The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population
. Although recent reports reveal that the Omicron variant robustly escapes ...vaccine-associated and therapeutic neutralization antibodies
, the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.
The evaluation of childhood trauma is essential for the treatment of schizophrenia. The short form of Childhood Trauma Questionnaire (CTQ-SF) is a widely used measure of the experience of childhood ...trauma in the general population. Nevertheless, data regarding the psychometric property of CTQ-SF for assessing childhood trauma of patients with schizophrenia are very limited.
Two hundred Chinese inpatients with schizophrenia completed the Chinese CTQ-SF, the Child Psychological Maltreatment Scale (CPMS), the Impact of Events Scale-Revised (IES-R), and the Dissociative Experiences Scale-II (DES-II). To assess test-retest reliability of the CTQ-SF, all patients completed the CTQ-SF again two weeks later. Concurrent and convergent validity was assessed by analyzing Pearson bivariate correlation coefficients between CTQ-SF and CPMS, IES-R, and DES-II.
The Cronbach's α coefficient of the Chinese CTQ-SF was 0.81, and the two-week re-test reliability was 0.81 (P<0.01). The criterion-related validity coefficients of CTQ-SF with the CMPS, IES-R and DES-II were 0.61, 0.41, and 0.51, respectively.
The Chinese CTQ-SF has satisfactory psychometric properties to measure childhood abuse or neglect in Chinese inpatients with schizophrenia.
Background/Aims: Ischemic stroke is still one of the leading debilitating diseases with high morbidity and mortality. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) play an important role ...in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism underlying the regulation of ROS generation is still not fully elucidated. This study aims to explore the role of transforming growth beta (TGF-β) signals in ROS generation. Methods: Sprague–Dawley rats were subjected to I/R injury, and PC-12 cells were challenged by hypoxia/reoxygenation (H/R) and/or treated with activin receptor-like kinase (ALK5) inhibitor Sb505124 or siRNA against ALK5. Brain damage was evaluated using neurological scoring, triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, infarct volume measurement, TUNEL staining, and caspase-3 activity measurement. Expression of TGF-β and oxidative stress-related genes was analyzed by real-time polymerase chain reaction and Western blot; NOX activity and ROS level were measured using spectrophotometry and fluorescence microscopy, respectively. Results: I/R contributed to severe brain damage (impaired neurological function, brain infarction, tissue edema, apoptosis), TGF-β signaling activation (upregulation of ALK5, phosphorylation of SMAD2/3) and oxidative stress (upregulation of NOX2/4, rapid release of ROS oxidative burst). However, Sb505124 significantly reversed these alterations and protected rats against I/R injury. As in the animal results, H/R also contributed to TGF-β signaling activation and oxidative stress. Likewise, the inhibition of ALK5 or ALK5 knockdown significantly reversed these alterations in PC-12 cells. Other than ALK5 knockdown, ALK5 inhibition had no effect on the expression of ALK5 in PC-12 cells. Conclusions: Our studies demonstrated that TGF-β signaling activation is involved in the regulation of NOX2/NOX4 expression and exacerbates cerebral I/R injury.
Ionic liquid (IL)-assisted pretreatment of lignocellulosic biomass has been extensively studied. Cellulose and hemicelluloses are rich resources of sugars for biofuels. Lignin is a valuable feedstock ...for aromatic-based platform chemicals. In this study, a series of ionic liquids (ILs) were prepared with one-step synthesis and were investigated for their activity to pretreat lignocelluloses. High yields of lignin (61.0% and 60.4%) were achieved through HpyCl and HmimCl pretreatment of poplar. Lignin yields of 51.7% and 50.3% were obtained with a HpyCl and HnmpCl pretreatment of bamboo. Improving enzymatic hydrolysis was observed from the regenerated poplar with HpyCl pretreatment and the regenerated bamboo with HmimCl pretreatment. The isolated fractions were characterized by FTIR (Fourier transform infrared) spectroscopy. SEM (Scanning electron microscopy) and XRD (X-ray diffractometry) were employed to examine the cellulose-rich materials. A 2D
1
H-
13
C heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy was employed to analyze lignin fraction. These ionic liquids were particularly effective to extract lignin from lignocelluloses to obtain cellulose-rich materials for biofuels.
Ionic liquid (IL)-assisted pretreatment of lignocellulosic biomass has been extensively studied.
Tumor recurrence and unfavorable bacterial biofilm formation on implants after bone tumor resection remain challenging in clinical settings. However, this dilemma also provides inspiration for the ...development of bioactive implants and a new route for the management of bone tumors through biofilm formation. Here, based on the characteristic that bacteria prefer to adhere to implants, 3D‐printing bioceramic scaffolds modified with probiotic biofilms are designed to augment antitumor immunity. In comparison with Akkermansia muciniphila, Lactobacillus rhamnosus GG (LGG) is demonstrated to more easily form biofilms on bioceramics and is selected to engineer etched bioceramics. The LGG biofilm subjected to pasteurization guarantees good biocompatibility and enhanced doxorubicin (Dox) loading. Furthermore, the LGG biofilm combined with Dox imparts the scaffolds with multiple properties of direct chemo‐killing for tumor cells and potent immune activation. The modified scaffolds efficiently inhibit bone tumor recurrence and bone metastasis in murine tumor model receives surgical resection. Moreover, based on 3D‐printing technology, the probiotic biofilm modified scaffolds with adjustable shapes are also demonstrated to repair shape‐specific bone defects after tumor elimination. Collectively, the multifunctional 3D‐printing scaffolds realize the integrated treatment of tumor elimination and bone repair, providing a promising strategy for clinical treatment of bone tumors.
Probiotic biofilm modified 3D‐printing scaffolds are developed for management of bone tumors and osteogenesis. Remarkable curative effects and systematic immune protection from chemo‐immunotherapy mediated by probiotic biofilm modified scaffolds are demonstrated. The multifunctional 3D‐printing scaffolds realize the integrated treatment of tumor elimination and bone repair, providing a promising strategy for clinical treatment of bone tumors.
SARS-CoV-2 B.1.1.529.1 (Omicron BA.1) emerged in November 2021 and quickly became the predominant circulating SARS-CoV-2 variant globally. Omicron BA.1 contains more than 30 mutations in the spike ...protein, which contribute to its altered virological features when compared to the ancestral SARS-CoV-2 or previous SARS-CoV-2 variants. Recent studies by us and others demonstrated that Omicron BA.1 is less dependent on transmembrane serine protease 2 (TMPRSS2), less efficient in spike cleavage, less fusogenic, and adopts an altered propensity to utilize the plasma membrane and endosomal pathways for virus entry. Ongoing studies suggest that these virological features of Omicron BA.1 are in part retained by the subsequent Omicron sublineages. However, the exact spike determinants that contribute to these altered features of Omicron remain incompletely understood. In this study, we investigated the spike determinants for the observed virological characteristics of Omicron. By screening for the individual changes on Omicron BA.1 and BA.2 spike, we identify that 69-70 deletion, E484A, and H655Y contribute to the reduced TMPRSS2 usage while 25-27 deletion, S375F, and T376A result in less efficient spike cleavage. Among the shared spike mutations of BA.1 and BA.2, S375F and H655Y reduce spike-mediated fusogenicity. Interestingly, the H655Y change consistently reduces serine protease usage while increases the use of endosomal proteases. In keeping with these findings, the H655Y substitution alone reduces plasma membrane entry and facilitates endosomal entry when compared to SARS-CoV-2 WT. Overall, our study identifies key changes in Omicron spike that contributes to our understanding on the virological determinant and pathogenicity of Omicron.
Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with ...an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism to wildtype mouse and potentially other murines. Our study evaluated this possibility with substantial public health importance.
We investigated the capacity of wildtype (WT) SARS-CoV-2 and SARS-CoV-2 variants in infecting mice (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Susceptibility to infection was evaluated with RT-qPCR, plaque assays, immunohistological stainings, and neutralization assays.
Our results reveal that B.1.1.7 and other N501Y-carrying variants but not WT SARS-CoV-2 can infect wildtype mice. High viral genome copies and high infectious virus particle titres are recovered from the nasal turbinate and lung of B.1.1.7-inocluated mice for 4-to-7 days post infection. In agreement with these observations, robust expression of viral nucleocapsid protein and histopathological changes are detected from the nasal turbinate and lung of B.1.1.7-inocluated mice but not that of the WT SARS-CoV-2-inoculated mice. Similarly, B.1.1.7 readily infects wildtype rats with production of infectious virus particles.
Our study provides direct evidence that the SARS-CoV-2 variant, B.1.1.7, as well as other N501Y-carrying variants including B.1.351 and P.3, has gained the capability to expand species tropism to murines and public health measures including stringent murine control should be implemented to facilitate the control of the ongoing pandemic.
A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4 expression.
The aims of this ...study are to investigate whether VB-1 can protect the rat brain against ischemia/ reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of certain miRNAs expression.
Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of miR-92b.
Administration of VB-1 reduced I/R cerebral injury accompanied by a reverse in NOX4 and miR-92b expression. Similar results were achieved in a neuron H/R injury model. Next, we evaluated the association of miR-92b with NOX4 by its mimics in the H/R model. H/R treatment increased neurons apoptosis concomitant with an upregulation of NOX4 and NOX activity while downregulation of miR-92b. All these effects were reversed in the presence of miR-92b mimics, confirming the function of miR-92b in suppressing NOX4 expression.
We conclude the protective effect of VB-1 against rat cerebral I/R injury through a mechanism involving modulation of miR-92b/NOX4 pathway.
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