The bacterial and fungal profiles of patients hospitalized with non-COVID-19 lower respiratory tract infections in Wuhan, China, 2019-2021.

AIMS: A severe lockdown occurred in Wuhan during the COVID-19 pandemic, followed by a remission phase in the pandemic's aftermath. This study analyzed the bacterial and fungal profiles of respiratory pathogens in patients hospitalized with non-COVID-19 lower respiratory tract infections (LRTIs) during this period to determine the pathogen profile distributions in different age groups and hospital departments in Wuhan. METHODS AND RESULTS: We collected reports of pathogen testing in the medical records of patients hospitalized with non-COVID-19 LRTI between 2019 and 2021. These cases were tested for bacterial and fungal pathogens using 16S and internal transcribed spacer sequencing methods on bronchoalveolar lavage fluid samples. The study included 1368 cases. The bacteria most commonly identified were Streptococcus pneumoniae (12.50%) and Mycoplasma pneumoniae (8.33%). The most commonly identified fungi were Aspergillus fumigatus (2.49%) and Pneumocystis jirovecii (1.75%). Compared to 2019, the S. pneumoniae detection rates increased significantly in 2021, and those of M. pneumoniae decreased. Streptococcus pneumoniae was detected mainly in children. The detection rates of almost all fungi were greater in the respiratory Intensive Care Unit compared to respiratory medicine. Streptococcus pneumoniae and M. pneumoniae were detected more frequently in the pediatric department. CONCLUSIONS: Before and after the COVID-19 outbreak, a change in the common pathogen spectrum was detected in patients with non-COVID-19 in Wuhan, with the greatest change occurring among children. The major pathogens varied by the patient's age and the hospital department.

The etiological diagnostic value of metagenomic next-generation sequencing in suspected community-acquired pneumonia.

BACKGROUND: The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP. METHODS: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy. RESULTS: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy. CONCLUSIONS: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.

Estimating neighborhood-based mortality risk associated with air pollution: A prospective study.

Effect modification of integrated neighborhood environment on associations of air pollution with mortality remained unclear. We analyzed data from UK biobank prospective study (n = 421,650, median 12.5 years follow-up) to examine disparities of mortality risk associated with air pollution among varied neighborhood settings. Fine particulate matter (PM2.5), PM10 and nitrogen dioxide (NO2) were measured and assigned to each participants' address. Diverse ecological and societal settings of neighborhoods were integrated with principal component analysis and categorized into disadvantaged, intermediate and advantaged levels. We estimated mortality risk associated with air pollution across diverse neighborhoods using Cox regression. We calculated community-level proportions of mortality attributable to air pollutants. There was evidence of higher all-cause and respiratory disease mortality risk associated with PM2.5 and NO2 among those in disadvantaged neighborhoods. In disadvantaged communities, air pollutants explained larger proportions of deaths and such disparities persisted over past decades. Across 2010-2021, reducing PM2.5 and NO2 to 10 µg/m3 (World Health Organization limits) would save 87,000 (52,000-120,000) and 91,000 (37,000-145,000) deaths of populations aged ≥ 40 years, with 150 000 deaths occurred in disadvantaged neighborhood settings. These findings suggested that disadvantaged neighborhoods can exacerbate mortality risk associated with air pollution.

Some evidence supporting the use of optically pure R-(-)-diniconazole: Toxicokinetics and configuration conversion on chiral diniconazole.

Diniconazole is a chiral pesticide that exists in two enantiomers, R-(-)-diniconazole and S-(+)-diniconazole, with the R-enantiomer being much more active than the S-enantiomer. Previous enantioselective toxicology studies of diniconazole focused mostly on simple environmental model organisms. In this study, we evaluated the toxicokinetics of the two diniconazole enantiomers in rats and mice to provide a more comprehensive risk assessment. The two enantiomers displayed clear differences in their stereoselective contents in vivo. The t1/2 of R-(-)-diniconazole was 7.06 ± 3.35 h, whereas that of S-(+)-diniconazole was 9.14 ± 4.60 h, indicating that R-(-)-diniconazole was eliminated faster in vivo. The excretion rates of R-(-)-diniconazole and S-(+)-diniconazole were 4.08 ± 0.50 % and 2.68 ± 0.58 %, respectively, indicating more excretion of R-(-)-diniconazole. S-(+)-diniconazole had a higher bioavailability than R-(-)-diniconazole (52.19 % vs. 42.44 %). S-(+)-Diniconazole was also found in relatively high abundance in tissues such as the stomach, large intestine, small intestine, cecum, liver, kidney, brain, and testes, with the abundance being 1.71-2.48-fold that of R-(-)-diniconazole. The selective degradation of both enantiomers in the tissues and their mutual conversion in vivo were not observed, and this could indicate that configuration conversion did not contribute to the differences in the content of enantiomers in the tissues. Instead, such differences were mainly caused by the differences in affinity of each enantiomer for the tissues. Furthermore, investigation of the interconversion between optically pure R-(-)-diniconazole and S-(+)-diniconazole monomers in soil revealed no interconversion. All of the above results indicated no interconversion between R-(-)-diniconazole and S-(+)-diniconazole in vivo and in the soil, and that S-(+)-diniconazole tends to have a greater potential to accumulate in vivo. Thus, if only R-(-)-diniconazole is used as a pesticide, the negative impact on mammals and the environment will be reduced, suggesting that in agriculture, the application of optically pure R-(-)-diniconazole may be a better strategy.

Qualitative and quantitative analysis of major components of Qiye Shen'an tablet by UPLC Q-TOF/MS and UPLC-TQS-MS/MS.

The Qiye Shen'an tablet is formulated using total saponins extracted from Notoginseng stems and leaves. At present, the study on its chemical composition remains scarce and the quality control indicators are limited, which seriously hindering the effective quality control and clinical research. Hence, this study aims to comprehensively identify and characterize the Qiye Shen'an tablet while controlling its main component contents. To achieve a comprehensive understanding of this tablet, an ultra-high performance liquid coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) method was employed for its separation and characterization. Through the analysis of 99 batches of Qiye Shen'an tablet produced by 9 enterprises, the characteristic quantitative components were further obtained. A total of 113 compounds were characterized and identified, among which 17 representative compounds were selected, and the ultra-high performance liquid-triple quadrupole tandem mass spectrometry (UPLC-TQS-MS/MS) method was established for further quantitative determination. It has been successfully applied to the content determination of 99 batches of Qiye Shen'an tablet, and a new quality control method is being formed. This study provides a new method for chemical spectrum analysis and determination of labeled compounds of Qiye Shen'an tablet, and lays a solid foundation for further study of potential active ingredients and comprehensive quality evaluation.

The changing health effects of air pollution exposure for respiratory diseases: a multicity study during 2017-2022.

BACKGROUND: Multifaceted SARS-CoV-2 interventions have modified exposure to air pollution and dynamics of respiratory diseases. Identifying the most vulnerable individuals requires effort to build a complete picture of the dynamic health effects of air pollution exposure, accounting for disparities across population subgroups. METHODS: We use generalized additive model to assess the likely changes in the hospitalisation and mortality rate as a result of exposure to PM2.5 and O3 over the course of COVID-19 pandemic. We further disaggregate the population into detailed age categories and illustrate a shifting age profile of high-risk population groups. Additionally, we apply multivariable logistic regression to integrate demographic, socioeconomic and climatic characteristics with the pollution-related excess risk. RESULTS: Overall, a total of 1,051,893 hospital admissions and 34,954 mortality for respiratory disease are recorded. The findings demonstrate a transition in the association between air pollutants and hospitalisation rates over time. For every 10 µg/m3 increase of PM2.5, the rate of hospital admission increased by 0.2% (95% CI: 0.1-0.7%) and 1.4% (1.0-1.7%) in the pre-pandemic and dynamic zero-COVID stage, respectively. Conversely, O3-related hospitalization rate would be increased by 0.7% (0.5-0.9%) in the pre-pandemic stage but lowered to 1.7% (1.5-1.9%) in the dynamic zero-COVID stage. Further assessment indicates a shift of high-risk people from children and young adolescents to the old, primarily the elevated hospitalization rates among the old people in Lianyungang (RR: 1.53, 95%CI: 1.46, 1.60) and Nantong (RR: 1.65, 95%CI: 1.57, 1.72) relative to those for children and young adolescents. Over the course of our study period, people with underlying diseases would have 26.5% (22.8-30.3%) and 12.7% (10.8-14.6%) higher odds of having longer hospitalisation and over 6 times higher odds of deaths after hospitalisation. CONCLUSIONS: Our estimates provide the first comprehensive evidence on the dynamic pollution-health associations throughout the pandemic. The results suggest that age and underlying diseases collectively determines the disparities of pollution-related health effect across population subgroups, underscoring the urgency to identifying the most vulnerable individuals to air pollution.

Potato glycoside alkaloids exhibit antifungal activity by regulating the tricarboxylic acid cycle pathway of Fusarium solani.

Fusarium solani is a pathogenic fungus that causes significant harm, leading to crop yield reduction, fruit quality reduction, postharvest decay, and other diseases. This study used potato glycoside alkaloids (PGA) as inhibitors to investigate their effects on the mitochondrial structure and tricarboxylic acid (TCA) cycle pathway of F. solani. The results showed that PGA could inhibit the colony growth of F. solani (54.49%), resulting in the disappearance of the mitochondrial membrane and the loss of contents. PGA significantly decreased the activities of aconitase (ACO), isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH), fumarase (FH), malate dehydrogenase (MDH), succinyl-CoA synthetase (SCS), and increased the activity of citrate synthase (CS) in F. solani. After PGA treatment, the contents of acetyl coenzyme A (CoA), citric acid (CA), malic acid (L-MA), and α-ketoglutaric acid (α-KG) in F. solani were significantly decreased. The contents of isocitric acid (ICA), succinyl coenzyme A (S-CoA), succinic acid (SA), fumaric acid (FA), and oxaloacetic acid (OA) were significantly increased. Transcriptomic analysis showed that PGA could significantly affect the expression levels of 19 genes related to TCA cycle in F. solani. RT-qPCR results showed that the expression levels of ACO, IDH, α-KGDH, and MDH-related genes were significantly down-regulated, and the expression levels of SDH and FH-related genes were significantly up-regulated, which was consistent with the results of transcriptomics. In summary, PGA can achieve antifungal effects by reducing the tricarboxylic acid cycle's flow and regulating key genes' expression levels. This study reveals the antifungal mechanism of PGA from the perspective of TCA cycle, and provides a theoretical basis for the development and application of PGA as a biopesticide.

The Cambrian microfossil Qingjiangonema reveals the co-evolution of sulfate-reducing bacteria and the oxygenation of Earth's surface.

Sulfate reduction is an essential metabolism that maintains biogeochemical cycles in marine and terrestrial ecosystems. Sulfate reducers are exclusively prokaryotic, phylogenetically diverse, and may have evolved early in Earth's history. However, their origin is elusive and unequivocal fossils are lacking. Here we report a new microfossil, Qingjiangonema cambria, from ∼518-million-year-old black shales that yield the Qingjiang biota. Qingjiangonema is a long filamentous form comprising hundreds of cells filled by equimorphic and equidimensional pyrite microcrystals with a light sulfur isotope composition. Multiple lines of evidence indicate Qingjiangonema was a sulfate-reducing bacterium that exhibits similar patterns of cell organization to filamentous forms within the phylum Desulfobacterota, including the sulfate-reducing Desulfonema and sulfide-oxidizing cable bacteria. Phylogenomic analyses confirm separate, independent origins of multicellularity in Desulfonema and in cable bacteria. Molecular clock analyses infer that the Desulfobacterota, which encompass a majority of sulfate-reducing taxa, diverged ∼2.41 billion years ago during the Paleoproterozoic Great Oxygenation Event, while cable bacteria diverged ∼0.56 billion years ago during or immediately after the Neoproterozoic Oxygenation Event. Taken together, we interpret Qingjiangonema as a multicellular sulfate-reducing microfossil and propose that cable bacteria evolved from a multicellular filamentous sulfate-reducing ancestor. We infer that the diversification of the Desulfobacterota and the origin of cable bacteria may have been responses to oxygenation events in Earth's history.

Astragalus polysaccharide alleviates polycystic ovary syndrome by reducing insulin resistance and oxidative stress and increasing the diversity of gut microbiota.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, which is frequently accompanied by insulin resistance, oxidative stress (OS), and dyslipidemia. Astragalus polysaccharide (APS)-as a water-soluble heteropolysaccharide-can lower blood sugar and lipid and exert anti-aging effects and thus has been proven to be beneficial to various types of metabolic diseases. However, specific mechanisms of the action of APS on PCOS are yet to be studied. METHODS: Herein, BALB/C female mice aged 3 weeks were randomly divided into three groups (10 mice/group): oil + PBS group, DHEA + PBS group, and DHEA + APS group. Changes in the estrous cycle, ovarian tissue sections, serum levels of the hormone, blood glucose, blood lipid, and OS were studied. The intestinal microbiome was sequenced and Spearman correlation analysis was used to analyze the correlation between serum metabolic indexes and microflora. RESULTS: The results revealed that APS treatment ameliorated insulin resistance, OS, and dyslipidemia in PCOS mice. The results of 16S rDNA sequencing indicated that there were significant differences in the composition and diversity of intestinal microorganisms between DHEA and APS treatments. Firmicutes, Lachnospiraceae, Bacilli, Lactobacillaceae, and Lachnospiraceae_NK4A13_group were abundant in the oil + PBS group. Bacteroidota and Muribaculaceae were enriched in the DHEA + PBS group, while Rikenellaceae, Odoribacter, and Marinifilaceae were enriched in the DHEA + APS group. Furthermore, Spearman correlation analysis showed that there were close interactions and correlations between intestinal bacteria and indicators of blood glucose, blood lipids, steroid hormones, and OS in PCOS mice. CONCLUSIONS: Overall, the study showed that APS improved PCOS in mice by correcting serum metabolic disorders and increasing microbiome diversity, which may provide insight into understanding the pathogenesis and be a beneficial intervention for PCOS.

The changing pattern of common respiratory viruses among children from 2018 to 2021 in Wuhan, China.

BACKGROUND: Acute respiratory infections in children are a global public health challenge. Owing to the coronavirus disease (COVID-19) pandemic, non-pharmaceutical interventions, including patient isolation, social distancing, hand washing, and mask wearing, have been widely implemented, impacting the transmission of common respiratory viruses. The aim of this study was to clarify the epidemiological features of respiratory viruses in children less than 14 years of age in Wuhan before and after COVID-19. METHODS: Respiratory specimens were collected from patients aged < 14 years at two hospitals in Wuhan, China, from January 2018 to December 2021. Seven respiratory viruses were identified using an immunofluorescence assay. Pathogen profiles and seasonality were analysed. RESULTS: The number of visits and virus detection rate decreased dramatically after February 2020. The respiratory virus detection rate peaked in January and December and decreased dramatically in February and August. The detection rate was lower in 2021 than in 2018 and 2019. Respiratory syncytial virus (RSV) was identified as the leading pathogen in children aged < 1 year and 1-4 years before and after the COVID-19 pandemic. In children aged 5-14 years, influenza virus was detected at the highest rate before, and RSV after, the COVID-19 pandemic. RSV was the most common virus in coinfections. CONCLUSIONS: This study revealed the epidemiological patterns of common respiratory viruses from 2018 to 2021. The spectrum of pathogens involved in paediatric respiratory infections had partly changed. Non-pharmaceutical interventions resulted in fewer opportunities for the spread of common viruses but also in an "immunity debt" that could have negative consequences when the pandemic is under control in Wuhan.

Effect of Potato Glycoside Alkaloids on Energy Metabolism of Fusarium solani.

Fusarium solani is one of the primary pathogens causing root rot of wolfberry. The aims of this study were to investigate the inhibitory effect of potato glycoside alkaloids (PGA) on F. solani and its energy metabolism. In this study, the effects of PGA treatment on the growth and development of F. solani were investigated and the changes in the glycolytic pathway (EMP), ATPase activity, mitochondrial complex activity, mitochondrial structure, and energy charge level were analyzed to elucidate the possible antifungal mechanism of PGA on F. solani. The results showed that PGA treatment inhibited the colony growth, biomass, and spore germination of F. solani. PGA treatment reduced the glucose content and Hexokinase (HK) activity of F. solani, but increased the activity of Fructose-6-Phosphate Kinase (PFK) and Pyruvate Kinase (PK) and promoted the accumulation of pyruvic acid. In addition, PGA treatment inhibited the activities of H+-ATPase, Ca2+-ATPase, and mitochondrial complex IV, increased the mitochondrial inner membrane Ca2+ content and mitochondrial membrane permeability transition pore, and decreased the contents of ATP, ADP, and AMP as well as the energy charge. These results indicate that PGA treatment inhibits the growth and development of F. solani, activates the glycolysis pathway, inhibits ATPase activity and mitochondrial complex activity, and destroys the structure and function of mitochondrial membrane, resulting in a lower energy charge level.

Tunable, Wide-Temperature, and Macroscale Superlubricity Enabled by Nanoscale Van Der Waals Heterojunction-to-Homojunction Transformation.

Achieving macroscale superlubricity of van der Waals (vdW) nanopowders is particularly challenging, due to the difficulty in forming ordered junctions before friction and the friction-induced complex contact restructuration among multiple nanometer-sized junctions. Here, a facile way is reported to achieve vdW nanopowder-to-heterojunction conversion by graphene edge-oxygen (GEO) incorporation. The GEO effectively weakens the out-of-plane edge-edge and in-plane plane-edge states of the vdW nanopowder, leading to a coexistent structure of nanoscale homojunctions and heterojunctions on the grinding balls. When sliding on diamond-like carbon surfaces, the ball-supported structure governs macroscale superlubricity by heterojunction-to-homojunction transformation among the countless nanoscale junctions. Furthermore, the transformation guides the tunable design of superlubricity, achieving superlubricity (µ ≈ 0.005) at wide ranges of load, velocity, and temperature (-200 to 300 °C). Atomistic simulations reveal the GEO-enhanced conversion of vdW nanopowder to heterojunctions and demonstrate the heterojunction-to-homojunction transformation superlubricity mechanism. The findings are of significance for the macroscopic scale-up and engineering application of structural superlubricity.

Associations between ecological diversity and rodent plague circulation in Yunnan Province, China, 1983-2020: A data-informed modelling study.

BACKGROUND: Following its resurgence in 1982, rodent plague has been linked to a wide range of circulation risks in Yunnan Province. The most serious public health concern associated with effective plague control is determining how various ecological variables influence the differential risk of transmission. METHODS: We investigated the population dynamics of the hosts and vectors using large-scale epidemiological surveillance data. In a seasonal eco-epidemiological model, we evaluated the impact of ecological conditions on the vectored flea index (VFI) to determine the rate of plague transmission. RESULTS: The findings revealed a changing species composition in natural foci over time. Additionally, shifting distributional ranges of species by elevation may be vital in modulating the VFI. The model estimates indicate that the dynamic VFI contributes to spatiotemporal variance in transmission. CONCLUSIONS: The VFI could be a critical ecological indicator, allowing for real-time tracking and prompt intervention in the circulation of rodent plague. Understanding eco-epidemiological diversity can provide essential insights into effective responses to future plague resurgence.

Global age-structured spatial modeling for emerging infectious diseases like COVID-19.

Modeling the global dynamics of emerging infectious diseases (EIDs) like COVID-19 can provide important guidance in the preparation and mitigation of pandemic threats. While age-structured transmission models are widely used to simulate the evolution of EIDs, most of these studies focus on the analysis of specific countries and fail to characterize the spatial spread of EIDs across the world. Here, we developed a global pandemic simulator that integrates age-structured disease transmission models across 3,157 cities and explored its usage under several scenarios. We found that without mitigations, EIDs like COVID-19 are highly likely to cause profound global impacts. For pandemics seeded in most cities, the impacts are equally severe by the end of the first year. The result highlights the urgent need for strengthening global infectious disease monitoring capacity to provide early warnings of future outbreaks. Additionally, we found that the global mitigation efforts could be easily hampered if developed countries or countries near the seed origin take no control. The result indicates that successful pandemic mitigations require collective efforts across countries. The role of developed countries is vitally important as their passive responses may significantly impact other countries.

Cross-regional analysis of the association between human mobility and COVID-19 infection in Southeast Asia during the transitional period of "living with COVID-19".

BACKGROUND: In response to COVID-19, Southeast Asian (SEA) countries had imposed stringent lockdowns and restrictions to mitigate the pandemic ever since 2019. Because of a gradually boosting vaccination rate along with a strong demand for economic recovery, many governments have shifted the intervention strategy from restrictions to "Living with COVID-19" where people gradually resumed their normal activities since the second half of the year 2021. Noticeably, timelines for enacting the loosened strategy varied across Southeast Asian countries, which resulted in different patterns of human mobility across space and time. This thus presents an opportunity to study the relationship between mobility and the number of infection cases across regions, which could provide support for ongoing interventions in terms of effectiveness. OBJECTIVE: This study aimed to investigate the association between human mobility and COVID-19 infections across space and time during the transition period of shifting strategies from restrictions to normal living in Southeast Asia. Our research results have significant implications for evidence-based policymaking at the present of the COVID-19 pandemic and other public health issues. METHODS: We aggregated weekly average human mobility data derived from the Facebook origin and destination Movement dataset. and weekly average new cases of COVID-19 at the district level from 01-Jun-2021 to 26-Dec-2021 (a total of 30 weeks). We mapped the spatiotemporal dynamics of human mobility and COVID-19 cases across countries in SEA. We further adopted the Geographically and Temporally Weighted Regression model to identify the spatiotemporal variations of the association between human mobility and COVID-19 infections over 30 weeks. Our model also controls for socioeconomic status, vaccination, and stringency of intervention to better identify the impact of human mobility on COVID-19 spread. RESULTS: The percentage of districts that presented a statistically significant association between human mobility and COVID-19 infections generally decreased from 96.15% in week 1 to 90.38% in week 30, indicating a gradual disconnection between human mobility and COVID-19 spread. Over the study period, the average coefficients in 7 SEA countries increased, decreased, and finally kept stable. The association between human mobility and COVID-19 spread also presents spatial heterogeneity where higher coefficients were mainly concentrated in districts of Indonesia from week 1 to week 10 (ranging from 0.336 to 0.826), while lower coefficients were mainly located in districts of Vietnam (ranging from 0.044 to 0.130). From week 10 to week 25, higher coefficients were mainly observed in Singapore, Malaysia, Brunei, north Indonesia, and several districts of the Philippines. Despite the association showing a general weakening trend over time, significant positive coefficients were observed in Singapore, Malaysia, western Indonesia, and the Philippines, with the relatively highest coefficients observed in the Philippines in week 30 (ranging from 0.101 to 0.139). CONCLUSIONS: The loosening interventions in response to COVID-19 in SEA countries during the second half of 2021 led to diverse changes in human mobility over time, which may result in the COVID-19 infection dynamics. This study investigated the association between mobility and infections at the regional level during the special transitional period. Our study has important implications for public policy interventions, especially at the later stage of a public health crisis.

Supply chains create global benefits from improved vaccine accessibility.

Ensuring a more equitable distribution of vaccines worldwide is an effective strategy to control global pandemics and support economic recovery. We analyze the socioeconomic effects - defined as health gains, lockdown-easing effect, and supply-chain rebuilding benefit - of a set of idealized COVID-19 vaccine distribution scenarios. We find that an equitable vaccine distribution across the world would increase global economic benefits by 11.7% ($950 billion per year), compared to a scenario focusing on vaccinating the entire population within vaccine-producing countries first and then distributing vaccines to non-vaccine-producing countries. With limited doses among low-income countries, prioritizing the elderly who are at high risk of dying, together with the key front-line workforce who are at high risk of exposure is projected to be economically beneficial (e.g., 0.9%~3.4% annual GDP in India). Our results reveal how equitable distributions would cascade more protection of vaccines to people and ways to improve vaccine equity and accessibility globally through international collaboration.

Role of immune cell infiltration and small molecule drugs in adhesive capsulitis: Novel exploration based on bioinformatics analyses.

Background: Adhesive capsulitis (AC) is a type of arthritis that causes shoulder joint pain, stiffness, and limited mobility. The pathogenesis of AC is still controversial. This study aims to explore the role of immune related factors in the occurrence and development of AC. Methods: The AC dataset was downloaded from Gene Expression Omnibus (GEO) data repository. Differentially expressed immune-related genes (DEIRGs) were obtained based on R package "DESeq2" and Immport database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to explore the functional correlation of DEIRGs. MCC method and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the hub genes. The immune cell infiltration in shoulder joint capsule between AC and control was evaluated by CIBERSORTx, and the relationship between hub genes and infiltrating immune cells was analyzed by Spearman's rank correlation. Finally, potential small molecule drugs for AC were screened by the Connectivity Map database (CMap) and further verified by molecular docking. Results: A total of 137 DEIRGs and eight significantly different types of infiltrating immune cells (M0 macrophages, M1 macrophages, regulatory T cells, Tfh cells, monocytes, activated NK cells, memory resting CD4+T cells and resting dendritic cells) were screened between AC and control tissues. MMP9, FOS, SOCS3, and EGF were identified as potential targets for AC. MMP9 was negatively correlated with memory resting CD4+T cells and activated NK cells, but positively correlated with M0 macrophages. SOCS3 was positively correlated with M1 macrophages. FOS was positively correlated with M1 macrophages. EGF was positively correlated with monocytes. Additionally, dactolisib (ranked first) was identified as a potential small-molecule drug for the targeted therapy of AC. Conclusions: This is the first study on immune cell infiltration analysis in AC, and these findings may provide a new idea for the diagnosis and treatment of AC.

How to avoid a local epidemic becoming a global pandemic.

Here, we combine international air travel passenger data with a standard epidemiological model of the initial 3 mo of the COVID-19 pandemic (January through March 2020; toward the end of which the entire world locked down). Using the information available during this initial phase of the pandemic, our model accurately describes the main features of the actual global development of the pandemic demonstrated by the high degree of coherence between the model and global data. The validated model allows for an exploration of alternative policy efficacies (reducing air travel and/or introducing different degrees of compulsory immigration quarantine upon arrival to a country) in delaying the global spread of SARS-CoV-2 and thus is suggestive of similar efficacy in anticipating the spread of future global disease outbreaks. We show that a lesson from the recent pandemic is that reducing air travel globally is more effective in reducing the global spread than adopting immigration quarantine. Reducing air travel out of a source country has the most important effect regarding the spreading of the disease to the rest of the world. Based upon our results, we propose a digital twin as a further developed tool to inform future pandemic decision-making to inform measures intended to control the spread of disease agents of potential future pandemics. We discuss the design criteria for such a digital twin model as well as the feasibility of obtaining access to the necessary online data on international air travel.

Hydrogen-Enhanced Catalytic Conversion of Amorphous Carbon to Graphene for Achieving Superlubricity.

The solid-state conversion of amorphous carbon into graphene is extremely difficult, but it can be achieved in the friction experiments that induce macroscale superlubricity. However, the underlying conversion mechanisms remain elusive. Here, the friction experiments with Cu nanoparticles and (non-hydrogen (H) or H) a-C in vacuum, show the H-induced conversion of mechanical to chemical wear, resulting in the a-C's tribosoftening and nanofragmentating that produce hydrocarbon nanoclusters or molecules. It is such exactly hydrocarbon species that yield graphene at hydrogen-rich a-C friction interface, through reaction of them with Cu nanoparticles. In comparison, graphene isn't formed at Cu/non-H a-C friction interface. Atomistic simulations reveal the hydrogen-enhanced tribochemical decomposition of a-C and demonstrate the energetically favorable graphitization transformation of hydrocarbons on Cu substrates. The findings are of importance to achieve solid-state transformation between different carbon allotropes and provide a good strategy to synthesize other graphitic encapsulated catalysts with doped elements.