Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins.

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

Exosomes in tumor-stroma crosstalk: Shaping the immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) is a multifaceted disease characterized by a complex interaction between tumor cells and the surrounding microenvironment. Within this intricate landscape, exosomes have emerged as pivotal players in the tumor-stroma crosstalk, influencing the immune microenvironment of CRC. These nano-sized vesicles, secreted by both tumoral and stromal cells, serve as molecular transporters, delivering a heterogeneous mix of biomolecules such as RNAs, proteins, and lipids. In the CRC context, exosomes exert dual roles: they promote tumor growth, metastasis, and immune escape by altering immune cell functions and activating oncogenic signaling pathways and offer potential as biomarkers for early CRC detection and treatment targets. This review delves into the multifunctional roles of exosomes in the CRC immune microenvironment, highlighting their potential implications for future therapeutic strategies and clinical outcomes.

Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis.

AIMS: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. METHODS: We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. RESULTS: Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. CONCLUSIONS: The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.

Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

Synthesis of silyl indenes by ruthenium-catalyzed aldehyde- and acylsilane-enabled C-H alkylation/cyclization.

A ruthenium-catalyzed C-H alkylation/cyclization sequence is presented to prepare silyl indenes with atom and step-economy. This domino reaction is triggered by acyl silane-directed C-H activation, and an aldehyde controlled the following enol cyclization/condensation other than ß-H elimination. The protocol tolerates a broad substitution pattern, and the further synthetic elaboration of silyl indenes allows access to a diverse range of interesting indene and indanone derivatives.

Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin.

Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Perioperative complications of minor and major reinterventions for peripheral arterial disease.

INTRODUCTION: Patients with peripheral arterial disease (PAD) frequently require reinterventions after lower-extremity revascularization (LER) to maintain perfusion. Current Society for Vascular Surgery guidelines define reinterventions as major or minor based on the magnitude of the procedure. While prior studies have compared primary LER procedures of different magnitudes, similar studies for reinterventions have not been performed. The objective of this study is to compare perioperative outcomes associated with major and minor reinterventions. METHODS: Patients undergoing LER for PAD at a tertiary care center from 2013 to 2017 were included. A retrospective review of electronic medical records was performed, and reinterventions were categorized as major or minor based on the procedure magnitude. Minor reinterventions included endovascular procedures and open revision with patch angioplasty, while major reinterventions were characterized by open surgical or endovascular LER with catheter-directed thrombolysis (CDT). Perioperative outcomes following LER were captured and compared for major and minor reinterventions. An additional subgroup analysis was performed comparing outcomes associated with major reinterventions stratified into open major surgical reinterventions and CDT. RESULTS: This study included 713 patients over a mean follow-up of 2.5 years. A total of 291 patients underwent 696 ipsilateral reinterventions (range = 1-12 reinterventions). Most reinterventions were minor (72.1%, N = 502) and 27.9% (N = 194) were major. Patients receiving reinterventions had an average age of 67.2 ± 11.5 and most were white (73.5%) males (60.1%) initially treated for claudication (58.2%) and CLTI (41.8%). There was significantly higher post-operative bleeding (9.8% vs 3.4%, p = .001), arterial thrombosis (3.1% vs 1.0%, p = .047), and acute renal failure (6.2% vs 2.4%, p = .014) after major reinterventions than minor. Additionally, major reinterventions had significantly higher return to the OR (17.0% vs 11.3%, p = .046) and longer hospital stays (7.5 vs 4.3 days, p = <.0001). Overall, major reinterventions were associated with significantly increased perioperative morbidity (37.6% vs 19.7%, p ≤ .001) with no difference in perioperative mortality. In the subgroup analysis, open reinterventions resulted in significantly longer hospital stays (8.6 days vs 5.5 days, p ≤ .001) and more wound infections than CDT (11.0% vs 0%, p = .017). However, there was no other significant difference in morbidity or mortality following treatment with open surgical reinterventions or CDT. CONCLUSIONS: In this study, major reinterventions after LER were associated with greater perioperative morbidity than minor reinterventions, with no difference in mortality. Major reinterventions performed via open surgery and CDT had similar morbidity and mortality.

DNA methylation analysis reveals the effect of arsenic on gestational diabetes mellitus.

BACKGROUND: Arsenic (As) exposure is one of the risk factors for gestational diabetes mellitus (GDM). This study aimed to explore the effect of As-exposure on DNA methylation in GDM and to establish a risk assessment model of GDM in As exposed pregnant women. METHOD: We collected elbow vein blood of pregnant women before delivery to measure As concentration and DNA methylation data. Then compared the DNA methylation data and established a nomogram. RESULT: We identified a total of 10 key differentially methylated CpGs (DMCs) and found 6 corresponding genes. Functions were enriched in Hippo signaling pathway, cell tight junction, prophetic acid metabolism, ketone body metabolic process, and antigen processing and presentation. A nomogram was established that can predict GDM risks (c-index = 0.595, s:p = 0.973). CONCLUSION: We found 6 genes associated with GDM with high As exposure. The prediction of the nomograms has been proven to be effective.

Study on the mechanism of action of methane production by co-fermentation of sludge and lignite.

To improve the methanogenic efficiency of lignite anaerobic fermentation and explore innovative approaches to sludge utilization, a co-fermentation technique involving lignite and sludge was employed for converting biomass into biomethane. Volatile suspended solids were introduced as a native enrichment of the sludge and mixed with lignite for fermentation. The synergistic fermentation mechanism between sludge and lignite for biomethane production was analyzed through biochemical methane potential experiments, measurement of various parameters pre- and post-fermentation, observation of bacterial population changes during the peak of reaction, carbon migration assessment, and evaluation of rheological characteristics. The results showed that the addition of sludge in the anaerobic fermentation process improved the microorganisms' ability to degrade lignite and bolstered biomethane production. Notably, the maximum methane production recorded was 215.52 mL/g-volatile suspended solids, achieved at a sludge to coal ratio of 3:1, with a synergistic growth rate of 25.37%. Furthermore, the removal rates of total suspended solids, and total chemical oxygen demand exhibited an upward trend with an increasing percentage of sludge in the mixture. The relative abundance and activity of the methanogens population were found to increase with an appropriate ratio of sludge to lignite. This observation confirmed the migration of carbon between the solid-liquid-gas phases, promoting enhanced system affinity. Additionally, the changes in solid-liquid phase parameters before and after the reaction indicated that the addition of sludge improved the system's degradation capacity. The results of the study hold significant implications in realizing the resource utilization of sludge and lignite while contributing to environmental protection endeavors.

Effects of biotin and coated cobalamin on lactation performance, nutrient digestion and rumen fermentation in Holstein dairy cows.

Biotin (BI) and cobalamin (CA) are essential for rumen propionate production and hepatic gluconeogenesis. The study evaluated the influence of BI or/and coated CA (CCA) on milk performance and nutrient digestion in cows. Sixty Holstein dairy cows were assigned in a 2 × 2 factorial arrangement and randomised block design to four groups. The factors were BI at 0 or 20 mg/day and CCA at 0 or 9 mg CA/day. Dry matter intake increased with BI addition but was unchanged with CCA supply. Addition of BI or CCA increased fat-corrected milk, milk fat and milk protein yields and feed efficiency. Moreover, lactose yield was increased by CCA addition. Dry matter, organic matter, crude protein and acid detergent fibre total-tract digestibility increased for BI or CCA supply. When CCA was supplemented, positive response of neutral detergent fibre digestibility to BI addition was enhanced. Supplementing BI did not affect pH, propionate content and acetate to propionate ratio, but increased total volatile fatty acids (VFA) and acetate contents. Supplementing CCA decreased pH and acetate to propionate ratio, but increased total VFA, acetate and propionate contents. Rumen protease and carboxymethyl-cellulase activities and fungi, bacteria and Butyrivibrio fibrisolvens numbers increased for BI or CCA supply. In addition, protozoa increased for BI addition, and protease activity and Prevotella ruminicola increased for CCA supply. When CCA was supplemented, positive responses of R. albus and Ruminobacter amylophilus numbers to BI addition were enhanced. Blood glucose concentration was unchanged with BI supply, but increased for CCA supply. Blood nonesterified fatty acids and ß-hydroxybutyrate contents reduced with BI or CCA supply. Supplementation with BI or CCA increased blood BI or CA content. The results showed that supplementing BI or/and CCA improved lactation performance and nutrient digestion, and CCA supply did not enhance the lactation performance response to BI supply.

Genome-wide Association Study Identifies HLA-DPB1 as a Significant Risk Factor for Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a rare disorder characterized by hypoplastic bone marrow and progressive pancytopenia. The etiology of acquired SAA is not understood but is likely related to abnormal immune responses and environmental exposures. We conducted a genome-wide association study of individuals with SAA genetically matched to healthy controls in discovery (359 cases, 1,396 controls) and validation sets (175 cases, 1,059 controls). Combined analyses identified linked SNPs in distinct blocks within the major histocompatibility complex on 6p21. The top SNP encodes p.Met76Val in the P4 binding pocket of the HLA class II gene HLA-DPB1 (rs1042151A>G, odds ratio [OR] 1.75, 95% confidence interval [CI] 1.50-2.03, p = 1.94 × 10-13) and was associated with HLA-DP cell surface expression in healthy individuals (p = 2.04 × 10-6). Phylogenetic analyses indicate that Val76 is not monophyletic and likely occurs in conjunction with different HLA-DP binding groove conformations. Imputation of HLA-DPB1 alleles revealed increased risk of SAA associated with Val76-encoding alleles DPB1∗03:01, (OR 1.66, p = 1.52 × 10-7), DPB1∗10:01 (OR 2.12, p = 0.0003), and DPB1∗01:01 (OR 1.60, p = 0.0008). A second SNP near HLA-B, rs28367832G>A, reached genome-wide significance (OR 1.49, 95% CI 1.22-1.78, p = 7.27 × 10-9) in combined analyses; the association remained significant after excluding cases with clonal copy-neutral loss-of-heterozygosity affecting class I HLA genes (8.6% of cases and 0% of controls). SNPs in the HLA class II gene HLA-DPB1 and possibly class I (HLA-B) are associated with SAA. The replacement of Met76 to Val76 in certain HLA-DPB1 alleles might influence risk of SAA through mechanisms involving DP peptide binding specificity, expression, and/or other factors affecting DP function.

Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study.

BACKGROUND: Despite the substantial burden caused by childhood cancer globally, childhood cancer incidence obtained in a nationwide childhood cancer registry and the accessibility of relevant health services are still unknown in China. We comprehensively assessed the most up-to-date cancer incidence in Chinese children and adolescents, nationally, regionally, and in specific population subgroups, and also examined the association between cancer incidence and socioeconomic inequality in access to health services. METHODS: In this national cross-sectional study, we used data from the National Center for Pediatric Cancer Surveillance, the nationwide Hospital Quality Monitoring System, and public databases to cover 31 provinces, autonomous regions, and municipalities in mainland China. We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China through stratified proportional estimation. We classified regions by socioeconomic status using the human development index (HDI). Incidence rates of 12 main groups, 47 subgroups, and 81 subtypes of cancer were reported and compared by sex, age, and socioeconomic status, according to the third edition of the International Classification of Childhood Cancer. We also quantified the geographical and population density of paediatric oncologists, pathology workforce, diagnoses and treatment institutions of paediatric cancer, and paediatric beds. We used the Gini coefficient to assess equality in access to these four health service indicators. We also calculated the proportions of cross-regional patients among new cases in our surveillance system. FINDINGS: We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China from Jan 1, 2018, to Dec 31, 2020. An estimated 121 145 cancer cases were diagnosed among children and adolescents in China between 2018 and 2020, with world standard age-standardised incidence rates of 122·86 (95% CI 121·70-124·02) per million for children and 137·64 (136·08-139·20) per million for adolescents. Boys had a higher incidence rate of childhood cancer (133·18 for boys vs 111·21 for girls per million) but a lower incidence of adolescent cancer (133·92 for boys vs 141·79 for girls per million) than girls. Leukaemias (42·33 per million) were the most common cancer group in children, whereas malignant epithelial tumours and melanomas (30·39 per million) surpassed leukaemias (30·08 per million) in adolescents as the cancer with the highest incidence. The overall incidence rates ranged from 101·60 (100·67-102·51) per million in very low HDI regions to 138·21 (137·14-139·29) per million in high HDI regions, indicating a significant positive association between the incidence of childhood and adolescent cancer and regional socioeconomic status (p<0·0001). The incidence in girls showed larger variation (48·45% from the lowest to the highest) than boys (36·71% from lowest to highest) in different socioeconomic regions. The population and geographical densities of most health services also showed a significant positive correlation with HDI levels. In particular, the geographical density distribution (Gini coefficients of 0·32-0·47) had higher inequalities than population density distribution (Gini coefficients of 0·05-0·19). The overall proportion of cross-regional patients of childhood and adolescent cancer was 22·16%, and the highest proportion occurred in retinoblastoma (56·54%) and in low HDI regions (35·14%). INTERPRETATION: Our study showed that the burden of cancer in children and adolescents in China is much higher than previously nationally reported from 2000 to 2015. The distribution of the accessibility of health services, as a social determinant of health, might have a notable role in the socioeconomic inequalities in cancer incidence among Chinese children and adolescents. With regards to achieving the Sustainable Development Goals, policy approaches should prioritise increasing the accessibility of health services for early diagnosis to improve outcomes and subsequently reduce disease burdens, as well as narrowing the socioeconomic inequalities of childhood and adolescent cancer. FUNDING: National Major Science and Technology Projects of China, National Natural Science Foundation of China, Chinese Academy of Engineering Consulting Research Project, Wu Jieping Medical Foundation, Beijing Municipal Administration of Hospitals Incubating Program.

Association of frailty with the incidence risk of cardiovascular disease and type 2 diabetes mellitus in long-term cancer survivors: a prospective cohort study.

BACKGROUND: Comorbidities among cancer survivors remain a serious healthcare burden and require appropriate management. Using two widely used frailty indicators, this study aimed to evaluate whether frailty was associated with the incidence risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) among long-term cancer survivors. METHODS: We included 13,388 long-term cancer survivors (diagnosed with cancer over 5 years before enrolment) free of CVD and 6101 long-term cancer survivors free of T2DM, at the time of recruitment (aged 40-69 years), from the UK Biobank. Frailty was assessed by the frailty phenotype (FP_Frailty, range: 0-5) and the frailty index (FI_Frailty, range: 0-1) at baseline. The incident CVD and T2DM were ascertained through linked hospital data and primary care data, respectively. The associations were examined using Cox proportional hazards regression models. RESULTS: Compared with non-frail participants, those with pre-frailty (FP_Frailty [met 1-2 of the components]: hazard ratio [HR]=1.18, 95% confidence interval [CI]: 1.05, 1.32; FI_Frailty [0.10< FI ≤0.21]: HR=1.51, 95% CI: 1.32, 1.74) and frailty (FP_Frailty [met ≥3 of the components]: HR=2.12, 95% CI: 1.73, 2.60; FI_Frailty [FI >0.21]: HR=2.19, 95% CI: 1.85, 2.59) had a significantly higher risk of CVD in the multivariable-adjusted model. A similar association of FI_Frailty with the risk of incident T2DM was observed. We failed to find such an association for FP_Frailty. Notably, the very early stage of frailty (1 for FP_Frailty and 0.1-0.2 for FI_Frailty) was also positively associated with the risk of CVD and T2DM (FI_Frailty only). A series of sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: Frailty, even in the very early stage, was positively associated with the incidence risk of CVD and T2DM among long-term cancer survivors, although discrepancies existed between frailty indicators. While the validation of these findings is required, they suggest that routine monitoring, prevention, and interventive programs of frailty among cancer survivors may help to prevent late comorbidities and, eventually, improve their quality of life. Especially, interventions are recommended to target those at an early stage of frailty when healthcare resources are limited.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

Tunable ultra-narrow linewidth diode laser for multiple metastable rare gas pumping.

We present what we believe to be a novel external cavity feedback structure based on a double-layer laser diode array with volume Bragg grating (VBG). Diode laser collimation and external cavity feedback result in a high-power and ultra-narrow linewidth diode laser pumping source with a central wavelength of 811.292 nm, spectral linewidth of 0.052 nm, and output power exceeding 100 W, with external cavity feedback and electro-optical conversion efficiencies exceeding 90% and 46%, respectively. The temperature of VBG is controlled to tune the central wavelength from 811.292 nm to 811.613 nm, covering the Kr* and Ar* absorption spectra. We believe this is the first report of an ultra-narrow linewidth diode laser that can pump two metastable rare gases.

Characteristics and 1-year outcomes of patients with rupture of small abdominal aortic aneurysms.

OBJECTIVES: Ruptured abdominal aortic aneurysms (rAAA) are associated typically with a large sac diameter; however, some patients experience rupture before reaching operative thresholds for elective repair. We aim to investigate the characteristics and outcomes of patients who experience small rAAA. METHODS: The Vascular Quality Initiative database for open AAA repair and endovascular aneurysm repair from 2003 to 2020 were reviewed for all rAAA cases. Based on the 2018 Society for Vascular Surgery guidelines on operative size thresholds for elective repair, patients with infrarenal aneurysms of less than 5.0 cm in women or less than 5.5 cm in men were categorized as a small rAAA. Patients who met operative thresholds or had a concomitant iliac diameter 3.5 cm or greater were categorized as a large rAAA. Patient characteristics and perioperative as well as long-term outcomes were compared via univariate regression. Inverse probability of treatment weighting using propensity scores was used to examine the relationship between rAAA size and adverse outcomes. RESULTS: There were 3962 cases that met inclusion criteria, with 12.2% small rAAA. The mean aneurysm diameter was 42.3 mm and 78.5 mm in the small and large rAAA groups, respectively. Patients in the small rAAA group were significantly more likely to be younger, African American, have a lower body mass index, and had significantly higher rates of hypertension. Small rAAA were more likely to be repaired via endovascular aneurysm repair (P = .001). Hypotension was significantly less likely in patients with small rAAA (P<.001). Rates of perioperative myocardial infarction (P < .001), total morbidity (P < .004) and mortality (P < .001) were significantly higher for large rAAA cases. After propensity matching, there was no significant difference in mortality between the two groups, but smaller rAAA was associated with lower rates of myocardial infarction (odds ratio, 0.50; 95% confidence interval, 0.31-0.82). On long-term follow-up, no difference in mortality was noted between the two groups. CONCLUSIONS: Patients presenting with small rAAA represent 12.2% of all rAAA and are more likely to be African American. Small rAAA is associated with similar risk of perioperative and long-term mortality compared with rupture at larger size after risk adjustment.

Effects of folic acid and riboflavin on growth performance, nutrient digestion and rumen fermentation in Angus bulls.

This study examined the influences of coated folic acid (CFA) and coated riboflavin (CRF) on bull performance, nutrients digestion and ruminal fermentation. Forty-eight Angus bulls based on a randomised block and 2 × 2 factorial design were assigned to four treatments. The CFA of 0 or 6 mg of folic acid/kg DM was supplemented in diets with CRF 0 or 60 mg riboflavin (RF)/kg DM. Supplementation of CRF in diets with CFA had greater increase in daily weight gain and feed efficiency than in diets without CFA. Supplementation with CFA or CRF enhanced digestibility of DM, organic matter, crude protein, neutral-detergent fibre and non-fibre carbohydrate. Ruminal pH and ammonia N content decreased and total volatile fatty acids concentration and acetate to propionate ratio elevated for CFA or CRF addition. Supplement of CFA or CRF increased the activities of fibrolytic enzymes and the numbers of total bacteria, protozoa, fungi, dominant fibrolytic bacteria and Prevotella ruminicola. The activities of α-amylase, protease and pectinase and the numbers of Butyrivibrio fibrisolvens and Ruminobacter amylophilus were increased by CFA but were unaffected by CRF. Blood concentration of folate elevated and homocysteine decreased for CFA addition. The CRF supplementation elevated blood concentrations of folate and RF. These findings suggested that CFA or CRF inclusion had facilitating effects on performance and ruminal fermentation, and combined addition of CFA and CRF had greater increase in performance than CFA or CRF addition alone in bulls.

Quantitative analysis of adipose tissue for predicting Crohn's disease postoperative endoscopic recurrence and anastomotic ulcer.

OBJECTIVE: Inflammation and ulcers at the anastomotic site are frequently observed after intestinal resection surgery for Crohn's disease (CD), which often signify postoperative recurrence. Crohn's disease causes abnormalities in whole-body fat metabolism, and alterations in subcutaneous and visceral fat are potential indicators of disease development. This study aimed to quantify the areas of subcutaneous (SFA) and visceral fat (VFA) and investigate the relationship between fat tissue and endoscopic recurrence and anastomotic ulceration after Crohn's disease surgery. METHODS: We conducted a retrospective analysis of clinical data from 279 patients diagnosed with Crohn's disease. Using abdominal CT (Computed Tomography) scans at the level of the umbilicus, we measured the area of subcutaneous and visceral fat, and calculated the Mesenteric Fat Index (MFI), which is defined as the ratio of the area of visceral fat to subcutaneous fat. We compared the changes in fat tissue between surgical Crohn's disease patients and non-surgical patients in remission, as well as changes in fat tissue before and after surgery, and between patients with and without endoscopic recurrence after surgery. RESULTS: The MFI value of the surgical group was higher than that of the non-surgical group(0.88(1.27 ± 1.26) VS 0.39(0.44 ± 0.21), P < 0.001), while the SFA value was lower(70.16(92.97 ± 78.23) VS 157.64(175.96 ± 101.58), P < 0.001). Of the 134 surgical patients who underwent abdominal CT examination after surgery, the SFA value was significantly higher after surgery(143.61 ± 81.86 VS 90.87 ± 71.93, P < 0.001), and the MFI value decreased accordingly(0.57 ± 0.36 VS 1.30 ± 1.35, P < 0.001). Multivariate Cox analysis indicated that high VFA and MFI values, smoking history, and preoperative biologic therapy were all risk factors for postoperative endoscopic recurrence(p < 0.05), while high MFI values and preoperative biologic therapy were also risk factors for anastomotic ulcers(p < 0.05). The Kaplan-Meier analysis showed that these factors increased the risk of reaching the endpoint with time(p < 0.05). The ROC curve results showed that MFI value had high diagnostic value for postoperative endoscopic recurrence [AUC:0.831, 95% CI: 0.75-0.91, p < 0.001] and anastomotic ulcers [AUC:0.801, 95% CI: 0.71-0.89, p < 0.001]. CONCLUSIONS: Surgical CD patients have significantly higher MFI values but the values decline after surgery. When the preoperative MFI value is > 0.82, the risk of postoperative endoscopic recurrence increases significantly, and when the MFI value is ≥ 1.10, the risk of anastomotic ulceration after surgery increases significantly. Meanwhile, biologic therapy preoperatively also is a high-risk factor for early postoperative endoscopic recurrence or anastomotic ulcers after intestinal resection surgery.