One-step-one-pot hydrothermally derived metal-organic-framework-nanohybrids for integrated point-of-care diagnostics of SARS-CoV-2 viral antigen/pseudovirus utilizing electrochemical biosensor chip.

The COVID-19 pandemic has become a global catastrophe, affecting the health and economy of the human community. It is required to mitigate the impact of pandemics by developing rapid molecular diagnostics for SARS-CoV-2 virus detection. In this context, developing a rapid point-of-care (POC) diagnostic test is a holistic approach to the prevention of COVID-19. In this context, this study aims at presenting a real-time, biosensor chip for improved molecular diagnostics including recombinant SARS-CoV-2 spike glycoprotein and SARS-CoV-2 pseudovirus detection based on one-step-one-pot hydrothermally derived CoFeBDCNH2-CoFe2O4 MOF-nanohybrids. This study was tested on a PalmSens-EmStat Go POC device, showing a limit of detection (LOD) for recombinant SARS-CoV-2 spike glycoprotein of 6.68 fg/mL and 6.20 fg/mL in buffer and 10% serum-containing media, respectively. To validate virus detection in the POC platform, an electrochemical instrument (CHI6116E) was used to perform dose dependent studies under similar experimental conditions to the handheld device. The results obtained from these studies were comparable indicating the capability and high detection electrochemical performance of MOF nanocomposite derived from one-step-one-pot hydrothermal synthesis for SARS-CoV-2 detection for the first time. Further, the performance of the sensor was tested in the presence of Omicron BA.2 and wild-type D614G pseudoviruses.

Metabolomics-based investigation of SARS-CoV-2 vaccination (Sinovac) reveals an immune-dependent metabolite biomarker.

SARS-CoV-2 and its mutant strains continue to rapidly spread with high infection and fatality. Large-scale SARS-CoV-2 vaccination provides an important guarantee for effective resistance to existing or mutated SARS-CoV-2 virus infection. However, whether the host metabolite levels respond to SARS-CoV-2 vaccine-influenced host immunity remains unclear. To help delineate the serum metabolome profile of SARS-CoV-2 vaccinated volunteers and determine that the metabolites tightly respond to host immune antibodies and cytokines, in this study, a total of 59 sera samples were collected from 30 individuals before SARS-CoV-2 vaccination and from 29 COVID-19 vaccines 2 weeks after the two-dose vaccination. Next, untargeted metabolomics was performed and a distinct metabolic composition was revealed between the pre-vaccination (VB) group and two-dose vaccination (SV) group by partial least squares-discriminant and principal component analyses. Based on the criteria: FDR < 0.05, absolute log2 fold change greater than 0.25, and VIP >1, we found that L-glutamic acid, gamma-aminobutyric acid (GABA), succinic acid, and taurine showed increasing trends from SV to VB. Furthermore, SV-associated metabolites were mainly annotated to butanoate metabolism and glutamate metabolism pathways. Moreover, two metabolite biomarkers classified SV from VB individuals with an area under the curve (AUC) of 0.96. Correlation analysis identified a positive association between four metabolites enriched in glutamate metabolism and serum antibodies in relation to IgG, IgM, and IgA. These results suggest that the contents of gamma-aminobutyric acid and indole in serum could be applied as biomarkers in distinguishing vaccinated volunteers from the unvaccinated. What's more, metabolites such as GABA and taurine may serve as a metabolic target for adjuvant vaccines to boost the ability of the individuals to improve immunity.

In situ electrospun aloe-nanofiber membrane for chronic wound healing.

Alleviating excessive inflammation while accelerating chronic wound healing to prevent wound infection has remained challenging, especially during the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 when patients experienced difficulties with receive appropriate healthcare. We addressed this issue by developing handheld electrospun aloe-nanofiber membranes (ANFMs) with convenient, environmentally friendly properties and a therapeutic capacity for wound closure. Our results showed that ANFMs fabricated with high molecular weight polyvinyl alcohol (PVA) to form fibers during electrospinning had uniform fibrous architecture and a porous structure. Given the value of aloe gel in accelerating wound healing, liquid extracts from ANFMs significantly downregulated the expression of the pro-inflammatory genes, interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), and markedly suppress the generation of reactive oxygen species (ROS) induced by lipopolysaccharide in RAW264.7 macrophages. These results indicated the excellent antioxidant and anti-inflammatory effects of ANFMs. After implantation into a mouse diabetic wound model for 12 days in situ, ANFMs notably expedited chronic wound healing via promoting angiogenesis and enhancing cell viability. Our ANFMs generated by handheld electrospinning in situ healed chronic wounds offer a convenient and promising alternative for patients to heal their own wounds under variable conditions.

Autocrine, Paracrine, and Endocrine Signals That Can Alter Alveolar Macrophages Function.

Alveolar macrophages (AMs) are extremely versatile cells with complex functions involved in health or diseases such as pneumonia, asthma, and pulmonary alveolar proteinosis. In recent years, it has been widely identified that the different functions and states of macrophages are the results from the complex interplay between microenvironmental signals and macrophage lineage. Diverse and complicated signals to which AMs respond are mentioned when they are described individually or in a particular state of AMs. In this review, the microenvironmental signals are divided into autocrine, paracrine, and endocrine signals based on their secreting characteristics. This new perspective on classification provides a more comprehensive and systematic introduction to the complex signals around AMs and is helpful for understanding the roles of AMs affected by physiological environment. The existing possible treatments of AMs are also mentioned in it. The thorough understanding of AMs signals modulation may be contributed to the development of more effective therapies for AMs-related lung diseases.

Outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in hospitalized hemodialysis patients: An epidemiologic and genomic investigation.

We performed an epidemiological investigation and genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to define the source and scope of an outbreak in a cluster of hospitalized patients. Lack of appropriate respiratory hygiene led to SARS-CoV-2 transmission to patients and healthcare workers during a single hemodialysis session, highlighting the importance of infection prevention precautions.

Amygdala connectivity related to subsequent stress responses during the COVID-19 outbreak.

Introduction: The amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak. Methods: Data collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity. Results: We found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic. Discussion: Our findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

Severe Acute Respiratory Syndrome Coronavirus 2 Evolution and Escape From Combination Monoclonal Antibody Treatment in a Person With HIV.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from combination monoclonal antibody treatment is rarely reported. We describe an immunocompromised individual with human immunodeficiency virus and persistent SARS-CoV-2 infection in whom substantial SARS-CoV-2 evolution occurred, including the emergence of 2 mutations associated with escape from the monoclonal antibody cocktail received.

Gut microbiota: A new insight into lung diseases.

The human gut microbiota is a complex ecosystem involved in the metabolism, immunity, and health of the host. The microbiome plays a key role in the development of the host's innate and adaptive immune system, while the immune system orchestrates the maintenance of host-microbe symbiosis. Lung diseases are usually accompanied by dysbiosis of the intestinal flora and an immune-inflammatory response. The intestinal flora and its metabolites are directly or indirectly involved in the immune regulation of the host in lung disease. However, the exact mechanism of action of the gut-lung axis crosstalk remains unclear. This review is aimed to summarize the latest advances in gut microbiota and their metabolites in typical lung diseases, such as pulmonary hypertension, COPD, and lung cancer. Especially COVID-19, a problem troubling the world, is also discussed in it. Moreover, it is concentrated on the action mechanisms between the identified gut microbiota or their metabolites and the specific lung diseases, and on the link among the gut microbiota, its metabolites, and immune regulation, which could be used as a breakthrough to find new mechanisms and targets for some diseases without specific therapeutic drugs in clinic. It is also discussed a new therapeutic tool "drug-bacterial interaction" and the potential of therapeutic applications in clinic. This review would provide a clear direction for future research on gut microbiota and lung diseases, and propose a new therapeutic strategy targeting "drug-bacterial interaction" in clinic.

RBM24 inhibits the translation of SARS-CoV-2 polyproteins by targeting the 5'-untranslated region.

SARS-CoV-2 is a betacoronavirus with single-stranded positive-sense RNA, which is a serious global threat to human health. Understanding the molecular mechanism of viral replication is crucial for the development of antiviral drugs. The synthesis of viral polyproteins is a crucial step in viral progression. The synthesis of viral polyproteins in coronaviruses is regulated by the 5'-untranslated region (UTR); however, the detailed regulatory mechanism needs further investigation. The present study demonstrated that the RNA binding protein, RBM24, interacts with the RNA genome of SARS-CoV-2 via its RNA recognition submotifs (RNPs). The findings revealed that RBM24 recognizes and binds to the GUGUG element at stem-loop 4 (SL4) in the 5'-UTR of SARS-CoV-2. The interaction between RBM24 and 5'-UTR prevents 80S ribosome assembly, which in turn inhibits polyproteins translation and the replication of SARS-CoV-2. Notably, other RNA viruses, including SARS-CoV, MERS-CoV, Ebolavirus, rhinovirus, West Nile virus, Zika virus, Japanese encephalitis virus, yellow fever virus, hepatitis C virus, and human immunodeficiency virus-1 also contain one or several G(U/C/A)GUG sequences in the 5'-UTR, which is also targeted by RBM24. In conclusion, the present study demonstrated that RBM24 functions by interacting with the 5'-UTR of SARS-CoV-2 RNA, and elucidated that RBM24 could be a host restriction factor for SARS-CoV-2 and other RNA viruses.

Mifepristone (RU-486®) as a Schedule IV Controlled Drug-Implications for a Misleading Drug Policy on Women's Health Care.

BACKGROUND: Mifepristone (RU-486) has been approved for abortion in Taiwan since 2000. Mifepristone was the first non-addictive medicine to be classified as a schedule IV controlled drug. As a case of the "misuse" of "misuse of drugs laws," the policy and consequences of mifepristone-assisted abortion for pregnant women could be compared with those of illicit drug use for drug addicts. METHODS: The rule-making process of mifepristone regulation was analyzed from various aspects of legitimacy, social stigma, women's human rights, and access to health care. RESULTS AND DISCUSSION: The restriction policy on mifepristone regulation in Taiwan has raised concerns over the legitimacy of listing a non-addictive substance as a controlled drug, which may produce stigma and negatively affect women's reproductive and privacy rights. Such a restriction policy and social stigma may lead to the unwillingness of pregnant women to utilize safe abortion services. Under the threat of the COVID-19 pandemic, the US FDA's action on mifepristone prescription and dispensing reminds us it is time to consider a change of policy. CONCLUSIONS: Listing mifepristone as a controlled drug could impede the acceptability and accessibility of safe mifepristone use and violates women's right to health care.

Specific Pandemic-Related Worries Predict Higher Attention-Related Errors and Negative Affect Independent of Trait Anxiety in UK-Based Students.

Background: The COVID-19 pandemic has resulted in many individuals experiencing increased symptoms of anxiety. We predict that this increase may be underpinned by pandemic-related worry (PRW), characterised by repetitive negative thinking about pandemic-specific outcomes; and that this relationship is mediated through reduced attentional capacity required to regulate negative affect. Methods: We developed a novel scale to measure the contents of PRW in an initial sample of 255 participants, and explored its relationship with cognitive functioning and negative affect in a sample of 382 UK-based university students, whilst controlling for recalled pre-pandemic trait anxiety. Results: A five-factor model of PRW was identified, with factors reflecting worry about decline in quality of life (QoL) and probability of infection correlating with attention and memory-related errors. Importantly, attention-related errors partially mediated the positive relationship between PRW and negative affect, even when controlling for pre-pandemic trait anxiety. Conclusion: PRW's relationship with negative affect was partially mediated through attentional function, consistent with models of anxiety and attentional control. In UK-based students PRW may be predominantly focused on the decline in QoL; therefore, interventions targeting worry about the decline in QoL caused by COVID-19 are especially important in this population in the wake of the pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-022-10336-7.

Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases.

ABSTRACT: Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.