Search

Abstract: SARS-CoV-2 is a disease that endangers both human life and the economy. There was an 11- month period of relative evolutionary standstill following the appearance of SARS-CoV-2 in late 2019. However, the emergence of clusters of mutations known as' variants of concern 'with variable viral properties such as transmissibility and antigenicity defined the evolution of SARS-CoV-2. Several efforts have been made in recent months to understand the atomic level properties of SARS-CoV-2. A review of the literature on SARS-CoV-2 mutations is offered in this paper. The critical activities performed by different domains of the SARS-CoV-2 genome throughout the virus's entry into the host and overall viral life cycle are discussed in detail. These structural traits may potentially pave the way for the development of a vaccine and medication to combat the SARS-CoV-2 sickness.

Introduction: Adenoidectomy is a common procedure in children who have adenoid hypertrophy (AH), but anesthesia risks should be considered. We proposed a novel classification system for adenoids based on their appearance. Additionally, we explored whether the novel classification of adenoids correlates with the response to therapy and thus might be helpful for further treatment recommendations. Methods: We used fiberoptic nasal endoscopy to determine the degree and appearance of AH. Obstructive Sleep Apnea Questionnaire (OSA-18) was used to assess the quality of life of children with AH. The adenoids were divided into three types: edematous type, common type, and fibrous type. In adenoid tissues, the eosinophils were counted. Immunohistochemistry and Western blot were done to determine the expression of CysLTR1, CysLTR2, CGR-α, and CGR-β in different types of adenoids. Results: 70.67% (106/150) of AH patients presented with allergic rhinitis (AR), and of them, 68% (72/106) of adenoids were the edematous type. The expressions of CGR-α, CGR-β, and eosinophil count were higher in the edematous compared with the common and fibrous types. The expression of the leukotriene receptor was similar in all types. Upon montelukast combined with nasal glucocorticoid therapy, improvement of OSA-18 scores and AH grade was significantly compared to montelukast monotherapy for edematous type. There was not any statistically significant difference between the scores upon montelukast combined with nasal glucocorticoid and montelukast monotherapy for common and fibrous type. We observed a positive correlation between eosinophil count in the blood and in the adenoid tissue. Conclusion: AR was the risk factor for the development of edematous AH. All subtypes of AH responded to montelukast, while there was an additional effect of nasal glucocorticoid in the edematous type. A combination therapy of nasal glucocorticoid with leukotriene receptor antagonist can be recommended for AH patients with AR, patients with edematous adenoids, and/or patients with increased eosinophils in blood routine.

Our patient is a 60-year-old woman of Indian ethnicity with background of diabetes mellitus for 10 years. She presented with persistent vomiting, giddiness and significant weight loss for 1 month. Of note, she had recent hypoglycaemia necessitating gradual reduction in doses of glucose-lowering

Introduction: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. Method: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. Results: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P

Recombinant protein drugs, which are typically produced by mammalian host cells, have been approved for the treatment of a range of diseases. Accordingly, systems for selecting recombinant cell lines with efficient protein expression and for testing the content of recombinant proteins in vivo are crucial to the large-scale production and application of protein-based therapeutic drugs. In this study, we designed three aptamer beacons to detect His-tag, a common label of recombinant proteins. We found that all three beacons could specifically and quantitatively measure the His-tagged recombinant proteins with a short reaction time. Among these three beacons, the 6H5-MU beacon had the highest sensitivity for His polypeptides with a detection limit of 250 ng/mL and the shortest detection time within 1 min. Furthermore, we established a rapid and highly effective recombinant cell line construction system, which could obtain monoclonal cell lines with high yields of target proteins within 21 days, by combining 6H5-MU with pSB, a novel plasmid composed of a Sleeping Beauty transposase and a transposon. Finally, 6H5-MU also discriminately tested the serum concentration of His-tagged recombinant proteins in vivo, with consistent results compared to enzyme-linked immunosorbent assay (ELISA). We thus established a rapid and high-throughput method for generating recombinant cell lines and in vivo monitoring of recombinant protein levels, thereby providing a new platform for the development and preparation of recombinant protein drugs. KEY POINTS: • The 6H5-MU aptamer beacon rapidly and accurately binds to His-tagged recombinant proteins. • A system for rapid and high-throughput generation of recombinant cell lines is established using 6H5-MU and pSB. • 6H5-MU allows in vivo monitoring of recombinant protein levels.

Well-established surveillance and monitoring systems for respiratory viruses need to be improved, and epidemiological data on respiratory viruses in China are scarce. This study aimed to investigate the epidemiological characteristics of respiratory viruses among hospitalized children aged ≤2 years with acute respiratory tract infections (ARTIs) in Xiamen, China, from October 2014 to September 2017. The clinical records of 7,248 children hospitalized for ARTIs were retrospectively analyzed. Respiratory syncytial virus (RSV) (22.3%) was the most common virus among hospitalized children aged ≤2 years, followed by parainfluenza (5.0%), adenovirus (3.5%), and influenza (1.7%). RSV-infected children had a higher disease burden, including a higher intensive care unit (ICU) admission rate (12.7%) and higher hospital charges ($635.36). Particularly, infants aged6 months had the highest risk of RSV infection (odds ratio = 2.4; 95% CI, 1.9-2.9) and a higher ICU admission rate (12.1% vs. 4.5%, 4.6%) and hospital cost ($923.3 vs. $785.5, $811.7) than the other age groups. Therefore, infants aged 0-6 months, particularly premature infants and children with congenital diseases, should receive more attention. There is an urgent need to develop effective immunization strategies to protect these infants during the first 6 months of life and in the RSV season.

Objectives Time-resolved, 2D-phase-contrast MRI (2D-CINE-PC-MRI) enables in vivo blood flow analysis. However, accurate vessel contour delineation (VCD) is required to achieve reliable results. We sought to evaluate manual analysis (MA) compared to the performance of a deep learning (DL) application for fully-automated VCD and flow quantification and corrected semi-automated analysis (corSAA). Methods We included 97 consecutive patients (age = 52.9 ± 16 years, 41 female) with 2D-CINE-PC-MRI imaging on 1.5T MRI systems at sinotubular junction (STJ), and 28/97 also received 2D-CINE-PC at main pulmonary artery (PA). A cardiovascular radiologist performed MA (reference) and corSAA (built-in tool) in commercial software for all cardiac time frames (median: 20, total contours per analysis: 2358 STJ, 680 PA). DL-analysis automatically performed VCD, followed by net flow (NF) and peak velocity (PV) quantification. Contours were compared using Dice similarity coefficients (DSC). Discrepant cases (> ± 10 mL or > ± 10 cm/s) were reviewed in detail. Results DL was successfully applied to 97% (121/125) of the 2D-CINE-PC-MRI series (STJ: 95/97, 98%, PA: 26/28, 93%). Compared to MA, mean DSC were 0.91 ± 0.02 (DL), 0.94 ± 0.02 (corSAA) at STJ, and 0.85 ± 0.08 (DL), 0.93 ± 0.02 (corSAA) at PA; this indicated good to excellent DL-performance. Flow quantification revealed similar NF at STJ (p = 0.48) and PA (p > 0.05) between methods while PV assessment was significantly different (STJ: p < 0.001, PA: p = 0.04). A detailed review showed noisy voxels in MA and corSAA impacted PV results. Overall, DL analysis compared to human assessments was accurate in 113/121 (93.4%) cases. Conclusions Fully-automated DL-analysis of 2D-CINE-PC-MRI provided flow quantification at STJ and PA at expert level in > 93% of cases with results being available instantaneously. Key Points • Deep learning performed flow quantification on clinical 2D-CINE-PC series at the sinotubular junction and pulmonary artery at the expert level in > 93% of cases. • Location detection and contouring of the vessel boundaries were performed fully-automatic with results being available instantaneously compared to human assessments which approximately takes three minutes per location. • The evaluated tool indicates usability in daily practice.

Changes in population density have profound impacts on mating behaviors in group-living animals. The plasticity of mating behavior enables insects to respond to social signals and adjust mating frequency in accordance with rival competition and reproductive opportunity.In this study, we found that low levels of cis-vaccenyl acetate (cVA), a Drosophila pheromone, increased mating rates of Bactrocera dorsalis, but high concentrations of cVA inhibited mating, indicating a functional role of cVA in regulating mating behaviors in insect species other than Drosophila. Moreover, we demonstrated that group housing conditions had positive effects for B. dorsalis on their mating rates, responses toward cVA and cVA-mediated mating behaviors, which are dependent on the activity of c-AMP reponse element binding protein (CREB) binding protein (CBP).Our data suggest that CBP-mediated plasticity in mating behavior and chemical recognition enables insects to adapt to different housing conditions and highlight the potential of cVA as an efficient agent in regulating mating behaviors in insect species other than Drosophila. © 2022 Society of Chemical Industry.

Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge.This research intended to explore and analyse research trends and frontiers in this field during the last 10 years, providing new inspiration for clinical decision-making and scientific research.Publications on hepatic cirrhosis research were retrieved from the Web of Science Core Collection on April 4, 2021. Bibliometric visualisation was conducted through VOSviewer and CiteSpace.The analytic research was based on original articles and reviews. A total of 7775 records of hepatic cirrhosis published from 2011 to 2020 were retrieved. In the past ten years, the number of related annual publications has increased significantly, especially in the United States and China. All publications were distributed among 109 countries. The United States contributed the most (21.95%) and was consistently the leading driving force, with a solid academic reputation in this area. The University of Barcelona distributed the most related articles (177 articles) and was cited the most frequently. TheThis study identified developing trends in the evolution of liver cirrhosis to provide new inspiration for researchers.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p

Tiger pufferfish (Takifugu rubripes) is one of Asia's most economically valuable aquaculture species. However, winter production of this species in North China is limited by low water temperature and unavailability of high-quality feed, resulting in high mortality and low profitability. Therefore, the aim of this study was to evaluate the effect of feeding frequency (F1: one daily meal; F2: two daily meals; F3: four daily meals; F4: continuous diurnal feeding using a belt feeder) on the growth performance, plasma biochemistry, digestive and antioxidant enzyme activities, and expression of appetite-related genes in T. rubripes (initial weight: 266.80 ± 12.32 g) cultured during winter (18.0 ± 1.0 °C) for 60 days. The results showed that fish in the F3 group had the highest final weight, weight gain rate, specific growth rate, survival rate, and best feed conversion ratio. Additionally, daily feed intake increased significantly with increasing feeding frequency. The protein efficiency and lipid efficiency ratios of fish in the F3 group were significantly higher than those of fish in the other groups. Furthermore, total cholesterol, triglycerides, and glucose levels increased with increasing feeding frequency, peaking in the F2 group and decreasing under higher feeding frequencies. The antioxidant (superoxide dismutase, catalase, glutathione, and glutathione peroxidase) and digestive (trypsin, amylase, and lipase) enzyme activities of fish in the F1 group were significantly higher than those of fish in the F3 and F4 groups. Additionally, there was a decrease in orexin expression with increasing feeding frequency. In contrast, the expression levels of tachykinin, cholecystokinin, and leptin increased with increasing feeding frequency, peaking in the F4 group. Overall, the findings of this study indicated that a feeding frequency of four meals per day was optimal for improved growth performance of pufferfish juveniles cultured during winter.

Background. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in the treatment of hypertension. Hypertension is often accompanied by osteoporosis. However, the relationship between ACEI/ARB and fractures remains controversial. The purpose of this meta-analysis was to update the potential relationship between ACEI/ARB and fractures. Methods. This meta-analysis was identified through PubMed, EMBASE, Cochrane Library, and Web of Science. Related studies about ACEI/ARB with the risk of fracture were published from inception to June 2022. Results. Nine qualified prospective designed studies, involving 3,649,785 subjects, were included in this analysis. Overall, the RRs of ACEI compared with the nonusers were 0.98 (95% CI: 0.88, 1.10; P < 0.001 ) for composite fractures and 0.96 (95% CI: 0.87, 1.05; P = 0.048 ) for hip fractures; the RRs of ARB compared to the nonusers were 0.82 (95% CI: 0.73, 0.91; P < 0.001 ) for composite fractures and 0.85 (95% CI: 0.74, 0.97; P = 0.028 ) for hip fractures. Furthermore, in the subgroup analysis, male may benefit from ARB (RR = 0.65, 95% CI: 0.49, 0.89, P = 0.028 ), and the European may also benefit from ARB (RR = 0.86, 95% CI: 0.80, 0.93, P = 0.015 ). Conclusions. ACEI usage will not decrease the risk of osteoporosis fracture. On the contrary, ARB usage can decrease the risk of total fracture and hip fracture, especially for males and Europeans. Compared with ACEI, for patients at higher risk of fracture in cardiovascular diseases such as hypertension, the protective effect of ARB should be considered.

Lesions of breast imaging reporting and data system (BI-RADS) 4 at mammography vary from benign to malignant, leading to difficulties for clinicians to distinguish between them. The specificity of magnetic resonance imaging (MRI) in detecting breast is relatively low, leading to many false-positive results and high rates of re-examination or biopsy. Diffusion-weighted imaging (DWI), combined with perfusion-weighted imaging (PWI), might help to distinguish between benign and malignant BI-RADS 4 breast lesions at mammography.To evaluate the value of DWI and PWI in diagnosing BI-RADS 4 breast lesions.This is a retrospective study which included patients who underwent breast MRI between May 2017 and May 2019 in the hospital. The lesions were divided into benign and malignant groups according to the classification of histopathological results. The diagnostic efficacy of DWI and PWI were analyzed respectively and combinedly. The 95 lesions were divided according to histopathological diagnosis, with 46 benign and 49 malignant. The main statistical methods used included the Student t-test, the Mann-Whitney U-test, the chi-square test or Fisher's exact test.The mean apparent diffusion coefficient (ADC) values in the parenchyma and lesion area of the normal mammary gland were 1.82 ± 0.22 × 10DWI, combined with PWI, might possibly distinguish between benign and malignant BI-RADS 4 breast lesions at mammography.

Xanthomonas axonopodis pv. glycines (Xag) is the causal agent of bacterial pustule disease and results in enormous losses in soybean production. Although isoflavones are known to be involved in soybean resistance against pathogen infection, the effects of exogenous isoflavones on soybean plants remain unexplored.Irrigation of soybean plants with isoflavone genistein inhibited plant growth for short periods, probably by inhibiting the tyrosine (brassinosteroids) kinase pathway, and increased disease resistance against Xag. The number of lesions was reduced by 59%-63% when applying 50 μg mlThe effects of exogenous genistein on soybean plants were examined for the first time, revealing new insights into the roles of isoflavones in soybean defense and demonstrating that irrigation with genistein can be a suitable method to induce disease resistance in soybean plants. © 2022 Society of Chemical Industry.

PurposeThe purpose of this study is to analyze the dynamic changes of the arms trade network not only from the network structure but also the influence mechanism from the aspects of the economy, politics, security, strategy and transaction costs.Design/methodology/approachThe study employs the Temporal Exponential Random Graph Model and the Separable Temporal Exponential Random Graph Model to analyze the endogenous network structure effect, the attribute effect and the exogenous network effect of 47 major arms trading countries from 2015 to 2020.FindingsThe results show that the international arms trade market is unevenly distributed, and there are great differences in military technology. There is a fixed hierarchical structure in the arms trade, but the rise of emerging countries is expected to break this situation. In international arms trade relations, economic forces dominate, followed by political, security and strategic factors.Practical implicationsEconomic and political factors play an important role in the arms trade. Therefore, countries should strive to improve their economic strength and military technology. Also, countries should increase political mutual trust and gain a foothold in the industrial chain of arms production to enhance their military power.Originality/valueThe contribution of this paper is to analyze the special trade area of arms trade from a dynamic network perspective by incorporating economic, political, security, strategic and transaction cost factors together into the TERGM and STERGM models.

Acinetobacter is present in the livestock environment, but little is known about their antibiotic resistance and pathogenic species in the farm groundwater. Here we investigated antibiotic resistance of Acinetobacter in the swine farm groundwater (JZPG) and residential groundwater (JZG) of a swine farming village, in comparison to a nearby (3.5 km) non-farming village (WTG) using metagenomic and culture-based approaches. Results showed that the abundance of antibiotic resistome in some JZG and all JZPG (~3.4 copies/16S rRNA gene) was higher than that in WTG (~0.7 copies/16S rRNA gene), indicating the influence of farming activities on both groundwater types. Acinetobacter accounted for ~95.7% of the bacteria in JZG and JZPG, but only ~8.0% in WTG. They were potential hosts of ~95.6% of the resistome in farm affected groundwater, which includes 99 ARG subtypes against 23 antibiotic classes. These ARGs were associated with diverse intrinsic and acquired resistance mechanisms, and the predominant ARGs were tetracyclines and fluoroquinolones resistance genes. Metagenomic binning analysis elucidated that non-baumannii Acinetobacter including A. oleivorans, A. beijerinckii, A. seifertii, A. bereziniae and A. modestus might pose environmental risks because of multidrug resistance, pathogenicity and massive existence in the groundwater. Antibiotic susceptibility tests showed that the isolated strains were resistant to multiple antibiotics including sulfamethoxazole (resistance ratio: 96.2%), levofloxacin (42.5%), gatifloxacin (39.0%), ciprofloxacin (32.6%), tetracycline (32.0%), doxycycline (29.0%) and ampicillin (12.0%) as well as last-resort polymyxin B (31.7%), colistin (24.1%) and tigecycline (4.1%). The findings highlight potential prevalence of groundwater-borne antibiotic-resistant pathogenic Acinetobacter in the livestock environment.

Background China is progressing towards the goal of schistosomiasis elimination, but there are still some problems, such as difficult management of infection source and snail control. This study aimed to develop deep learning models with high-resolution remote sensing images for recognizing and monitoring livestock bovine, which is an intermediate source of Schistosoma japonicum infection, and to evaluate the effectiveness of the models for real-world application. Methods The dataset of livestock bovine’s spatial distribution was collected from the Chinese National Platform for Common Geospatial Information Services. The high-resolution remote sensing images were further divided into training data, test data, and validation data for model development. Two recognition models based on deep learning methods (ENVINet5 and Mask R-CNN) were developed with reference to the training datasets. The performance of the developed models was evaluated by the performance metrics of precision, recall, and F1-score. Results A total of 50 typical image areas were selected, 1125 bovine objectives were labeled by the ENVINet5 model and 1277 bovine objectives were labeled by the Mask R-CNN model. For the ENVINet5 model, a total of 1598 records of bovine distribution were recognized. The model precision and recall were 81.9% and 80.2%, respectively. The F1 score was 0.81. For the Mask R-CNN mode, 1679 records of bovine objectives were identified. The model precision and recall were 87.3% and 85.2%, respectively. The F1 score was 0.87. When applying the developed models to real-world schistosomiasis-endemic regions, there were 63 bovine objectives in the original image, 53 records were extracted using the ENVINet5 model, and 57 records were extracted using the Mask R-CNN model. The successful recognition ratios were 84.1% and 90.5% for the respectively developed models. Conclusion The ENVINet5 model is very feasible when the bovine distribution is low in structure with few samples. The Mask R-CNN model has a good framework design and runs highly efficiently. The livestock recognition models developed using deep learning methods with high-resolution remote sensing images accurately recognize the spatial distribution of livestock, which could enable precise control of schistosomiasis. Graphical Abstract

Objectives We aimed to identify in-hospital outcomes in young (≤ 65 years) and old (> 65 years) patients after coronary artery bypass grafting (CABG) by analyzing the effect of age on adverse events after on-pump or off-pump CABG. Methods Patients older than 65 years were defined as older patients and others were defined as younger patients. The qualitative data were compared by chi-square or Fisher's exact tests. The quantitative data were compared by the two-sample independent t-test or Mann–Whitney U test. Multifactor binary logistic regression was used to control for confounders and to investigate the effect of age on dichotomous outcome variables such as death. Results In the on-pump CABG population, the postoperative in-hospital mortality, the incidence of postoperative symptomatic cerebral infarction (POSCI) and postoperative atrial fibrillation (POAF) was higher in older patients than in younger patients (P value 65 years was associated with postoperative in-hospital mortality (OR = 2.370, P value = 0.031), POSCI (OR = 5.033, P value = 0.013), and POAF (OR = 1.499, P value P value 65 years was associated with POAF (OR = 1.392, P value = 0.011). Conclusion In-hospital outcomes after CABG are strongly influenced by age. In on-pump CABG, the risk of postoperative death, POSCI, and POAF was higher in older patients, and in off-pump CABG, the risk of POAF was higher in older patients.

A bacterial strain, designated AETb3-4

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the pandemic situation has begun to undergo positive changes with the joint efforts of various countries and world organizations. However, pressures such as the COVID-19 mutations and the sharp rise in confirmed cases have brought uncertainties to the prevention and control of the pandemic. The overall situation is still severe and complex. Based on the multi-dimensional spatial-temporal COVID-19 data collected by the open-source NetEase News (NEN) website and a real-time dynamic website, it is to explore the characteristics of the pandemic data, visualize the development trend, and analyze the spread of the pandemic in this paper. Moreover, it is to provide a rule basis for the prevention and control of the COVID-19 pandemic by constructing the decision tree model. From the results, some suggestions are provided for decision-makers.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in the global swine industry. A rapid and sensitive on-site detection method for PRRS virus (PRRSV) is critically important for diagnosing PRRS. In this study, we established a method that combines reverse transcription recombinase polymerase amplification (RT-RPA) with a lateral flow dipstick (LFD) for detecting North American PRRSV (PRRSV-2). The primers and probe were designed based on the conserved region of all complete PRRSV-2 genomic sequences available in China (n = 512) from 1996 to 2020. The detection limit of the assay was 5.6 × 10-1 median tissue culture infection dose (TCID50) per reaction within 30 min at 42 °C, which was more sensitive than that of reverse transcription polymerase chain reaction (RT-PCR) (5.6 TCID50 per reaction). The assay was highly specific for the epidemic lineages of PRRSV-2 in China and did not cross-react with pseudorabies virus, porcine circovirus 2, classical swine fever virus, or porcine epidemic diarrhea virus. The assay performance was evaluated by testing 179 samples and comparing the results with those of quantitative RT-PCR (RT-qPCR). The results showed that the detection coincidence rate of RT-RPA and RT-qPCR was 100% when the cycle threshold values of RT-qPCR were < 32. The assay provides a new alternative for simple and reliable detection of PRRSV-2 and has great potential for application in the field. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05349-8.

A Gram-negative, non-motile, facultatively anaerobic, rod-shaped bacterium, designated strain RS1-74T, was isolated from the surface water of Sayram Lake, Xinjiang Uygur Autonomous Region, China. The strain was able to grow optimally at 30 °C and pH 7.0–7.5, and in the presence of 0–0.5 % (v/w) NaCl. Catalase and oxidase activities were present. H2S was produced. Chemotaxonomic analysis showed Q-10 was the sole respiratory quinone. The polar lipids were composed of phosphatidylethanolamine, diphosphatidylglycerol, two glycolipids, phosphatidylglycerol, sphingoglycolipid and two unidentified lipids. Summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) were the predominant fatty acids. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain RS1-74T was closely related to ‘ Sandaracinobacter neustonicus ’ JCM 30 734 (98.65 %), ‘ Sandaracinobacter sibiricus ’ RB16-17 (98.42 %) and Sandaracinobacteroides hominis SZY PN-1T (97.09%). The genomic DNA G+C content was 66.45 mol%. The average nucleotide identity and DNA–DNA hybridization values among the genomes of strain RS1-74T and ‘ Sandaracinobacter neustonicus ’ JCM 30734 and Sandaracinobacteroides hominis SZY PN-1T were 78.2 and 77.22 %, and 22.2 and 20.40 %, respectively. Based on the physiological, biochemical, phylogenetic and genomic data, strain RS1-74T represents a novel species within the genus Sandaracinobacteroides , for which the name Sandaracinobacteroides sayramensis sp. nov. is proposed, with type strain RS1-74T (=KCTC 82674T=MCCC 1K06282T).

Camptothecin (CPT), first isolated from Chinese tree Camptotheca acuminate, produces rapid and prolonged inhibition of DNA synthesis and induction of DNA damage by targeting topoisomerase I (top1), which is highly activated in cancer cells. CPT thus exhibits remarkable anticancer activities in various cancer types, and is a promising therapeutic agent for the treatment of cancers. However, it remains to be uncovered underlying its cytotoxicity toward germ cells. In this study we found that CPT, a cell cycle-specific anticancer agent, reduced fecundity and exhibited significant cytotoxicity toward GSCs and two-cell cysts. We showed that CPT induced GSC loss and retarded two-cell cysts differentiation in a niche- or apoptosis-independent manner. Instead, CPT induced ectopic expression of a differentiation factor, bag of marbles (Bam), and regulated the expression of cyclin A, which contributed to GSC loss. In addition, CPT compromised two-cell cysts differentiation by decreasing the expression of Bam and inducing cell arrest at G1/S phase via cyclin A, eventually resulting in two-cell accumulation. Collectively, this study demonstrates, for the first time in vivo, that the Bam–cyclin A axis is involved in CPT-mediated germline stem cell loss and two-cell cysts differentiation defects via inducing cell cycle arrest, which could provide information underlying toxicological effects of CPT in the productive system, and feature its potential to develop as a pharmacology-based germline stem cell regulation agent.

This study evaluates the cost-effectiveness of daratumumab (D) in combination with lenalidomide and dexamethasone (Rd) for treatment of relapsed and/or refractory multiple myeloma in patients who have received at least one prior therapy in Singapore. A 3-state partitioned survival model was developed to evaluate the cost-effectiveness of lenalidomide and dexamethasone with or without daratumumab from a healthcare system perspective over 10 years. Clinical inputs were obtained from the POLLUX trial. Health state utilities were derived from the literature and direct medical costs obtained from public healthcare institutions. Sensitivity and scenario analyses were conducted to explore uncertainties. DRd was associated with a high base-case incremental cost-effectiveness ratio (ICER) of US$576,247 per quality-adjusted life year (QALY) gained, compared with Rd. According to one-way sensitivity analysis, ICER was most heavily influenced by time horizon, discount rate for outcomes, progression-free utility and cost of daratumumab. Regardless of the variation, DRd remained not cost-effective. Even when the cost of both daratumumab and lenalidomide dropped by 20% and 80%, the ICERs remained high at US$470,400 and US$152,860 per QALY gained. At current prices, the addition of daratumumab to lenalidomide and dexamethasone does not represent cost-effective use of healthcare resources in Singapore.

Background: Cerebral small vessel disease (CSVD), which comprises the typical features of white matter hyperintensity (WMH) and Vichor-Robin spaces (VRSs) in the brain, is one of the leading causes of aging-related cognitive decline and, ultimately, contributes to the occurrence of dementia, including Alzheimer’s disease (AD). Objective: To investigate whether CSVD imaging markers modify the pathological processes of AD and whether these markers improve AD diagnosis. Methods: 208 participants were enrolled in the China Aging and Neurodegenerative Initiative (CANDI). Fluid AD biomarkers were detected using a single-molecule array, and cerebral small vessel dysfunction was determined using magnetic resonance imaging. Results: WMH contributed to AD pathology only within the NC and MCI groups (CDR ≤0.5), whereas VRSs had no effect on AD pathology. The associations between AD biomarkers and cognitive mental status were consistent with the presence of CSVD pathology. That is, within individuals without CSVD pathology, the MMSE scores were correlated with AD fluid biomarkers, except for plasma Aβ42 and Aβ40. Increased plasma p-Tau levels were associated with worse cognitive performance in individuals with WMH (β= –0.465, p = 0.0016) or VRSs (β= –0.352, p = 0.0257) pathology. Plasma AD biomarkers combined with CSVD markers showed high accuracy in diagnosing dementia. Conclusion: Findings from this cross-sectional cohort study support the notion that CSVD is a risk factor for dementia and highlights that vascular pathology can promote AD biomarker levels, especially in the early course of the disease. Moreover, our results suggest that adding a vascular category to the ATN framework improves the diagnostic accuracy of AD.

Background There is a raising concern of a higher infectious Omicron BA.2 variant and the latest BA.4, BA.5 variant, made it more difficult in the mitigation process against COVID-19 pandemic. Our study aimed to find optimal control strategies by transmission of dynamic model from novel invasion theory. Methods Based on the public data sources from January 31 to May 31, 2022, in four cities (Nanjing, Shanghai, Shenzhen and Suzhou) of China. We segmented the theoretical curves into five phases based on the concept of biological invasion. Then, a spatial autocorrelation analysis was carried out by detecting the clustering of the studied areas. After that, we choose a mathematical model of COVID-19 based on system dynamics methodology to simulate numerous intervention measures scenarios. Finally, we have used publicly available migration data to calculate spillover risk. Results Epidemics in Shanghai and Shenzhen has gone through the entire invasion phases, whereas Nanjing and Suzhou were all ended in the establishment phase. The results indicated that Rt value and public health and social measures (PHSM)-index of the epidemics were a negative correlation in all cities, except Shenzhen. The intervention has come into effect in different phases of invasion in all studied cities. Until the May 31, most of the spillover risk in Shanghai remained above the spillover risk threshold (18.81–303.84) and the actual number of the spillovers (0.94–74.98) was also increasing along with the time. Shenzhen reported Omicron cases that was only above the spillover risk threshold (17.92) at the phase of outbreak, consistent with an actual partial spillover. In Nanjing and Suzhou, the actual number of reported cases did not exceed the spillover alert value. Conclusions Biological invasion is positioned to contribute substantively to understanding the drivers and mechanisms of the COVID-19 spread and outbreaks. After evaluating the spillover risk of cities at each invasion phase, we found the dynamic zero-COVID strategy implemented in four cities successfully curb the disease epidemic peak of the Omicron variant, which was highly correlated to the way to perform public health and social measures in the early phases right after the invasion of the virus. Graphical Abstract

Mechanochromic (MC) luminescence of organic molecules has been emerging as a promising smart material for optical recording and memory devices. At the same time, pressure-induced blue-shifted and enhanced luminescence are rarely reported now. Herein, a series of cyanostilbene-based AIEgens with different substituents were synthesized to evaluate the influence of morphology transformation and push-pull electronic effect on the MC luminescence. Among these luminophores, compound 1 with one cyano group and diethylamino group was more susceptible to mechanical stimuli and obtained blue-shifted and enhanced fluorescence in response to anisotropic grinding. Powder X-ray diffraction patterns indicated that the MC behaviors were ascribed to the solid-state morphology transition from crystal-to-crystal. Analysis of crystal structures revealed that loose molecular packing is a key factor for high high-contrast MC luminescence. The smart molecular design, together with the excellent performance, verified that luminophores with twisted structures are ideal candidates for MC luminogens.

Prevention of neointima formation is the key to improving long-term outcomes after stenting or coronary artery bypass grafting. RNA N

The incidence of bladder cancer and patient survival vary greatly among different populations, but the influence of the associated molecular features and evolutionary processes on its clinical treatment and prognostication remains unknown. Here, we analyze the genomic architectures of 505 bladder cancer patients from Asian/Black/White populations. We identify a previously unknown association between AHNAK mutations and activity of the APOBEC-a mutational signature, the activity of which varied substantially across populations. All significantly mutated genes but only half of arm-level somatic copy number alterations (SCNAs) are enriched with clonal events, indicating large-scale SCNAs as rich sources of bladder cancer clonal diversities. The prevalence of TP53 and ATM clonal mutations as well as the associated burden of SCNAs is significantly higher in Whites/Blacks than in Asians. We identify a trans-ancestry prognostic subtype of bladder cancer characterized by enrichment of non-muscle-invasive patients and muscle-invasive patients with good prognosis, increased CREBBP/FGFR3/HRAS/NFE2L2 mutations, decreased intra-tumor heterogeneity and genome instability, and an activated tumor microenvironment.

Introduction: Surgical resection of the primary and metastatic tumour is increasingly recommended in suitable patients with metastatic colorectal cancer (CRC). While the role of metastasectomy is well studied and established in colorectal liver metastasis, evidence remains limited in pulmonary metastases. This systematic review was conducted to examine the current evidence on the role of lung metastasectomy (LUM) in CRC. Methods: Three databases were systematically searched, to identify studies that compared survival outcomes of LUM, and factors that affected decision for LUM. Results: From a total of 5,477 records, 6 studies were eventually identified. Two papers reported findings from one randomised controlled trial and 4 were retrospective reviews. There was no clear survival benefit in patients who underwent LUM compared to those who did not. When compared against patients who underwent liver metastasectomy, there was also no clear survival benefit. Patients who underwent LUM were also more likely to have a single pulmonary tumour, and metachronous disease. Conclusion: The evidence suggests a role for LUM, but is limited by inherent selection bias in retrospective reviews, and the single randomised clinical trial performed was not completed. More prospective studies are required to understand the true effect of LUM on outcomes in metastatic CRC. Keywords: Colorectal cancer, pulmonary metastasectomy, pulmonary metastases, survival

Background The circulating concentration of 1α,25-dihydroxyvitamin D [1α,25(OH)2D] is very low, and the presence of multiple isomers may lead to inaccurate quantitation if not separated prior to analysis. Antibody-based immunoextraction procedures are sometimes used to remove structurally related isomers of 1α,25(OH)2D prior to an LC-MS/MS analysis. However, immunoextraction increases sample preparation time and cost. In addition, some dihydroxyvitamin D metabolites are not completely removed by immunoextraction. Method We developed an HPLC method using a phenyl-hexyl column to investigate interfering isomers of 1α,25(OH)2D. Result Using this method, 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) derivatization product of 1α,25(OH)2D was found to be present as 2 epimers, which were separated chromatographically with an area ratio of 2:1. PTAD derivatized metabolite of 25-hydroxyvitamin D3 [i.e., 4β,25-dihydroxyvitamin D3 (4β,25(OH)2D3)] eluted out between 6R and 6S epimers of derivatized 1α,25(OH)2D3. If not chromatographically resolved, 4β,25(OH)2D can affect 1α,25(OH)2D quantitation. In a method comparison study, it was found that the presence of 4β,25(OH)2D produced positive bias up to 127% on 1α,25(OH)2D3 quantitation. Conclusion The LC-MS/MS method we developed without an immunoextraction procedure was able to resolve the major interference peak from 1α,25(OH)2D and achieved reliable quantitation of 1α,25(OH)2D.