We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome-related coronaviruses from ...horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.
It is well‐known that ground‐level ozone is not just a local or regional air quality problem; emission sources from super‐regional (sources outside the PRD region) scales are known to contribute ...significantly to local ozone concentrations. However, source apportionment studies differentiating the relative contributions of local, regional, and super‐regional ozone precursors are still limited. In this paper, using the Pearl River Delta (PRD) as an example, we have conducted a detailed apportionment (by source categories and by source regions) study of surface ozone using photochemical model source apportionment tools. Our results show that, while the super‐regional contribution is dominant under mean ozone conditions, elevated local and regional sources are the causative factor for the formation of high ozone episodes. In particular, the local and PRD regional contributions increase from about 30% during non‐episode days to about 50% during high ozone episode days in the autumn (November 2006) and even up to about 70% during high ozone episodes in the summer (July 2006). These results suggest that local and regional controls of ozone precursors are still very important for ozone reduction, particularly for episodic events. Furthermore, our results show that mobile emission is by far the highest contributing source category to ozone levels in the PRD for episodic ozone events. Moreover, we find substantial seasonal variations in the way ozone precursors from neighboring areas affect ozone levels in any particular city, suggesting that regional collaborations are important for developing effective long‐term strategies to reduce ozone over the PRD region.
Key Points
Super‐regional contribution is dominant during non‐episode days
Local and regional sources become larger and are the main cause of ozone episodes
Mobile source is the dominant source category for ozone formation in the PRD
Severe acute respiratory syndrome coronavirus 2 did not replicate efficiently in 13 bat cell lines, whereas severe acute respiratory syndrome coronavirus replicated efficiently in kidney cells of its ...ancestral host, the Rhinolophus sinicus bat, suggesting different evolutionary origins. Structural modeling showed that RBD/RsACE2 binding may contribute to the differential cellular tropism.
Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of ...glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 SD years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 IQR: 1-9 years; mean HbA1c 7.4% ± 1.7%; mean body mass index BMI 25.3 ± 4.0 kg/m.sup.2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c greater than or equal to8.5% while on greater than or equal to2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval CI 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio HR: 1.07 95% CI 1.03-1.12 per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 95% CI 1.06-1.46 per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta SE = 0.312 0.057 per SD; P = 5.84 x 10.sup.-8) but not glycemic progression (HR: 1.01 95% CI 0.96-1.05 per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.
Background: Endothelial dysfunction is one of the mechanisms linked to an increased risk of cardiovascular disease. Objective: We assessed the association between several diet-quality scores and ...plasma concentrations of markers of inflammation and endothelial dysfunction. Design: Diet-quality scores on the Healthy Eating Index (HEI), Alternate Healthy Eating Index (AHEI), Diet Quality Index Revised (DQI-R), Recommended Food Score (RFS), and the alternate Mediterranean Diet Index (aMED) were calculated by using a food-frequency questionnaire that was administered in 1990 to 690 women in the Nurses' Health Study (ages 43-69 y, no cardiovascular disease or diabetes). Blood collection was completed in the same year. We used regression analysis to assess the associations between these diet-quality scores and plasma concentrations of C-reactive protein, interleukin 6, E-selectin, soluble intercellular cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1. Results: The various diet-quality scores were significantly correlated with each other; correlation coefficients ranged from 0.56 to 0.80 (all P values < 0.0001). After adjustment for age, body mass index, alcohol intake, physical activity, smoking status, and energy intake, the HEI and DQI-R were not significantly associated with any of the biomarkers, whereas the AHEI and aMED scores were associated with significantly lower concentrations of most biomarkers. The RFS was significantly associated with a lower concentration of E-selectin only. C-reactive protein concentrations were 30% (P < 0.05) and 24% (P < 0.05) lower in the top than in the bottom quintile of the AHEI and of the aMED, respectively Conclusion: Higher AHEI and aMED scores were associated with lower concentrations of biomarkers of inflammation and endothelial dysfunction and therefore may be useful as guidelines for reducing the risk of diseases involving such biological pathways.
Baicalein (a) could reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA efflux pump in vitro (b). The inhibition of MRSA PK (c) by baicalein could lead to a deficiency of ATP ...which might further contribute to the antibacterial actions of baicalein against MRSA.
Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness of β-lactam antibiotics and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA). With multiple therapeutic benefits, the antibacterial actions of baicalein may also be involved in overcoming other bacterial resistance mechanisms. The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms.
A panel of clinical MRSA strains was used for further confirmation of the antibacterial activities of baicalein. The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined.
In the checkerboard dilution test and time-kill assay, baicalein at 16μg/ml could synergistically restore the antibacterial actions of ciprofloxacin against the NorA efflux pump overexpressed SA-1199B, but not with the poor NorA substrate, pefloxacin. Moreover, synergistic effects were observed when baicalein was combined with ciprofloxacin against 12 out of 20 clinical ciprofloxacin resistant strains. For MRSA PK studies, baicalein alone could inhibit the enzymatic activity of MRSA PK in a dose-dependent manner.
Our results demonstrated that baicalein could significantly reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA efflux pump in vitro. The inhibition of MRSA PK by baicalein could lead to a deficiency of ATP which might further contribute to the antibacterial actions of baicalein against MRSA.
Kaposiform haemangioendothelioma (KHE) is a rare childhood disease classified by the International Society for the Study of Vascular Anomalies (ISSVA) as a locally aggressive vascular tumor. It has ...been reported to affect any site, with a predilection for the extremities and trunk. Although it typically manifests as an enlarging cutaneous or soft tissue lesion, less than 10% of cases have no skin involvement, with the retroperitoneum being the most frequently involved extracutaneous site. Approximately twenty cases of KHE with bony involvement have been reported in the literature to date, with only five of those cases involving the spine specifically.
We present a, rare case of KHE who presented with progressive fixed hyperlordotic deformity, multiple non-specific spinal lesions, and abnormal blood tests, posing a clinical and radiological diagnostic challenge. Additionally, we conducted a thorough review of the literature to compare and contrast the various multimodality imaging manifestations of KHE involving the spine.
With the rising food demands from the future world population, more intense agricultural activities are expected to cause substantial perturbations to the global nitrogen cycle, aggravating surface ...air pollution and imposing stress on terrestrial ecosystems. Much less studied, however, is how the terrestrial ecosystem changes induced by agricultural nitrogen deposition may modify biosphere–atmosphere exchange and further exert secondary feedback effects on global air quality. Here we examined the responses of surface ozone air quality to terrestrial ecosystem changes caused by year 2000 to year 2050 changes in agricultural ammonia emissions and the subsequent nitrogen deposition by asynchronously coupling between the land and atmosphere components within the Community Earth System Model framework. We found that global gross primary production is enhanced by 2.1 Pg C yr−1, following a 20 % (20 Tg N yr−1) increase in global nitrogen deposition by the end of the year 2050 in response to rising agricultural ammonia emissions. Leaf area index was simulated to be higher by up to 0.3–0.4 m2 m−2 over most tropical grasslands
and croplands and 0.1–0.2 m2 m−2 across boreal and temperate
forests at midlatitudes. Around 0.1–0.4 m increases in canopy height were
found in boreal and temperate forests, and there were ∼0.1 m increases in tropical grasslands and croplands. We found that these vegetation changes could lead to surface ozone changes by ∼0.5 ppbv (part per billion by volume) when prescribed meteorology was used (i.e., large-scale meteorological responses to terrestrial changes were not allowed), while surface ozone could typically be modified by 2–3 ppbv when meteorology was dynamically simulated in response to vegetation changes. Rising soil NOx emissions, from 7.9 to 8.7 Tg N yr−1, could enhance surface ozone by 2–3 ppbv with both prescribed and dynamic meteorology. We, thus, conclude that, following enhanced nitrogen deposition, the modification of the meteorological environment induced by vegetation changes and soil biogeochemical changes are the more important pathways that can modulate future ozone pollution, representing a novel linkage between agricultural activities and ozone air quality.
Shortly after its emergence in southern China in 2002/2003, Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) was confirmed to be the cause of SARS. Subsequently, SARS-related CoVs ...(SARSr-CoVs) were found in palm civets from live animal markets in Guangdong and in various horseshoe bat species, which were believed to be the ultimate reservoir of SARSr-CoV. Till November 2018, 339 SARSr-CoV genomes have been sequenced, including 274 from human, 18 from civets and 47 from bats mostly from Chinese horseshoe bats (Rhinolophus sinicus), n = 30; and greater horseshoe bats (Rhinolophus ferrumequinum), n = 9. The human SARS-CoVs and civet SARSr-CoVs were collected in 2003/2004, while bat SARSr-CoVs were continuously isolated in the past 13 years even after the cessation of the SARS epidemic. SARSr-CoVs belong to the subgenus Sarbecovirus (previously lineage B) of genus Betacoronavirus and occupy a unique phylogenetic position. Overall, it is observed that the SARSr-CoV genomes from bats in Yunnan province of China possess the highest nucleotide identity to those from civets. It is evident from both multiple alignment and phylogenetic analyses that some genes of a particular SARSr-CoV from bats may possess higher while other genes possess much lower nucleotide identity to the corresponding genes of SARSr-CoV from human/civets, resulting in the shift of phylogenetic position in different phylogenetic trees. Our current model on the origin of SARS is that the human SARS-CoV that caused the epidemic in 2002/2003 was probably a result of multiple recombination events from a number of SARSr-CoV ancestors in different horseshoe bat species.
•313 SARSr-CoV genomes have been sequenced (274 from human, 18 civets and 47 bats).•SARSr-CoV genomes of bats in Yunnan possess highest nt identity to those from civets.•The origin of human SARS-CoV was probably a result of multiple recombination events.•Recombination from a number of SARSr-CoV ancestors in different horseshoe bat species.
Gut microbiota is believed to be a major determinant of health outcomes. We hypothesised that a novel oral microbiome formula (SIM01) can reduce the risk of adverse health outcomes in at-risk ...subjects during the coronavirus disease 2019 (COVID-19) pandemic. In this single-centre, double-blind, randomised, placebo-controlled trial, we recruited subjects aged ≥65 years or with type two diabetes mellitus. Eligible subjects were randomised in a 1:1 ratio to receive three months of SIM01 or placebo (vitamin C) within one week of the first COVID-19 vaccine dose. Both the researchers and participants were blinded to the groups allocated. The rate of adverse health outcomes was significantly lower in the SIM01 group than the placebo at one month (6 2.9% vs. 25 12.6,
< 0.001) and three months (0 vs. 5 3.1%,
= 0.025). At three months, more subjects who received SIM01 than the placebo reported better sleep quality (53 41.4% vs. 22 19.3%,
< 0.001), improved skin condition (18 14.1% vs. 8 7.0%,
= 0.043), and better mood (27 21.2% vs. 13 11.4%,
= 0.043). Subjects who received SIM01 showed a significant increase in beneficial Bifidobacteria and butyrate-producing bacteria in faecal samples and strengthened the microbial ecology network. SIM01 reduced adverse health outcomes and restored gut dysbiosis in elderly and diabetes patients during the COVID-19 pandemic.