Protein function annotation and virulence factor identification of Klebsiella pneumoniae genome by multiple machine learning models.

Klebsiella pneumoniae is a type of Gram-negative bacterium which can cause a range of infections in human. In recent years, an increasing number of strains of K. pneumoniae resistant to multiple antibiotics have emerged, posing a significant threat to public health. The protein function of this bacterium is not well known, thus a systematic investigation of K. pneumoniae proteome is in urgent need. In this study, the protein functions of this bacteria were re-annotated, and their function groups were analyzed. Moreover, three machine learning models were built to identify novel virulence factors. Results showed that the functions of 16 uncharacterized proteins were first annotated by sequence alignment. In addition, K. pneumoniae proteins share a high proportion of homology with Haemophilus influenzae and a low homology proportion with Chlamydia pneumoniae. By sequence analysis, 10 proteins were identified as potential drug targets for this bacterium. Our model achieved a high accuracy of 0.901 in the benchmark dataset. By applying our models to K. pneumoniae, we identified 39 virulence factors in this pathogen. Our findings could provide novel clues for the treatment of K. pneumoniae infection.

Quantitative differentiation of non-invasive bladder urothelial carcinoma and inverted papilloma based on CT urography.

PURPOSE: To investigate the value of CT urography (CTU) indicators in the quantitative differential diagnosis of bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB). MATERIAL AND METHODS: The clinical and preoperative CTU imaging data of continuous 103 patients with histologically confirmed BUC or IPB were retrospectively analyzed. The imaging data included 6 qualitative indicators and 7 quantitative measures. The recorded clinical information and imaging features were subjected to univariate and multivariate logistic regression analysis to find independent risk factors for BUC, and a combined multi-indicator prediction model was constructed, and the prediction model was visualized using nomogram. ROC curve analysis was used to calculate and compare the predictive efficacy of independent risk factors and nomogram. RESULTS: Junction smoothness, maximum longitudinal diameter, tumor-wall interface and arterial reinforcement rate were independent risk factors for distinguishing BUC from IPB. The AUC of the combined model was 0.934 (sensitivity = 0.808, specificity = 0.920, accuracy = 0.835), and its diagnostic efficiency was higher than that of junction smoothness (AUC=0.667, sensitivity = 0.654, specificity = 0.680, accuracy = 0.660), maximum longitudinal diameter (AUC=0.757, sensitivity = 0.833, specificity = 0.604, accuracy = 0.786), tumor-wall interface (AUC=0.888, sensitivity = 0.755, specificity = 0.808, accuracy = 0.816) and Arterial reinforcement rate (AUC=0.786, sensitivity = 0.936, specificity = 0.640, accuracy = 0.864). CONCLUSION: Above qualitative and quantitative indicators based on CTU and the combination of them may be helpful to the differential diagnosis of BUC and IPB, thus better assisting in clinical decision-making. KEY POINTS: 1. Bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB) exhibit similar clinical symptoms and imaging presentations. 2. The diagnostic value of CT urography (CTU) in distinguishing between BUC and IPB has not been documented. 3. BUC and IPB differ in lesion size, growth pattern and blood supply. 4. The diagnostic efficiency is optimized by integrating multiple independent risk factors into the prediction model.

Cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for the treatment of acute ischemic stroke: a Chinese health care perspective.

BACKGROUND: Edaravone dexborneol and dl-3-n-butylphthalide are two innovative brain cytoprotective drugs from China that have been approved and widely prescribed for acute ischemic stroke, and the cost of the two drugs are partially paid by the Chinese medical insurance system. This study aimed to investigate and compare the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke from the Chinese healthcare system's perspective. METHODS: A model combining a short-term decision tree model with 90 days and a long-term Markov model with a life-time horizon (40 years) was developed to simulate the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke over a lifetime horizon. Since the absence of a head-to-head clinical comparison of two therapies, an unanchored matching-adjusted indirect comparison (MAIC) was conducted by adjusting the patient characteristics using individual patient data from pivotal phase III trial of edaravone dexborneol and published aggregated data of dl-3-n-butylphthalide. Health outcomes were measured in quality-adjusted life years (QALYs). Utilities and costs (Chinese Yuan, CNY) were derived from publications and open-access database. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of results. RESULTS: Compared with patients in dl-3-n-butylphthalide arm, edaravone dexborneol arm was found to be cost-effective in 90 days and highly cost-effective as the study horizons extended. With a similar direct medical cost, patients in edaravone dexborneol arm slightly gained an additional 0.1615 QALYs in life-time. In the long term (40 years), patients in edaravone dexborneol arm and dl-3-n-butylphthalide arm yielded 8.0351 and 7.8736 QALYs with the overall direct medical cost of CNY 29,185.23 and CNY 29,940.28, respectively. The one-way sensitivity analysis suggested that the incremental cost-effectiveness ratio was most sensitive to the price of edaravone dexborneol and dl-3-n-butylphthalide. CONCLUSION: Edaravone dexborneol is a cost-effective alternative compared with dl-3-n-butylphthalide for acute ischemic stroke patients in current medical setting of China.

Two cases report of febuxostat-induced acute liver injury: acute heart failure as a probable risk factor?

Drug induced liver injury, as a sub-type of hepatotoxicity, is rare but practical problem, producing challenges for clinicians. Within the recent two months, two patients with heart failure develop febuxostat-induced acute liver injury during hospital stay. To the best of our knowledge, very few cases of febuxostat-induced hepatotoxicity have been reported up to now. In this paper, two unusual cases of febuxostat-induced acute liver injury are herein described. The medical history, drug treatment, clinical symptoms, liver function tests, diagnosis and prognosis are fully given in this paper. It should be noticed that, two liver injury happen in patients of heart failure with reduced ejection fraction. Whether heart failure is a risk factor of febuxostat related liver injury, deserves further research. This paper reminds the clinicians that more attention should be paid to the acute liver injury caused by febuxostat, and liver function tests are suggested especially for patients of heart failure.

Favorable Loci Identified for Stripe Rust Resistance in Chinese Winter Wheat Accessions via Genome-Wide Association Study.

Stripe rust (or yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat worldwide. Currently, the utilization of resistant cultivars is the most viable way to reduce yield losses. In this study, a panel of 188 wheat accessions from China was evaluated for stripe rust resistance, and genome-wide association studies were performed using high-quality Diversity Arrays Technology markers. According to the phenotype and genotype data, a total of 26 significant marker-trait associations were identified, representing 18 quantitative trait loci (QTLs) on chromosomes 1B, 2A, 2B, 3A, 3B, 5A, 5B, 6B, 7B, and 7D. Of the 18 QTLs, almost all were associated with adult plant resistance (APR) except QYr.nwsuaf-6B.2, which was associated with all-stage resistance (also known as seedling resistance). Three of the 18 QTLs were mapped far from previously identified Pst resistance genes and QTLs and were considered potentially new loci. The other 15 QTLs were mapped close to known resistance genes and QTLs. Subsequent haplotype analysis for QYr.nwsuaf-2A and QYr.nwsuaf-7B.3 revealed the degrees of resistance of the panel in the APR stage. In summary, the favorable alleles identified in this study may be useful in breeding for disease resistance to stripe rust.

Piericones A and B as Potent Antithrombotics: Nanomolar Noncompetitive Protein Disulfide Isomerase Inhibitors with an Unexpected Chemical Architecture.

Extracellular protein disulfide isomerase (PDI) is a promising target for thrombotic-related diseases. Four potent PDI inhibitors with unprecedented chemical architectures, piericones A-D (1-4), were isolated from Pieris japonica. Their structures were elucidated by spectroscopic data analysis, chemical methods, quantum 13C nuclear magnetic resonance DP4+ and electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Piericones A (1) and B (2) were nanomolar noncompetitive PDI inhibitors possessing an unprecedented 3,6,10,15-tetraoxatetracyclo[7.6.0.04,9.01,12]pentadecane motif with nine contiguous stereogenic centers. Their biosynthetic pathways were proposed to include a key intermolecular aldol reaction and an intramolecular 1,2-migration reaction. Piericone A (1) significantly inhibited in vitro platelet aggregation and fibrin formation and in vivo thrombus formation via the inhibition of extracellular PDI without increasing the bleeding risk. The molecular docking and dynamics simulation of 1 and 2 provided a novel structure basis to develop PDI inhibitors as potent antithrombotics.

Glutathione S-transferase interactions enhance wheat resistance to powdery mildew but not wheat stripe rust.

Wheat stripe rust and powdery mildew are important worldwide diseases of wheat (Triticum aestivum). The wheat cultivar Xingmin318 (XM318) is resistant to both wheat stripe rust and powdery mildew, which are caused by Puccinia striiformis f. sp. tritici (Pst) and Blumeria graminis f. sp. tritici (Bgt), respectively. To explore the difference between wheat defense response against Pst and Bgt, quantitative proteomic analyses of XM318 inoculated with either Pst or Bgt were performed using tandem mass tags technology. A total of 741 proteins were identified as differentially accumulated proteins (DAPs). Bioinformatics analyses indicated that some functional categories, including antioxidant activity and immune system process, exhibited obvious differences between Pst and Bgt infections. Intriguingly, only 42 DAPs responded to both Pst and Bgt infections. Twelve DAPs were randomly selected for reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis, and the mRNA expression levels of 11 were consistent with their protein expression. Furthermore, gene silencing using the virus-induced gene silencing system indicated that glutathione S-transferase (TaGSTU6) has an important role in resistance to Bgt but not to Pst. TaGSTU6 interacted with the cystathionine beta-synthase (CBS) domain-containing protein (TaCBSX3) in both Pst and Bgt infections. Knockdown of TaCBSX3 expression only reduced wheat resistance to Bgt infection. Overexpression of TaGSTU6 and TaCBSX3 in Arabidopsis (Arabidopsis thaliana) promoted plant resistance to Pseudomonas syringae pv. Tomato DC3000. Our results indicate that TaGSTU6 interaction with TaCBSX3 only confers wheat resistance to Bgt, suggesting that wheat has different response mechanisms to Pst and Bgt stress.

Predicting clinically significant prostate cancer with a deep learning approach: a multicentre retrospective study.

PURPOSE: This study aimed to develop deep learning (DL) models based on multicentre biparametric magnetic resonance imaging (bpMRI) for the diagnosis of clinically significant prostate cancer (csPCa) and compare the performance of these models with that of the Prostate Imaging and Reporting and Data System (PI-RADS) assessment by expert radiologists based on multiparametric MRI (mpMRI). METHODS: We included 1861 consecutive male patients who underwent radical prostatectomy or biopsy at seven hospitals with mpMRI. These patients were divided into the training (1216 patients in three hospitals) and external validation cohorts (645 patients in four hospitals). PI-RADS assessment was performed by expert radiologists. We developed DL models for the classification between benign and malignant lesions (DL-BM) and that between csPCa and non-csPCa (DL-CS). An integrated model combining PI-RADS and the DL-CS model, abbreviated as PIDL-CS, was developed. The performances of the DL models and PIDL-CS were compared with that of PI-RADS. RESULTS: In each external validation cohort, the area under the receiver operating characteristic curve (AUC) values of the DL-BM and DL-CS models were not significantly different from that of PI-RADS (P > 0.05), whereas the AUC of PIDL-CS was superior to that of PI-RADS (P < 0.05), except for one external validation cohort (P > 0.05). The specificity of PIDL-CS for the detection of csPCa was much higher than that of PI-RADS (P < 0.05). CONCLUSION: Our proposed DL models can be a potential non-invasive auxiliary tool for predicting csPCa. Furthermore, PIDL-CS greatly increased the specificity of csPCa detection compared with PI-RADS assessment by expert radiologists, greatly reducing unnecessary biopsies and helping radiologists achieve a precise diagnosis of csPCa.

Detecting Adverse Pathology of Prostate Cancer With a Deep Learning Approach Based on a 3D Swin-Transformer Model and Biparametric MRI: A Multicenter Retrospective Study.

BACKGROUND: Accurately detecting adverse pathology (AP) presence in prostate cancer patients is important for personalized clinical decision-making. Radiologists' assessment based on clinical characteristics showed poor performance for detecting AP presence. PURPOSE: To develop deep learning models for detecting AP presence, and to compare the performance of these models with those of a clinical model (CM) and radiologists' interpretation (RI). STUDY TYPE: Retrospective. POPULATION: Totally, 616 men from six institutions who underwent radical prostatectomy, were divided into a training cohort (508 patients from five institutions) and an external validation cohort (108 patients from one institution). FIELD STRENGTH/SEQUENCES: T2-weighted imaging with a turbo spin echo sequence and diffusion-weighted imaging with a single-shot echo plane-imaging sequence at 3.0 T. ASSESSMENT: The reference standard for AP was histopathological extracapsular extension, seminal vesicle invasion, or positive surgical margins. A deep learning model based on the Swin-Transformer network (TransNet) was developed for detecting AP. An integrated model was also developed, which combined TransNet signature with clinical characteristics (TransCL). The clinical characteristics included biopsy Gleason grade group, Prostate Imaging Reporting and Data System scores, prostate-specific antigen, ADC value, and the lesion maximum cross-sectional diameter. STATISTICAL TESTS: Model and radiologists' performance were assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The Delong test was used to evaluate difference in AUC. P < 0.05 was considered significant. RESULTS: The AUC of TransCL for detecting AP presence was 0.813 (95% CI, 0.726-0.882), which was higher than that of TransNet (0.791 [95% CI, 0.702-0.863], P = 0.429), and significantly higher than those of CM (0.749 [95% CI, 0.656-0.827]) and RI (0.664 [95% CI, 0.566-0.752]). DATA CONCLUSION: TransNet and TransCL have potential to aid in detecting the presence of AP and some single adverse pathologic features. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 4.

Machine learning-based radiomics model to predict benign and malignant PI-RADS v2.1 category 3 lesions: a retrospective multi-center study.

PURPOSE: To develop machine learning-based radiomics models derive from different MRI sequences for distinction between benign and malignant PI-RADS 3 lesions before intervention, and to cross-institution validate the generalization ability of the models. METHODS: The pre-biopsy MRI datas of 463 patients classified as PI-RADS 3 lesions were collected from 4 medical institutions retrospectively. 2347 radiomics features were extracted from the VOI of T2WI, DWI and ADC images. The ANOVA feature ranking method and support vector machine classifier were used to construct 3 single-sequence models and 1 integrated model combined with the features of three sequences. All the models were established in the training set and independently verified in the internal test and external validation set. The AUC was used to compared the predictive performance of PSAD with each model. Hosmer-lemeshow test was used to evaluate the degree of fitting between prediction probability and pathological results. Non-inferiority test was used to check generalization performance of the integrated model. RESULTS: The difference of PSAD between PCa and benign lesions was statistically significant (P = 0.006), with the mean AUC of 0.701 for predicting clinically significant prostate cancer (internal test AUC = 0.709 vs. external validation AUC = 0.692, P = 0.013) and 0.630 for predicting all cancer (internal test AUC = 0.637 vs. external validation AUC = 0.623, P = 0.036). T2WI-model with the mean AUC of 0.717 for predicting csPCa (internal test AUC = 0.738 vs. external validation AUC = 0.695, P = 0.264) and 0.634 for predicting all cancer (internal test AUC = 0.678 vs. external validation AUC = 0.589, P = 0.547). DWI-model with the mean AUC of 0.658 for predicting csPCa (internal test AUC = 0.635 vs. external validation AUC = 0.681, P = 0.086) and 0.655 for predicting all cancer (internal test AUC = 0.712 vs. external validation AUC = 0.598, P = 0.437). ADC-model with the mean AUC of 0.746 for predicting csPCa (internal test AUC = 0.767 vs. external validation AUC = 0.724, P = 0.269) and 0.645 for predicting all cancer (internal test AUC = 0.650 vs. external validation AUC = 0.640, P = 0.848). Integrated model with the mean AUC of 0.803 for predicting csPCa (internal test AUC = 0.804 vs. external validation AUC = 0.801, P = 0.019) and 0.778 for predicting all cancer (internal test AUC = 0.801 vs. external validation AUC = 0.754, P = 0.047). CONCLUSIONS: The radiomics model based on machine learning has the potential to be a non-invasive tool to distinguish cancerous, noncancerous and csPCa in PI-RADS 3 lesions, and has relatively high generalization ability between different date set.

Potentially inappropriate medications among older patients with Parkinson's disease: a cross-sectional analysis of a national health insurance database in China.

BACKGROUND: With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson's disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China. METHODS: We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients' characteristics were estimated using multivariate logistic regression. RESULTS: A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65-74] vs. 59.5% [75-84; OR, 1.22; 95% CI, 1.14-1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38-1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72-0.82). CONCLUSIONS: Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population.

Drug shortages in China: a cross-sectional study.

BACKGROUND: Drug shortages significantly threaten public health and medical service provision worldwide. Research evidence on the complete picture of drug shortages is currently scant in China. This study aimed to provide a descriptive overview and a reference for alleviating of drug shortages in China. METHODS: National and provincial lists of drug shortages issued in China from 2018 to 2021 were collected and summarized. The information on essential medicines, medical insurance drugs, emergency drugs, and volume-based purchasing drugs was then matched with a drug shortage list to analyse the characteristics, proportion and incidence of drug shortage on each list based on the analysis of information such as dosage form, shortage frequency, and Anatomical Therapeutic Chemical (ATC) classification of the drugs in shortage. RESULTS: A total of 24 provinces issued drug shortages lists involving 408 drugs from 2018 to 2021. All 58 drugs in the national drug list were included on the provincial drug shortage list. Among all the drugs in shortage, the most significant shortage involved injections, accounting for 45.3% (185/408). Ninety-five drugs (23.3%) were in shortage 5 times (annual shortage > 1 time) or more in the provincial lists, and 199 drugs (48.8%) were on the shortage list only once. In terms of therapeutic property, nearly all categories of drugs had been reported in shortage, among which cardiovascular drugs, nervous system drugs, anti-tumor and immunomodulatory drugs, and blood and hematopoietic organ drugs accounted for more than 10%. There is no significant difference in drug shortage among economic regions. Comparing drugs in shortage and various lists, 81.9% (334/408), 51.0% (208/408) and 67.9% (277/408) fell on the National Medical Insurance Drug List, National Essential Medicines List, and WHO Model List of Essential Medicines, respectively, while the volume-based purchasing drugs accounted for 3.4% (14 drugs). The incidence of drug shortages on NEML, WHO Model List of Essential Medicines and medical insurance category A was significantly higher than that of medical insurance category B and volume-based purchasing drugs (P < 0.05). Of the Emergency Drugs List, 72.0% (36/50) also experienced shortages, significantly higher than all the above categories (P < 0.05). CONCLUSIONS: In China, drug shortages were severe and complicated. Drug shortages vary among economic regions but are not significant. In comparison, the national procurement pattern of volume-based drug purchasing may be conducive to alleviating the drug shortage problem. Collaboration of all partners was recommended to ensure the supply of clinically necessary drugs.

SSRI/SNRI -induced Hyponatremia: A Case Series of 26 Patients in a Single Institution from 2018 to 2020.

Antidepressant medications are widely used by patients with depression or a depressive disorder. In spite of a generally favorable safety profile of selective serotonin reuptake inhibitors or serotonin - norepinephrine reuptake inhibitors (SSRI/SNRI), several cases of a possible connection between SSRI/SNRI and hyponatremia have been reported. To describe the clinical characteristics of patients with hyponatremia after SSRI/SNRI exposure, and to examine the association between SSRI/SNRI exposure and the presence of hyponatremia in a Chinese population. A retrospective single-center case series study. We performed a retrospective evaluation of inpatients with SSRI/SNRI-induced hyponatremia from a single institution in China between 2018 and 2020. Clinical data were obtained through review of medical records. Patients who met the initial inclusion criteria but did not develop hyponatremia acted as controls. The study was approved by the Clinical Research Ethics Board of Beijing Hospital (Beijing, P.R. China). We identified 26 patients with SSRI/SNRI-induced hyponatremia. The incidence rate of hyponatremia was 1.34% (26/1937) in the study population. The mean age at diagnosis was 72.58 (±12.84) years, with a male: female ratio of 1:1.42. The duration between SSRI/SNRI exposure and the onset of hyponatremia was 7.65 (±4.88) days. The minimum serum sodium level was 2328.23 (±107.25) mg/dL in the study group. Seventeen patients (65.38%) received sodium supplements. Four patients (15.38%) switched to another antidepressant. Fifteen patients (57.69%) recovered by the time of discharge. There were significant differences in serum potassium, serum magnesium and serum creatinine level between the two groups (p < 0.05). The rate of use of sertraline was significantly higher in the study group compared with the control group (p < 0.05). This pattern was not found in other SSRI/SNRI (p > 0.05). The results of our study show that SSRI/SNRI exposure, in addition to hyponatremia, may also affect the level of serum potassium, serum magnesium and serum creatinine. A history of hyponatremia and exposure to SSRI/SNRI may be potential risk factors for the development of hyponatremia. Future prospective studies are needed to validate these findings.

Safety and Immunogenicity of a Recombinant Adenovirus Type-5-Vectored Coronavirus Disease 2019 (COVID-19) Vaccine With a Homologous Prime-Boost Regimen in Healthy Participants Aged ≥6 Years: A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Trial.

BACKGROUND: We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)-vectored coronavirus disease 2019 (COVID-19) vaccine with homologous prime-boost regimens in healthy participants aged ≥6 years. METHODS: In this randomized, double-blind, placebo-controlled trial, participants received vaccine or placebo 56 days apart. Enzyme-linked immunosorbent assay (ELISA) antibodies to the receptor binding domain (RBD) and pseudovirus neutralizing antibodies were detected. Adverse events were monitored for 28 days following each vaccination. RESULTS: A total of 430 participants were enrolled in the study, with 30 participants aged 18-55 years (MID cohort), 250 aged ≥56 years (OLD cohort), and 150 aged 6-17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies that decreased with increasing age, with geometric mean titers (GMTs) of 1037.5 in the MIN cohort, 647.2 in the MID cohort, and 338.0 in the OLD cohort receiving 5 × 1010 viral particles on day 28 following boost vaccination. Pseudovirus neutralizing antibodies showed a similar pattern, with GMTs of 168.0 in the MIN cohort, 76.8 in the MID cohort, and 79.7 in the OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by 2 doses in adults, with GMTs of 1091.6 and 96.6 for ELISA antibody and neutralizing antibody, respectively. Homologous prime-boost vaccination was safe and tolerable. CONCLUSIONS: Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6-17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine.Ad5-vectored COVID-19 vaccine with a single dose was safe and tolerated, and induced robust immune responses in children and adolescents aged 6-17 years. The boosting effect on immune responses of the homologous prime-boost regime given 56 days apart was limited. CLINICAL TRIALS REGISTRATION: NCT04566770.

Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial.

BACKGROUND: Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF). METHODS AND FINDINGS: We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study limitations include the absence of vaccine effectiveness in a real-world setting and current lack of immune persistence data. CONCLUSIONS: Heterologous boosting with ZF2001 following primary vaccination with Convidecia is more immunogenic than a single dose of Convidecia and is not associated with safety concerns. These results support flexibility in cooperating viral vectored and recombinant protein vaccines. TRIAL REGISTRATION: Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine; ClinicalTrial.gov NCT04833101.

Association between the triglyceride-glucose index and severity of coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index, which is a reliable surrogate marker of insulin resistance (IR), has been associated with cardiovascular diseases. However, evidence of the impact of the TyG index on the severity of coronary artery disease (CAD) is limited. This study investigated the relationship between the TyG index and CAD severity of individuals with different glucose metabolic statuses. METHODS: This study enrolled 2792 participants with CAD in China between January 1, 2018 and December 31, 2021. All participants were divided into groups according to the tertiles of the TyG index as follows: T1 group, TyG index < 6.87; T2 group, TyG index ≥ 6.87 to < 7.38; and T3 group, TyG index ≥ 7.38. The glucose metabolic status was classified as normal glucose regulation, pre-diabetes mellitus (pre-DM), and diabetes mellitus according to the standards of the American Diabetes Association. CAD severity was determined by the number of stenotic vessels (single-vessel CAD versus multi-vessel CAD). RESULTS: We observed a significant relationship between the TyG index and incidence of multi-vessel CAD. After adjusting for sex, age, body mass index, smoking habits, alcohol consumption, hypertension, estimated glomerular filtration rate, antiplatelet drug use, antilipidemic drug use, and antihypertensive drug use in the logistic regression model, the TyG index was still an independent risk factor for multi-vessel CAD. Additionally, the highest tertile of the TyG group (T3 group) was correlated with a 1.496-fold risk of multi-vessel CAD compared with the lowest tertile of the TyG group (T1 group) (odds ratio [OR], 1.496; 95% confidence interval [CI], 1.183-1.893; P < 0.001) in the multivariable logistic regression model. Furthermore, a dose-response relationship was observed between the TyG index and CAD severity (non-linear P = 0.314). In the subgroup analysis of different glucose metabolic statuses, the T3 group (OR, 1.541; 95% CI 1.013-2.344; P = 0.043) were associated with a significantly higher risk of multi-vessel CAD in individuals with pre-DM. CONCLUSIONS: An increased TyG index was associated with a higher risk of multi-vessel CAD. Our study indicated that TyG as an estimation index for evaluating IR could be a valuable predictor of CAD severity, especially for individuals with pre-DM.

Analysis of Optical Coherence Tomography in Acute versus Chronic Central Serous Chorioretinopathy.

SIGNIFICANCE: Central serous chorioretinopathy (CSC) is a common retinal disease that causes vision loss worldwide. Studying the imaging characteristics of CSC is helpful for the differential diagnosis of diseases. This study analyzed the differences between acute and chronic CSC and provide related information. PURPOSE: The aim of this study was to describe the optical coherence tomography features in patients with acute and chronic CSC. METHODS: Sixty-two eyes of 56 patients with CSC were included in the study. Optical coherence tomography was performed to observe the image features. The photoreceptor outer-segment (PROS) thickness above the pigment epithelium detachment (PED) coinciding with the leakage point in fundus fluorescein angiography was measured and compared with the mean PROS thickness outside the PED in acute cases. The SPSS 23.0 software (IBM Co., Chicago, IL) was used for statistical analysis. RESULTS: Of our 56 patients (62 eyes), 41 (73.21%) were male and 15 (26.79%) were female. There were 53 eyes (85.48%) with acute CSC and 9 eyes (14.52%) with chronic CSC. Besides other common features, the new feature of a high-reflection band in the outer nuclear layer was found to be limited to the macular detachment area. In acute cases, the mean PROS thickness above the retinal pigment epithelium layer protuberance coinciding with the leakage point was 22.7 ± 8.8 µm, which was less than the mean PROS thickness outside the PED at 64.3 ± 21.3 µm (P ≤ .001). CONCLUSIONS: The high-reflection band in the outer nuclear layer within the serous neurosensory detachment limited to the macular area was a new finding in CSC patients. This finding can be used as an imaging feature to aid in the diagnosis of CSC.

First Report of leaf spot on Cucumber Caused by Pantoea ananatis in Hainan of China.

Cucumber (Cucumis sativus L.) is one of the most important vegetables cultivated in the world. It is widely cultivated and mostly grown under greenhouse conditions (Sallam et al. 2021). Cucumber has a long growth cycle and is particularly susceptible to bacterial diseases. In May 2021, bacterial leaf spot was found on cucumbers of the variety Lyuyou NO.3 in Hainan Province, China. In the early stage of the disease, the leaves showed small yellow-brown spots in the shape of water stains. When exposed to light, a yellow halo around the disease spots could be seen. In later stages, the lesions gradually become larger and more yellow. The leaf veins around the disease site also gradually turned yellow (Figure 2a). In serious cases, the whole leaf turned yellow, resulting in leaf death. We collected plants with the same symptoms from 25 different farms in Hainan Province. Five plants were selected from each farm by the classic five-point sampling method and three leaves were selected from each plant, for a total of 15 leaves collected from each farm. Then three leaves were randomly selected from the 15 leaves on each farm for isolation of the pathogen, and a total of 75 leaves were isolated. We found that the incidence of the disease was from 20% to 30% based on a diagnostic test, which conducted on 75 cucumber leaves samples suspected of same symptom of cucumber, collected from Hainan Province. Using microscopy, bacterial streaming was observed to tentatively identify the causal agent as a bacteria. Tissue isolation was used to isolate the responsible pathogens. A 5 mm × 5 mm sample of tissue at the junction of diseased and healthy sections was collected. First, the surface of the tissue was disinfected in a 75% ethanol solution for 30 sec; then it was soaked in 2% NaOCl for 5-7 min, and finally, it was washed thrice in sterile distilled water. The tissues were inoculated onto lysogen broth culture media (LB) and cultured in a 28℃ incubator for 2 days. Bacterial colonies that emerged from the tissues were cultured in LB. Four isolated colonies were selected for verification. The colonies of isolated from the diseased leaves of cucumber are round, egg yellow and slightly sticky (Figure 2c). The isolate named PA-1 was identified by PCR amplification and sequencing of the partial 16S rRNA gene with the primer 27F/1492R (Lane 1991) and gyrB gene (Li et al. 2019). Sequences were stored in GenBank with the accession numbers OK576932.1 (16S rRNA, PA-1) and OL978577 (gyrB); BLASTn was used to compare these with other GenBank sequences. Sequencing of the 16S rRNA gene showed that PA-1 had a sequence length of 1403bp, with 99.78% genetic similarity to Pantoea ananatis strain MZ007857.1. Sequencing of the gyrB gene showed that the sequence length of PA-1 was 1136bp, with 99.29% genetic similarity to P. ananatis strain MW981331.1. Then, a pathogenicity text was conducted to verify Koch's postulates, which was done by first inoculating P. ananatis into LB liquid medium (shake culture at 28°C, 180 r/min). The log phase cell was collected by centrifugation (5,000 r/min for 2 min at 4°C), and inoculated strains were resuspended in sterile water at OD600 = 0.5. The bacterial suspension was inoculated on healthy cucumber leaves with a syringe. The control was sterile water, which was injected onto healthy cucumber leaves using the same methodology. The plants were placed in a greenhouse with a diurnal temperature difference of 21- 27°C and were observed daily. After two weeks, all bacterial inoculated plants developed symptoms of shriveling and necrosis (Figure 2b), while the control group showed no symptoms. From the symptomatic plants, the pathogen was isolated again and identified by morphological and molecular characterization. The sequences of the isolates recovered from the inoculated experiment matched 100% the sequences of the isolate PA-1. Koch's postulates were completed by following the previously described method. To our knowledge, this is the first report of P. ananatis causing leaf spot of cucumber.

Genome-Wide Association Mapping of Resistance to Powdery Mildew in Regional Trials of Wheat Mainly from China.

Wheat powdery mildew (Blumeria graminis f. sp. tritici [Bgt]) is a widespread disease that causes significant economic losses to common wheat (Triticum aestivum L.) crops worldwide. To identify effective resistance genes, we evaluated 120 common wheat accessions mainly from different wheat producing regions in China for responses to different Bgt isolates in the seedling stage and to natural infection in three field trials and genotyped them with a wheat 55K iSelect single-nucleotide polymorphism array for a genome-wide association study. A total of 26 loci were identified, which explained 6.6 to 26.2% of the phenotypic variation depending on individual locus. Of the 26 loci, 10 were detected in the A genomes, 10 in the B genomes, and only 6 in the D genome. Sixteen loci overlapped with known powdery mildew resistance genes or quantitative trait loci, and the remaining 10 loci were potentially novel. This study improves the understanding of the genetic structure of wheat powdery mildew resistance and provides germplasms and information on genes and markers for breeding new wheat cultivars with effective resistance to powdery mildew.

A new megastimane sesquiterpenoid from the leaves of Cinnamomum cassia.

A new megastimane sesquiterpenoid, cassianol A (1), and five known analogues (2-6) were isolated from the leaves extract of Cinnamomum cassia. Their structures were elucidated by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. All the isolates were isolated from C. cassia for the first time. The anti-inflammatory activities of compounds 1-6 were evaluated against nitric oxide (NO) production in LPS-induced RAW 264.7 mouse macrophages.