Background
The impacts of chronic airway diseases on coronavirus disease 2019 (COVID‐19) are far from understood.
Objective
To explore the influence of asthma and chronic obstructive pulmonary ...disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID‐19 patients.
Methods
A total of 961 hospitalized COVID‐19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin‐converting enzyme II (ACE2) expression. BEAS‐2B cell line was stimulated with various cytokines.
Results
In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525‐360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461‐267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID‐19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF‐α, IL‐2 receptor, IL‐10, IL‐8, and IL‐6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL‐4 and IL‐13 downregulated, but TNF‐α, IL‐12, and IL‐17A upregulated ACE2 expression in BEAS‐2B cells.
Conclusion
Patients with asthma and COPD likely have different risk of severe COVID‐19, which may be associated with different ACE2 expression.
After adjusting for confounding factors, COVID‐19 patients with COPD have higher risks of developing severe illness and acute respiratory distress syndrome than COVID‐19 patients with asthma. COPD patients have increased, whereas asthmatics have decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL‐17A, TNF‐α, and IL‐12 promote, while IL‐4 and IL‐13 suppress ACE2 expression in airway BEAS‐2B cells. Abbreviations: ACE2, angiotensin‐converting enzyme II; ARDS, acute respiratory distress syndrome; BEAS‐2B, adenovirus‐12 SV40 hybrid virus transformed bronchial epithelial cells; COPD, chronic obstructive pulmonary disease; COVID‐19, coronavirus disease 2019.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We use an on-chip superconducting resonator as a sensitive meter to probe the properties of graphene double quantum dots at microwave frequencies. Specifically, we investigate the charge dephasing ...rates in a circuit quantum electrodynamics architecture. The dephasing rates strongly depend on the number of charges in the dots, and the variation has a period of four charges, over an extended range of charge numbers. Although the exact mechanism of this fourfold periodicity in dephasing rates is an open problem, our observations hint at the fourfold degeneracy expected in graphene from its spin and valley degrees of freedom.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Osteosarcoma is a quickly developing, malignant cancer of the bone, which is associated with a bad prognosis. In osteosarcoma, hypoxia promotes the malignant phenotype, which results in a cascade of ...immunosuppressive processes, poor prognosis, and a high risk of metastasis. Nonetheless, additional methodologies for the study of hyperoxia in the tumor microenvironment also need more analysis. We obtained 88 children patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and 53 children patients with RNA sequence and clinicopathological data from the Gene Expression Omnibus (GEO). We developed a four-gene signature related to hypoxia to reflect the immune microenvironment in osteosarcoma that predicts survival. A high-risk score indicated a poor prognosis and immunosuppressive microenvironment. The presence of the four-gene signature related to hypoxia was correlated with clinical and molecular features and was an important prognostic predictor for pediatric osteosarcoma patients. In summary, we established and validated a four-gene signature related to hypoxia to forecast recovery and presented an independent prognostic predictor representing overall immune response strength within the osteosarcoma microenvironment.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The construction of bifunctional highly active and durable electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is attractive and challenging for overall water ...splitting. Herein, we reported a Ni–Co phosphide @phosphate nanocages (NCPP NCs) catalyst prepared by phosphorization of Ni–Co layered double hydroxide (Ni–Co LDH) with in-situ formation of phosphate. The NCPP NCs exhibited an improved wettability with a contact angle of approximately 0° compared with those of Ni–Co LDH (52°) and nickel-cobalt phosphides (NiCoP) (99°). NCPP NCs have been used for enhancing the water-splitting efficiency, and it only required the overpotentials of 291 mV and 140 mV for OER and HER in 0.1 M KOH to achieve the current densities of 10 mA cm−2, respectively. Impressively, the overpotential of NCPP NCs decreased by 42 mV and 64 mV at 10 mA cm−2 for OER in comparison with those of RuO2 and NiCoP (without phosphate phase). Consequently, NCPP NCs, as the bifunctional catalysts, displayed an outstanding performance for the whole water-splitting process with a small potential of 1.60 V at 10 mA cm−2 and long-term stability. These performances enabled this material to be a promising catalyst for overall water electrolysis.
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•NCPP, as bifunctional catalysts, were prepared by phosphorization of Ni–Co LDH.•NCPP NCs exhibited excellent OER and HER performances.•NCPP NCs exhibited superior whole water-splitting activity and excellent cycling stability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their ...infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found.
From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses.
As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon.
The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A mild and efficient method for the photocatalytic radical cyclization of α-halo hydrazones with β-ketocarbonyls has been described. This strategy provides a potential protocol for the construction ...of functionalized 4,5-dihydropyrazoles in moderate to high yields.
Abstract
Background
The growing epidemics of severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne disease in East Asia, and its high case fatality rate have raised serious ...public health concerns.
Methods
Surveillance data on laboratory-confirmed SFTS cases in China were collected. The spatiotemporal dynamics and epidemiological features were explored. The socioeconomic and environmental drivers were identified for SFTS diffusion using survival analysis and for SFTS persistence using a two-stage generalized boosted regression tree model.
Results
During 2010‒2018, a total of 7721 laboratory-confirmed SFTS cases were reported in China, with an overall case fatality rate (CFR) of 10.5%. The average annual incidence increased >20 times and endemic areas expanded from 27 to 1574 townships, whereas the CFR declined from 19% to 10% during this period. Four geographical clusters—the Changbai Mountain area, the Jiaodong Peninsula, the Taishan Mountain area, and the Huaiyangshan Mountain area—were identified. Diffusion and persistence of the disease were both driven by elevation, high coverages of woods, crops, and shrubs, and the vicinity of habitats of migratory birds but had different meteorological drivers. Residents ≥60 years old in rural areas with crop fields and tea farms were at increased risk to SFTS.
Conclusions
Surveillance of SFTS and intervention programs need to be targeted at areas ecologically suitability for vector ticks and in the vicinity of migratory birds to curb the growing epidemic.
This retrospective study determined the spatiotemporal patterns of severe fever with thrombocytopenia syndrome (SFTS) and socioeconomic and environmental risk drivers for its diffusion and persistence, which bridges the knowledge gap in the epidemiology and ecology of the disease. The ecological model can be used to assess risks of STFS in countries where the disease or vector ticks are emerging to guide the planning of surveillance and controls.
Systemic lupus erythematosus (SLE) is a common autoimmune disease that impacts various organs. Lupus nephritis (LN) significantly contributes to death in children with SLE. Toll-like receptor (TLR) ...adaptor interacting with SLC15A4 on the lysosome (TASL) acts as an innate immune adaptor for TLR and is implicated in the pathogenesis of SLE. A transcription factor known as signal transducer and activator of transcription 3 (STAT3), which is known to be linked to autoimmune diseases, is also involved in the development of SLE.
Bioinformatics and real-time quantitative PCR (qRT-PCR) was used to detect the expression of STAT3 and TASL in peripheral blood of SLE patients and their correlation. Bioinformatics analysis, qRT-PCR, luciferase assay and chromatin immunoprecipitation (ChIP) were used to verify the regulation of transcription factor STAT3 on TASL. The expression levels of STAT3, TASL and apoptosis-related genes in LPS-induced HK2 cells were detected by qRT-PCR and Western blot. TUNEL staining were used to detect the apoptosis of HK2 cells after LPS stimulation. ELISA and qRT-PCR were used to detect the levels of inflammatory cytokines in the cell culture supernatant. TASL knockdown in HK2 cells was used to detect the changes in apoptosis-related genes and inflammatory factors. The expression level of TASL in LPS-stimulated HK2 cells and its effect on cell apoptosis and inflammatory factors were observed by knocking down and overexpressing STAT3, respectively. It was also verified in a rescue experiment.
The expressions of STAT3 and TASL were higher in SLE than in healthy children, and the expression of STAT3 was positively correlated with TASL. Transcription factor STAT3 can directly and positively regulate the expression of TASL through the promoter region binding site. The expression of STAT3, TASL and inflammatory cytokines was elevated, and the change of apoptosis was up-regulated in LPS-stimulated HK2 cells. Inhibition of STAT3 alleviates LPS-stimulated apoptosis and inflammatory response in HK2 cells through transcriptional regulation of TASL.
These findings provide new insights into the transcriptional regulation of TASL and provide new evidence of a direct regulatory relationship between signaling nodes in the lupus signaling network.
Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus ...on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection.
440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 ...spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed.
BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients.
BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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