. Our work further confirms the positive pressure effects in nickelate superconductors and gives more insight to further enhance its superconducting transition temperature.
ABSTRACT
Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.
Subject(s)
Paraquat , Poisoning , Humans , Retrospective Studies , Prognosis , ROC Curve , Lactate Dehydrogenases , Poisoning/diagnosisABSTRACT
A crucial lesson gained through the pandemic preparedness and response to COVID-19 is that all measures for epidemic control must be law-based. The legal system is related not only to public health emergency management per se but also to all aspects of the institutional supporting system throughout the lifecycle. Based on the lifecycle emergency management model, this article analyses the problems of the current legal system and the potential solutions. It is suggested that the lifecycle emergency management model shall be followed to establish a more comprehensive public health legal system and to gather the intelligence and consensus of experts with different expertise, including epidemiologists, sociologists, economists, jurist and others, which will collaboratively promote the science-based legislation in the field of epidemic preparedness and response for the establishment of a comprehensive legal system for public health emergency management and with Chinese characteristics.
Subject(s)
Disaster Planning , Public Health , Humans , China , Pandemics/prevention & control , EmergenciesABSTRACT
The successful synthesis of superconducting infinite-layer nickelate thin films with the highest Tc ≈ 15 K has ignited great enthusiasm for this material class as potential analogs of the high-Tc cuprates. Pursuing a higher Tc is always an imperative task in studying a new superconducting material system. Here we report high-quality Pr0.82Sr0.18NiO2 thin films with Tconset ≈ 17 K synthesized by carefully tuning the amount of CaH2 in the topotactic chemical reduction and the effect of pressure on its superconducting properties by measuring electrical resistivity under various pressures in a cubic anvil cell apparatus. We find that the onset temperature of the superconductivity, Tconset, can be enhanced monotonically from ~17 K at ambient pressure to ~31 K at 12.1 GPa without showing signatures of saturation upon increasing pressure. This encouraging result indicates that the Tc of infinite-layer nickelates superconductors still has room to go higher and it can be further boosted by applying higher pressures or strain engineering in the heterostructure films.
ABSTRACT
We report an unusual pressure-induced superconducting state that coexists with an antiferromagnetic ordering of Eu2+ moments and shows a large upper critical field comparable to the Pauli paramagnetic limit in EuTe2. In concomitant with the emergence of superconductivity with Tc ≈ 3-5 K above Pc ≈ 6 GPa, the antiferromagnetic transition temperature TN(P) experiences a quicker rise with the slope increased dramatically from dTN/dP = 0.85(14) K/GPa for P ≤ Pc to 3.7(2) K/GPa for P ≥ Pc. Moreover, the superconducting state can survive in the spin-flop state with a net ferromagnetic component of the Eu2+ sublattice under moderate magnetic fields µ0H ≥ 2 T. Our findings establish the pressurized EuTe2 as a rare magnetic superconductor possessing an intimated interplay between magnetism and superconductivity.
ABSTRACT
Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC50 values in the 4-8 µM range. The here described high-throughput-compatible assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Humans , Luciferases/genetics , Molecular Docking Simulation , Peptide Hydrolases , Protease Inhibitors/pharmacology , Viral ProteasesABSTRACT
OBJECTIVE: To investigate the clinical and immunological features of cardiac involvement in patients with anti-synthetase syndrome (ASS). METHODS: In the study, 96 patients diagnosed with ASS hospitalized in the Department of Rheumatology and Immunology, Peking University People's Hospital from April 2003 to November 2020 were included. The patients were divided into two groups according to whether they were accompanied with cardiac involvement. Demographic features, clinical characteristics (Gottron's sign/papules, muscle damage, etc.), comorbidities, laboratory indices (creatine kinase, inflammatory indicators, immunoglobulin, complement, lymphocyte subset, autoantibodies, etc.) were collected and the differences between the two groups were analyzed statistically. RESULTS: The prevalence of cardiac involvement in the patients with ASS was 25.0% (24/96). The ASS patients complicated with cardiac involvement presented with elevated cardiac troponin I (cTnI, 75.0%, 18/24), pericardial effusion (33.3%, 8/24), reduction of left ventricular function (33.3%, 8/24) and valves regurgitation (33.3%, 8/24). The age of onset of the patients with cardiac involvement was older than that of the patients without cardiac involvement [(54.58±10.58) years vs. (48.47±13.22) years, P=0.043). Arthritis was observed less frequently in the patients with cardiac involvement than those without cardiac involvement (37.5% vs. 61.1%, P=0.044). In addition, rapidly progressive interstitial lung disease (54.2% vs. 30.6%, P=0.037) was observed more frequently in the patients with cardiac involvement than those without cardiac involvement. As compared with the ASS patients without cardiac involvement, C-reactive protein (CRP) [(13.55 (8.96, 38.35) mg/L vs. 4.60 (1.37, 17.40) mg/L, P=0.001], and lactate dehydrogenase (LDH) [408.0 (255.0, 587.0) U/L vs. 259.5 (189.8, 393.8) U/L, P=0.007] were significantly higher in the patients with cardiac involvement. Anti-Ro-52 antibody was detected more commonly in the ASS patients with cardiac involvement compared with the patients without cardiac involvement (91.7% vs. 69.4%, P=0.029). No significant differences were found in the comorbidities, alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), erythrocyte sedimentation rate (ESR), ferritin (Fer), immunoglobulin G (IgG), complement 3 (C3), complement 4 (C4), lymphocyte subset between the two groups. CONCLUSION: Cardiac involvement is common in ASS, mainly manifested as myocardial damage. It is necessary to be aware of cardiac complications in patients with elevated CRP, elevated LDH and positive anti-Ro-52 antibody.
Subject(s)
Heart Diseases/complications , Myositis/diagnosis , Adult , Aged , Antibodies, Antinuclear , Autoantibodies , Blood Sedimentation , C-Reactive Protein , Humans , Immunoglobulin G , L-Lactate Dehydrogenase , Middle Aged , Myositis/complicationsABSTRACT
Objective: The purpose of this study is to analyze the surveillance data of the Integrated HCV surveillance in Shanghai and provide a scientific basis for HCV's elimination strategies. Methods: Descriptive statistical analysis and multivariate logistic regression analysis were performed using the multi-dimension results of the Integrated HCV surveillance in Shanghai from 2014 to 2019. Data related to reported HCV cases, HCV gene subtypes surveillance, HCV behavioral risk factors surveillance and HCV-antibody testing results of the community-based general population and high-risk/key populations. Results: The reported incidence rate of acute hepatitis C in Shanghai decreased from 2014 to 2019 (Z=-4.07, P<0.01); meanwhile, the reported incidence rate of chronic hepatitis C met an upward trend (Z=10.26,P<0.01), with an annual average, reported incidence rates of 0.18 per 100 000 and 8.60 per 100 000, respectively. Seven hundred forty-four blood samples were subtyped with 16 subtypes from 4 genotypes (GT1, GT2, GT3, and GT6). Among above, 1b (324 cases, 43.55%), 3a (121 cases, 16.26%), 3b (111 cases, 14.92%) and 6a (47 cases, 6.32%) were the principal subtypes. The composition of genotypes varied with decreased 1b and increased 3b and 6a. The major risk factors for HCV infection were blood transfusion (OR=4.18, 95%CI: 2.79-6.27), surgery (OR=1.63, 95%CI: 1.26-2.12), sharing syringe (OR=4.18, 95%CI: 2.75-6.34), pedicure (OR=2.01, 95%CI: 1.54-2.62), sharing razors (OR=4.09, 95%CI:1.24-13.51), and unsafe beauty practices (OR=3.15, 95%CI: 2.13-4.65). HCV antibody screening of 11 groups of high-risk/key populations showed that drug users had the highest HCV-antibody positive rate of 18.81% (1 008/5 358). The anti-HCV positive rate of the general population was 0.16% (7/4 268), which was significantly lower than that of high-risk/key populations from the same year, 2.50%(501/20 002) (χ2=94.04, P<0.01). Conclusions: Shanghai is a low-endemic area of HCV. Constantly carrying out integrated surveillance and analysis is of great value for early identification of HCV infected people and its risk factors, timely adjustment of prevention and control strategies, and eliminating the public health threat of HCV.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , China/epidemiology , Genotype , Hepacivirus/genetics , Hepatitis C/epidemiology , Hepatitis C Antibodies , Humans , PrevalenceABSTRACT
CsV_{3}Sb_{5} is a newly discovered Z_{2} topological kagome metal showing the coexistence of a charge-density-wave (CDW)-like order at T^{*}=94 K and superconductivity (SC) at T_{c}=2.5 K at ambient pressure. Here, we study the interplay between CDW and SC in CsV_{3}Sb_{5} via measurements of resistivity, dc and ac magnetic susceptibility under various pressures up to 6.6 GPa. We find that the CDW transition decreases with pressure and experience a subtle modification at P_{c1}≈0.6-0.9 GPa before it vanishes completely at P_{c2}≈2 GPa. Correspondingly, T_{c}(P) displays an unusual M-shaped double dome with two maxima around P_{c1} and P_{c2}, respectively, leading to a tripled enhancement of T_{c} to about 8 K at 2 GPa. The obtained temperature-pressure phase diagram resembles those of unconventional superconductors, illustrating an intimated competition between CDW-like order and SC. The competition is found to be particularly strong for the intermediate pressure range P_{c1}≤P≤P_{c2} as evidenced by the broad superconducting transition and reduced superconducting volume fraction. The modification of CDW order around P_{c1} has been discussed based on the band structure calculations. This work not only demonstrates the potential to raise T_{c} of the V-based kagome superconductors, but also offers more insights into the rich physics related to the electron correlations in this novel family of topological kagome metals.
ABSTRACT
Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for high-throughput screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified four molecules, including the broad-spectrum antiviral merimepodib/VX-497, which show anti-nsp5 activity and inhibit SARS-CoV-2 replication in A549-ACE2 cells with IC 50 values in the 4-21 µM range. The here described assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.
ABSTRACT
BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.
Subject(s)
Brain Ischemia , Hyperglycemia , Ischemic Stroke , Stroke , Animals , Biomarkers , Brain Ischemia/complications , Brain Ischemia/genetics , Humans , Hyperglycemia/complications , Hyperglycemia/genetics , RNA, Long Noncoding , Stroke/complications , Stroke/genetics , fas ReceptorABSTRACT
The criterion for optimizing the high-power acousto-optically ${Q}$Q-switched self-Raman yellow laser is originally explored for the repetition rate within 100-500 kHz. The minimum allowed value for the gate-open time is experimentally verified to be determined by the pulse buildup time. By using the minimum allowed gate-open time, the highest conversion efficiency can be achieved to raise the output power by approximately 20% in comparison with the conventional results. At a repetition rate of 200 kHz, the maximum output power at 588 nm can be up to 8.8 W at an incident pump power of 26 W. Furthermore, a practical formula is developed to accurately calculate the threshold pump power as a function of the gate-open time for a given repetition rate.
Subject(s)
Alopecia/physiopathology , Hardness , Scalp/physiopathology , Case-Control Studies , Dermis/physiopathology , Epidermis/physiopathology , Female , Humans , MaleABSTRACT
KEY MESSAGE: WSL8 encoding a deoxyribonucleoside kinase (dNK) that catalyzes the first step in the salvage pathway of nucleotide synthesis plays an important role in early chloroplast development in rice. The chloroplast is an organelle that converts light energy into chemical energy; therefore, the normal differentiation and development of chloroplast are pivotal for plant survival. Deoxyribonucleoside kinases (dNKs) play an important role in the salvage pathway of nucleotides. However, the relationship between dNKs and chloroplast development remains elusive. Here, we identified a white stripe leaf 8 (wsl8) mutant that exhibited a white stripe leaf phenotype at seedling stage (before the four-leaf stage). The mutant showed a significantly lower chlorophyll content and defective chloroplast morphology, whereas higher reactive oxygen species than the wild type. As the leaf developed, the chlorotic mutant plants gradually turned green, accompanied by the restoration in chlorophyll accumulation and chloroplast ultrastructure. Map-based cloning revealed that WSL8 encodes a dNK on chromosome 5. Compared with the wild type, a C-to-G single base substitution occurred in the wsl8 mutant, which caused a missense mutation (Leu 349 Val) and significantly reduced dNK enzyme activity. A subcellular localization experiment showed the WSL8 protein was targeted in the chloroplast and its transcripts were expressed in various tissues, with more abundance in young leaves and nodes. Ribosome and RNA-sequencing analysis indicated that some components and genes related to ribosome biosynthesis were down-regulated in the mutant. An exogenous feeding experiment suggested that the WSL8 performed the enzymic activity of thymidine kinase, especially functioning in the salvage synthesis of thymidine monophosphate. Our results highlight that the salvage pathway mediated by the dNK is essential for early chloroplast development in rice.
Subject(s)
Chloroplasts/enzymology , Chloroplasts/metabolism , Oryza/enzymology , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Chlorophyll/metabolism , Chloroplasts/pathology , Chloroplasts/ultrastructure , Cloning, Molecular , Gene Expression Regulation, Plant , Mutation, Missense , Oryza/genetics , Oryza/growth & development , Oryza/ultrastructure , Phenotype , Phosphotransferases (Alcohol Group Acceptor)/genetics , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Proteins/genetics , Plants, Genetically Modified , Reactive Oxygen Species/metabolism , Ribosomes/metabolism , Seedlings/genetics , Seedlings/metabolismABSTRACT
This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.
Subject(s)
Fibroblast Growth Factors/blood , Graves Disease/blood , Minerals/metabolism , Phosphorus/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Bone Remodeling , Bone and Bones/metabolism , Calcium/blood , Case-Control Studies , Female , Fibroblast Growth Factor-23 , Humans , Male , Middle Aged , Minerals/blood , Parathyroid Hormone/blood , Vitamin D/analogs & derivatives , Vitamin D/blood , Young AdultABSTRACT
Streptococcus pneumoniae is one of the world's leading bacterial pathogens, causing pneumonia, septicemia, and meningitis. In recent years, it has been shown that genetic rearrangements in a type I restriction-modification system (SpnIII) can impact colony morphology and gene expression. By generating a large panel of mutant strains, we have confirmed a previously reported result that the CreX (also known as IvrR and PsrA) recombinase found within the locus is not essential for hsdS inversions. In addition, mutants of homologous recombination pathways also undergo hsdS inversions. In this work, we have shown that these genetic rearrangements, which result in different patterns of genome methylation, occur across a wide variety of serotypes and sequence types, including two strains (a 19F and a 6B strain) naturally lacking CreX. Our gene expression analysis, by transcriptome sequencing (RNAseq), confirms that the level of creX expression is impacted by these genomic rearrangements. In addition, we have shown that the frequency of hsdS recombination is temperature dependent. Most importantly, we have demonstrated that the other known pneumococcal site-specific recombinases XerD, XerS, and SPD_0921 are not involved in spnIII recombination, suggesting that a currently unknown mechanism is responsible for the recombination of these phase-variable type I systems.IMPORTANCEStreptococcus pneumoniae is a leading cause of pneumonia, septicemia, and meningitis. The discovery that genetic rearrangements in a type I restriction-modification locus can impact gene regulation and colony morphology led to a new understanding of how this pathogen switches from harmless colonizer to invasive pathogen. These rearrangements, which alter the DNA specificity of the type I restriction-modification enzyme, occur across many different pneumococcal serotypes and sequence types and in the absence of all known pneumococcal site-specific recombinases. This finding suggests that this is a truly global mechanism of pneumococcal gene regulation and the need for further investigation of mechanisms of site-specific recombination.
Subject(s)
Bacterial Proteins/metabolism , DNA Nucleotidyltransferases/metabolism , DNA Restriction-Modification Enzymes/metabolism , Recombination, Genetic , Streptococcus pneumoniae/enzymology , Streptococcus pneumoniae/genetics , Bacterial Proteins/genetics , DNA Methylation , DNA Nucleotidyltransferases/genetics , DNA Restriction-Modification Enzymes/geneticsABSTRACT
The effects of acarbose and sitagliptin on blood glucose fluctuation and islet ß-cell function in patients with type 2 diabetes mellitus (T2DM) were studied. One hundred and three patients with poorly controlled T2DM with insulin aspart 30 were selected and randomly divided into three groups: group A [continuous subcutaneous insulin infusion (CSII) treatment group], group B (CSII combined with acarbose treatment), group C (CSII combined with sitagliptin treatment). The treatment lasted for two weeks and the clinical indicators in the three groups were measured. The insulin dosage was adjusted according to the blood glucose statuses of the three groups of patients. In the final three days, 72 h of continuous glucose monitoring (CGM) were carried out, and the OGTT test was performed again. The results showed that the MODD (absolute means of daily difference), intra-day blood glucose fluctuation indices [(24 h MBG (mean blood glucose), LAGE (largest amplitude of glycemic excursions) and MAGE (average blood glucose fluctuation)] and postprandial blood glucose fluctuation indices [PGS (postprandial glucose spike), â³t, PPGE (postprandial glucose excursion) and T (time) total] in group C and group B were significantly lower than those in group A. Compared with group B, the difference in blood glucose fluctuation indices in group C was not statistically significant (P>0.05). The HOMA-islet (homeostasis model assessment of islet) (CP-DM) index and FC-P (Fasting c-peptide) levels in group C and group B were significantly higher than those in group A (P less than 0.01). The HOMA-IR (CP) index of groups B and C was significantly lower than that of group A (P less than 0.01), and there was no statistically significant difference between groups B and C (P less than 0.05). Sitagliptin combined with intensive insulin pump therapy can reduce blood glucose fluctuation throughout the day, reduce insulin dosage, improve islet B cell function and reduce hypoglycemia better than intensive insulin pump therapy alone.