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Background Investigations of disease incidence, mortality, and disability-adjusted life years (DALYs) are valuable for facilitating preventive measures and health resource planning. We examined the tracheal, bronchus, and lung (TBL) cancer burdens worldwide according to sex, age, and social development index (SDI) at the global, regional, and national levels. Methods We assessed the TBL cancer burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories in the diagnostic period 1990–2017. The data of TBL cancer-related mortality and DALYs attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were calculated. Results Incident cases, deaths, and DALYs of TBL cancer increased worldwide (100.44%, 82.30%, and 61.27%, respectively). The age-standardized incidence rate (ASIR) was stable (EAPC = 0.02, 95% confidence interval [CI] − 0.03 to 0.08), but the age-standardized death (EAPC = − 0.34, 95%CI − 0.38 to − 0.3) and DALY rate decreased generally (EAPC = − 0.74, 95%CI − 0.8 to − 0.68). However, the change trend of ASIR and ASDR among sexes was on the contrary. China and the USA always had the highest incidence, mortality, and DALYs of TBL cancer. Significant positive correlations between ASRs and SDI were observed, especially among females. High (36.86%), high-middle (28.78%), and middle SDI quintiles (24.91%) carried the majority burden of TBL cancer. Tobacco remained the top cause of TBL cancer death and DALYs, followed by air pollution, the leading cause in the low-middle and low-SDI quintiles. Metabolic risk-related TBL cancer mortality and DALYs among females increased but was stable among males. The main ages of TBL cancer onset and death were > 50 years, and the DALYs concentrated in 50 − 69 years. Conclusions To significantly reduce the growing burden of TBL cancer, treatment resources need to be skewed according to factors such as risks and geography, especially for high-risk groups and high-burden areas. Asia had the greatest TBL cancer burden, followed by high-income North America. Tobacco remains the leading cause of death and DALYs, followed by air pollution. Effective prevention measures against tobacco and air pollution should be strengthened.

Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

Super-resolution microscopy is typically not applicable to in situ imaging through a narrow channel due to the requirement for complex optics. Although multimode fibres (MMFs) have emerged as a potential platform for cost-effective and precise endoscopic imaging, they suffer from extreme sensitivity to bending and other external conditions. Here we demonstrate imaging through a single thin MMF for in vivo light-field encoded imaging with subcellular resolution. We refer to the technique as spatial-frequency tracking adaptive beacon light-field-encoded (STABLE) endoscopy. Spatial-frequency beacon tracking provides up to 1 kHz disorder tracking frequency, thus ensuring stable imaging through long-haul MMFs under fibre bending and various operating conditions. The full-vector modulation and fluorescence emission difference are combined to enhance the imaging signal-to-noise ratio and achieve a subdiffraction resolution of 250 nm. We integrate STABLE in a white-light endoscope and demonstrate cross-scale imaging in a bronchus model and in vivo imaging in mice models. The high-resolution and resilience to observation in a minimally invasive manner paves the way to the expansion of MMF in endoscopy to the study of disease mechanisms in biomedical sciences and clinical studies.Spatial-frequency tracking adaptive beacon light-field encoded endoscopy enables imaging through a single multimode fibre under bending and twisting. In vivo imaging with subcellular resolution is demonstrated in mice models.

The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.During homeostasis TH1 cells activate a cell-intrinsic inflammatory shutdown program and shift to IL-10 production. Chauss et al. find that this TH1 homeostatic program is dependent on vitamin D signaling and is disrupted in severe COVID-19.

In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

Background and aims Cancer will soon become the leading cause of death in every country in the twenty-first century. This study aimed to analyze the mortality and morbidity of 29 types of cancer in 204 countries or regions from 1990 to 2019 to guide global cancer prevention and control. Methods Detailed information for 29 cancer groups was collected from the Global Burden of Disease Study in 2019. The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of the 29 cancer groups were calculated based on sex, age, region, and country. In addition, separate analyses were performed for major cancer types. Results In 2019, more than 10 million people died from cancer, which was approximately twice the number in 1990. Tracheal, bronchus, and lung (TBL) cancers collectively showed the highest death rate, and the ASDR of pancreatic cancer increased by 24%, which was cancer with the highest case fatality rate (CFR). The global cancer ASIR showed an increasing trend, with testicular cancer, thyroid cancer, and malignant skin melanoma showing a significant increase. The ASDR and ASIR of cancer in males were about 1.5 times higher than that in females. Individuals over 50 years had the highest risk of developing cancer, with incidences and deaths in this age group accounting for more than 85% of cancers in all age groups. Asia has the heaviest cancer burden due to its high population density, with esophageal cancer in this region accounting for 53% of the total fatalities related to this type of cancer in the world. In addition, the mortality and morbidity of most cancers increased with the increase in the development or socio-demographic index (SDI) in the SDI regions based on the World Bank's Human Development Index (HDI), with cancer characteristics varying in the different countries globally. Conclusions The global cancer burden continues to increase, with substantial mortality and morbidity differences among the different regions, ages, countries, gender, and cancer types. Effective and locally tailored cancer prevention and control measures are essential in reducing the global cancer burden in the future.

The emergence of SARS-CoV-2 variants of concern with progressively increased transmissibility between humans is a threat to global public health. The Omicron variant of SARS-CoV-2 also evades immunity from natural infection or vaccines 1 , but it is unclear whether its exceptional transmissibility is due to immune evasion or intrinsic virological properties. Here we compared the replication competence and cellular tropism of the wild-type virus and the D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) variants in ex vivo explant cultures of human bronchi and lungs. We also evaluated the dependence on TMPRSS2 and cathepsins for infection. We show that Omicron replicates faster than all other SARS-CoV-2 variants studied in the bronchi but less efficiently in the lung parenchyma. All variants of concern have similar cellular tropism compared to the wild type. Omicron is more dependent on cathepsins than the other variants of concern tested, suggesting that the Omicron variant enters cells through a different route compared with the other variants. The lower replication competence of Omicron in the human lungs may explain the reduced severity of Omicron that is now being reported in epidemiological studies, although determinants of severity are multifactorial. These findings provide important biological correlates to previous epidemiological observations. Omicron replicates faster than the wild-type, D614G, Alpha, Beta and Delta SARS-CoV-2 variants in the bronchi but less efficiently in the lung parenchyma.

Respiratory immune characteristics associated with Coronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8 + T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19. Single-cell transcriptome and T cell receptor analysis of bronchoalveolar lavage fluid suggests enrichment of proinflammatory macrophages in patients with severe COVID-19 and the presence of clonally expanded CD8 + T cells in patients with moderate COVID-19.