Efficacy, immunogenicity, and safety of a monovalent mRNA vaccine, ABO1020, in adults: A randomized, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed. METHODS: We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.gov: NCT05636319). Participants were randomly assigned (1:1) to receive either 2 doses of ABO1020 (15 µg per dose) or placebo, administered 28 days apart. The primary endpoint was the vaccine efficacy in preventing symptomatic COVID-19 cases that occurred at least 14 days post-full vaccination. The second endpoint included the neutralizing antibody titers against Omicron BA.5 and XBB and safety assessments. FINDINGS: A total of 14,138 participants were randomly assigned to receive either vaccine or placebo (7,069 participants in each group). A total of 366 symptomatic COVID-19 cases were confirmed 14 days after the second dose among 93 participants in the ABO1020 group and 273 participants in the placebo group, yielding a vaccine efficacy of 66.18% (95% confidence interval: 57.21-73.27, p < 0.0001). A single dose or two doses of ABO1020 elicited potent neutralizing antibodies against both BA.5 and XBB.1.5. The safety profile of ABO1020 was characterized by transient, mild-to-moderate fever, pain at the injection site, and headache. CONCLUSION: ABO1020 was well tolerated and conferred 66.18% protection against symptomatic COVID-19 in adults. FUNDING: National Key Research and Development Project of China, Innovation Fund for Medical Sciences from the CAMS, National Natural Science Foundation of China.

Specific immunological characteristics and risk factor of XBB variants re-infection in nasopharyngeal carcinoma patients after BA.5 infection.

OBJECTIVES: The specific humoral immune response resulting from inactivated vaccination following by BA.5 infection, and predictors of XBB variants re-infection in BA.5 infection-recovered nasopharyngeal carcinoma (BA.5-RNPC) patients, were explored. METHODS: Serum SARS-CoV-2 specific antibody levels were assessed using enzyme-linked-immunosorbent-assay. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with the magnitude of specific humoral immunity and susceptibility to re-infection by XBB variants. RESULTS: Our data demonstrates that SARS-CoV-2 specific antibody levels were comparable between BA.5-RNPC patients and BA.5 infection-recovered-non-cancerous (BA.5-RNC) individuals. Specifically, serum levels of anti-ancestral-S1-IgG, anti-ancestral-nucleocapsid-protein (NP)-IgG, anti-BA.5-receptor binding domain (RBD)-IgG and anti-XBB.1.1.6-RBD-IgG were higher in BA.5-RNPC patients compared to those without a prior infection. Compared to BA.5-RNPC patients without vaccination, individuals who received inactivated vaccination exhibited significantly higher levels of anti-ancestral-S1-IgG and anti-XBB.1.16-RBD-IgG. Multivariate logistic regression analysis revealed that inactivated vaccination was the most significant predictor of all tested SARS-CoV-2 specific antibodies response. Subsequent analysis indicated that a low globulin level is an independent risk factor for XBB re-infection in BA.5-RNPC patients. CONCLUSIONS: The SARS-CoV-2 specific antibodies have been improved in vaccinated BA.5-RNPC patients. However, the baseline immunity status biomarker IgG is an indicators of XBB variant re-infection risk in BA.5-RNPC patients.

Determination of Essential Minerals in the Indigenous Vegetables Solanum nigrum (Stout Shade) and Gynandropsis gynandra (Spider Plant) from Two Agroecological Zones in Kisii County, Kenya.

Vegetables are good sources of essential mineral elements that promote good health and immunity. Information on the nutritional contents of indigenous vegetables is scarce. Therefore, this study sought to ascertain the concentrations of magnesium, manganese, chrome, zinc, copper, and iron in Solanum nigrum and Gynandropsis gynandra indigenous vegetables from two agroecological zones (upper midland and lower highland) of Kisii County, Kenya, using inductively coupled plasma optical emission spectroscopy (ICP‒OES). For Gnandropsis gynandra, the most abundant erythrocytic synthesis element was Fe (1856.67 ± 15.28 mg/kg DW) for plants harvested from Nyanchwa (UM), and the least was Cu (8.90 ± 0.44 mg/kg DW) in plants harvested from Kari (LH). In addition, Mg was the hypoglycemic element with the highest concentration (5975.00 ± 10.00 mg/kg DW), and Cr lowest (3.16 ± 0.45 mg/kg DW) in samples harvested from Matongo (UM). For Solanum nigrum, the most erythrocytic synthesis element was Fe (1280.00 ± 10.00 mg/kg DW for samples collected from Kiamabundu (UM), and the least was Cu (9.08 ± 0.15 mg/kg DW) in the samples from Nyanchwa (UM), whereas Mg in samples from Nyabioto (UM) was the hypoglycemic element with the highest concentration (4920.00 ± 10.00 mg/kg DW) and Cr in samples from Mariba (LH had the lowest concentration) (3.95 ± 1.63 mg/kg DW). The concentrations of elements in the two indigenous vegetables from the UM agroecological zone were slightly greater than those in the LH agroecological zone. Nonetheless, the variations observed were not statistically significant (P < 0.05). Enzymatically bio accessed concentrations of iron, zinc, chromium, magnesium, manganese, and copper were higher than those obtained aquatically. The indigenous vegetable bio avails substantial amounts of iron and copper to enable them be used in the management pernicious anaemia; on the other hand, the substantial bio availed levels of zinc, manganese, magnesium, and chromium enables the vegetable to be used in the management of diabetes.

Systematic review of the mechanism and assessment of liver fibrosis in biliary atresia.

PURPOSE: This study systematically reviewed our team's research on the mechanism and assessment of liver fibrosis in BA, summarized our experience, and discussed the future development direction. METHODS: In this study, Pubmed and Wanfang databases were searched to collect the literature published by our team on the mechanisms of liver fibrosis in BA and the assessment of liver fibrosis in BA, and the above research results were systematically reviewed. RESULTS: A total of 58 articles were retrieved. Among the included articles, 25 articles related to the mechanism of liver fibrosis in BA, and five articles evaluated liver fibrosis in BA. This article introduces the key pathways and molecules of liver fibrosis in BA and proposes a new grading system for liver fibrosis in BA. CONCLUSIONS: The new BA liver fibrosis grading method is expected to assess children's conditions, guide treatment, and improve prognosis more accurately. In addition, we believe that the TGF-ß1 signaling pathway is the most important in the study of liver fibrosis in BA, and at the same time, the study of EMT occurrence in BA should also be deepened to resolve the controversy on this issue.

Specific humoral immune response and XBB variants re-infection risk of hemodialysis patients after Omicron BA.5 infection in China.

BACKGROUND: Currently, there is limited understanding of the specific humoral immune response in BA.5-infected hemodialysis patients (BA.5-CHDPs) with previous COVID-19 vaccination. Additionally, the relevant risk factors for reinfection with XBB variants in BA.5-CHDPs have yet to be elucidated. METHOD: A total of 178 BA.5-CHDPs were enrolled in this study among 53 patients who had previous vaccination. To compare hemodialysis patients in both unvaccinated and vaccinated for their immune response to the BA.5 subtype infection, we assessed serum levels of anti-ancestral-S1-IgG, anti-BA.5-receptor binding domain (RBD)-IgG, and anti-XBB.1.16-RBD-IgG using enzyme-linked immunosorbent assay, the neutralizing antibody titer against BA.5 and XBB.1.16 was determined using pseudovirus neutralization assays. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with severe infection, the magnitude of specific humoral immunity and susceptibility to XBB variants reinfection. RESULT: Our findings indicate that BA.5-CHDPs with full or booster vaccinations have higher levels of anti-ancestral-S1-IgG than unvaccinated individuals. However, levels of anti-BA.5-RBD-IgG and anti-XBB.1.16-RBD-IgG are much lower. Booster-vaccinated BA.5-CHDPs have significantly higher levels of BA.5 and XBB.1.16 specific antibodies and neutralizing antibodies than unvaccinated patients. Low globulin levels and shorter hemodialysis duration are independent risk factors for XBB reinfection in BA.5-CHDPs. CONCLUSION: Although XBB.1.16 specific neutralizing antibody levels were low in BA.5-CHDPs, these levels cannot predict the risk of reinfection; other potential risk factors need to be investigated in the future.

Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial.

BACKGROUND: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone or as a bivalent preparation with the prototype vaccine (NVX-CoV2373) to assess antibody responses to SARS-CoV-2. METHODS: Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or the bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed. RESULTS: Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated a superior neutralizing antibody response to BA.1 vs NVX-CoV2373 (n = 274) at day 14 (geometric mean titer ratio, 1.6; 95% CI, 1.33-2.03). Seroresponse rates were 73.4% (91/124; 95% CI, 64.7-80.9) for NVX-CoV2515 vs 50.9% (59/116; 95% CI, 41.4-60.3) for NVX-CoV2373. All formulations were similarly well tolerated. CONCLUSIONS: NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant as compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT05372588).

SARS-CoV-2 BA.4/5 infection triggers more cross-reactive FcγRIIIa signaling and neutralization than BA.1, in the context of hybrid immunity.

SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing and antibody-dependent cellular cytotoxic (ADCC) antibodies with variable cross-reactivity. Omicron BA.4/5 was approved for inclusion in bivalent vaccination boosters, and therefore the antigenic profile of antibodies elicited by this variant is critical to understand. Here, we investigate the ability of BA.4/5-elicited antibodies following the first documented (primary) infection (n = 13) or breakthrough infection after vaccination (n = 9) to mediate neutralization and FcγRIIIa signaling across multiple SARS-CoV-2 variants including XBB.1.5 and BQ.1. Using a pseudovirus neutralization assay and a FcγRIIIa crosslinking assay to measure ADCC potential, we show that unlike SARS-CoV-2 Omicron BA.1, BA.4/5 infection triggers highly cross-reactive functional antibodies. Cross-reactivity was observed both in the absence of prior vaccination and in breakthrough infections following vaccination. However, BQ.1 and XBB.1.5 neutralization and FcγRIIIa signaling were significantly compromised compared to other VOCs, regardless of prior vaccination status. BA.4/5 triggered FcγRIIIa signaling was significantly more resilient against VOCs (<10-fold decrease in magnitude) compared to neutralization (10- to 100-fold decrease). Overall, this study shows that BA.4/5 triggered antibodies are highly cross-reactive compared to those triggered by other variants. Although this is consistent with enhanced neutralization and FcγRIIIa signaling breadth of BA.4/5 vaccine boosters, the reduced activity against XBB.1.5 supports the need to update vaccines with XBB sublineage immunogens to provide adequate coverage of these highly antibody evasive variants. IMPORTANCE: The continued evolution of SARS-CoV-2 has resulted in a number of variants of concern. Of these, the Omicron sublineage is the most immune evasive. Within Omicron, the BA.4/5 sublineage drove the fifth wave of infection in South Africa prior to becoming the dominant variant globally. As a result this spike sequence was approved as part of a bivalent vaccine booster, and rolled out worldwide. We aimed to understand the cross-reactivity of neutralizing and Fc mediated cytotoxic functions elicited by BA.4/5 infection following infection or breakthrough infection. We find that, in contrast to BA.1 which triggered fairly strain-specific antibodies, BA.4/5 triggered antibodies that are highly cross-reactive for neutralization and antibody-dependent cellular cytotoxicity potential. Despite this cross-reactivity, these antibodies are compromised against highly resistant variants such as XBB.1.5 and BQ.1. This suggests that next-generation vaccines will require XBB sublineage immunogens in order to protect against these evasive variants.

The Latest Evidence on Bempedoic Acid: Meta-Analysis of Safety and Efficacy in High Cardiovascular Risk Patients With Hypercholesterolemia⋆.

Background: Bempedoic Acid (BA) is a novel drug that has a potential to serve as an alternative to statins to decrease lipid levels and improve cardiovascular disease (CVD) outcomes, particularly for statin-intolerant individuals. However, insufficient statistical power has limited our understanding of the efficacy and safety of BA. This meta-analysis utilizes the latest data to improve our knowledge of BA's effects on lipids and CVD with increased statistical power. Methods: MEDLINE, Embase, Cochrane Central, Clinicaltrials.gov, abstracts of national and international conferences, and reference lists of studies were searched for relevant studies. Rayyan was used to screen the search results, and Revman 5.3 was used for the meta-analysis and sensitivity analysis. Results: Our final analysis included seven randomized control trials (RCTs) with 17,782 participants, 53.6 % in the BA group (n = 9535) and 46.4 % in the placebo group (n = 8247). BA significantly decreased major adverse cardiovascular events (MACE) (OR: 0.86; 95 % CI 0.78-0.95; p = 0.03), non-fatal myocardial infarction (OR 0.72; 95 % CI 0.61-0.85; p = 0.0001), and new onset/worsening diabetes (OR:0.55; 95 % CI 0.30-0.98, p = 0.04), while reducing low-density lipoprotein cholesterol (LDL-C) levels by 22.5 % (MD: -22.53 %; 95 % CI -25.54 to -19.52, p < 0.00001). Conclusion: The findings of this meta-analysis suggest that BA is a promising and effective alternative to statin therapy, particularly for statin-intolerant and high CVD-risk patients. However, further studies with diverse populations are needed to quantify the long-term efficacy and safety endpoints.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals, or no treatment: a retrospective cohort study.

BACKGROUND: The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland. METHODS: Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021-October 25, 2022, using Scottish administrative health data. We included adult patients who met ≥ 1 of the National Health Service highest risk criteria for early COVID-19 treatment and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of COVID-19 diagnosis or early COVID-19 treatment. Baseline characteristics and acute clinical outcomes in the 28 days following index were reported. Values of ≤ 5 were suppressed. RESULTS: In total, 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709: eligible highest risk untreated). Patients aged ≥ 75 years accounted for 6.9% (n = 34/492), 21.0% (n = 58/276), 16.9% (n = 12/71) and 13.2% (n = 225/1709) of the cohorts, respectively. Advanced renal disease was reported in 6.7% (n = 33/492) of sotrovimab-treated and 4.7% (n = 81/1709) of untreated patients, and ≤ 5 nirmatrelvir/ritonavir-treated and molnupiravir-treated patients. All-cause hospitalizations were experienced by 5.3% (n = 25/476) of sotrovimab-treated patients, 6.9% (n = 12/175) of nirmatrelvir/ritonavir-treated patients, ≤ 5 (suppressed number) molnupiravir-treated patients and 13.3% (n = 216/1622) of untreated patients. There were no deaths in the treated cohorts; mortality was 4.3% (n = 70/1622) among untreated patients. CONCLUSIONS: Sotrovimab was often used by patients who were aged < 75 years. Among patients receiving early COVID-19 treatment, proportions of 28-day all-cause hospitalization and death were low.

Spike structures, receptor binding, and immune escape of recently circulating SARS-CoV-2 Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants.

The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections.

Clinical Evaluation of the Accuracy of the Panbio™ COVID-19/Flu A&B Rapid Panel: A Combination Antigen Rapid Diagnostic Test for the Omicron Variant and Influenza A Virus.

It is difficult to differentiate between coronavirus disease 2019 (COVID-19) and influenza based on the symptoms. In the present study, a newly developed antigen rapid diagnostic test (Ag-RDT) called Panbio™ COVID-19/Flu A&B that can simultaneously detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B virus was evaluated. Its accuracy was evaluated using 235 pairs of nasopharyngeal samples collected from patients with respiratory symptoms and fever (>37.5°C). Reverse transcription polymerase chain reaction was used as a reference method to evaluate the accuracy of the SARS-CoV-2 detection. We confirmed the accuracy of the developed Ag-RDT against the Omicron variant where the sensitivity and specificity were 94.8% and 100%, respectively. In addition, to identify the influenza A virus, a noninferiority test was conducted using a commercial Ag-RDT, which has a sensitivity and specificity in comparison with viral culture of 94.8% and 98.4%, respectively. The positive and negative predictive values for influenza A virus were 98.5% and 98.1%, respectively, for the Panbio COVID-19/Flu A&B test. The evaluation of this newly developed Ag-RDT using clinical samples suggests that it has a high efficacy in clinical settings.

Novel Sol-Gel Synthesis Route for Ce- and V-Doped Ba0.85Ca0.15Ti0.9Zr0.1O3 Piezoceramics.

To meet the current demand for lead-free piezoelectric ceramics, a novel sol-gel synthesis route is presented for the preparation of Ba0.85Ca0.15Ti0.9Zr0.1O3 doped with cerium (Ce = 0, 0.01, and 0.02 mol%) and vanadium (V = 0, 0.3, and 0.4 mol%). X-ray diffraction patterns reveal the formation of a perovskite phase (space group P4mm) for all samples after calcination at 800 °C and sintering at 1250, 1350, and 1450 °C, where it is proposed that both dopants occupy the B site. Sintering studies show that V doping allows the sintering temperature to be reduced to at least 1250 °C. Undoped BCZT samples sintered at the same temperature show reduced functional properties compared to V-doped samples, i.e., d33 values increase by an order of magnitude with doping. The dissipation factor tan δ decreases with increasing sintering temperature for all doping concentrations, while the Curie temperature TC increases for all V-doped samples, reaching 120 °C for high-concentration co-doped samples. All results indicate that vanadium doping can facilitate the processing of BCZT at lower sintering temperatures without compromising performance while promoting thermal property stability.

Statistical comparison for assessing agreement between two mass spectrometric methods for the analysis of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs) in contaminated soils.

A gas chromatography coupled to high-resolution mass spectrometry (GC-HR/MS) has been used as the standard method for the quantification of polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs), which are regulated at screening and action levels in the environment. However, several alternative methods have been attempted due to the disadvantage of its high cost. Although a gas chromatography with triple quadrupole mass spectrometry (GC-QqQ-MS/MS) has been used in a wide variety of sample matrices, showing that they are interchangeable, there has been a lack of comprehensive studies on statistical agreement with GC-HR/MS. In this study, a pairwise comparison of the total concentrations of PCDDs/Fs in 90 soil field samples obtained by two mass spectrometric methods was performed using the Passing-Bablok (P&B) regression and Bland-Altman (B&A) analysis for the method comparison. According to the result of the B&A analysis, the concentration range of PCDDs/Fs was between 98.2 and 1760 pg/g showed good agreement between two methods at the 95 % confidence level (CL). Although there was a large discrepancy between the two methods in the low concentrations (<16.5 pg/g of PCDDs/Fs), this result was similar to the P&B regression analysis. As the verification results by B&A and P&B regression analysis, the interchangeable concentration range between the two methods was confirmed to be adequate for the monitoring of PCDDs/Fs regulating levels in soils.

The Mechanism of Exogenous Salicylic Acid and 6-Benzylaminopurine Regulating the Elongation of Maize Mesocotyl.

The elongation of the mesocotyl plays an important role in the emergence of maize deep-sowing seeds. This study was designed to explore the function of exogenous salicylic acid (SA) and 6-benzylaminopurine (6-BA) in the growth of the maize mesocotyl and to examine its regulatory network. The results showed that the addition of 0.25 mmol/L exogenous SA promoted the elongation of maize mesocotyls under both 3 cm and 15 cm deep-sowing conditions. Conversely, the addition of 10 mg/L exogenous 6-BA inhibited the elongation of maize mesocotyls. Interestingly, the combined treatment of exogenous SA-6-BA also inhibited the elongation of maize mesocotyls. The longitudinal elongation of mesocotyl cells was the main reason affecting the elongation of maize mesocotyls. Transcriptome analysis showed that exogenous SA and 6-BA may interact in the hormone signaling regulatory network of mesocotyl elongation. The differential expression of genes related to auxin (IAA), jasmonic acid (JA), brassinosteroid (BR), cytokinin (CTK) and SA signaling pathways may be related to the regulation of exogenous SA and 6-BA on the growth of mesocotyls. In addition, five candidate genes that may regulate the length of mesocotyls were screened by Weighted Gene Co-Expression Network Analysis (WGCNA). These genes may be involved in the growth of maize mesocotyls through auxin-activated signaling pathways, transmembrane transport, methylation and redox processes. The results enhance our understanding of the plant hormone regulation of mesocotyl growth, which will help to further explore and identify the key genes affecting mesocotyl growth in plant hormone signaling regulatory networks.

The Effects of Exogenous Benzoic Acid on the Physicochemical Properties, Enzyme Activities and Microbial Community Structures of Perilla frutescens Inter-Root Soil.

This study analyzed the effects of benzoic acid (BA) on the physicochemical properties and microbial community structure of perilla rhizosphere soil. The analysis was based on high-throughput sequencing technology and physiological and biochemical detection. The results showed that with the increase in BA concentration, soil pH significantly decreased, while the contents of total nitrogen (TN), alkaline nitrogen (AN), available phosphorus (AP), and available potassium (AK) significantly increased. The activities of soil conversion enzymes urease and phosphatase significantly increased, but the activities of catalase and peroxidase significantly decreased. This indicates that BA can increase soil enzyme activity and improve nutrient conversion; the addition of BA significantly altered the composition and diversity of soil bacterial and fungal communities. The relative abundance of beneficial bacteria such as Gemmatimonas, Pseudolabrys, and Bradyrhizobium decreased significantly, while the relative abundance of harmful fungi such as Pseudogymnoascus, Pseudoeurotium, and Talaromyces increased significantly. Correlation analysis shows that AP, AN, and TN are the main physicochemical factors affecting the structure of soil microbial communities. This study elucidates the effects of BA on the physicochemical properties and microbial community structure of perilla soil, and preliminarily reveals the mechanism of its allelopathic effect on the growth of perilla.

New variants of COVID-19 (XBB.1.5 and XBB.1.16, the "Arcturus"): A review of highly questioned concerns, a brief comparison between different peaks in the COVID-19 pandemic, with a focused systematic review on expert recommendations for prevention, vaccination, and treatment measures in the general population and at-risk groups.

INTRODUCTION: The COVID-19 pandemic has taken many forms and continues to evolve, now around the Omicron wave, raising concerns over the globe. With COVID-19 being declared no longer a "public health emergency of international concern (PHEIC)," the COVID pandemic is still far from over, as new Omicron subvariants of interest and concern have risen since January of 2023. Mainly with the XBB.1.5 and XBB.1.16 subvariants, the pandemic is still very much "alive" and "breathing." METHODS: This review consists of five highly concerning questions about the current state of the COVID Omicron peak. We searched four main online databases to answer the first four questions. For the last one, we performed a systematic review of the literature, with keywords "Omicron," "Guidelines," and "Recommendations." RESULTS: A total of 31 articles were included. The main symptoms of the current Omicron wave include a characteristically high fever, coughing, conjunctivitis (with itching eyes), sore throat, runny nose, congestion, fatigue, body ache, and headache. The median incubation period of the symptoms is shorter than the previous peaks. Vaccination against COVID can still be considered effective for the new subvariants. CONCLUSION: Guidelines recommend continuation of personal protective measures, third and fourth dose boosters, along with administration of bivalent messenger RNA vaccine boosters. The consensus antiviral treatment is combination therapy using Nirmatrelvir and Ritonavir, and the consensus for pre-exposure prophylaxis is Tixagevimab and Cilgavimab combination. We hope the present paper raises awareness for the continuing presence of COVID and ways to lower the risks, especially for at-risk groups.

A longitudinal study on SARS-CoV-2 seroconversion, reinfection and neutralisation spanning several variant waves and vaccination campaigns, Heinsberg, Germany, April 2020 to November 2022.

BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age: 50 years, range: 2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spike (S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+ CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.

Microbiota metabolized Bile Acids accelerate Gastroesophageal Adenocarcinoma via FXR inhibition.

Background: The incidence of Barrett esophagus (BE) and Gastroesophageal Adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BA) support fat digestion and undergo microbial metabolization in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis. The capacity of inhibiting cancer-related processes when activated, make FXR an appealing therapeutic target. In this work, we assess the role of diet on the microbiota-BA axis and evaluate the role of FXR in disease progression. Results: Here we show that high fat diet (HFD) accelerated tumorigenesis in L2-IL1B mice (BE- and GEAC- mouse model) while increasing BA levels and enriching gut microbiota that convert primary to secondary BA. While upregulated in BE, expression of FXR was downregulated in GEAC in mice and humans. In L2-IL1B mice, FXR knockout enhanced the dysplastic phenotype and increased Lgr5 progenitor cell numbers. Treatment of murine organoids and L2-IL1B mice with the FXR agonist obeticholic acid (OCA) deacelerated GEAC progression. Conclusion: We provide a novel concept of GEAC carcinogenesis being accelerated via the diet-microbiome-metabolome axis and FXR inhibition on progenitor cells. Further, FXR activation protected with OCA ameliorated the phenotype in vitro and in vivo, suggesting that FXR agonists have potential as differentiation therapy in GEAC prevention.

Cognitive function of children with biliary atresia after primary living donor liver transplantation.

BACKGROUND: The survival rate of children with biliary atresia (BA) after liver transplantation (LT) is significantly improved, and their quality of life has attracted much attention.This study aimed to investigate the cognition and its influencing factors in children with BA after primary living donor LT (BA-pLDLT) during infancy. METHODS: Children with BA were recruited 6 months after pLDLT at Children's Hospital of Chongqing Medical University (2018-2022). Demographic and clinical data were collected from the health information system. Cognition was assessed using the Chinese version of the Griffiths Mental Development scale (GMDS-C). Multivariate linear regression were used to analyze the influencing factors of their cognitive function. RESULTS: In total, 57 children with BA-pLDLT, aged 5.00(3.90-9.30) months at transplantation and 25.00(14.00-60.80) months at evaluation were included. The general developmental quotient (89.02 ± 12.07) and motor, language, eye-hand coordination, performance, and practical reasoning quotients of these children were significantly lower than the normative mean values of GMDS-C(P < 0.05). Of the 57 children, 16 (28.07%) had borderline developmental delay (DQ between 70 and 84), 3 (5.26%) had developmental delay (DQ < 70), and 11(19.29%) had language delay. Reoperation for biliary or vascular complications after pLDLT was a risk factor for decreased general development quotient and motor quotient and lower ZW at assessment was associated with decline motor quotient. CONCLUSION: Children with BA-pLDLT have varying degrees of developmental delays in early life. Reoperation and nutritional deficiencies had adverse effects on cognitive development.

Low pre-infection levels of neutralizing antibody in breakthrough infections after bivalent BA.4-5 vaccine and practical application of dried blood spots.

The level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4-5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50 % using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4-5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation.