Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus.

In 2022, the monkeypox virus (mpox virus, MPXV) exhibited global dissemination across six continents, representing a notable challenge owing to the scarcity of targeted antiviral interventions. Passive immunotherapy, such as the use of monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), has emerged as a promising option for antiviral regimens. Here, we generated several mAbs against M1R and B6R of MPXV, and subsequently characterized the antiviral activity of these antibodies both in vitro and in vivo. Two neutralizing mAbs, M1H11 and M3B2, targeting M1R, and one B6R-specific mAb, B7C9, were identified. They exhibited varying antiviral efficacy against vaccinia virus (VACV) in vitro and in vivo. A cocktail comprising M1H11 and M3B2 demonstrated a superior protective effect in vivo. A bsAb, Bis-M1M3, was engineered by conjugating the fragment crystallizable (Fc) region of the human-mouse chimeric engineered M1H11 with the single-chain fragment variable (scFv) of M3B2. In mice challenged with MPXV, Bis-M1M3 showed a notable protective effects. Analysis of neutralization mechanism showed that these mAbs and Bis-M1M3 exerted virus-neutralizing effects before the virus infects cells. In vivo pharmacokinetic experiments showed that Bis-M1M3 has a long half-life in rhesus macaques. This study provides crucial insights for further research on broad-spectrum antiviral drugs against MPXV and other orthopoxviruses.

Longitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study.

Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.

Fe3O4/biochar modified with molecularly imprinted polymer as efficient persulfate activator for salicylic acid removal from wastewater: Performance and specific recognition mechanism.

In this study, a novel Fe3O4-based biochar coupled surface-imprinted polymer was constructed via simple hydrothermal route for salicylic acid recognition and degradation in advanced oxidation processes. The material exhibited excellent adsorption capability, up to 118.23 mg g-1, and efficient degradation performance, 87.44% removal rate within 240 min, based on integrating the advantages of both huge specific surface area as well as abundant functional groups from biochars and specific recognition sites from imprinted cavities. Moreover, high selectivity coefficient (11.67) showed stable recognition in single and binary systems. SO4•- and •OH were confirmed as reactive oxygen species in catalytic reaction according to quenching experiments and EPR analysis. The degradation mechanism and pathway were unraveled by DFT calculations and LC-MS. Furthermore, the results of toxicity evaluation, stability and reusability demonstrated application potential in the field of water environment restoration. This study confirmed that molecular imprinting provided a promising solution to targeted removal of emerging environmental pollutants by degrading after the enrichment of pollutants to the composites surface.

miR-30a Serves as a Tumor Suppressor for Hepatocellular Carcinoma by Downregulating ADAMTS14.

BACKGROUND: Hepatocellular carcinoma (HCC) is a very common malignancy in the world, but the effect of therapies on advanced HCC has not improved for decades. The present study aimed to investigate the role of miR-30a in the tumorigenesis of HCC. METHODS: The expression of miR-30a and ADAMTS14 in HCC tissues were determined. Luciferase reporter gene detection confirmed the correlation between miR-30a and ADAMTS14. Cell viability and apoptosis rate were examined using an MTT assay and flow cytometry. Cell migration and invasion ability were detected by a transwell assay. The protein expression of ADAMTS14, ß-catenin, GSK-3ß, and p-GSK-3ß were determined using western blotting. RESULTS: miR-30a was negatively correlated with the expression of ADAMTS14 in HCC tissues. Further research confirmed that ADAMTS14 is the direct target of miR-30a. In addition, the expression of ADAMTS14, cell viability and apoptosis were suppressed by miR-30a overexpression, while knockdown of miR-30a led to the opposite result. miR-30a also inhibits the phosphorylation of GSK-3ß and ß-catenin, without changing the total GSK-3ß level. CONCLUSIONS: miR-30a acts as a tumor suppressor in the progression of HCC and can be used as a biomarker for early prediction and diagnosis.

Corrigendum: A Recombinant Human Adenovirus Type 5 (H101) Combined With Chemotherapy for Advanced Gastric Carcinoma: A Retrospective Cohort Study.

[This corrects the article DOI: 10.3389/fonc.2021.752504.].

A Recombinant Human Adenovirus Type 5 (H101) Combined With Chemotherapy for Advanced Gastric Carcinoma: A Retrospective Cohort Study.

BACKGROUND: This retrospective cohort study aimed to evaluate the clinical outcomes of H101 combined with chemotherapy for advanced gastric carcinoma (GC) patients. METHODS: The advanced GC patients, who were treated with H101 and/or chemotherapy, were enrolled and divided into three groups according to treatment method. The clinical characteristics of patients, clinical short-term and long-term outcomes, followed up, and complication were analyzed. RESULTS: A total of 95 patients (30 patients in group A were treated with H101, 33 in group B patients were treated with chemotherapy, 32 patients in group C were treated with H101 combined with chemotherapy) were retrospectively reviewed. The disease control rate (DCR) and overall response rate (ORR) were significantly greater in group C (81.3% and 50.0%) than in groups A (63.3% and 30.0%) and B (66.7% and 33.3%, all p < 0.05). The 1- and 2-year survival rates and progression-free survival were significantly greater in group C than in groups A and B (all p < 0.05). There was no significant difference in complication among the three groups. At dose levels of 0.5 × 1012 vp/day, 1.0 × 1012 vp/day, and 1.5 × 1012 vp/day, complications were not increased as increased of dose. CONCLUSIONS: H101 combined with chemotherapy may be a potential therapeutic option for patients with advanced GC, and prospective studies with proper assessment of toxicity will be needed in the future.

C1QTNF6 is overexpressed in gastric carcinoma and contributes to the proliferation and migration of gastric carcinoma cells.

In the present study, proteins differentially expressed between gastric cancer tissue and para­tumoral normal gastric tissues were screened, and the function of the highly expressed protein C1QTNF6 in gastric carcinoma was investigated. The differential expression of mRNAs extracted from the tumor and adjacent tissues was analyzed using GeneChip assay. An AGS si­C1QTNF6 cell line was constructed using shRNA­C1QTNF6 lentivirus. The cell invasion and migration ability of C1QTNF6­knockdown cells were determined by Transwell chamber migration and wound healing assays, respectively. The effects of C1QTNF6 on AGS cell cycle distribution and apoptosis were detected using a FACScan flow cytometer. The results demonstrated that the expression of 109 genes was increased and the expression of 129 was decreased in tumor tissues. Among these genes, the C1QTNF6 gene was highly expressed in tumor tissues and the AGS7901 cell line. C1QTNF6­knockdown decreased the cell growth, and the proliferative and migration ability, as well as increasing the apoptosis of gastric carcinoma cells. In addition, the number of AGS cells in the G2/M phase was significantly increased after 5 days of C1QTNF6­shRNA lentivirus infection. The results of the present study indicated that C1QTNF6 serves an important role in the development of gastric carcinoma. C1QTNF6 is involved in promoting the proliferation and migration, and in reducing the apoptosis of gastric carcinoma cells. These results provided a potential therapeutic target for the treatment of gastric carcinoma.

Efficacies of Various Surgical Regimens in the Treatment of Renal Calculi Patients: a Network Meta-Analysis in 25 Enrolled Controlled Clinical Trials.

BACKGROUND/AIMS: Renal calculi, or kidney stones, are masses made of crystals that affect people of all geographical, cultural, and racial groups. We conduct this study with the aim of comparing the efficacy of various surgical methods in the treatment of renal calculi. METHODS: Controlled clinical trials (CCTs) related to different surgical treatment approaches for renal calculi were included in this study by retrieving them from electronic English databases. The odds ratios (OR), the weighted mean difference (WMD), 95% confidence intervals (95% CI) and surface under the cumulative ranking curves (SUCRA) were evaluated, followed by a cluster analysis. RESULTS: Compared with the extracorporeal shockwave lithotripsy (SWL), minimally invasive percutaneous nephrolithotomy (mini-PCNL), retrograde intrarenal surgery (RIRS), standard percutaneous nephrolithotomy (standard PCNL), ureterorenoscopy (URS) and micro-percutaneous nephrolithotomy (microperc) regimens, the open anatrophic nephrolithotomy (Open AN), URS + RIRS and laparoscopic pyelolithotomy (LP) surgical procedures all presented with a higher stone-free rate in renal calculi. Lower auxiliary procedures were found in the URS + RIRS treatment approach compared with SWL, RIRS, URS and microperc regimens. In addition, the SWL regimen indicated a lower stone-free rate than the mini-PCNL, standard PCNL, Open AN, URS + RIRS and LP regimens. Finally, the RIRS regimen presented with the shortest in-patient stay compared to the mini-PCNL, standard PCNL, Open AN, URS, URS + RIRS and LP regimens. CONCLUSION: This meta-analysis demonstrated that the URS + RIRS surgical procedure has the best stone-free rate and the lowest number of auxiliary procedures. The RIRS and Microperc both have the shortest hospital stay and operative time.