SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Room-Temperature Growth of Square-Millimeter Single-Crystalline Two-Dimensional Metal Halides on Silicon.

Silicon is the cornerstone of electronics and photonics. In this context, almost all integrated devices derived from two-dimensional (2D) materials stay rooted in silicon technology. However, as the growth substrate, silicon has long been thought to be a hindrance for growing 2D materials through bottom-up methods that require high growth temperatures, and thus, indirect routes are usually considered instead. Although promising growth of large-area 2D materials on silicon has been demonstrated, the direct growth of single-crystalline materials using low-thermal-budget synthesis methods remains challenging. Here, we report the room-temperature growth of millimeter-scale single-crystal 2D metal halides on silicon substrates with a hydroxyl-terminated surface. Theoretical calculations reveal that the activation energy for surface diffusion can be reduced by an order of magnitude by terminating the surface with hydroxyl groups, from which on-silicon growth is greatly facilitated at room temperature and enables a 4-order-of-magnitude increase in area. The high quality and uniformity of the resulting single crystals are further evidenced. The optoelectronic devices employing the as-grown materials show an ultralow dark current of 10-13 A and a high detectivity of 1013 Jones, thereby corroborating a weak-light detection ability. These results would point to a rich space of surface modulation that can be used to surmount current limitations and demonstrate a promising strategy for growing 2D materials directly on silicon at room temperature to produce large single crystals.

Protocol for isolating small cytosolic dsDNA from cultured murine cells.

We recently identified a class of small cytosolic double-stranded DNA (scDNA) approximately 20-40 bp in size in human and mouse cells. Here, we present a protocol for scDNA isolation from cultured murine cells. We describe steps for cytosolic compartment separation, DNA isolation in the cytosolic fraction using phenol-chloroform extraction, and ethanol precipitation. We then detail procedures for denaturing purified cytosolic DNA through urea polyacrylamide gel electrophoresis and obtaining scDNA in the cytosolic DNA fraction via gel purification. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Neutralization of EG.5, EG.5.1, BA.2.86, and JN.1 by antisera from dimeric receptor-binding domain subunit vaccines and 41 human monoclonal antibodies.

BACKGROUND: The recently circulating Omicron variants BA.2.86 and JN.1 were identified with more than 30 amino acid changes on the spike protein compared to BA.2 or XBB.1.5. This study aimed to comprehensively assess the immune escape potential of BA.2.86, JN.1, EG.5, and EG.5.1. METHODS: We collected human and murine sera to evaluate serological neutralization activities. The participants received three doses of coronavirus disease 2019 (COVID-19) vaccines or a booster dose of the ZF2022-A vaccine (Delta-BA.5 receptor-binding domain [RBD]-heterodimer immunogen) or experienced a breakthrough infection (BTI). The ZF2202-A vaccine is under clinical trial study (ClinicalTrials.gov: NCT05850507). BALB/c mice were vaccinated with a panel of severe acute respiratory syndrome coronavirus 2 RBD-dimer proteins. The antibody evasion properties of these variants were analyzed with 41 representative human monoclonal antibodies targeting the eight RBD epitopes. FINDINGS: We found that BA.2.86 had less neutralization evasion than EG.5 and EG.5.1 in humans. The ZF2202-A booster induced significantly higher neutralizing titers than BTI. Furthermore, BA.2.86 and JN.1 exhibited stronger antibody evasion than EG.5 and EG.5.1 on RBD-4 and RBD-5 epitopes. Compared to BA.2.86, JN.1 further lost the ability to bind to several RBD-1 monoclonal antibodies and displayed further immune escape. CONCLUSIONS: Our data showed that the currently dominating sub-variant, JN.1, showed increased immune evasion compared to BA.2.86 and EG.5.1, which is highly concerning. This study provides a timely risk assessment of the interested sub-variants and the basis for updating COVID-19 vaccines. FUNDING: This work was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, the Beijing Life Science Academy, the Bill & Melinda Gates Foundation, and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (CPSF).

Microelectromechanical system for in situ quantitative testing of tension-compression asymmetry in nanostructures.

Tension-compression asymmetry is a topic of current interest in nanostructures, especially in strain engineering. Herein, we report a novel on-chip microelectromechanical system (MEMS) that can realize in situ quantitative mechanical testing of nanostructures under tension-compression functions. The mechanical properties of three kinds of nanostructures fabricated by focused ion beam (FIB) techniques were systematically investigated with the presented on-chip testing system. The results declare that both Pt nanopillars and C nanowires exhibit plastic deformation behavior under tension testing, with average Young's moduli of 70.06 GPa and 58.32 GPa, respectively. However, the mechanical deformation mechanisms of the two nanostructures changed in compression tests. The Pt nanopillar exhibited in-plane buckling behavior, while the C nanowire displayed 3D twisting behavior with a maximum strain of 25.47%, which is far greater than the tensile strain. Moreover, asymmetric behavior was also observed in the C nanospring during five loading-unloading tension-compression deformation tests. This work provides a novel insight into the asymmetric mechanical properties of nanostructures, with potential applications in nanotechnology research.

Upregulation of CELSR1 expression promotes ovarian cancer cell proliferation, migration, and invasion.

Cadherin epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an epithelial sheet or multicellular clusters. CELSR1 has been suggested to play a role in glioma, breast cancer, and chronic lymphocytic leukemia development; however, whether it has a role in the pathogenesis of ovarian cancer remains unknown. The aim of this study was to determine the role of CELSR1 in ovarian cancer and elucidate its underlying molecular mechanisms. By analyzing gene expression data downloaded from the Cancer Genome Atlas database, we found that CELSR1 expression was upregulated in ovarian cancer tissues compared to that in normal ovarian tissues. High CELSR1 expression levels were associated with poor prognosis in patients with ovarian cancer. Cell proliferation, scratch, and transwell assays revealed that CELSR1 promoted the proliferation, migration, and invasion of ovarian cancer cells in vitro. In addition, transcriptome sequencing analysis revealed that CELSR1 knockdown in T29H cells resulted in the dysregulation of the expression of 1320 genes. Further analysis revealed that genes involved in proliferation- and migration-associated signaling pathways were regulated by CELSR1. Our study demonstrates that CELSR1 is highly expressed in ovarian cancer cells and regulates their proliferation and migration, suggesting its potential as a diagnostic marker and therapeutic target.

Mutual communication between radiosensitive and radioresistant esophageal cancer cells modulates their radiosensitivity.

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.

Association Between Negative Affect and Perceived Mortality Threat During the COVID-19 Pandemic: The Role of Brain Activity and Connectivity.

The prevalence of the novel coronavirus (COVID-19) has been considered a major threat to physical and mental health around the world, causing great pressure and mortality threat to most people. The current study aimed to investigate the neurological markers underlying the relationship between perceived mortality threat (PMT) and negative affect (NA). We examined whether the regional amplitude of low-frequency fluctuations (ALFF) and resting-state functional connectivity (RSFC) before the COVID-19 outbreak (October 2019 to December 2019, wave 1) were predictive for NA and PMT during the mid-term of the COVID-19 pandemic (February 22 to 28, 2020, wave 2) among 603 young adults (age range 17-22, 70.8% females). Results indicated that PMT was associated with spontaneous activity in several regions (e.g., inferior temporal gyrus, medial occipital gyrus, medial frontal gyrus, angular gyrus, and cerebellum) and their RSFC with the distributed regions of the default mode network and cognitive control network. Furthermore, longitudinal mediation models showed that ALFF in the cerebellum, medial occipital gyrus, medial frontal gyrus, and angular gyrus (wave 1) predicted PMT (wave 2) through NA (wave 2). These findings revealed functional neural markers of PMT and suggest candidate mechanisms for explaining the complex relationship between NA and mental/neural processing related to PMT in the circumstance of a major crisis.

Classification of five SARS-CoV-2 serotypes based on RBD antigenicities.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a significant number of variants, particularly with the emergence of Omicron with many sub-variants. These variants have exhibited increased immune escape, leading to reduced efficacy of existing vaccines and therapeutic antibodies. Given the diminished cross-neutralization observed among these variants, it is plausible that SARS-CoV-2 has developed multiple serotypes. As the major antigenic site, the receptor-binding domain (RBD) of viral spike (S) protein was chosen for serotyping. We selected 23 representative variants, including pre-Omicron variants and Omicron sub-variants, and classified them into five serotypes based on systematic evaluation of the antigenicities of their RBDs. Each serotype includes several genetically distinct variants. Serotype-I encompasses all pre-Omicron variants (with two subtypes), while the remaining four serotypes are all comprised of Omicron sub-variants at different stages of evolution. We propose that these serotypes can serve as a foundation for rapid classification of newly emerging SARS-CoV-2 variants, and guide the development of future broad-spectrum vaccines and neutralizing antibodies against the coronavirus disease 2019 (COVID-19).

Evaluating the value of 18F-PSMA-1007 PET/CT in the detection and identification of prostate cancer using histopathology as the standard.

BACKGROUND: Prostate-specific membrane antigen (PSMA) PET/CT is a highly regarded radionuclide imaging modality for prostate cancer (PCa). This study aimed to evaluate the diagnostic performance of 18F-PSMA-1007 PET/CT in detecting intraprostatic lesions of PCa using radical prostatectomy (RP) specimens as a reference standard and to establish an optimal maximum standardized uptake value (SUVmax) cutoff for distinguishing between PCa and non-PCa lesions. METHODS: We retrospectively collected 117 patients who underwent 18F-PSMA-1007 PET/CT before RP. The uptake of the index tumor and contralateral non-PCa lesion was assessed. Histopathology of RP specimens was used as the gold standard. Kappa test was used to evaluate the consistency of preoperative PSMA PET/CT staging and postoperative pathological staging. Finally, an SUVmax cutoff value was identified by receiver operating characteristic (ROC) curve analysis to distinguish PCa lesions from non-PCa lesions. A prospective cohort including 76 patients was used to validate the results. RESULTS: The detection rate of 18F-PSMA-1007 PET/CT for prostate cancer was 96.6% (113/117). 18F-PSMA-1007 had a sensitivity of 91.2% and a positive predictive value (PPV) of 89.8% for the identification of intraprostatic lesions. The consistency test (Kappa = 0.305) indicated poor agreement between the pathologic T-stage and PSMA PET/CT T-stage. Based on ROC curve analysis, the appropriate SUVmax to diagnose PCa lesions was 8.3 (sensitivity of 71.3% and specificity 96.8%) with an area under the curve (AUC) of 0.93 (P < 0.001). This SUVmax cutoff discriminated PCa lesions from non-PCa lesions with a sensitivity of 74.4%, a specificity of 95.8% in the prospective validation group. CONCLUSIONS: 18F-PSMA-1007 PET/CT demonstrated excellent performance in detecting PCa. An optimal SUVmax threshold (8.3) could be utilized to identify lesions of PCa by 18F-PSMA-1007 PET/CT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04521894, Registered: August 17, 2020.

A pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery.

Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent need for new antivirals with pan-SARS-CoV-2 inhibitory activity. We previously reported that a peptide fusion inhibitor, P3, targeting heptad repeated-1 (HR1) of SARS-CoV-2 spike (S) protein, could inhibit viral infections. Here, we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative, the P315V3, showed the most efficient antiviral activity against SARS-CoV-2 variants and several other sarbecoviruses, as well as other human-CoVs (HCoVs). P315V3 also exhibited effective prophylactic efficacy against the SARS-CoV-2 Delta and Omicron variants in mice via intranasal administration. These results suggest that P315V3, which is in Phase II clinical trial, is promising for further development as a nasal pan-SARS-CoV-2 or pan-CoVs inhibitor to prevent or treat CoV diseases.

Upregulation of FAM50A promotes cancer development.

FAM50A encodes a nuclear protein involved in mRNA processing; however, its role in cancer development remains unclear. Herein, we conducted an integrative pan-cancer analysis using The Cancer Genome Atlas, Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium databases. Based on the gene expression data from TCGA and GTEx databases, we compared FAM50A mRNA levels in 33 types of human cancer tissues to those in corresponding normal tissues and found that FAM50A mRNA level was upregulated in 20 of the 33 types of common cancer tissues. Then, we compared the DNA methylation status of the FAM50A promoter in tumor tissues to that in corresponding normal tissues. FAM50A upregulation was accompanied by promoter hypomethylation in 8 of the 20 types of tumor tissues, suggesting that promoter hypomethylation contributes to the upregulation of FAM50A in these cancer tissues. Elevated FAM50A expression in 10 types of cancer tissues was associated with poor prognosis in patients with cancer. FAM50A expression was positively correlated with CD4+ T-lymphocyte and dendritic cell infiltration in cancer tissues but was negatively correlated with CD8+ T-cell infiltration in cancer tissues. FAM50A knockdown caused DNA damage, induced interferon beta and interleukin-6 expression, and repressed the proliferation, invasion, and migration of cancer cells. Our findings indicate that FAM50A might be useful in cancer detection, reveal insights into its role in cancer development, and may contribute to the development of cancer diagnostics and treatments.

Small cytosolic double-stranded DNA represses cyclic GMP-AMP synthase activation and induces autophagy.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.

T cell receptor and B cell receptor exhibit unique signatures in tumor and adjacent non-tumor tissues of hepatocellular carcinoma.

Background: The tumor microenvironment in hepatocellular carcinoma (HCC) is complicated. Tumor-infiltrating T and B cells play a pivotal role in anti-tumor immunity. T cell receptor (TCR) and B cell receptor (BCR) features may reflect the disease-associated antigen response. Methods: By combining bulk TCR/BCR-sequencing, RNA-sequencing, whole exome-sequencing, and human leukocyte antigen-sequencing, we examined the immune repertoire (IR) features of tumor and adjacent non-tumor tissues obtained from 64 HCC patients. Results: High IR heterogeneity with weak similarity was discovered between tumor and non-tumor tissues. Higher BCR diversity, richness, and somatic hypermutation (SHM) were found in non-tumor tissues, while TCRα and TCRß diversity and richness were comparable or higher in tumor. Additionally, lower immune infiltration was found in tumor than non-tumor tissues; the microenvironment in tumor appeared to keep stably inhibited and changed slightly with tumor progression. Moreover, BCR SHM was stronger, whereas TCR/BCR diversity declined with HCC progression. Importantly, we found that higher IR evenness in tumor and lower TCR richness in non-tumor tissues indicated better survival in HCC patients. Collectively, the results revealed that TCR and BCR exhibited distinct features in tumor and non-tumor tissues. Conclusions: We demonstrated that IR features vary between different tissues of HCC. IR features may represent a biomarker for the diagnosis and treatment of HCC patients, providing references for subsequent immunotherapy research and strategy selection.

Research Progress on Metal-Organic Frameworks by Advanced Transmission Electron Microscopy.

Metal-organic frameworks (MOFs), composed of metal nodes and inorganic linkers, are promising for a wide range of applications due to their unique periodic frameworks. Understanding structure-activity relationships can facilitate the development of new MOFs. Transmission electron microscopy (TEM) is a powerful technique to characterize the microstructures of MOFs at the atomic scale. In addition, it is possible to directly visualize the microstructural evolution of MOFs in real time under working conditions via in situ TEM setups. Although MOFs are sensitive to high-energy electron beams, much progress has been made due to the development of advanced TEM. In this review, we first introduce the main damage mechanisms for MOFs under electron-beam irradiation and two strategies to minimize these damages: low-dose TEM and cryo-TEM. Then we discuss three typical techniques to analyze the microstructure of MOFs, including three-dimensional electron diffraction, imaging using direct-detection electron-counting cameras, and iDPC-STEM. Groundbreaking milestones and research advances of MOFs structures obtained with these techniques are highlighted. In situ TEM studies are reviewed to provide insights into the dynamics of MOFs induced by various stimuli. Additionally, perspectives are analyzed for promising TEM techniques in the research of MOFs' structures.

The prognostic value of 18F-PSMA-1007 PET/CT in predicting pathological upgrading of newly diagnosed prostate cancer from systematic biopsy to radical prostatectomy.

Objective: This study aimed to evaluate predictors for upgrading of newly diagnosed prostate cancer from systematic biopsy (SB) to radical prostatectomy (RP) using fluorine-18 prostate-specific membrane antigen 1007 (18F-PSMA-1007) positron emission tomography/computed tomography (PET/CT) and association with clinical parameters. Materials and methods: We retrospectively collected data from biopsy-confirmed prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT prior to RP from July 2019 and October 2022. Imaging characteristics derived from 18F-PSMA-1007 PET/CT and clinical parameters were compared in patients of pathological upgrading and concordance subgroups. Univariable and multivariable logistic regressions were performed to analyze factors predicting histopathological upgrading from SB to RP specimens. Discrimination ability of independent predictors was further evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC). Results: Pathological upgrading occurred in 26.97% (41/152) PCa patients, and 23.03% (35/152) of all patients experienced pathological downgrading. Concordance rate reached 50% (76/152). International Society of Urological Pathology grade group (ISUP GG) 1(77.78%) and ISUP GG 2 (65.22%) biopsies were related with the highest rate of upgrading. Multivariable logistic regression analyses showed that prostate volume (OR= 0.933; 95% CI, 0.887-0.982; p = 0.008), ISUP GG 1 vs. 4 (OR= 13.856; 95% CI: 2.467-77.831; p = 0.003), and total uptake of PSMA-avid lesions (PSMA-TL) (OR = 1.003; 95% CI, 1.000-1.006; p = 0.029) were found to be independent risk factors of pathological upgrading after RP. The AUCs and corresponding sensitivity and specificity of the independent predictors of synthesis for upgrading were 0.839, 78.00%, and 83.30% respectively, which showed good discrimination capacity. Conclusion: 18F-PSMA-1007 PET/CT may help to predict pathological upgrading between biopsy and RP specimens, particularly for ISUP GG 1 and ISUP GG 2 patients with higher PSMA-TL and smaller prostate volume.

Rapid evaluation of heterologous chimeric RBD-dimer mRNA vaccine for currently-epidemic Omicron sub-variants as booster shot after inactivated vaccine.

With continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines, especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries. Previously, we developed a coronavirus disease 2019 (COVID-19) protein subunit vaccine ZF2001® based on the tandem homo-prototype receptor-binding domain (RBD)-dimer of the SARS-CoV-2 spike protein. We upgraded the antigen into a hetero-chimeric prototype (PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms. Herein, we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine (IV) in mice. Our data demonstrated that the chimeric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the variants, and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice, shedding light on the antigen design for the next-generation COVID-19 vaccines.

Assessing the chronic hepatitis B adaptive immune response by profiling specific T-cell receptor repertoire.

Challenges in assessing hepatitis B virus (HBV)-specific T cell immunity as an immunological biomarker still remain in chronic hepatitis B (CHB), such as the requirement of large quantities of cells. This study aims to conveniently assess HBV-specific T cells immunity in chronic HBV infected patients. We obtained T cell receptor ß chains (TCRßs) from public databases and six acute hepatitis B patients to establish an HBV-specific TCRßs dataset. For some TCRs from one acute patient, their specificities and epitopes were verified. The potential HBV-specific TCRßs from CHB patients were analyzed using GLIPH2 and established dataset. By analyzing two antiviral therapy cohorts including 42 CHB patients, we showed that individuals with better therapy response may depend more on newly emerging potential HBV-specific TCRßs. In a cross-sectional study containing 207 chronic HBV infected patients, the results exhibited that the characteristics of potential HBV-specific clusters were divergent between CHB and hepatocellular carcinoma patients. Our strategy could profile potential HBV-specific TCRß repertoire using a small blood sample, which will complement traditional methods for assessing the HBV-specific T cell immunity.

An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB.

Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of Omicron BA.1, BA.1.1, BA.2, and BA.3 from an atlas of 50 monoclonal antibodies (mAbs), covering seven epitope classes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD). Here, we update the atlas of totally 77 mAbs against emerging sub-variants including BQ.1.1 and XBB and find that BA.4/5, BQ.1.1, and XBB display further evasion. Besides, investigation into the correlation of binding and neutralization of mAbs reveals the important role of antigenic conformation in mAb functioning. Moreover, the complex structures of BA.2 RBD/BD-604/S304 and BA.4/5 RBD/BD-604/S304/S309 further elucidate the molecular mechanism of antibody evasion by these sub-variants. By focusing on the identified broadly potent mAbs, we find a general hotspot epitope on the RBD, which could guide the design of vaccines and calls for new broad-spectrum countermeasures against COVID-19.