Efficacy of the combination of BRII-196/BRII-198 in the treatment of COVID-19 vaccine breakthrough infections.

BACKGROUND: BRII-196 and BRII-198 are two recombinant human immunoglobulin (Ig) G1 monoclonal antibodies (mAbs) that non-competitively target distinct epitope regions within the receptor-binding domain (RBD) of the coronavirus spike glycoproteins. These antibodies are derived directly from human B cells of individuals who recovered from COVID-19. OBJECTIVE: To analyze the efficacy of BRII-196/BRII-198 in the treatment of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections. METHODS: COVID-19 patients at high risk of progressing to severe and critical illness, with an initial SARS-CoV-2 immunoglobulin (Ig) G antibody level < 1.0 S/CO (detected within 24-48 hours post COVID-19 diagnosis), were treated with BRII-196/BRII-198 within three days of symptom onset. Treatment continued until the antibody level exceeded 1.0 S/CO. Patients whose absolute lymphocyte count (ALC) at first detection (within 24-48 h post-diagnosis) was < 0.8 × 109/L received thymalfasin therapy within three days of symptom onset, continuing until the ALC level surpassed 0.8 × 109/L. We determined the correlation of SARS-CoV-2 IgG antibody level and ALC with the condition of COVID-19 patients. Additionally, we analyzed the effects of BRII-196/BRII-198 on SARS-CoV-2 nucleic acid (NA) negative conversion, lymphocyte count recovery, and the change in SARS-CoV-2 IgG antibody level from the first positive NA test for SARS-CoV-2 to negative conversion in COVID-19 patients. RESULTS: A total of 61 cases of breakthrough infections were observed, classified as 10 mild cases, 31 ordinary cases, and 20 severe cases. Among these, 20%, 48.4% and 75% of the patients with mild, ordinary, and severe COVID-19, respectively, had initial SARS-CoV-2 IgG antibody level < 1.0 S/CO. Additionally, 0%, 35% and 70% had initial ALC < 0.8 × 109/L, respectively. Fifteen ordinary and 15 severe COVID-19 patients were treated with BRII-196/BRII-198. In severely infected patients, BRII-196/BRII-198 treatment showed statistically significant differences in NA negative conversion time and changes in SARS-CoV-2 IgG antibody levels (P < 0.05). However, in patients classified with ordinary severity, BRII-196/BRII-198 treatment did not lead to notable differences in NA negative conversion time or changes in SARS-CoV-2 IgG antibody level (P > 0.05). BRII-196/BRII-198 therapy was not associated with lymphocyte count recovery time in patients with either ordinary and/or severe COVID-19 (P > 0.05). CONCLUSIONS: The initial levels of SARS-CoV-2 IgG antibody and lymphocytes in fully vaccinated patients with breakthrough infections are inversely correlated with the severity of the disease. Early treatment with BRII-196/BRII-198 can shorten NA negative conversion time in severe COVID-19 patients and increase in vivo neutralizing antibody levels post-conversion, providing lasting protection. However, BRII-196/BRII-198 does not influence lymphocyte count recovery in patients with either ordinary and/or severe COVID-19.

A multidisciplinary collaborative diagnosis and rehabilitation program for dysphagia in general hospitals.

Dysphagia is a common complication of various clinical conditions, with an increased incidence as age advances. Complications such as aspiration, malnutrition, and aspiration pneumonia caused by dysphagia significantly affect the overall treatment outcomes of patients. Scholars both domestically and internationally are increasingly focusing on early rehabilitation for dysphagia. This article summarizes common conditions causing dysphagia, clinical manifestations, complications, screening assessment, diagnosis, rehabilitation, and nutritional support related to dysphagia. It emphasizes the arrival at a multidisciplinary collaborative diagnosis and formulation of a rehabilitation management plan for dysphagia in general hospitals in order to provide strategic suggestions for establishing a multidisciplinary collaborative model for swallowing disorder management in general hospitals.

Highly elastic, fatigue-resistant, antibacterial, conductive, and nanocellulose-enhanced hydrogels with selenium nanoparticles loading as strain sensors.

The fabrication of highly elastic, fatigue-resistant and conductive hydrogels with antibacterial properties is highly desirable in the field of wearable devices. However, it remains challenging to simultaneously realize the above properties within one hydrogel without compromising excellent sensing ability. Herein, we fabricated a highly elastic, fatigue-resistant, conductive, antibacterial and cellulose nanocrystal (CNC) enhanced hydrogel as a sensitive strain sensor by the synergistic effect of biosynthesized selenium nanoparticles (BioSeNPs), MXene and nanocellulose. The structure and potential mechanism to generate biologically synthesized SeNPs (BioSeNPs) were systematically investigated, and the role of protease A (PrA) in enhancing the adsorption between proteins and SeNPs was demonstrated. Additionally, owing to the incorporation of BioSeNPs, CNC and MXene, the synthesized hydrogels showed high elasticity, excellent fatigue resistance and antibacterial properties. More importantly, the sensitivity of hydrogels determined by the gauge factor was as high as 6.24 when a high strain was applied (400-700 %). This study provides a new horizon to synthesize high-performance antibacterial and conductive hydrogels for soft electronics applications.

Rapid Initiation of Antiretroviral Therapy with Coformulated Bictegravir, Emtricitabine, Tenofovir Alafenamide Versus Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate in HIV-positive Men Who Have Sex with Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

BACKGROUND: Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with HIV-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400-mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among HIV-positive men who have sex with men (MSM). METHODS: This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV(400-mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/ml) at 48 weeks per FDA Snapshot analysis. RESULTS: Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression; and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (p < 0.001), respectively, discontinued treatment due to adverse effects, death, or loss to follow-up. The median increase of CD4 count was 181 and 223 cells/µL (p = 0.020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < 0.001). CONCLUSION: BIC/FTC/TAF was more efficacious and safer than EFV(400-mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

Molecular characterization of a novel mycovirus from binucleate Rhizoctonia AG-A strain A46.

The complete genome sequence of a positive-sense single-stranded RNA (+ ssRNA) virus, Rhizoctonia beny-like virus 1 (RBLV1), isolated from binucleate Rhizoctonia AG-A strain A46, was determined. The RBLV1 genome is 10,280 nt in length and contains a short stretch of adenines at the 3' terminus. It contains a single open reading frame (ORF) encoding a 376.30-kDa protein with viral helicase and RNA-dependent RNA polymerase (RdRp) motifs. The encoded protein exhibited the highest sequence similarity to Rhizoctonia cerealis beny-like virus 0928-1 (RcBeLV 0928-1, 45.25%), with a sequence coverage of 63%. Phylogenetic analysis based on ORF protein sequences revealed that RBLV1 is a novel unclassified mycovirus.

FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS) that is characterized by myelin damage, followed by axonal and ultimately neuronal loss, which has been found to be associated with mitophagy. The etiology and pathology of MS remain elusive. However, the role of FK506 binding protein 5 (FKBP5, also called FKBP51), a newly identified gene associated with MS, in the progression of the disease has not been well defined. Here, we observed that the progress of myelin loss and regeneration in Fkbp5ko mice treated with demyelination for the same amount of time was significantly slower than that in wild-type mice, and that mitophagy plays an important regulatory role in this process. To investigate the mechanism, we discovered that the levels of FKBP5 protein were greatly enhanced in the CNS of cuprizone (CPZ) mice and the myelin-denuded environment stimulates significant activation of the PINK1/Parkin-mediated mitophagy, in which the important regulator, PPAR-γ, is critically regulated by FKBP5. This study reveals the role of FKBP5 in regulating a dynamic pathway of natural restorative regulation of mitophagy through PPAR-γ in pathological demyelinating settings, which may provide potential targets for the treatment of demyelinating diseases.

Highly Conductive, Anti-Freezing Hemicellulose-Based Hydrogels Prepared via Deep Eutectic Solvents and Their Applications.

Hydrogels containing renewable resources, such as hemicellulose, have received a lot of attention owing to their softness and electrical conductivity which could be applied in soft devices and wearable equipment. However, traditional hemicellulose-based hydrogels generally exhibit poor electrical conductivity and suffer from freezing at lower temperatures owing to the presence of a lot of water. In this study, we dissolved hemicellulose by employing deep eutectic solvents (DESs), which were prepared by mixing choline chloride and imidazole. In addition, hemicellulose-based DES hydrogels were fabricated via photo-initiated reactions of acrylamide and hemicellulose with N, N'-Methylenebisacrylamide as a crosslinking agent. The produced hydrogels demonstrated high electrical conductivity and anti-freezing properties. The conductivity of the hydrogels was 2.13 S/m at room temperature and 1.97 S/m at -29 °C. The hydrogel's freezing point was measured by differential scanning calorimetry (DSC) to be -47.78 °C. Furthermore, the hemicellulose-based DES hydrogels can function as a dependable and sensitive strain sensor for monitoring a variety of human activities.

Analysis of risk factors of precocious puberty in children.

BACKGROUND: The purpose of this study is to explore the related factors of precocious puberty in children. METHODS: 1239 children who underwent physical examination in our hospital from January 2020 to December 2022 were analyzed, including 198 precocious children and 1041 normal children. According to the age of 198 precocious children and 1041 normal children, 205 normal children were selected, and the remaining 836 normal children were excluded. They were divided into precocious group and normal group. The general data of the two groups were recorded. Logistic regression was used to analyze the influencing factors of precocious puberty in children. RESULTS: There were statistically significant differences (P < 0.05) between the two groups in sex, bone age, daily exercise time, E2, FSH, LH, leptin, mother's menarche time, living environment, consumption of nutritional supplements, consumption of foods containing pigments and preservatives, consumption of high-protein foods, and sleeping time. The multifactor logistic regression analysis shows that the risk factors of children's precocious puberty included gender (female), bone age (> 10 years old), and daily exercise time (< 0.9 h), E2 (≥ 66.00pmol/L), FSH (≥ 6.00U/L), LH (≥ 3.50U/L), leptin (≥ 8.00 µ G/L), mother's menarche time (< 12 years old), living environment (chemical industry zone), consumption of nutritional supplements (often), consumption of high-protein food (often), and sleep time (< 10 h). CONCLUSION: In conclusion, children's gender, bone age, exercise habits, E2, FSH, LH, leptin, mother's menarche time, living environment, eating habits, sleep time and other factors are closely related to precocious puberty in children. Reminding parents to actively prevent related factors in clinical work is helpful to prevent the occurrence of precocious puberty in children.

Prevalence of Intimate Partner Violence and Associated Factors Among People With HIV: A Large-Sample Cross-Sectional Study in China.

To assess the prevalence and exacerbating factors of intimate partner violence in people with human immunodeficiency virus (PWH) in China, we conducted a cross-sectional study, involving 2792 PWH in 4 provinces in China from 1 September 2020 to 1 June 2021. The categories of intimate partner violence (IPV) included physical violence, sexual violence, emotional abuse, and controlling behavior. The severity of a violent act was divided into mild, moderate, and severe. Among PWH, the prevalence of IPV was 15.4% (95% confidence interval, 14.1%-16.8%). The severity of physical violence was mainly moderate, and the severity of sexual violence, emotional abuse, and controlling behavior was mainly mild. The prevalence of IPV in men was higher than that in women. Results from the multivariable logistic regression showed that age, ethnic, registered residence, education, and duration of HIV antiretroviral therapy were factors related to IPV in PWH (P < .05).

SHP2 Contributes to Resistance of KRAS p.G12C-Driven Lung Cancer Cells to MRTX849 by Regulating ß-catenin/c-MYC Axis.

OBJECTIVE: SHP2 has been promulgated to be involved in chemoresistance in a variety of cancers. However, its relationship with MRTX849-resistance in KRAS G12C mutant lung cancer has not been revealed. METHODS: Lung cancer cell lines resistant to MRTX849 were first constructed by repeated dosing over 10 months, and the parental and drug-resistant strains were evaluated for SHP2 expression at different time points (2, 4, 6, 8, 10 months). We further analyzed whether SHP2 knockdown affects the sensitivity of MRTX849-resistant cells to MRTX849, and overexpression of SHP2 in the parental cell line to assess its effect on MRTX849 resistance, mainly by CCK-8, clonogenic assay, TUNEL staining and Western blotting to assess cell viability, proliferation, apoptosis, as well as ß-catenin/c-MYC pathway protein expression. RESULTS: SHP2 expression remained largely unchanged in the parental cell line, whereas they were gradually upregulated in a time-dependent manner in the resistant cell line. SHP2 knockdown enhanced the sensitivity of MRTX849-resistant cell lines to MRTX849 and encouraged the killing of lung cancer cells by MRTX849, as indicated by a more significant decrease in cell viability and proliferation after knockdown of SHP2 in the presence of MRTX849 compared with MRTX849 untreated, while apoptosis was more significantly enhanced. Additionally, SHP2 overexpression enhanced the resistance of MRTX849 to lung cancer cells. Eventually, we confirmed that the MRTX849-resistance effect of SHP2 on lung cancer cells was through the activation of the ß-catenin/c-MYC pathway. CONCLUSION: SHP2 contributes to resistance of KRAS G12C-driven lung cancer cells to MRTX849 by regulating ß-catenin/c-MYC axis.

Exploring Associations Between Short-Term Air Pollution and Daily Outpatient Visits for Allergic Rhinitis.

Purpose: Many studies have reported that exposure to air pollution increases the likelihood of acquiring allergic rhinitis (AR). This study investigated associations between short-term air pollution exposure and AR outpatient visits. Patients and Methods: The Department of Otorhinolaryngology, Affiliated Hospital of Hangzhou Normal University provided AR outpatient data from January 1, 2019 to December 31, 2021. Daily air quality information for that period was gathered from the Hangzhou Air Quality Inspection Station. We used the Poisson's generalized additive model (GAM) to investigate relationships between daily outpatient AR visits and air pollution, and investigated lag-exposure relationships across days. Subgroup analyses were performed by age (adult (>18 years) and non-adult (<18 years)) and sex (male and female). Results: We recorded 20,653 instances of AR during the study period. Each 10 g/m3 increase in fine particulate matter (PM10 and PM2.5) and carbon monoxide (CO) concentrations was associated with significant increases in AR outpatient Visits. The relative risks (RR) were: 1.007 (95% confidence interval (CI): 1.001-1.013), 1.026 (95% CI: 1.008-1.413), and 1.019 (95% CI: 1.008-1.047). AR visits were more likely due to elevated PM2.5, PM10, and CO levels. Additionally, children were more affected than adults. Conclusion: To better understand the possible effects of air pollution on AR, short-term exposure to ambient air pollution (PM2.5, PM10, and CO) may be linked to increased daily outpatient AR visits.

Comparison of visual quality after SMILE correction of low-to-moderate myopia in different optical zones.

OBJECTIVE: To compare the effects of different optical zones for small-incision lenticule extraction (SMILE) on postoperative visual quality in low-to-moderate myopia. METHODS: This retrospective case-control study involved patients who underwent SMILE using two optical-zone diameters: 6.5 mm (50 patients, 100 eyes) and 6.8 mm (50 patients, 100 eyes). Uncorrected visual acuity (UCVA), best corrected visual acuity, spherical equivalent (SE), corneal higher-order aberrations (HOAs), and subjective visual-quality questionnaire scores were assessed. RESULTS: Postoperatively, UCVA and SE did not differ between the two groups (P > 0.05). In both groups, corneal HOAs, spherical aberration, and coma significantly increased at 1 and 3 months postoperatively (P < 0.05), while trefoil was unchanged after surgery (P > 0.05). Corneal HOAs, spherical aberration, and coma significantly differed between the groups at 1 and 3 months (P < 0.05), while trefoil did not (P > 0.05). Visual-quality scores were higher in the 6.8 mm group than in the 6.5 mm group at 1 month (P = 0.058), but not at 3 months (P > 0.05). In both groups, subjective scores significantly decreased at 1 month (P < 0.05) and gradually returned to the preoperative level at 3 months (P > 0.05). The subjective visual-quality scores were negatively and positively correlated with pupillary and optical-zone diameter, respectively (P < 0.05 for both). Objective visual-quality indicators (HOAs, spherical aberration, and coma) were negatively correlated with optical-zone diameter (P < 0.05) but not pupillary diameter (P > 0.05). CONCLUSION: SMILE in different optical zones effectively corrected low-to-moderate myopia. The larger the optical-zone diameter, the better the early postoperative visual quality.

Role of Proviral HIV-1 DNA Genotyping for People Living with HIV (PLWH) Who Had Low-Level Viremia While Receiving Antiretroviral Therapy.

Objective: To analyze the antiretroviral resistance in people living with HIV (PLWH) who developed low-level viremia (LLV) during antiretroviral therapy (ART) via sequencing of their HIV-1 proviral DNA and RNA and comparisons of their proviral DNA genotyping data with their past and synchronous RNA genotyping data. Patients and Methods: PLWH with LLV while receiving ART for 6 months or longer from January 2020 to September 2021 were included. HIV-1 proviral DNA and RNA were extracted from white-blood cells and concentrated plasma by ultracentrifugation, respectively, and HIV-1 pol gene fragments were amplified and sequenced. The concordance in the detection of resistance-associated mutations (RAMs) were examined between proviral DNA vs past RNA genotyping and proviral DNA vs synchronous RNA genotyping. Results: Of the 150 PLWH with LLV, 117 proviral DNA pol sequences detected in 105 PLWH were successfully amplified and RAMs were present in 27.6% and the rate of RAMs conferring low-level or greater resistance to antiretrovirals examined was 17.1%. Fifty-six and 57 PLWH had results of past and synchronous RNA genotyping, respectively, for comparisons with those of proviral DNA genotyping; and the concordance rates were 76.8% and 75.4%, respectively. However, proviral DNA genotyping lost than gained partial information on antiretroviral resistance compared with past or synchronous RNA genotyping. Conclusion: We found that the concordance between proviral DNA and past and synchronous RNA genotyping was moderate. Proviral DNA genotyping lost than gained more information on antiretroviral resistance compared with past or synchronous RNA genotyping. To optimize ART in PLWH with LLV, antiretroviral resistance profile should be interpreted in combination with proviral DNA and RNA genotyping and a comprehensive review of previous treatment history.

Malnutrition accelerates the occurrence of infectious complications in patients with chronic kidney disease: A cross-sectional survey of 682 patients with chronic kidney disease.

BACKGROUND: To investigate the influencing factors of infectious complications in patients with chronic kidney disease (CKD) and provide a basis for clinical diagnosis and prognosis evaluation of CKD. METHODS: A total of 682 patients with CKD were selected and divided into CKD stage 1-5 subgroups according to their glomerular filtration rate. Infectious complications, length of hospital stay, and total cost of hospitalization were recorded. The Global Leadership Initiative on Malnutrition (GLIM) diagnostic tool was used to assess the detection rate of malnutrition among patients. Univariate and multivariate analyses were performed in patients with and without infectious complications. RESULTS: The incidence rates of infectious complications in CKD stages 1-5 were 45.6%, 22.7%, 28.3%, 30.8%, and 40.4%, respectively. The overall detection rate of malnutrition among patients based on the GLIM criteria was 16.7%. The total detection rate of severe malnutrition was 14.2%, with all patients with severe malnutrition in CKD stages 3-5. The incidences of infectious complications in patients with and without malnutrition were 62.3% and 29%, respectively. Binary multivariate logistic regression analysis shows that malnutrition is a risk factor for infectious complications in patients with CKD, who are at 2.41 times higher risk than patients without malnutrition. There were significant differences in length of hospital stay and hospitalization costs between the patients with CKD with and without infectious complications (P < 0.01). CONCLUSION: Infectious complications are relatively common in patients with CKD. As CKD advances, the incidence of infectious complications increases. Moreover, malnutrition accelerates the occurrence of infectious complications in patients with CKD.

Lomatogonium rotatum extract alleviates diabetes mellitus induced by a high-fat, high-sugar diet and streptozotocin in rats.

BACKGROUND: Lomatogonium rotatum (LR) is traditionally used in Mongolian folk medicine as a hypoglycemic agent, but its evidence-based pharmacological effects and me-chanisms of action have not been fully elucidated. AIM: To emphasize the hypoglycemic action mechanism of LR in a type 2 diabetic rat model and examine potential biomarkers to obtain mechanistic understanding regarding serum metabolite modifications. METHODS: A high-fat, high-sugar diet and streptozotocin injection-induced type 2 diabetic rat model was established. The chemical composition of the LR was identified by high performance liquid chromatography. LR extract administrated as oral gavage at 0.5 g/kg, 2.5 g/kg, and 5 g/kg for 4 wk. Anti-diabetic effects of LR extract were evaluated based on histopathological examination as well as the measurement of blood glucose, insulin, glucagon-like peptide 1 (GLP-1), and lipid levels. Serum metabolites were analyzed using an untargeted metabolomics approach. RESULTS: According to a chemical analysis, swertiamarin, sweroside, hesperetin, coumarin, 1.7-dihydroxy-3,8-dimethoxyl xanthone, and 1-hydroxy-2,3,5 trimethoxanone are the principal active ingredients in LR. An anti-diabetic experiment revealed that the LR treatment significantly increased plasma insulin and GLP-1 levels while effectively lowering blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and oral glucose tolerance test compared to the model group. Furthermore, untargeted metabolomic analysis of serum samples detected 236 metabolites, among which 86 were differentially expressed between the model and the LR group. It was also found that LR considerably altered the levels of metabolites such as vitamin B6, mevalonate-5P, D-proline, L-lysine, and taurine, which are involved in the regulation of the vitamin B6 metabolic pathway, selenium amino acid metabolic pathway, pyrimidine metabolic pathway, and arginine and proline metabolic pathways. CONCLUSION: These findings indicated that LR may have a hypoglycemic impact and that its role may be related to changes in the serum metabolites and to facilitate the release of insulin and GLP-1, which lower blood glucose and lipid profiles.

Tris(1,3-dichloro-2-propyl) phosphate causes female-biased growth inhibition in zebrafish: Linked with gut microbiota dysbiosis.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is ubiquitous in aquatic environment, but its effect on intestinal health of fish has yet not been investigated. In the present study, the AB strain zebrafish embryos were exposed to environmentally realistic concentrations (0, 30, 300, and 3000 ng·L-1) of TDCIPP for 90 days, after which the fish growth and physiological activities were evaluated, and the intestinal microbes were analyzed by 16S rRNA gene high-throughput sequencing. Our results manifested that the body length and body weight were significantly reduced in the female zebrafish but not in males. Further analyses revealed that TDCIPP resulted in notable histological injury of intestine, which was accompanied by impairment of epithelial barrier integrity (decreased tight junction protein 2), inflammation responses (increased interleukin 1ß), and disruption of neurotransmission (increased serotonin) in female intestine. Male intestines maintained intact intestinal structure, and the remarkably increased activity of glutathione peroxidase (GPx) might protect the male zebrafish from inflammation and intestinal damage. Furthermore, 16S rRNA sequencing analysis showed that TDCIPP significantly altered the microbial communities in the intestine in a gender-specific manner, with a remarkable increase in alpha diversity of the gut microbiome in male zebrafish, which might be another mechanism for male fish to protect their intestines from damage by TDCIPP. Correlation analysis revealed that abnormal abundances of pathogenic bacteria (Chryseobacterium, Enterococcus, and Legionella) might be partially responsible for the impaired epithelial barrier integrity and inhibition in female zebrafish growth. Taken together, our study for the first time demonstrates the high susceptibility of intestinal health and gut microbiota of zebrafish to TDCIPP, especially for female zebrafish, which could be partially responsible for the female-biased growth inhibition.

Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development.

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy. Supplementary Information: The online version contains supplementary material available at 10.1186/s12645-023-00190-x.