Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3.

SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.

Apigenin analogs as α-glucosidase inhibitors with antidiabetic activity.

This study investigated the inhibitory potential of a series of synthesized compounds (L1-L27) on α-glucosidase. Among them, compound L22 showed significant inhibitory effect. Through enzymatic kinetics studies, we demonstrated that L22 acts via a non-competitive inhibition mode with a Ki value of 2.61 µM, highlighting its high affinity for the enzyme. Molecular docking studies revealed the formation of hydrogen bonds between L22 and α-glucosidase and diverse interactions with neighboring amino acid residues. Furthermore, molecular dynamics simulations confirmed the stability of the L22-α-glucosidase complex. In a mouse model of type 2 diabetes, treatment with L22 significantly lowered fasting blood glucose levels, and reduced insulin resistance, suggesting its potential as a therapeutic agent for type 2 diabetes. Furthermore, L22 showed a protective effect against oxidative stress in the liver and alleviated liver and pancreatic abnormalities. These results provide valuable insights into the mechanism of action of L22 and its potential applications to treat type 2 diabetes, and improve liver health.

Neutrophil-to-lymphocyte ratio and monocyte-to-eosinophil ratio as prognostic indicators for advanced nasopharyngeal carcinoma.

OBJECTIVE: To determine the predictive value of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-eosinophil ratio (LER), monocyte-to-eosinophil ratio (MER), systemic inflammatory response index (SIRI), and ratio of inflammatory cells before and after treatment for predicting survival in advanced nasopharyngeal carcinoma (NPC) and to provide a reference for treatment. METHODS: A retrospective review of 70 patients was performed. Serological indexes were obtained by drawing blood before and after systemic therapy. The cutoff values of these indexes were determined by receiver operating characteristic (ROC) curves. The prognostic value of the indexes for overall survival (OS) and distant metastasis free survival (DMFS) was evaluated. RESULTS: Survival analysis showed that a smaller pretreatment LMR value was associated with poor OS; larger pretreatment NER, LER, MER, and SIRI values were associated with poor OS; a smaller posttreatment LMR value was associated with poor OS; larger posttreatment NLR, NER, MER, and SIRI values were associated with poor OS; a smaller pretreatment LMR value was associated with poor DMFS; larger pretreatment NLR, NER, LER, and MER values were associated with poor DMFS; and larger posttreatment NLR, NER, LER, and MER values were associated with poor DMFS. Furthermore, a larger neutrophil after treatment-to-neutrophil before treatment ratio was associated with poor OS and DMFS. Logistic regression analysis showed that pretreatment MER and posttreatment NLR were independent predictors of OS in patients with advanced NPC; moreover, pretreatment and posttreatment MER and NLR were independent prognostic factors for DMFS in patients with advanced NPC. CONCLUSIONS: The NLR, NER and MER can be used to predict survival in advanced NPC patients. Eosinophils might be one of the factors for the good prognosis of NPC patients. In addition, an increased number of neutrophils after treatment may indicate a favorable prognosis.

Bioinformatics analysis of markers based on m6 A related to prognosis combined with immune invasion of renal clear cell carcinoma.

The incidence rate of renal cell carcinoma (RCC) is about 3% of all adult cancers. Of these, the Kidney clear cell renal cell carcinoma (KIRC) is the most common type, accounting for about 70%-75% of RCC. KIRC is difficult to be detected in time clinically. KIRC still has no effective treatment at this stage. We combined high-throughput bioinformatics analysis to obtained the structural sequence transcriptome data, relevant clinical information, and m6 A gene map of KIRC patients from genomics TCGA database. Pearson's correlation analysis was used to explore m6 A related gene long noncoding RNAs (lncRNAs), and then univariate Cox regression analysis was performed to screen the prognostic role of KIRC patients. Lasso-Cox regression was performed to establish the lncRNAs risk model associated with m6 A.LINC02154 and AC016773.2, Z98200.2, AL161782.1, EMX2OS, AC021483.2, CD27-AS1, AC006213.3 were iidentif. Compared with the low-risk group, the overall survival of patients in the high-risk group was significantly worse. Analyzing whether there are differences in immune cells between high-risk and low-risk subgroups. There were CD4 memory resting, Monocytes, Macrophages M1, Dendritic cells activated, Mast cells resting, which had higher infiltrations in the low-risk group. We performed Go enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and gene set enrichment analysis enrichment analysis. Overall, our results suggest that the component of m6A-related lncRNAs in the prognostic signal may be a key mediator in the immune microenvironment of KIRC, which represents a promising therapeutic effect.

Exosomes loaded with circPARD3 promotes EBV-miR-BART4-induced stemness and cisplatin resistance in nasopharyngeal carcinoma side population cells through the miR-579-3p/SIRT1/SSRP1 axis.

OBJECTIVE: To explore the effects of exosomes loaded with circular RNA PARD3 on EBV-miR-BART4-induced stemness and resistance of cisplatin in nasopharyngeal carcinoma side population (NPC-SP) cells through the miR-579-3p/SIRT1/SSRP1 axis. METHODS: Sixty-five cancer tissues and 65 noncancerous tissues were collected from NPC patients or patients with rhinitis. The expressions of circPARD3, miR-579-3p, SIRT1, and SSRP1 were detected by qRT-PCR, western blot, or immunohistochemistry. In vivo tumor formation assay was performed in nude mice. Immunofluorescence and qRT-PCR were conducted for the determination of CD44 and CD133 expressions, and flow cytometry combined with Hoechst 33,342 dye efflux for identifying SP cells, CCK-8 and EdU assays for cell proliferation, and Transwell assay for migration and invasion. RESULTS: CircPARD3, SIRT1, and SSRP1 were upregulated while miR-579-3p was downregulated in NPC tissues and cells. CircPARD3 was positively correlated with the expressions of SIRT1 and SSRP1, and miR-579-3p was negatively correlated with circPARD3, SIRT1, and SSRP1. Exosomes loaded with circPARD3 promoted EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells, while miR-579-3p reversed the effect of exosomal circPARD3 on EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells. Additionally, miR-579-3p suppressed EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells by regulating SIRT1. SIRT1 upregulated SSRP1 expression by catalyzing H3K4 methylation and down-regulation of SSRP1 reversed the effect of SIRT1 on EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells. CONCLUSION: Exosomes loaded with circPARD3 promoted EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells through the miR-579-3p/SIRT1/SSRP1 axis. Graphical Headlights • EBV-miR-BART4 induces the stemness and resistance of NPC-SP cells. • CircPARD3 regulates SIRT1 by miR-579-3p. • SIRT1 regulates SSRP1 expression by histone methylation. • Exosomes loaded with circPARD3 promotes EBV-miR-BART4-induced NPC-SP cell stemness and resistance by the miR-579-3p/SIRT1/SSRP1 axis.

Blood eosinophil count in the diagnosis of allergic-like rhinitis with chronic rhinosinusitis.

BACKGROUND: Allergic rhinitis (AR) and nonallergic rhinitis (NAR) often are comorbid with chronic rhinosinusitis (CRS). Finding a convenient test that distinguishes these complex conditions is helpful for effective treatment. We aimed to analyse blood parameter differences between AR and NAR patients with/without CRS. METHODS: Eight hundred thirteen patients, including AR and NAR with different conditions [CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP)] were analysed in this retrospective study. Patients with a nasal deviation alone were included as healthy controls (HC). Receiver operating characteristic analysis was used to assess the value of blood parameters for diagnosing AR or NAR with/without CRS. RESULTS: Compared to nonallergic-like rhinitis (HC, CRSwNP and CRSsNP), the blood eosinophil count was significantly increased in the allergic-like rhinitis groups, except for NAR-CRSsNP (AR, AR-CRSwNP, AR-CRSsNP, NAR and NAR-CRSwNP). The NAR-CRSsNP group had a higher level of eosinophils than the HC and CRSsNP groups. Among allergic-like rhinitis patients, eosinophils were higher in allergic-like rhinitis patients with CRSwNP (AR-CRSwNP and NAR-CRSwNP) than in allergic-like rhinitis patients without CRSwNP (AR, AR-CRSsNP, NAR and NAR-CRSsNP). However, no difference in blood eosinophils was observed between AR and NAR. There was also no difference among nonallergic-like rhinitis patients. Similar findings were found for the blood eosinophil proportion. Furthermore, the blood eosinophil count was a good predictor of allergic-like rhinitis, especially allergic-like rhinitis with CRSwNP. CONCLUSION: The blood eosinophil count and proportion may be good diagnostic predictors of allergic-like rhinitis but cannot differentiate between AR and NAR. This indicator may be much better in predicting allergic-like rhinitis with CRSwNP.

Increased miR-124-3p alleviates type 2 inflammatory response in allergic rhinitis via IL-4Rα.

BACKGROUND AND OBJECTIVES: miRNAs play a crucial role in regulating immune responses. However, the effect of miR-124-3p on type 2 inflammation in allergic rhinitis (AR) is unclear. We aimed to study the immune regulation of miR-124-3p in AR and the mechanisms involved. METHODS: The direct interaction between miR-124-3p and IL-4Rα was confirmed through a dual-luciferase reporter assay. In vitro splenic lymphocytes from mice and peripheral blood mononuclear cells (PBMCs) from healthy individuals were cultured and treated with miR-124-3p mimic/inhibitor. Twenty-four female C57BL/C mice were divided into four groups: control, AR model, miR-124-3p agomir, and miR-124-3p antagomir groups (n = 6 per group). The allergic responses were evaluated based on the number of sneezing and nasal scratching, the serum HDM-specific IgE (sIgE) levels, and the degree of nasal mucosa eosinophil infiltration. The expression of IL-4Rα, p-STAT6, and type 2 inflammatory cytokines (IL-4, IL-5 and IL-13) in lymphocytes or nasal mucosa was determined by qPCR, western blotting, flow cytometry, immunohistochemistry and immunofluorescence. RESULTS: miR-124-3p directly targets the 3'UTR of IL-4Rα. The miR-124-3p mimic lowered the IL-4Rα, p-STAT6, IL-4, IL-5, and IL-13 expression levels in both mouse splenic lymphocytes and human PBMCs in vitro, and the miR-124-3p inhibitor rescued these changes. Furthermore, the miR-124-3p agomir decreased the levels of IL-4Rα and IL-4 in nasal mucosa, Th2 differentiation in spleen, and allergic response in AR mice. Moreover, the miR-124-3p antagonist increased the IL-4Rα and IL-4 levels and further aggravated the allergic responses. CONCLUSIONS: miR-124-3p might attenuate type 2 inflammation in AR by regulating IL-4Rα signaling, and miR-124-3p may be a promising new target in AR treatment.

Photosynthetic Microorganisms-Based Biophotothermal Therapy with Enhanced Immune Response.

The production of oxygen by photosynthetic microorganisms (PSMs) has recently attracted interest concerning the in vivo treatment of multiple diseases for their photosynthetic oxygen production in vivo, since PSMs have good biological safety. Here, the first evidence that PSMs can be used as a photothermal source to perform biophotothermal therapy (bio-PTT) is provided. In vitro and in vivo experiments proved that PSMs can generate heat for the direct elimination of tumors and release a series of pathogen-associated molecular patterns and adjuvants for immune stimulation under light irradiation. Bio-PTT enabled a local tumor inhibition rate exceeding 90% and an abscopal tumor inhibition rate exceeding 75%. This strategy also produced a stronger antitumor immune memory effect to prevent tumor recurrence. The bio-PTT strategy provides a novel direction for photothermal therapy as it simultaneously produces local and abscopal antitumor effects.

COVID-19 illness and autoimmune diseases: recent insights.

BACKGROUND: The aim of this review is to explore whether patients with autoimmune diseases (AIDs) were at high risk of infection during the COVID-19 epidemic and how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected immune system. METHODS: A systematic literature search was performed using the foreign databases (NCBI, web of science, EBSCO, ELSEVIER ScienceDirect) and Chinese databases (WanFang, CNKI (China National Knowledge Infrastructure), VIP, CBM) to locate all relevant publications (up to January 10, 2021). The search strategies used Medical Search Headings (MeSH) headings and keywords for "COVID-19" or "SARS-CoV-2" or "coronavirus" and "autoimmune disease". RESULTS: This review evaluates the effect of SARS-CoV-2 on the immune system through ACE-2 receptor binding as the main pathway for cell attachment and invasion. It is speculated that SARS-COV-2 infection can activate lymphocytes and inflammatory response, which may play a role in the clinical onset of AIDs and also patients were treated with immunomodulatory drugs during COVID-19 outbreak. Preliminary studies suggested that the risk of developing severe forms of COVID-19 in patients with AIDs treated with immunomodulators or biologics might not increase. A large number of samples are needed for further verification, leading to an excessive immune response to external stimuli. CONCLUSION: The relationship between autoimmune diseases and SARS-CoV-2 infection is complex. During the COVID-19 epidemic, individualized interventions for AIDs should be provided such as Internet-based service.

Rutaecarpine alleviates acute pancreatitis in mice and AR42J cells by suppressing the MAPK and NF-κB signaling pathways via calcitonin gene-related peptide.

Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. Previous studies have shown that rutaecarpine (RUT), an important alkaloid component of Evodia rutaecarpa, exhibits certain protective effects against AP in rats by upregulating calcitonin gene-related peptide (CGRP). However, the molecular mechanism of RUT in AP remains unknown. This study aimed to investigate the effects of RUT on cerulein-induced AP in vivo and in vitro, and to explore the underlying molecular mechanisms. In cerulein/LPS-treated wild-type mice, but not CGRP gene knock-out mice, RUT significantly ameliorated pancreatic inflammation by alleviating histopathological changes, reducing IL-6 and TNF-α levels, and increasing in IL-10 levels. Moreover, RUT improved AP by suppressing the MAPK and NF-κB signaling pathways. These effects were mostly mediated through CGRP. Cell-based studies revealed that RUT significantly improved cell viability while suppressing the apoptosis of AR42J cells with cerulein-induced AP, downregulating IL-6 and TNF-α, stimulating IL-10 release, and inhibiting MAPK, NF-κB, and STAT3 signaling activation, all in a CGRP-dependent manner. RUT ameliorated cerulein/LPS-induced AP inflammatory responses in mice and AR42J cells in a CGRP-dependent manner and thus may represent a potential therapeutic option for AP patients. Our study provides valuable insights for AP drug development.

Flavonoid analogues as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation.

A series of novel flavonoid analogues were designed and synthesized. The aimed compounds for urease inhibitory activities were clearly superior to the control drug thiourea (more than 10 times). Among these compounds, L2 (IC50 = 1.343 µM) and L12 (IC50 = 1.207 µM) exhibited the most excellent urease inhibitory activity in vitro. The molecular dockings of L2, L12 and L22 into urease were performed to explore the binding modes and their structure-activity relationship. Furthermore, these aimed compounds showed good druggable properties.

Characterization and Genome Analysis of a Novel Salmonella Phage vB_SenS_SE1.

Salmonella is a significant food-borne pathogen that infects a large number of people worldwide. In this study, a lytic bacteriophage vB_SenS_SE1 capable of infecting Salmonella is isolated from municipal wastewater in Beijing, and its biological and genomic features are analyzed. Transmission electron micrograph shows that vB_SenS_SE1 is likely a Siphoviridae virus, with an icosahedral head and a long non-contracted tail. The stability test in vitro reveals that it is stable at 4-50 °C and pH 4-12. Based on the one-step growth curve, vB_SenS_SE1 has a 60-min exponential phase and a low burst size (19 PFU per cell). Bioinformatics analysis reveals that vB_SenS_SE1 consists of a circular, double-stranded DNA molecule of 40,987 bp with a GC content of 51.2%. Its genome carries 63 predicted open reading frames (orfs), with 22 orfs encoding known proteins. Phylogenetic analysis of the large terminase subunit shows that vB_SenS_SE1 exhibits strong homology to Salmonella phage St161, St162, VSiP, and FSL SP-031. The CoreGenes analysis shows that it is a member of the virus genus Cornellvirus. The features of phage vB_SenS_SE1 suggest that it has the potential to be an agent to control Salmonella.

Characterization and complete genome sequence of the virulent phage ST20 infecting Escherichia coli O165:H8.

A virulent phage, named ST20, infecting Escherichia coli O165:H8 was isolated from wastewater and subjected to genomic sequencing using the Illumina HiSeq system. Genomic analysis revealed that it contains double-stranded DNA, and its complete genome consists of 44,517 nucleotides with an average GC content of 50.81%. Morphological observations showed that phage ST20 belongs to the order Caudovirales and the family Siphoviridae due to its characteristic icosahedral capsid and a long noncontractile tail. This phage was further characterized by one-step growth curve analysis and measurement of its stability at 4 °C. The study has implications for the development of potential biocontrol agents.

Severe acute respiratory infection risk following glucocorticosteroid treatment in uncomplicated influenza-like illness resulting from pH1N1 influenza infection: a case control study.

BACKGROUND: Current studies regarding glucocorticosteroid treatment of influenza have only estimated risk of critical illness or death which can be easily confounded by timing of treatment administration. We used severe acute respiratory infection (sARI) as an endpoint and investigated risk associated with receiving glucocorticosteroids before sARI onset. METHODS: sARI cases were defined as influenza-like illness (ILI) with pH1N1 infection and respiratory distress. Controls were defined as pH1N1 cases other than sARI and randomly selected from the community. We compared glucocorticosteroids and other medications used before sARI onset using a matched case control study adjusted for age group as well as underlying disease. Time-dependent risk and dose responses at different time periods over the course of sARI cases were also examined. RESULTS: Of the sARI cases, 34% received glucocorticosteroids before sARI onset compared to 3.8% of controls during equivalent days (ORM-H = 17,95%CI = 2.1-135). Receiving glucocorticosteroids before sARI onset increased risk of developing subsequent critical illness or death (ORM-H = 5.7,95%CI = 1.6-20.2), and the ORM-H increased from 5.7 to 8.5 for continued glucocorticosteroid use after sARI onset. However, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness (ORM-H = 1.1,95%CI = 0.3-4.6). Each increase in glucocorticosteroids dose of 1 mg/kg/day before sARI onset resulted in an increase of 0.62 (R2 = 0.87) in the pMEWS score at the time of sARI onset. CONCLUSIONS: Early glucocorticosteroid treatment increased risk of sARI and subsequent critical illness or death; however, only receiving glucocorticosteroids after sARI onset did not increase risk of severe illness.

Complete genome sequence of a novel virulent phage ST31 infecting Escherichia coli H21.

More and more virulent phages that are fundamental materials for phage therapy have been isolated, characterized and categorized on GenBank. Phage ST31 infecting Escherichia coli H21 was isolated from wastewater and sequenced using an Illumina Hiseq system. Opening reading frames were identified using PHASTER and predicted using BLASTp analysis. Genomic analyses revealed that this was a virulent phage containing a circular double-stranded DNA and that the complete genome consisted of 39,693 nucleotides with an average GC content of 49.98 %. This study may provide possible alternative materials for phage therapy.

The complete genome sequence of PE3-1, a novel E. coli O153 phage.

A novel virulent phage PE3-1 against E. coli O153 was isolated from an aeration tank in a wastewater treatment plant. Transmission electron microscopy images showed that phage PE3-1 had an icosahedral head and a short tail, which revealed that it was a member of the family Podoviridae of the order Caudovirales. The complete PE3-1 genome consisted of 39,093 bp and was a linear double-stranded DNA with an average GC content of 49.93 %. Phage PE3-1 showed homology to the T7-like phages in 48 open reading frames (ORFs), but it differed from previously reported E .coli phages in morphology and bioinformatics analysis. This indicated that phage PE3-1 is a new member of the genus T7 virus.

Serum Proteomic Analysis Revealed Biomarkers for Eosinophilic Chronic Rhinosinusitis with Nasal Polyps Pathophysiology.

Background: Individuals with eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) exhibited worse outcomes and higher postoperative recurrence rates. This study aimed to identify biomarkers that can aid in the early differentiation of eCRSwNP and enhance our comprehension of its pathophysiology. Methods: We recruited two independent cohorts. In the discovery cohort, CRSwNP was categorized into eCRSwNP and non-eosinophilic CRSwNP(neCRSwNP), and serum proteomics was performed to identify differentially expressed proteins between the two groups. These candidate proteins were chosen and confirmed in the validation cohort using an enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and their predictive values and associations with tissue eosinophilic pathophysiology were evaluated. Results: We identified a total of 39 differential proteins between the two groups, including 20 proteins upregulated and 19 downregulated in the eCRSwNP group. Further validation was conducted on the top 5 proteins that were up or down-regulated. Results from the ELISA showed that levels of serum MRC1, CDH13, and MMP2 were significantly higher, TRIM28 was lower in the eCRSwNP group compared to the neCRSwNP group (all P<0.05), and serum MRC1 (AUC=0.742, P<0.001) and MMP2 (AUC=0.766, P<0.001) levels exhibited promising predicting values for eCRSwNP. Moreover, qRT-PCR and WB analysis found that MMP2 and MRC1 expressions were enhanced in the eCRSwNP group compared to the neCRSwNP group (all P<0.01), and their levels were positively correlated with the number and percentages of tissue eosinophils (all P<0.01). The IF suggested that MMP2 and MRC1 were overexpressed in the nasal polyps tissues of eCRSwNP patients, and MMP2 was mainly located on eosinophils. Conclusion: Circulating proteins identified by proteomics could serve as potential preoperative biomarkers for distinguishing eCRSwNP. Among them, MMP2 was enhanced in eCRSwNP and correlated with tissue eosinophilia, which provided valuable insights into the pathophysiology of eCRSwNP.

Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.

Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.

Clinical efficacy and risk factors for suction curettage and hysteroscopy in patients with type I and II cesarean scar pregnancy.

OBJECTIVE: To investigate the clinical efficacy and evaluate risk factors for suction curettage (SC) and hysteroscopy in the treatment of type I and II cesarean scar pregnancy (CSP). METHODS: This was a retrospective study including 100 women diagnosed with type I/II CSP. Patients were treated with either ultrasound-guided SC (SC group) or hysteroscopy resection (surgery group). The success rates, mean operation time, hospitalization duration, hospitalization cost, risk factors, adverse events, and complications were analyzed. RESULTS: The success rate of the SC and surgery groups were 85% and 100%, respectively, and the difference was statistically significant (P = 0.032). There was one case of type I CSP and eight cases of type II CSP that failed SC treatment. No failed cases were found in the surgery group. Analysis of the causes of treatment failure revealed that diameter of the gestational sac was a risk factor for SC failure (odds ratio, 19.66 [95% confidence interval {CI}, 1.70-227.72], P = 0.017). Comparing the clinical outcomes between the SC and surgery groups, although the mean operation time of the SC group was significantly shorter than the surgery group (15 [CI, 15-20] vs. 30 [CI, 27-40], P = 0.001), the cost and duration of hospitalization were significantly lower in the surgery group than that in the SC group. No significant differences were observed for adverse events and complications between the two groups (P > 0.05). CONCLUSION: Hysteroscopy is an effective and economical method for treating type I/II CSP. Moreover, SC is not recommended for patients with type I/II CSP with a gestation age ≥8 weeks.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain.

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.