Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Evaluating the effect of SARS-CoV-2 spike mutations with a linear doubly robust learner.

Driven by various mutations on the viral Spike protein, diverse variants of SARS-CoV-2 have emerged and prevailed repeatedly, significantly prolonging the pandemic. This phenomenon necessitates the identification of key Spike mutations for fitness enhancement. To address the need, this manuscript formulates a well-defined framework of causal inference methods for evaluating and identifying key Spike mutations to the viral fitness of SARS-CoV-2. In the context of large-scale genomes of SARS-CoV-2, it estimates the statistical contribution of mutations to viral fitness across lineages and therefore identifies important mutations. Further, identified key mutations are validated by computational methods to possess functional effects, including Spike stability, receptor-binding affinity, and potential for immune escape. Based on the effect score of each mutation, individual key fitness-enhancing mutations such as D614G and T478K are identified and studied. From individual mutations to protein domains, this paper recognizes key protein regions on the Spike protein, including the receptor-binding domain and the N-terminal domain. This research even makes further efforts to investigate viral fitness via mutational effect scores, allowing us to compute the fitness score of different SARS-CoV-2 strains and predict their transmission capacity based solely on their viral sequence. This prediction of viral fitness has been validated using BA.2.12.1, which is not used for regression training but well fits the prediction. To the best of our knowledge, this is the first research to apply causal inference models to mutational analysis on large-scale genomes of SARS-CoV-2. Our findings produce innovative and systematic insights into SARS-CoV-2 and promotes functional studies of its key mutations, serving as reliable guidance about mutations of interest.

Patients with advanced pancreatic and biliary cancer appear vulnerable to SARS-CoV-2 Omicron variant: An observational study during the COVID-19 outbreak in Shanghai.

Background: The COVID-19 pandemic has spread rapidly across the globe. Cancer patients have a higher risk of severe infections and associated mortality than the general population. However, the lethal effect of Omicron-variant affection on advanced pancreatic and biliary cancer patients is still not clear. Herein, we designed an observational study to shed light on the influence of the Omicron variant on this so-called "King of Cancer" and improve management of these patients with COVID-19 in the future. Methods: Omicron-infected patients with advanced pancreatic and biliary cancer were enrolled from 15 April to 31 May 2022. Four groups were set up in this study: Group 1, Omicron-infected cancer patients (N = 4); Group 2, non-infected cancer patients (N = 4); Group 3, infected non-cancer-afflicted subjects (N = 4); Group 4, non-infected non-cancer-afflicted subjects (N = 4). On Days 0, 7, and 14 after infection, the blood samples were collected dynamically from all subjects. The primary endpoints were disease severity and survival. Results: At the endpoint of this observational study, Patient Nos. 2, 3, and 4 died separately on Days 11, 25, and 13 after viral infection. All of them had advanced cancer, with a death rate of up to 75%. Group 1 presented an overall T-cell exhaustion status compared with other groups. Group 1 had obviously lower T-cell populations and higher B-cell percentages and CD4+T/CD8+T ratios (P <0.05). Time-course cytokine monitoring results showed that IL-1ß was significantly decreased in Group 1 (P <0.05) and generally kept at a low level without obvious fluctuation. IL-6 was markedly increased in infected cancer patients (P <0.01) but remained at a low level and had no apparent change during the whole infection process in non-cancer-afflicted subjects. Furthermore, several inflammatory parameter indexes indicated a tight association of Omicron infection with the disease course and prognosis of Omicron-infected cancer patients. Conclusions: Advanced pancreatic and biliary cancer patients with Omicron infection have severe symptoms and poor outcomes. More attention, protective measures, and routine healthcare services should be recommended to these vulnerable populations in clinical practice during the pandemic in the foreseeable future.

Mechanisms influencing the factors of urban built environments and coronavirus disease 2019 at macroscopic and microscopic scales: The role of cities

In late 2019, the coronavirus disease 2019 (COVID-19) pandemic soundlessly slinked in and swept the world, exerting a tremendous impact on lifestyles. This study investigated changes in the infection rates of COVID-19 and the urban built environment in 45 areas in Manhattan, New York, and the relationship between the factors of the urban built environment and COVID-19. COVID-19 was used as the outcome variable, which represents the situation under normal conditions vs. non-pharmacological intervention (NPI), to analyze the macroscopic (macro) and microscopic (micro) factors of the urban built environment. Computer vision was introduced to quantify the material space of urban places from street-level panoramic images of the urban streetscape. The study then extracted the microscopic factors of the urban built environment. The micro factors were composed of two parts. The first was the urban level, which was composed of urban buildings, Panoramic View Green View Index, roads, the sky, and buildings (walls). The second was the streets' green structure, which consisted of macrophanerophyte, bush, and grass. The macro factors comprised population density, traffic, and points of interest. This study analyzed correlations from multiple levels using linear regression models. It also effectively explored the relationship between the urban built environment and COVID-19 transmission and the mechanism of its influence from multiple perspectives.

Analysis of related factors of nucleic acid shedding in elderly patients infected with Omicron variant of SARS-CoV-2

Objective: To analyze the nucleic acid shedding time of Omicron variant of novel coronavirus in the elderly patients with non-severe infection, and to explore the related factors affecting the nucleic acid shedding time. Methods: A total of 104 elderly patients with non-severe COVID-19 were divided into early negative group (<10 days) and late negative group ( 10 d) by the nucleic acid shedding time. The population information, vaccination, previous diseases, blood biochemical and inflammatory indicators, nucleic acid ORFIab gene and N gene Ct values were collected and compared between the two groups. The Spearman rank correlation and multiple linear regression were conducted to explore the influencing factors of the nucleic acid shedding time. Results: The mean time of nucleic acid shedding of Omicron variant in the early negative group was 7.26: 1.54 d, compared with 12.96: 2.44 d in the late negative group. There were significant differences in age, the ratio of chronic heart failure, chronic pulmonary disease and booster vaccination for COVID-19 and the first nucleic acid Ct value between the two groups (P < 0.05). Spearman correlation analysis showed that the nucleic acid shedding time of Omicron was positively correlated with age, chronic heart failure and serum level of procalcitonin, but negatively correlated with the vaccination booster and the first tested nucleic acid Ct value. Multiple linear regression analysis showed that age, vaccination booster and the first tested nucleic acid Ct value were the independent influencing factors of the nucleic acid shedding time. Conclusions: Age, vaccination booster for COVID-19 and the first tested nucleic acid Ct value were the independent influencing factors of nucleic acid shedding in [the elderly non-severe patients infected by SARS-CoV-2 Omicron. Vaccination booster for COVID-19 in the elderly vulnerable groups can shorten the time of nucleic acid shedding.

Mechanisms influencing the factors of urban built environments and coronavirus disease 2019 at macroscopic and microscopic scales: The role of cities.

In late 2019, the coronavirus disease 2019 (COVID-19) pandemic soundlessly slinked in and swept the world, exerting a tremendous impact on lifestyles. This study investigated changes in the infection rates of COVID-19 and the urban built environment in 45 areas in Manhattan, New York, and the relationship between the factors of the urban built environment and COVID-19. COVID-19 was used as the outcome variable, which represents the situation under normal conditions vs. non-pharmacological intervention (NPI), to analyze the macroscopic (macro) and microscopic (micro) factors of the urban built environment. Computer vision was introduced to quantify the material space of urban places from street-level panoramic images of the urban streetscape. The study then extracted the microscopic factors of the urban built environment. The micro factors were composed of two parts. The first was the urban level, which was composed of urban buildings, Panoramic View Green View Index, roads, the sky, and buildings (walls). The second was the streets' green structure, which consisted of macrophanerophyte, bush, and grass. The macro factors comprised population density, traffic, and points of interest. This study analyzed correlations from multiple levels using linear regression models. It also effectively explored the relationship between the urban built environment and COVID-19 transmission and the mechanism of its influence from multiple perspectives.

Inactivated COVID-19 vaccine booster dose shortened the viral shedding time of patients infected with the Omicron variant BA.2.

OBJECTIVES: We assessed the effect of inactivated COVID-19 vaccine boosting immunization on the viral shedding time for patients infected with the Omicron variant BA.2. METHODS: We performed a real-world study by analyzing the outbreak data of patients infected with the COVID-19 Omicron variant BA.2 from March to May 2022 in Shanghai, China. Patients were categorized into three groups, including not fully vaccinated (zero and one dose), fully vaccinated (two doses), and booster-vaccinated (three doses). RESULTS: A total of 4443 patients infected with COVID-19 were included in the analysis. The proportion of viral shedding within 14 days in the three groups was 94.7%, 95.5%, and 96.7%, respectively (P <0.001). After adjusting for sex, age, underlying conditions, and clinical symptoms, the booster vaccination had a 29% increased possibility (hazard ratio: 1.29, 95% confidence interval: 1.18-1.41) of no detectable viral shedding within 14 days, whereas the fully vaccinated group had an 11% increased possibility of no detectable viral shedding (hazard ratio: 1.11, 95% confidence interval: 1.01-1.23). The effect of booster vaccination was more significant in males, the elderly, and people with underlying conditions or symptomatic infections. CONCLUSION: Our study confirmed that the booster vaccination could significantly shorten the viral shedding time of patients infected with the Omicron variant BA.2.

Prevalence and associated factors of depressive and anxiety symptoms among healthcare workers in the post-pandemic era of COVID-19 at a tertiary hospital in Shenzhen, China: A cross-sectional study.

Background: Healthcare workers were at high risk of psychological problems during the COVID-19 pandemic, but it remains not well-investigated in the post-pandemic era of COVID-19, with regular epidemic prevention and control embedded in burdened healthcare work. This study aimed to investigate the prevalence and potential risk factors of the symptoms of depression and anxiety among healthcare workers at a tertiary hospital in Shenzhen. Method: Our cross-sectional study was conducted among 21- to 64-year-old healthcare workers in December 2021 at a tertiary hospital in Shenzhen, using a simple random sampling strategy. A wide range of socio-demographic characteristics, individual information, and psychological condition of the subjects were extracted. Healthcare workers' psychological conditions were tested with the Center for Epidemiologic Studies Depression (CESD-10), General Anxiety Disorder (GAD-7), Insomnia Severity Index (ISI), Work-Family Conflict Scale (WFCS), 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and 17-item of Maslach's Burnout Inventory-Human Services Survey (MBI-HSS-17). Data were collected based on these questionnaires. Descriptive statistics were used to assess the difference between healthcare workers with depressive and anxiety symptoms among different groups. Hierarchical logistic regression analyses were conducted to investigate the association between focused variables and mental health outcomes. Results: A total of 245 healthcare workers were enrolled. The proportion of depressive symptoms, anxiety symptoms and their co-occurrence were 34.7, 59.6, and 33.1%, respectively. Logistic regression showed that for the three outcomes, no history of receiving psychological help and self-rated good or higher health were protective factors, whereas more severe insomnia and job burnout were risk factors. Junior or lower job title and higher psychological resilience were related to a lower prevalence of depressive symptoms, while relatively longer working hours and larger work-family conflict were positively associated with the anxiety symptoms. Psychological resilience was inversely associated with the co-occurrence of depressive and anxiety symptoms. Conclusions: Our study revealed a high proportion of psychological problems and proved that several similar factors which were significant during the pandemic were also associated with the symptoms of depression and anxiety among healthcare workers in the post-pandemic era of COVID-19. These results provide scientific evidence for psychological interventions for healthcare workers.

Therapeutic equine hyperimmune antibodies with high and broad-spectrum neutralizing activity protect rodents against SARS-CoV-2 infection.

The emergence of SARS-CoV-2 variants stresses the continued need for broad-spectrum therapeutic antibodies. Several therapeutic monoclonal antibodies or cocktails have been introduced for clinical use. However, unremitting emerging SARS-CoV-2 variants showed reduced neutralizing efficacy by vaccine induced polyclonal antibodies or therapeutic monoclonal antibodies. In our study, polyclonal antibodies and F(ab')2 fragments with strong affinity produced after equine immunization with RBD proteins produced strong affinity. Notably, specific equine IgG and F(ab')2 have broad and high neutralizing activity against parental virus, all SARS-CoV-2 variants of concern (VOCs), including B.1.1,7, B.1.351, B.1.617.2, P.1, B.1.1.529 and BA.2, and all variants of interest (VOIs) including B.1.429, P.2, B.1.525, P.3, B.1.526, B.1.617.1, C.37 and B.1.621. Although some variants weaken the neutralizing ability of equine IgG and F(ab')2 fragments, they still exhibited superior neutralization ability against mutants compared to some reported monoclonal antibodies. Furthermore, we tested the pre-exposure and post-exposure protective efficacy of the equine immunoglobulin IgG and F(ab')2 fragments in lethal mouse and susceptible golden hamster models. Equine immunoglobulin IgG and F(ab')2 fragments effectively neutralized SARS-CoV-2 in vitro, fully protected BALB/c mice from the lethal challenge, and reduced golden hamster's lung pathological change. Therefore, equine pAbs are an adequate, broad coverage, affordable and scalable potential clinical immunotherapy for COVID-19, particularly for SARS-CoV-2 VOCs or VOIs.

A bivalent subunit vaccine efficiently produced in Pichia pastoris against SARS-CoV-2 and emerging variants.

The emergence of severe acute respiratory syndrome coronavirus type II (SARS-CoV-2) variants have led to a decline in the protection of existing vaccines and antibodies, and there is an urgent need for a broad-spectrum vaccination strategy to reduce the pressure on the prevention and control of the pandemic. In this study, the receptor binding domain (RBD) of the SARS-CoV-2 Beta variant was successfully expressed through a glycoengineered yeast platform. To pursue a more broad-spectrum vaccination strategy, RBD-Beta and RBD-wild type were mixed at the ratio of 1:1 with Al(OH)3 and CpG double adjuvants for the immunization of BALB/c mice. This bivalent vaccine stimulated robust conjugated antibody titers and a broader spectrum of neutralizing antibody titers. These results suggested that a bivalent vaccine of RBD-Beta and RBD-wild type could be a possible broad-spectrum vaccination strategy.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration.

Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-[Formula: see text]1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-[Formula: see text]1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-[Formula: see text]1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-[Formula: see text]1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration.

Using time-dependent reproduction number to predict turning points of COVID-19 outbreak in Dalian, Liaoning province, China.

OBJECTIVES: To forecast the development trend of current outbreak in Dalian, mainly to predict turning points of COVID-19 outbreak in Dalian, Liaoning province, China, the results can be used to provide a scientific reference for timely adjustment of prevention and control strategies. METHODS: During the outbreak, Bayesian framework was used to calculated the time-dependent reproduction number ([Formula: see text]), and then above acquired [Formula: see text] and exponential trend equation were used to establish the prediction model, through the model, predict the [Formula: see text] value of following data and know when [Formula: see text] smaller than 1. RESULTS: From July 22 to August 5, 2020, and from March 14 to April 2, 2022, 92 and 632 confirmed cases and asymptomatic infected cases of COVID-19 were reported (324 males and 400 females) in Dalian. The R square for exponential trend equation were 0.982 and 0.980, respectively which fit the [Formula: see text] with illness onset between July 19 to July 28, 2020 and between March 5 to March 17, 2022. According to the result of prediction, under the current strength of prevention and control, the [Formula: see text] of COVID-19 will drop below 1 till August 2, 2020 and March 26, 2022, respectively in Dalian, one day earlier or later than the actual date. That is, the turning point of the COVID-19 outbreak in Dalian, Liaoning province, China will occur on August 2, 2020 and March 26, 2022. CONCLUSIONS: Using time-dependent reproduction number values to predict turning points of COVID-19 outbreak in Dalian, Liaoning province, China was effective and reliable on the whole, and the results can be used to establish a sensitive early warning mechanism to guide the timely adjustment of COVID-19 prevention and control strategies.

Lipid carriers for mRNA delivery

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

Empirical Study on Design Trend of Taiwan (1960s–2020): The Evolution of Theme, Diversity and Sustainability

With significance in improving and developing local design culture as well as in supplementing global design history, this essay describes a study on the past and a clear prediction of the future by exploring Taiwan’s design history from approximately the 1960s to 2020 based on the evolution of theme, diversity, and sustainability. In this research, the Python programming language is used to apply three algorithms of term frequency–inverse document frequency (TF-IDF), Simpson’s diversity index (SDI), and latent Dirichlet allocation (LDA) to conduct a text exploration of design journals. The results show the following: in the 1960s–1980s, the evolution of theme focused on evaluation strategies, technical practices, and foreign cultures, on digital design, multiculturalism, and design aesthetics in the 1990s, and on emotional human factors, intelligent technology, and local culture since the beginning of the 21st century. Local culture and intelligent technology are the main driving forces of the current design industry. Regarding diversity, after a period of rapid change and stable rising, it has shown a downward trend in recent years. This indicates that current design needs to be stimulated by external environmental variations. Sustainability was focused on technology, the market, and education during the 1960s–1980s;on consumers, design education, and eco-design during the 1990s;and on integration across fields during the 2000s–2020. In order to gain a wider perspective of the complete design context of Chinese culture, the results show the current and future trends of the academic community, in addition to a reference for the study of the design histories of other areas in the world.

A Vaccine with Multiple Receptor-Binding Domain Subunit Mutations Induces Broad-Spectrum Immune Response against SARS-CoV-2 Variants of Concern.

With the emergence of more variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune evasion of these variants from existing vaccines, the development of broad-spectrum vaccines is urgently needed. In this study, we designed a novel SARS-CoV-2 receptor-binding domain (RBD) subunit (RBD5m) by integrating five important mutations from SARS-CoV-2 variants of concern (VOCs). The neutralization activities of antibodies induced by the RBD5m candidate vaccine are more balanced and effective for neutralizing different SARS-CoV-2 VOCs in comparison with those induced by the SARS-CoV-2 prototype strain RBD. Our results suggest that the RBD5m vaccine is a good broad-spectrum vaccine candidate able to prevent disease from several different SARS-CoV-2 VOCs.

Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery.

The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy.

[Spatiotemporal Distribution and Risk Assessment of Pharmaceuticals in Typical Drinking Water Sources in the Middle Reaches of the Yangtze River].

The seasonal variation and spatial distribution of pharmaceuticals in typical drinking water sources in the middle reaches of the Yangtze River were analyzed using the solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry methods. Combined with the risk entropy method, the corresponding ecological risks for aquatic organisms were evaluated. The results showed that 80% of the target pharmaceuticals were detected in the drinking water sources, with average concentrations of 0.07-13.00 ng·L-1. The concentrations of the target pharmaceuticals were lower than or comparable with those in other drinking water sources reported in China. The spatiotemporal distribution of different pharmaceuticals varied. Generally, the detection level in winter was higher than that in summer, and there was no significant difference between that upstream and that downstream. This might be mainly attributed to seasonal/regional use and emissions of the pharmaceuticals, the impact of flow rate on dilution, and the impact of temperature on biodegradation. Compared with those before the COVID-19 epidemic, the detection concentrations of the target pharmaceuticals were relatively low. The reason for this might be that the prevention and control of the epidemic reduced the use and emission of the pharmaceuticals to a certain extent, and the high rainfall and runoff strengthened the dilution of water flow. The target pharmaceuticals, especially antibiotics, posed medium or low risks to aquatic organisms (especially algae). Considering the ecological risks and genotoxicity of pharmaceuticals and the potential risks of antibiotic-resistant genes, it is suggested to strengthen the investigation, evaluation, treatment, and control of pharmaceuticals in the water environment.

Use of Low-Cost Sensors to Characterize Occupational Exposure to PM2.5 Concentrations Inside an Industrial Facility in Santa Ana, CA: Results from a Worker- and Community-Led Pilot Study

PM2.5 is an air contaminant that has been widely associated with adverse respiratory and cardiovascular health, leading to increased hospital admissions and mortality. Following concerns reported by workers at an industrial facility located in Santa Ana, California, workers and community leaders collaborated with experts in the development of an air monitoring pilot study to measure PM2.5 concentrations to which employees and local residents are exposed during factory operating hours. To detect PM2.5, participants wore government-validated AtmoTube Pro personal air monitoring devices during three separate workdays (5 AM–1:30 PM) in August 2021. Results demonstrated a mean PM2.5 level inside the facility of 112.3 µg/m3, nearly seven-times greater than outdoors (17.3 µg/m3). Of the eight workers who wore personal indoor sampling devices, five showed measurements over 100 μg/m3. Welding-related activity inside the facility resulted in the greatest PM2.5 concentrations. This study demonstrates the utility of using low-cost air quality sensors combined with employee knowledge and participation for the investigation of workplace air pollution exposure as well as facilitation of greater health-related awareness, education, and empowerment among workers and community members. Results also underscore the need for basic measures of indoor air pollution control paired with ongoing air monitoring within the Santa Ana facility, and the importance of future air monitoring studies aimed at industrial facilities.