Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate for Preventing Vertical Transmission in Chronic Hepatitis B Mothers: A Systematic Review and Meta-Analysis.

OBJECTIVE: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. DESIGN: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. RESULTS: We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. CONCLUSION: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.

Sequence Note: Characterization of Two HIV-1 Strains with Novel Unique Recombinant Genome in Hebei, China.

In China, the proportion of HIV-1 infections due to men who have sex with men (MSM) has increased rapidly. More and more new subtypes are found among the MSM population besides known CRF01_AE, CRF07_BC, and B. The co-circulation of several HIV subtypes in the same population provides the opportunity to develop a new circulating recombinant form (CRF) and unique recombinant form (URF). Here we reported two new URFs from two HIV-1 positive subjects infected through homosexual contact in Hebei, China. Phylogenetic and recombinant analyses based on the near full-length genome (NFLG) of the two URFs are the second-generation recombinant strains that originated from B, CRF01_AE, and CRF07_BC. The CRF01_AE segments in the genome of two URFs originated from cluster 4 of CRF01_AE strains, while the CRF07_BC segments were clustered with 07BC_N in the phylogenetic tree. The emergence of the novel CRF01_AE/CRF07_BC and CRF01_AE/B recombinant forms indicated the importance of the continuous monitoring of the HIV-1 epidemic and new URFs among the MSM population.

Near-full-length genome analysis of two novel HIV second recombinant forms in Hebei, China.

The number of individuals infected with HIV-1 among men who have sex with men (MSM) has risen rapidly in recent years in China, and the subtypes CRF01_AE, CRF07_BC, and B, as well as many novel unique recombinant forms (URFs) are prevalent among them. Co-circulation of strains among MSM populations allows the generation of circulating recombinant forms (CRFs) and URFs. In this study, we identified two new URFs from two HIV-1-positive subjects who were infected through homosexual contact in Hebei, China. Analysis of near-full-length genome sequences, using phylogenetic and recombination analysis showed that the two URFs originated from CRF01_AE, CRF07_BC, and B, and CRF01_AE segments in the backbone of the URFs were derived from cluster 4 of CRF01_AE. The CRF07_BC segments of two URFs were clustered with 07BC_N in a phylogenetic tree. The identification of novel URFs with complex genomic structures shows that it is necessary to strengthen surveillance of HIV-1 variants in MSM populations in this region.

COVID-19 vaccination willingness among people living with HIV in Shijiazhuang, China: a cross-sectional survey.

Objectives: The COVID-19 pandemic imposed an enormous disease and economic burden worldwide. SARS-CoV-2 vaccination is essential to containing the pandemic. People living with HIV (PLWH) may be more vulnerable to severe COVID-19 outcomes; thus, understanding their vaccination willingness and influencing factors is helpful in developing targeted vaccination strategies. Methods: A cross-sectional study was conducted between 15 June and 30 August 2022 in Shijiazhuang, China. Variables included socio-demographic characteristics, health status characteristics, HIV-related characteristics, knowledge, and attitudes toward COVID-19 vaccination and COVID-19 vaccination status. Multivariable logistic regression was used to confirm factors associated with COVID-19 vaccination willingness among PLWH. Results: A total of 1,428 PLWH were included, with a 90.48% willingness to receive the COVID-19 vaccination. PLWH were more unwilling to receive COVID-19 vaccination for those who were female or had a fair/poor health status, had an allergic history and comorbidities, were unconvinced and unsure about the effectiveness of vaccines, were unconvinced and unsure about the safety of vaccines, were convinced and unsure about whether COVID-19 vaccination would affect ART efficacy, or did not know at least a type of domestic COVID-19 vaccine. Approximately 93.00% of PLWH have received at least one dose of the COVID-19 vaccine among PLWH, and 213 PLWH (14.92%) reported at least one adverse reaction within 7 days. Conclusion: In conclusion, our study reported a relatively high willingness to receive the COVID-19 vaccination among PLWH in Shijiazhuang. However, a small number of PLWH still held hesitancy; thus, more tailored policies or guidelines from the government should be performed to enhance the COVID-19 vaccination rate among PLWH.

Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study.

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. "Correlates of protection," including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron-reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.

Ensure the accuracy and consistency of biochemical analyzer test results: Chemometrics for instrument and inter-instrument item comparison in Chinese hospital laboratory.

Biochemical analyzers are vital instruments that utilize the principle of photoelectric colorimetry to quantify a specific chemical composition in body fluids. This analysis provides critical data for the diagnosis, treatment, prognosis, and overall health status of various diseases in clinical practice. However, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Therefore, it is imperative to regularly assess the performance of the analyzer to ensure consistent results for longitudinal studies and to maintain day-to-day data consistency. Additionally, when multiple analyzers are utilized, it is necessary to evaluate the performance of each instrument to ensure accurate results across multiple platforms. In this study, we developed and verified an experimental evaluation scheme for the analytical performance of the instrument, chemometrics for biochemical analyzers, utilizing national reference materials and patient sera as the experimental subjects. We evaluated the performance of the optical system, temperature control system, sample-adding system, and detection system to confirm the feasibility of this scheme. We also compared the analytical performance of different brands of biochemical analyzers for routine biochemical tests, such as liver function, kidney function, ion, blood lipids, blood glucose, and myocardial enzyme spectrum. Using the AU 5400 as a control and the ADVIA 2400 as the comparison system, the relative variation in inter-instrument comparison data was found to be acceptable at the clinical medicine decision level. In conclusion, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Regular evaluations are necessary to ensure accurate and consistent results across different analyzers. This study provides a feasible scheme for evaluating the analytical performance of biochemical analyzers that can be used to ensure the accuracy and consistency of the results of different brands of automatic chemical analyzers in the laboratory.

The function role of HIGD1A in nonalcoholic steatohepatitis from chronic hepatitis B.

BACKGROUND: Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. METHODS: We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. RESULTS: In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. CONCLUSION: Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context.

SARS-CoV-2 Vaccine Uptake among Patients with Chronic Liver Disease: A Cross-Sectional Analysis in Hebei Province, China.

Chronic liver disease (CLD) patients have higher mortality and hospitalization rates after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to explore SARS-CoV-2 vaccine perceptions, side effects, factors associated with nonvaccination and attitudes toward fourth-dose vaccine among CLD patients. The differences between vaccinated and unvaccinated groups among 1491 CLD patients and the risk factors associated with nonvaccination status were analyzed. In total, 1239 CLD patients were immunized against SARS-CoV-2. CLD patients have a high level of trust in the government and clinicians and were likely to follow their recommendations for vaccination. Reasons reported for nonvaccination were mainly concerns about the vaccines affecting their ongoing treatments and the fear of adverse events. However, only 4.84% of patients reported mild side effects. Risk factors influencing nonvaccination included being older in age, having cirrhosis, receiving treatments, having no knowledge of SARS-CoV-2 vaccine considerations and not receiving doctors' positive advice on vaccination. Furthermore, 20.6% of completely vaccinated participants refused the fourth dose because they were concerned about side effects and believed that the complete vaccine was sufficiently protective. Our study proved that SARS-CoV-2 vaccines were safe for CLD patients. Our findings suggest that governments and health workers should provide more SARS-CoV-2 vaccination information and customize strategies to improve vaccination coverage and enhance vaccine protection among the CLD population.

Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases.

Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.

Abundant diversity of accessory genetic elements and associated antimicrobial resistance genes in pseudomonas aeruginosa isolates from a single Chinese hospital.

OBJECTIVES: Pseudomonas aeruginosa has intrinsic antibiotic resistance and the strong ability to acquire additional resistance genes. However, a limited number of investigations provide detailed modular structure dissection and evolutionary analysis of accessory genetic elements (AGEs) and associated resistance genes (ARGs) in P. aeruginosa isolates. The objective of this study is to reveal the prevalence and transmission characteristics of ARGs by epidemiological investigation and bioinformatics analysis of AGEs of P. aeruginosa isolates taken from a Chinese hospital. METHODS: Draft-genome sequencing was conducted for P. aeruginosa clinical isolates (n = 48) collected from a single Chinese hospital between 2019 and 2021. The clones of P. aeruginosa isolates, type 3 secretion system (T3SS)-related virulotypes, and the resistance spectrum were identified using multilocus sequence typing (MLST), polymerase chain reaction (PCR), and antimicrobial susceptibility tests. In addition, 17 of the 48 isolates were fully sequenced. An extensive modular structure dissection and genetic comparison was applied to AGEs of the 17 sequenced P. aeruginosa isolates. RESULTS: From the draft-genome sequencing, 13 STs were identified, showing high genetic diversity. BLAST search and PCR detection of T3SS genes (exoT, exoY, exoS, and exoU) revealed that the exoS+/exoU- virulotype dominated. At least 69 kinds of acquired ARGs, involved in resistance to 10 different categories of antimicrobials, were identified in the 48 P. aeruginosa isolates. Detailed genetic dissection and sequence comparisons were applied to 25 AGEs from the 17 isolates, together with five additional prototype AGEs from GenBank. These 30 AGEs were classified into five groups -- integrative and conjugative elements (ICEs), unit transposons, IncpPBL16 plasmids, Incp60512-IMP plasmids, and IncpPA7790 plasmids. CONCLUSION: This study provides a broad-scale and deeper genomics understanding of P. aeruginosa isolates taken from a single Chinese hospital. The isolates collected are characterized by high genetic diversity, high virulence, and multiple drug resistance. The AGEs in P. aeruginosa chromosomes and plasmids, as important genetic platforms for the spread of ARGs, contribute to enhancing the adaptability of P. aeruginosa in hospital settings.

Association between SUMF1 polymorphisms and COVID-19 severity.

BACKGROUND: Evidence shows that genetic factors play important roles in the severity of coronavirus disease 2019 (COVID-19). Sulfatase modifying factor 1 (SUMF1) gene is involved in alveolar damage and systemic inflammatory response. Therefore, we speculate that it may play a key role in COVID-19. RESULTS: We found that rs794185 was significantly associated with COVID-19 severity in Chinese population, under the additive model after adjusting for gender and age (for C allele = 0.62, 95% CI = 0.44-0.88, P = 0.0073, logistic regression). And this association was consistent with this in European population Genetics Of Mortality In Critical Care (GenOMICC: OR for C allele = 0.94, 95% CI = 0.90-0.98, P = 0.0037). Additionally, we also revealed a remarkable association between rs794185 and the prothrombin activity (PTA) in subjects (P = 0.015, Generalized Linear Model). CONCLUSIONS: In conclusion, our study for the first time identified that rs794185 in SUMF1 gene was associated with the severity of COVID-19.

Decrease of 5-hydroxymethylcytosine in hepatitis B virus-related hepatocellular carcinoma: A cross-sectional study.

Many epigenetic studies had found the decrease of 5-hydroxymethylcytosine (5-hmC) in various tumor tissues. However, limited information is available for hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). The present study aimd to investigate whether the decrease also existed in tumor tissues of HBV-related HCC and, if possible, to disclose its mechanism. We used immunohistochemistry and Image Pro Plus 6.0 Image Analysis Software to quantify the expression of 5-hmC, 5-methylcytosine, 10-eleven translocation (TET), isocitrate dehydrogenase (IDH) in pathological sections of tumor tissues and its para cancerous tissues of 40 HBV-related HCC patients. Our results showed that 5-hmC was decreased while 5-methylcytosine was increased in tumor tissues. We also detected TET1 and IDH2 were decreased in the tumor tissues and the decrease were positively correlated with the 5-hmC. The results suggested that the deficiency of 5-hmC was an epigenetic characteristic of HBV-related HCC and was mainly caused by the decrease of TET1 and IDH2.

Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis.

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.

Diagnostic value and characteristic analysis of serum nucleocapsid antigen in COVID-19 patients.

Background: To date, several types of laboratory tests for coronavirus disease 2019 (COVID-19) diagnosis have been developed. However, the clinical importance of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen (N-Ag) remains to be fully elucidated. In this study, we sought to investigate the value of serum SARS-CoV-2 N-Ag for COVID-19 diagnosis and to analyze N-Ag characteristics in COVID-19 individuals. Methods: Serum samples collected from 215 COVID-19 patients and 65 non-COVID-19 individuals were used to quantitatively detect N-Ag via chemiluminescent immunoassay according to the manufacturer's instructions. Results: The sensitivity and specificity of the N-Ag assay were 64.75% (95% confidence interval (95% CI) [55.94-72.66%]) and 100% (95% CI [93.05-100.00%]), respectively, according to the cut-off value recommended by the manufacturer. The receiver operating characteristic (ROC) curve showed a sensitivity of 100.00% (95% CI [94.42-100.00%]) and a specificity of 71.31% (95% CI [62.73-78.59%]). The positive rates and levels of serum SARS-CoV-2 N-Ag were not related to sex, comorbidity status or disease severity of COVID-19 (all P < 0.001). Compared with RT‒PCR, there was a lower positive rate of serum N-Ag for acute COVID-19 patients (P < 0.001). The positive rate and levels of serum SARS-CoV-2 N-Ag in acute patients were significantly higher than those in convalescent patients (all P < 0.001). In addition, the positive rate of serum SARS-CoV-2 N-Ag in acute COVID-19 patients was higher than that of serum antibodies (IgM, IgG, IgA and neutralizing antibodies (Nab)) against SARS-CoV-2 (all P < 0.001). However, the positive rate of serum SARS-CoV-2 N-Ag in convalescent COVID-19 patients was significantly lower than that of antibodies (all P < 0.001). Conclusion: Serum N-Ag can be used as a biomarker for early COVID-19 diagnosis based on appropriate cut-off values. In addition, our study also demonstrated the relationship between serum N-Ag and clinical characteristics.

Clinical Features of Non-Alcoholic Fatty Liver Disease in the Non-Lean Population.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population. METHODS: Current study enrolled consecutive non-lean (body mass index [BMI] >23 kg/m2) patients with NAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23∼<28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage >1) were also analyzed through the logistic regression model. RESULTS: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT), and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87). CONCLUSIONS: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD.

Mechanism of pulmonary plague biphasic syndrome: inhibition or activation of NF-κB signaling pathway.

Background: Pneumonic plague is a fatal respiratory disease caused by Yersinia pestis. Time-course transcriptome analysis on the mechanism of pneumonic plague biphasic syndrome is lacking in the literature. Materials & methods: This study documented the disease course through bacterial load, histopathology, cytokine levels and flow cytometry. RNA-sequencing technology was used to investigate the global transcriptome profile of lung tissue in mice infected with Y. pestis. Results: Inflammation-related genes were significantly upregulated at 48 h post-infection, while genes related to cell adhesion and cytoskeletal structure were downregulated. Conclusion: NOD-like receptor and TNF signaling pathways play a plausible role in pneumonic plague biphasic syndrome and lung injury by controlling the activation and inhibition of the NF-κB signaling pathway.

CESSAT: A chemical additive-enhanced single-step accurate CRISPR/Cas13 testing system for field-deployable ultrasensitive detection and genotyping of SARS-CoV-2 variants of concern.

The continued emergence of SARS-CoV-2 variants of concern (VOCs) has raised great challenges for epidemic prevention and control. A rapid, sensitive, and on-site SARS-CoV-2 genotyping technique is urgently needed for individual diagnosis and routine surveillance. Here, a field-deployable ultrasensitive CRISPR-based diagnostics system, called Chemical additive-Enhanced Single-Step Accurate CRISPR/Cas13 Testing system (CESSAT), for simultaneous screening of SARS-CoV-2 and its five VOCs (Alpha, Beta, Gamma, Delta, and Omicron) within 40 min was reported. In this system, a single-step reverse transcription recombinase polymerase amplification-CRISPR/Cas13a assay was incorporated with optimized extraction-free viral lysis and reagent lyophilization, which could eliminate complicated sample processing steps and rigorous reagent storage conditions. Remarkably, 10% glycine as a chemical additive could improve the assay sensitivity by 10 times, making the limit of detection as low as 1 copy/µL (5 copies/reaction). A compact optic fiber-integrated smartphone-based device was developed for sample lysis, assay incubation, fluorescence imaging, and result interpretation. CESSAT could specifically differentiate the synthetic pseudovirus of SARS-CoV-2 and its five VOCs. The genotyping results for 40 clinical samples were in 100% concordance with standard method. We believe this simple but efficient enhancement strategy can be widely incorporated with existing Cas13a-based assays, thus leading a substantial progress in the development and application of rapid, ultrasensitive, and accurate nucleic acid analysis technology.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection.

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.