The promise and challenge of spatial omics in dissecting tumour microenvironment and the role of AI.

Growing evidence supports the critical role of tumour microenvironment (TME) in tumour progression, metastases, and treatment response. However, the in-situ interplay among various TME components, particularly between immune and tumour cells, are largely unknown, hindering our understanding of how tumour progresses and responds to treatment. While mainstream single-cell omics techniques allow deep, single-cell phenotyping, they lack crucial spatial information for in-situ cell-cell interaction analysis. On the other hand, tissue-based approaches such as hematoxylin and eosin and chromogenic immunohistochemistry staining can preserve the spatial information of TME components but are limited by their low-content staining. High-content spatial profiling technologies, termed spatial omics, have greatly advanced in the past decades to overcome these limitations. These technologies continue to emerge to include more molecular features (RNAs and/or proteins) and to enhance spatial resolution, opening new opportunities for discovering novel biological knowledge, biomarkers, and therapeutic targets. These advancements also spur the need for novel computational methods to mine useful TME insights from the increasing data complexity confounded by high molecular features and spatial resolution. In this review, we present state-of-the-art spatial omics technologies, their applications, major strengths, and limitations as well as the role of artificial intelligence (AI) in TME studies.

Assessment of the excretion of oxidative stress biomarkers and anabolic steroids based on sewage: A case study of college students and the general population.

The use of wastewater-based epidemiology to evaluate the health and lifestyle of the population is a novel research interest. However, studies concerning the excretion of endogenous metabolites due to oxidative stress and the consumption of anabolic steroids have rarely been involved. In this study, we compared the effects of events such as final examination and sports meeting on the levels of four oxidative stress biomarkers (8-isoPGF2α, HNE-MA, 8-OHdG, and HCY) and four prohibited anabolic steroids (Testosterone, Androstenedione, Boldenone, and Metandienone) in sewage, using university students and urban populations as studying target. It was found that the per capita mass load of the four oxidative stress biomarkers 8-isoPGF2α, HNE-MA, 8-OHdG, and HCY in the sewage of Guangzhou urban area and university town were 256.6 ± 76.1, 9.4 ± 3.8, 1.1 ± 0.5, and 0.9 ± 0.4 mg/d/1000, respectively. The mean mass load of 8-isoPGF2α was significantly higher than that before the COVID-19 pandemic (74.9 ± 29.6 mg/d/1000 people, P < 0.05). The per capita load levels of oxidative stress biomarkers were significantly higher (P < 0.05) during the 2022 exam week relative to the pre-exam period, indicating that the exams caused transient stress to students. The per capita mass load of androgenic steroids was 77.7 mg/d/1000 people. There was an increase in the per capita load level of androgenic steroids during the provincial sports meeting. In this study, we quantified the concentration of oxidative stress biomarkers and androgenic steroids in the sewage and better realized the application of WBE on the health level and lifestyle of the population during special events.

Knowledge graph of wastewater-based epidemiology development: A data-driven analysis based on research topics and trends.

Wastewater-based epidemiology (WBE) has contributed significantly to the monitoring of drug use and transmission of viruses that has been published in numerous research papers. In this paper, we used LitStraw, a self-developed text extraction tool, to extract, analyze, and construct knowledge graphs from nearly 900 related papers in PDF format collected in Web of Science from 2000 to 2021 to analyze the research hotspots and development trends of WBE. The results showed a growing number of WBE publications in multidisciplinary cross-collaboration, with more publications and close collaboration between the USA, Australia, China, and European countries. The keywords of illicit drugs and pharmaceuticals still maintain research hotness, but the specific research hotspots change significantly, among which the research hotspots of new psychoactive substances, biomarkers, and stability show an increasing trend. In addition, judging the spread of COVID-19 by the presence of SARS-CoV-2 RNA in sewage has become the focus since 2020. This work can show the development of WBE more clearly by constructing a knowledge graph and also provide new ideas for the paper mining analysis methods in different fields.

Epidemiological Characteristics of COVID-19 Outbreak in Yangzhou, China, 2021.

Objective: Epidemiological characteristics of COVID-19 outbreak in Yangzhou city caused by the highly contagious Delta variant strain of SARS-CoV-2 virus were investigated in this retrospective descriptive study to provide prevention and control guidelines for outbreaks in the future. Methods: All the epidemiological data used in this study were collected manually from the official website of the Yangzhou Municipal Health Committee from 28 July to 26 August 2021, and then were analyzed systematically and statistically in this study. Results: A total of 570 COVID-19 cases were reported during the short-term outbreak in Yangzhou City. The ages of infected individuals ranged from 1 to 90 years with the average age at 49.47 ± 22.69 years. As for gender distributions, the ratio of male- to-female patients was 1:1.36 (242:328). Geographic analysis showed that 377 patients (66.1%) were in Hanjiang District while 188 patients (33.0%) were in Guangling District. Clinical diagnosis showed that 175 people (30.7%) had mild symptoms, 385 people were in moderate conditions (67.5%), and 10 people were in severe situations (1.8%). Significant age differences were found among the three groups (P < 0.001). However, no significant difference was identified in terms of gender ratio (P > 0.05). Based on the transmission chain formed by 6 generations of infected persons with a clear transmission relationship, the age showed a gradually decreasing trend, while the median time of diagnosis in 2 adjacent generations was 3 days. In addition, the estimated basic reproduction number R 0 of the Delta variant was 3.3651 by the classical Susceptible, Infectious, and/or Recovered (SIR) model. Conclusion: The Delta variant of SARS-CoV-2 was highly infectious and has obvious clustering characteristics during the Yangzhou outbreak in China.

Traditional Uses, Phytochemistry, Pharmacology and Toxicology of Rhizoma phragmitis: A Narrative Review.

Rhizoma phragmitis is a common Chinese herbal medicine whose effects are defined as 'clearing heat and fire, promoting fluid production to quench thirst, eliminating irritability, stopping vomiting, and disinhibiting urine'. During the Novel Coronavirus epidemic in 2020, the Weijing Decoction and Wuye Lugen Decoction, with Rhizoma phragmitis as the main herbal component, were included in The Pneumonia Treatment Protocol for Novel Coronavirus Infection (Trial Version 5) due to remarkable antiviral effects. Modern pharmacological studies have shown that Rhizoma phragmitis has antiviral, antioxidative, anti-inflammatory, analgesic, and hypoglycemic functions, lowers blood lipids and protects the liver and kidney. This review aims to provide a systematic summary of the botany, traditional applications, phytochemistry, pharmacology and toxicology of Rhizoma phragmitis.

The Important Role of Volatile Components From a Traditional Chinese Medicine Dayuan-Yin Against the COVID-19 Pandemic.

Aromatic Chinese herbs have been used to prevent plagues since ancient times. Traditional Chinese medicine has unique advantages in the prevention and treatment of epidemic diseases. According to the traditional Chinese medicine treatment plan in the National COVID-19 Diagnosis and Treatment Plan (Trial Seventh Edition) of the National Health Commission, Chinese patent medicines or prescriptions rich in aromatic Chinese herbs are selected for prevention and treatment during the period of medical observation, clinical treatment, and recovery of confirmed COVID-19 patients. Some local health committees or traditional Chinese medicine administrations recommend a variety of other ways of using traditional aromatic Chinese herbs to prevent and cure COVID-19. These involve external fumigation, use of moxibustion, and wearing of sachet. The efficacy of aromatic Chinese herbs plays a decisive role in the prevention and treatment of COVID-19. The unique properties, chemical composition, and mechanism of action of aromatic Chinese herbs are worthy of extensive and in-depth experimental and clinical research. The findings are expected to provide a reference for follow-up treatment of novel coronavirus and the development of corresponding drugs. In 2003, Dayuan-Yin produced excellent results in the treatment of the SARS virus. Individually, 112 confirmed cases were administered this drug between January and April 2003, and more than 93.7% of the patients showed noticeable mitigation of the symptoms, as well as recovery. Dayuan-Yin also was selected as one of the nationally recommended prescriptions for the COVID-19. Based on the national recommendation of Dayuan-Yin prescription, this review discusses the role of volatile components in the prevention and treatment of COVID-19, and speculates the possible mechanism of action, so as to provide a basis for the prevention and treatment of COVID-19.

Targeting the catecholamine-cytokine axis to prevent SARS-CoV-2 cytokine storm syndrome (preprint)

The mortality of Coronavirus disease 2019 (COVID-19) appears to be driven by acute respiratory distress syndrome (ARDS) and a dysregulated immune response to SARS-CoV-2. Emerging evidence suggests that a subset of COVID-19 is characterized by the development of a cytokine storm syndrome (CSS), and interleukin (IL)-6 levels are predictors of COVID-19 severity and in-hospital mortality. Targeting hyper-inflammation in COVID-19 may be critical for reducing mortality. Catecholamines enhance inflammatory injury by augmenting the production of IL-6 and other cytokines through a self-amplifying feed-forward loop in immune cells that requires alpha-1 adrenergic receptor (1-AR) signaling. Prophylactic inhibition of catecholamine synthesis with the 1-AR antagonist prazosin reduced catecholamines and cytokine responses in mice, and resulted in markedly increased survival following various hyper-inflammatory stimuli. These findings offer a rationale for studying 1-AR antagonists in the prophylaxis of patients with COVID-19-CSS and ARDS. As high infection rates threaten to overwhelm hospital capacity during this pandemic, preventative approaches that ameliorate COVID-19 severity and reduce excessive mortality are desperately needed. We hypothesize that treatment with prazosin of individuals who test positive for SARS-CoV-2 could reduce catecholamine surges, secondary cytokine dysregulation, and mortality. To investigate a potential role for 1-AR antagonists in preventing poor outcomes in ARDS, we conducted a retrospective analysis of hospitalized patients diagnosed with ARDS. Using data from the Truven Health MarketScan Research Database (2010-2017), we identified 13,125 men (age 45-64) with ARDS, of whom 655 patients (5.0%) were prescribed 1-AR antagonists in the previous year. Applying logistic regression models, we found that patients with prior use of 1-AR antagonists had lower odds of invasive mechanical ventilation compared to non-users (adjusted OR=0.75, 95% CI 0.59-0.95, p=0.019). Perhaps more importantly, those patients had a ~36% lower incidence of both being ventilated and dying in the hospital (adjusted OR=0.59, 95% CI 0.34-0.95, p=0.042). By contrast, prior use of beta-adrenergic receptor ({beta}-AR) antagonists was not correlated with either outcome. We extended these analyses to patients admitted with pneumonia. Of 108,956 subjects in this cohort, 5,498 patients (5.0%) were taking 1-AR antagonist. Similar to ARDS, patients with pneumonia on 1-AR antagonists (but no {beta}-AR antagonists) had a lower odds of mechanical ventilation (adjusted OR=0.83, 95% CI 0.75-0.92, p<0.001) and of both being ventilated and dying in the hospital (adjusted OR=0.77, 95% CI 0.62-0.94, p=0.014) compared to non-users. Mirroring findings from pre-clinical models, these data support a clinical rationale to study 1-AR antagonists in the prevention of severe complications of pneumonia, ARDS, and COVID-19. Prospective, randomized clinical trials of alpha-1 receptor antagonists (e.g. prazosin) administered prior to the onset of severe symptoms are needed to assess their efficacy in preventing CSS and reducing mortality in COVID-19.