As the most compact variant in the Cas13 family, CRISPR-Cas13X holds considerable promise for gene therapy applications. The development of high-fidelity Cas13X (hfCas13X) mutants has enhanced the safety profile for in vivo applications. However, a notable reduction in on-target cleavage efficiency accompanies the diminished collateral cleavage activity in hfCas13X.
View Article and Find Full Text PDFLiver cancer, classified as a malignant hepatic tumor, can be divided into two categories: primary, originating within the liver, and secondary, resulting from metastasis to the liver from other organs. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and the third leading cause of cancer-related deaths. The diagnosis and prognosis of HCC using current methods still face numerous challenges.
View Article and Find Full Text PDFBackground: Norovirus is the predominant pathogen causing foodborne illnesses and acute gastroenteritis (AGE) outbreaks worldwide, imposing a significant disease burden. This study aimed to investigate the epidemiological characteristics and genotypic diversity of norovirus outbreaks in Hongshan District, Wuhan City.
Methods: A total of 463 AGE cases from 39 AGE-related outbreaks in Hongshan District between January 1, 2021, and June 30, 2023, were included in the study.
Two carbonyl and -NH-NO-containing energetic materials and their analogues were effectively designed, synthesized and fully characterized with multinuclear NMR, IR and elemental analyses. Their structures were also further confirmed X-ray diffraction. Among them, compound 7 exhibits good potential for application as a secondary explosive with extremely high density (2.
View Article and Find Full Text PDFCoronaviruses represent a significant threat to both human and animal health, encompassing a range of pathogenic strains responsible for illnesses, from the common cold to more severe diseases. VV116 is a deuterated derivative of Remdesivir with oral bioavailability that was found to potently inhibit SARS-CoV-2. In this work, we investigated the broad-spectrum antiviral activity of VV116 against a variety of human and animal coronaviruses.
View Article and Find Full Text PDFAs of 10 May 2022, at least 450 cases of pediatric patients with acute hepatitis of unknown cause have been reported worldwide. Human adenoviruses (HAdVs) have been detected in at least 74 cases, including the F type HAdV41 in 18 cases, which indicates that adenoviruses may be associated with this mysterious childhood hepatitis, although other infectious agents or environmental factors cannot be excluded. In this review, we provide a brief introduction of the basic features of HAdVs and describe diseases caused by different HAdVs in humans, aiming to help understand the biology and potential risk of HAdVs and cope with the outbreak of acute child hepatitis.
View Article and Find Full Text PDFPoly(butylene adipate-co-terephthalate) (PBAT), a polyester made of terephthalic acid (TPA), 1,4-butanediol, and adipic acid, is extensively utilized in plastic production and has accumulated globally as environmental waste. Biodegradation is an attractive strategy to manage PBAT, but an effective PBAT-degrading enzyme is required. Here, we demonstrate that cutinases are highly potent enzymes that can completely decompose PBAT films in 48 h.
View Article and Find Full Text PDFA new antibody diagnostic assay with more rapid and robust properties is demanded to quantitatively evaluate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in a large population. Here, we developed a nanometer-scale fluorescent biosensor system consisting of CdSe-ZnS quantum dots (QDs) coupled with the highly sensitive B-cell epitopes of SARS-CoV-2 that could remarkably identify the corresponding antibody with a detection limit of 100 pM. Intriguingly, we found that fluorescence quenching of QDs was stimulated more obviously when coupled with peptides than the corresponding proteins, indicating that the energy transfer between QDs and peptides was more effective.
View Article and Find Full Text PDFInt J Biol Macromol
June 2022
The biosynthesis of brasilane-type sesquiterpenoids (BTSs) attracts much attention owing to their unique skeleton of 5/6 bicyclic structure that contains five Me groups. Here, the crystal structures of a BTS cyclase TaTC6 from Trichoderma atroviride FKI-3849 and its complexes with farnesyl pyrophosphate (FPP) and analogue were reported. These structural information reveal that TaTC6 exploits a hydrophobic pocket to constrain the hydrocarbon region of FPP in a "U-shape" to facilitate the initial C1-C11 bond formation after pyrophosphate ionization.
View Article and Find Full Text PDFNonheme iron- and α-ketoglutarate (αKG)-dependent halogenases (NHFeHals), which catalyze the regio- and stereoselective halogenation of the unactivated C()-H bonds, exhibit tremendous potential in the challenging asymmetric halogenation. AdeV from Actinomadura sp. ATCC 39365 is the first identified carrier protein-free NHFeHal that catalyzes the chlorination of nucleotide 2'-deoxyadenosine-5'-monophosphate (2'-dAMP) to afford 2'-chloro-2'-deoxyadenosine-5'-monophosphate.
View Article and Find Full Text PDFFollowing the publication of the above article, an interested reader drew to the authors' attention that the 'NB‑4' and 'NB‑2' panels for the invasion and migration assays shown in Fig. 3B and C on p. 113 appeared to contain overlapping data, such that the data may have been derived from the same original source, even though the panels were intending to have shown results obtained under different experimental conditions.
View Article and Find Full Text PDFGlobal concern has been raised by the emergence and rapid transmission of the heavily mutated SARS-CoV-2 Omicron variant (B.1.1.
View Article and Find Full Text PDFBackground: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China.
Methods: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China.
Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulin G (IgG) was well maintained in most patients and potently neutralizes the infection of the original strain and the B.
View Article and Find Full Text PDFNational-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus.
View Article and Find Full Text PDFBackground: Extracellular adenosine triphosphate (ATP), a key danger-associated molecular pattern (DAMP) molecule, is released to the extracellular medium during inflammation by injured parenchymal cells, dying leukocytes, and activated platelets. ATP directly activates the plasma membrane channel P2X7 receptor (P2X7R), leading to an intracellular influx of K, a key trigger inducing NLRP3 inflammasome activation. However, the mechanism underlying P2X7R-mediated activation of NLRP3 inflammasome is poorly understood, and additional molecular mediators have not been identified.
View Article and Find Full Text PDFEnteroviruses infect gastrointestinal epithelium cells, cause multiple human diseases, and present public health risks worldwide. However, the mechanisms underlying host immune responses in intestinal mucosa against the early enterovirus infections remain elusive. Here, we showed that human enteroviruses including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1) predominantly induce type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), in cultured human normal and cancerous intestine epithelial cells (IECs), mouse intestine tissues, and human clinical intestine specimens.
View Article and Find Full Text PDFThe proteasome is a major protein degradation machinery with essential and diverse biological functions. Upon induction by cytokines, proteasome subunits β1, β2, and β5 are replaced by β1i/LMP2, β2i/MECL-1, and β5i/LMP7, resulting in the formation of an immunoproteasome (iProteasome). iProteasome-degraded products are loaded onto the major histocompatibility complex class I (MHC-I), regulating immune responses and inducing cytotoxic T lymphocytes (CTLs).
View Article and Find Full Text PDFThe immune system is not only required for preventing threats exerted by pathogens but also essential for developing immune tolerance to avoid tissue damage. This study identifies a distinct mechanism by which MYSM1 suppresses innate immunity and autoimmunity. The expression of MYSM1 is induced upon DNA virus infection and by intracellular DNA stimulation.
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