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Since the first description of a coronavirus-related pneumonia outbreak in December 2019, the virus SARS-CoV-2 that causes the infection/disease (COVID-19) has evolved into a pandemic, and as of today, >100 million people globally in over 210 countries have been confirmed to have been infected and two million people have died of COVID-19. This brief review summarized what we have hitherto learned in the following areas: epidemiology, virology, and pathogenesis, diagnosis, use of artificial intelligence in assisting diagnosis, treatment, and vaccine development. As there are a number of parallel developments in each of these areas and some of the development and deployment were at unprecedented speed, we also provided some specific dates for certain development and milestones so that the readers can appreciate the timing of some of these critical events. Of note is the fact that there are diagnostics, antiviral drugs, and vaccines developed and approved by a regulatory within 1 year after the virus was discovered. As a number of developments were conducted in parallel, we also provided the specific dates of a number of critical events so that readers can appreciate the evolution of these research data and our understanding. The world is working together to combat this pandemic. This review also highlights the research and development directions in these areas that will evolve rapidly in the near future.

Background Significant improvement in survival outcome with the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has been shown in advanced non-small cell lung cancer (NSCLC) patients compared with chemotherapy. However, the full spectrum of toxic events of PD-1/PD-L1 inhibitors was not well characterized. We conducted a comprehensive meta-analysis to state the safety profile of PD-1/PD-L1 inhibitors in NSCLC, and identify the exact incidence and relative risk (RR) of both summary and detailed AEs. Materials and methods Electronic databases (PubMed, EMBASE and the Cochrane library databases) and major conference proceedings were systematically searched for all clinical trials in lung cancer using PD-1/PD-L1 inhibitors. Eligible studies included randomized controlled trials (RCTs) comparing PD-1/PD-L1 inhibitors with chemotherapy in NSCLC patients reporting all-grade (1–4) or high-grade (3–4) AEs [toxic symptoms, hematologic toxicities, and immune-related AEs (irAEs)], treatment discontinuation due to toxicities, or toxic deaths. The pooled incidence, RR, and corresponding 95% confidence interval (CI) of toxicity outcomes were calculated. Results A total of 4413 patients from 8 RCTs (3 with nivolumab; 2 with atezolizumab, and 3 with pembrolizuma) were included. In terms of summary toxic events, PD-1/PD-L1 inhibitors had a significantly lower risk of any all-grade AEs (66.20 vs. 86.08%; RR 0.77) and high-grade AEs (14.26 vs. 43.53%; RR 0.32), treatment discontinuation (5.94 vs. 13.92%; RR 0.44), and toxic deaths (0.48 vs. 1.12%; RR 0.45) than chemotherapy. With regard to detailed toxic events, the risk of toxic symptoms (including all-grade fatigue, nausea, constipation, diarrhea and peripheral sensory neuropathy; high-grade fatigue, anorexia, diarrhea and peripheral sensory neuropathy) and hematologic toxicities (including all-grade and high-grade neutropenia, thrombocytopenia, and anemia) from PD-1/PD-L1 inhibitors was significantly lower than from chemotherapy. However, there was a small but significantly increased risk of irAEs, including all-grade rash, pruritus, colitis, hypothyroidism, hyperthyroidism, ALT/AST elevations and pneumonitis, as well as high-grade pneumonitis. Conclusion PD-1/PD-L1 inhibitors are generally safer and better tolerated than chemotherapy for patients with NSCLC with regard to summary toxic events, detailed toxic symptoms and hematologic toxicities. However, PD-1/PD-L1 inhibitors can generate a unique spectrum of irAEs, and several of them can be severe and even life-threatening. Clinicians should be aware of the risk of these AEs, as they may have a potentially negative impact on the patients’ quality of life and survival outcome.

Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally into invasive adenocarcinoma. The cellular heterogeneity and molecular events underlying this stepwise progression remain unclear. In this study, we perform single-cell RNA sequencing of 268,471 cells collected from 25 patients in four histologic stages of LUAD and compare them to normal cell types. We detect a group of cells closely resembling alveolar type 2 cells (AT2) that emerged during atypical adenomatous hyperplasia and whose transcriptional profile began to diverge from that of AT2 cells as LUAD progressed, taking on feature characteristic of stem-like cells. We identify genes related to energy metabolism and ribosome synthesis that are upregulated in early stages of LUAD and may promote progression. MDK and TIMP1 could be potential biomarkers for understanding LUAD pathogenesis. Our work shed light on the underlying transcriptional signatures of distinct histologic stages of LUAD progression and our findings may facilitate early diagnosis. The origin and progression of lung adenocarcinoma (LUAD) are still poorly understood. Here, the authors analyse LUAD composition and progression in patient samples using single-cell RNA-seq and multiplex imaging, revealing a potential transcriptional divergence from alveolar type 2 cells.

Due to various human activities, soil quality under different land use patterns is deteriorating all over the world. This deterioration is very complex in the river irrigation area and is caused by multi-point and non-point source pollution and seasonal variation. Therefore, the characteristics and sources of soil metal pollution in river irrigation area of Baoji city were analyzed. The contents of 8 metals were given by ICP-MS, in the soil samples. Statistical methods, geo-accumulation index ( I geo ) and potential ecological risk index ( RI ) were conducted to evaluate the spatial distribution features, sources and ecological risks of metal contamination from the study area soil. Principal component analysis and cluster analysis were used to analyze the pollution sources of metal. The analysis showed that Cd is the most polluted, and human activities represented a great impact on the contents of Zn, Ni, Cu and Cd in soil, Cd post moderate-strong pollution and strong risk, Cd has a maximum Igeo value of 3.17. All rivers were at risk of moderate pollution levels in study . Among them, some rivers had even reached strong pollution level. Pollution caused by human activities was the most significant pollution source of metal in the research area soil.

Current studies showed that idiopathic pulmonary fibrosis (IPF) may lead to a poor prognosis of lung cancer. We conducted a meta-analysis to explore the impact of concomitant IPF in lung cancer and its prognostic value. We searched the databases of PubMed, Web of Science, Embase up to Feb 10th, 2021 for relevant researches and merged the hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate the association between concomitant IPF and overall survival (OS) in patients with lung cancer. Twelve studies involving 58424 patients were included in our meta-analysis. The results indicated that concomitant IPF was correlated with poor prognosis of lung cancer patients (HR = 1.99, 95%CI, 1.59-2.51). The association remained consistent after subgroup analysis and meta-regression stratified by study region, sample size, tumor histology, and therapy. In addition, our results were robust even after sensitivity analysis. Concomitant IPF may be a prognostic factor of lung cancer, which can lead to poor survival. However, further studies were necessary for evidence in clinical application.

Post-operative recurrence rates of stage I non-small cell lung cancer (NSCLC) range from 20% to 40%. Nonetheless, the molecular mechanisms underlying recurrence hitherto remain largely elusive. Here, we generate genomic, epigenomic and transcriptomic profiles of paired tumors and adjacent tissues from 122 stage I NSCLC patients, among which 57 patients develop recurrence after surgery during follow-up. Integrated analyses illustrate that the presence of predominantly solid or micropapillary histological subtypes, increased genomic instability, and APOBEC-related signature are associated with recurrence. Furthermore, TP53 missense mutation in DNA-binding domain could contribute to shorter time to recurrence. DNA hypomethylation is pronounced in recurrent NSCLC, and PRAME is the significantly hypomethylated and overexpressed gene in recurrent lung adenocarcinoma (LUAD). Mechanistically, hypomethylation at TEAD1 binding site facilitates the transcriptional activation of PRAME . Inhibition of PRAME restrains the tumor metastasis via downregulation of epithelial–mesenchymal transition-related genes. We also identify that enrichment of AT2 cells with higher copy number variation burden, exhausted CD8 + T cells and Macro_SPP1, along with the reduced interaction between AT2 and immune cells, is essential for the formation of ecosystem in recurrent LUAD. Finally, multi-omics clustering could stratify the NSCLC patients into 4 subclusters with varying recurrence risk and subcluster-specific therapeutic vulnerabilities. Collectively, this study constitutes a promising resource enabling insights into the biological mechanisms and clinical management for post-operative recurrence of stage I NSCLC. The molecular mechanisms underlying stage I non-small cell lung cancer (NSCLC) remain poorly understood. Here, the authors do multi-omics profiling of paired tumor and normal adjacent tissues from NSCLC patients, finding molecular processes and cell type proportions that are associated with recurrence.

A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell–cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (Mφ) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of Mφ was FABP4- Mφ in LUAD and SPP1- Mφ in LUSC. Importantly, we identified a novel lymphocyte-related Mφ cluster, which we named SELENOP- Mφ, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of Mφ clusters could help design personalized treatment for lung cancer patients in clinical practice.

Despite an increasing understanding of chronic obstructive pulmonary disease (COPD) pathogenesis, the mechanisms of diverse cell populations in the human lung remain unknown. Using single-cell RNA sequencing (scRNA-Seq), we can reveal changes within individual cell populations in COPD that are important for disease pathogenesis and characteristics. We performed scRNA-Seq on lung tissue obtained from donors with non-COPD and mild-to-moderate COPD to identify disease-related genes within different cell types. We testified the findings using qRT-PCR, immunohistochemistry, immunofluorescence and Western blotting from 25 additional subjects and RAW 264.7 macrophages. Targeting ferroptosis with the ferroptosis inhibitor ferrostatin-1, iron chelator deferoxamine or HO-1 inhibitor zinc protoporphyrin was administered in the experimental cigarette smoke COPD mouse model. We identified two populations of alveolar macrophages (AMs) in the human lung that were dysregulated in COPD patients. We discovered that M2-like AMs modulate susceptibility to ferroptosis by disrupting lipid and iron homeostasis both in vivo and in vitro. The discrepancy in sensitivity to ferroptosis can be determined and regulated by HO-1. In contrast, M1-like AMs showed the ability to attenuate oxidative stress and exert resistance to ferroptosis. In addition, the expression of genes within M2-like AMs is also involved in defects in phagocytosis and lysosome distortion. This ferroptotic phenotype was ameliorated by antiferroptotic compounds, iron chelators and HO-1 inhibitors. During COPD, the accumulation of lipid peroxidation drives ferroptosis-sensitive M2-like AMs, while M1-like AMs show characteristics of ferroptosis resistance. Ferroptotic M2 AMs lose their anti-inflammatory and repair functions but provoke inflammatory responses, resulting in consistent inflammation and tissue damage in the presence of M1 AMs in COPD. Appropriate interventions in ferroptosis can reduce the occurrence of infections and acute onset, and delay the COPD process.

The Guanzhong Basin in central China features a booming economy and has suffered severe drought, resulting in serious groundwater depletion in the last 30 years. As a major water resource, groundwater plays a significant role in water supply. The combined impact of climate change and intensive human activities has caused a substantial decline in groundwater recharge and groundwater levels, as well as degradation of groundwater quality and associated changes in the ecosystems. Based on observational data, an integrated approach was used to assess the impact of climate change and human activities on the groundwater system and the base flow of the river basin. Methods included: river runoff records and a multivariate statistical analysis of data including historical groundwater levels and climate; hydro-chemical investigation and trend analysis of the historical hydro-chemical data; wavelet analysis of climate data; and the base flow index. The analyses indicate a clear warming trend and a decreasing trend in rainfall since the 1960s, in addition to increased human activities since the 1970s. The reduction of groundwater recharge in the past 30 years has led to a continuous depletion of groundwater levels, complex changes of the hydro-chemical environment, localized salinization, and a strong decline of the base flow to the river. It is expected that the results will contribute to a more comprehensive management plan for groundwater and the related eco-environment in the face of growing pressures from intensive human activities superimposed on climate change in this region.

Abstract Background: The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population. Methods: The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted. Results: A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR = 1.61, 95% CI: 1.48–1.76, P <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5 years, ≥5 years, ≥10 years, ≥20 years, and ≥30 years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR = 1.25, P <0.001), endometrial (SIR = 1.40, P = 0.019), cervical (SIR = 2.56, P <0.001), and ovarian cancer (SIR = 1.50, P = 0.010). Conclusion: FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer. Registration: International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/