Study on the role of CCM3 gene and lead exposure induced neurotoxicity through neurovascular units.

This study aimed to determine the toxic effects of vascular CCM3 gene deficiency and lead (Pb) exposure on the nervous system. Lentiviral transfection was performed to generate a stable strain of brain microvascular endothelial cells with low CCM3 expression. MTT assay assessed the survival rate of cells exposed to Pb, determining the dose and duration of Pb exposure in vitro. Proteomic analysis was performed on the differentially expressed proteins in bEnd3 and HT22 cells and flow cytometry was used to detect cell apoptosis. Finally, urine samples from pregnant and postpartum women were subjected to ICP-MS to detect Pb levels and HPLC to detect neurotransmitter metabolites. Based on the proteomic analysis of bEnd3 (CCM3-/-) cells co-cultured with HT22 cells, it was determined that HT22 cells and CCM3 genes interfered with bEnd3 cell differential proteins,2 including apoptosis and ferroptosis pathways. Electron microscopy observation, ICP-MS iron ion loading detection, and WB determination of protein GPX4 expression confirmed that HT22 cells undergo apoptosis, while bEnd3 cells undergo multiple pathways of iron death and apoptosis regulation. Furthermore, a linear regression model showed the interaction between maternal urine Pb levels, the rs9818496 site of the CCM3 SNP in peripheral blood DNA, and the concentration of the neurotransmitter metabolite 5-HIAA in maternal urine (F=4.198, P < 0.05). bEnd3 cells with CCM3 gene deficiency can induce HT22 cell apoptosis through iron death and apoptosis pathways under Pb exposure in a combined cell culture Pb exposure model, and CCM3 gene deficiency in endothelial cells and Pb exposure interacts with neural cell HT22. Epidemiological studies on maternal and newborn infants further confirmed the interaction between urine Pb levels in mothers and the SNP rs9818496 site of the CCM3 gene in peripheral blood DNA.

Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

Adenoviral Vector for Enhanced Prostate Cancer Specific Transferrin Conjugated Drug Targeted Therapy.

Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Unlike some other types of cancer, there is a lack of targeted therapy for prostate cancer patients that can kill cancer cells but do much less damage to the normal tissue. In this paper, we report on an adenoviral vector enhanced prostate cancer specific transferrin conjugated drug targeted therapy. In particular, a functional PCa-specific gene probe is introduced to drive and up-regulate the transferrin receptor expression on the PCa via adenoviral vector. As a result, significantly enhanced accumulation of nanoscale transferrin-doxorubicin (Tf-DOX) protein drug conjugates and concomitant notably elevated PCa tumor inhibition are observed. This conceptual strategy provides the proof-of-concept for the targeted therapy of PCa that is highly desired but not yet developed.

An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.

Effects of Antibiotic Treatment and Probiotics on the Gut Microbiome of 40 Infants Delivered Before Term by Cesarean Section Analysed by Using 16S rRNA Quantitative Polymerase Chain Reaction Sequencing.

BACKGROUND This study aimed to investigate the effects on the gut microbiome of 40 infants delivered before term by cesarean section between antibiotic treatment and probiotics as assessed by 16S rRNA quantitative polymerase chain reaction (qPCR) sequencing. MATERIAL AND METHODS We divided 40 premature infants delivered by cesarean section into 4 groups according to exposure to antibiotics or probiotics: N group (No-probiotics and No-antibiotics), A group (antibiotics), P group (probiotics), and the AP group (antibiotics+probiotics). Fecal samples were collected on days 1, 3, and 10, and the microflora data were generated using 16S rRNA qPCR sequencing technology. The BugBase tool was used for phenotype prediction, the Tax4Fun tool was used for function prediction, and iPath software was used to predict the metabolic pathways of intestinal bacteria. RESULTS Antibiotics increased the abundance of pathogenic bacteria and reduced the replication and repair function (P=0.049), nucleotide metabolism function (P=0.047), and the purine metabolism pathways (P<0.05) of the gut microbiota. Probiotics increased the abundance of beneficial bacteria and the cellular community prokaryote function (P=0.042) and contributed to the Bifidobacteria biofilm formation. Probiotics alleviated the damage of antibiotics to the composition and function of the gut microbiota. CONCLUSIONS The findings from this study showed that antibiotic treatment of preterm infants born by cesarean section changed the gut microbiome, but that the use of probiotics could restore the normal microbiome, which supports that restoration of the normal gut microbiota may be achieved with probiotics.

The role of influenza vaccination in mitigating the adverse impact of ambient air pollution on lung function in children: New insights from the Seven Northeastern Cities Study in China.

BACKGROUND: Ambient air pollution exposure and influenza virus infection have been documented to be independently associated with reduced lung function previously. Influenza vaccination plays an important role in protecting against influenza-induced severe diseases. However, no study to date has focused on whether influenza vaccination may modify the associations between ambient air pollution exposure and lung function. METHODS: We undertook a cross-sectional study of 6740 children aged 7-14 years into Seven Northeast Cities (SNEC) Study in China during 2012-2013. We collected information from parents/guardians about sociodemographic factors and influenza vaccination status in the past three years. Lung function was measured using portable electronic spirometers. Machine learning methods were used to predict 4-year average ambient air pollutant exposures to nitrogen dioxide (NO2) and particulate matter with an aerodynamic diameter <1 µm (PM1), <2.5 µm (PM2.5) and <10 µm (PM10). Two-level linear and logistic regression models were used to assess interactions between influenza vaccination and long-term ambient air pollutants exposure on lung function reduction, controlling for potential confounding factors. RESULTS: Ambient air pollution were observed significantly associated with reductions in lung function among children. We found significant interactions between influenza vaccination and air pollutants on lung function, suggesting greater vulnerability to air pollution among unvaccinated children. For example, an interaction (pinteraction = 0.002) indicated a -283.44 mL (95% CI: -327.04, -239.83) reduction in forced vital capacity (FVC) per interquartile range (IQR) increase in PM1 concentrations among unvaccinated children, compared with the -108.24 mL (95%CI: -174.88, -41.60) reduction in FVC observed among vaccinated children. Results from logistic regression models also showed stronger associations between per IQR increase in PM1 and lung function reduction measured by FVC and peak expiratory flow (PEF) among unvaccinated children than the according ORs among vaccinated children [i.e., Odds Ratio (OR) for PM1 and impaired FVC: 2.33 (95%CI: 1.79, 3.03) vs 1.65 (95%CI: 1.20, 2.28); OR for PM2.5 and impaired PEF: 1.45 (95%CI: 1.12,1.87) vs 1.04 (95%CI: 0.76,1.43)]. The heterogeneity of the modification by influenza vaccination of the associations between air pollution exposure and lung function reduction appeared to be more substantial in girls than in boys. CONCLUSION: Our results suggest that influenza vaccination may moderate the detrimental effects of ambient air pollution on lung function among children. This study provides new insights into the possible co-benefits of strengthening and promoting global influenza vaccination programs among children.

BCG-induced formation of neutrophil extracellular traps play an important role in bladder cancer treatment.

Bacillus Calmette-Guerin (BCG) is one of the most effective treatments for bladder cancer. Little attention has been paid to the possible role of neutrophils in BCG immunotherapy. In this study, we examined neutrophil extracellular traps (NETs) formation induced by BCG stimulation, and found that BCG-induced NETs exerted cytotoxicity, induced apoptosis and cell-cycle arrest, and inhibited migration in bladder tumor cells. BCG-activated tumor cells but not non-activated ones elicited NETs formation, in which IL-8 and TNF-α from activated tumor cells both took effect. Moreover, NETs activated peripheral blood mononuclear cells (PBMCs) exhibited a higher expression of CD4 and Th1 cytokines. Additionally, the role of NETs in vivo contributed to the recruitment of T cells and monocytes-macrophages and tissue damage, thus preventing tumor growth. NETs proteins mainly caused these effects on tumor and cellular immunity. In conclusion, we demonstrated a novel immunoregulatory role for NETs in the early stages of BCG immunotherapy.

Prognostic value of miR-221 in human malignancy: evidence from 3041 subjects.

BACKGROUND: MiR-221, acting as onco-miR or oncosuppressor-miR, plays an important role in tumor progression; however, the prognostic value of miR-221 in human carcinomas is controversial and inconclusive. The objective of our study was to conducted a systematic review and meta-analysis of miR-221 in various types of human cancers. METHODS: An online search of up-to-date electronic databases, including PubMed and Embase, was conducted to identify as many relevant papers as possible. 32 papers involving 3041 patients with different carcinomas were included in the analysis. Hazard ratios (HRs) of miR-221 were used to evaluate prognostic values. RESULTS: Thirty-two papers involving 15 cancers were included. MiR-221 was associated with a worse overall survival (OS) in patients, and a combined HR was 1.93 (95% CI of 1.43-2.60, 2080 patients, 22 studies, I-squared = 80.4%, P = 0.000); however, the combined HR for relapse-free survival (RFS) was 1.37 (95% CI of 0.75-2.48, 625 patients, 7 studies, I-squared = 78.8%, P = 0.000), and disease-free survival (DFS) was 1.24 (95% CI of 0.60-2.56, 539 patients, 5 studies, I-squared = 81.8%, P = 0.000). CONCLUSION: MiR-221 was shown to be associated with a poor OS in human carcinomas, and thus may serve as a useful predictor of clinical outcomes.

Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China.

Exposure to chemicals may affect liver enzyme to increase the risk of liver diseases. Perfluoroalkyl acids (PFAAs) are one kind of persistent organic pollutants with hepatotoxic effect in organism. However, data is scarce to characterize the hepatotoxic effects of specific structural PFAA isomers in general population. To address this data gap, we evaluated the association between serum PFAAs concentration and liver function biomarkers in the Isomers of C8 Health Project in China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure 18 serum PFAAs, except for linear and branched isomers of PFOA/PFOS, nine perfluorinated carboxylic acids (PFCAs) and two perfluorinated sulfonic acids (PFSAs) were also included, in 1605 adult residents of Shenyang, China. Values for nine serum liver function biomarkers were determined by full-automatic blood biochemical analyzer. Linear regression was used to evaluate associations between PFAAs and continuous liver function biomarkers and logistic regression to assess markers dichotomized per clinical reference intervals. Results indicated that serum PFAAs concentrations were associated with liver biomarker levels suggestive of hepatotoxicity, especially for liver cell injury. For example, a 1 ln-unit increase in total- perfluorooctanoic acid (PFOA) exposure was associated with a 7.4% [95% confidence interval (CI): 3.9%, 11.0%] higher alanine aminotransferase (ALT) level in serum. Interestingly, we observed association between branched PFAA isomers and liver biomarkers. For example, one ln-unit increase in branched perfluorooctane sulfonate (PFOS) isomers exposure was associated with a 4.3% increase in ALT level (95% CI: 1.2%, 7.4%) and a 33.0% increased odds of having abnormal ALT (95% CI: 5.0%, 67.0%). Also, we found that PFNA had positive association with ALT [(6.2%, 95% CI: 3.1%, 9.4%) and AST levels (2.5%, 95% CI: 0.5%, 4.5%)]. Logistic regression results showed that PFPeA, PFHxA, PFNA, PFDoDA, PFTrDA and PFTeDA had statistically association with abnormal prealbumin. Conclusively, our results support previous studies showing association between PFAAs exposure and liver function biomarkers. We found new evidence that branched PFAAs isomer exposure is associated with the risk of clinically relevant hepatocellular dysfunction.

Ambient PM1 air pollution, blood pressure, and hypertension: Insights from the 33 Communities Chinese Health Study.

No evidence exists concerning the association between blood pressure and ambient particles with aerodynamic diameter ≤ 1.0 µm (PM1), a major component of PM2.5 (≤ 2.5 µm) particles, and potentially causing more hazardous health effects than PM2.5. We aimed to examine the associations of blood pressure in adults with both PM1 and PM2.5 in China. In 2009, we randomly selected 24,845 participants aged 18-74 years from 33 communities in China. Using a standardized mercuric-column sphygmomanometer, we measured blood pressure. Long-term exposure (2006-08) to PM1 and PM2.5 were estimated using a spatial statistical model. Generalized linear mixed models were used to evaluate the associations between air pollutants and blood pressure and hypertension prevalence, controlling for multiple covariates. A 10-µg/m3 increase in PM1 was significantly associated with an increase of 0.57 (95% CI 0.31-0.83) mmHg in systolic blood pressure (SBP), 0.19 (95% CI 0.03-0.35) mmHg increase in diastolic blood pressure (DBP), and a 5% (OR=1.05; 95% CI 1.01-1.10) increase in odds for hypertension. Similar associations were detected for PM2.5. Furthermore, PM1-2.5 showed no association with blood pressure or hypertension. In summary, both PM1 and PM2.5 exposures were associated with elevated blood pressure levels and hypertension prevalence in Chinese adults. In addition, most of the pro-hypertensive effects of PM2.5 may come from PM1. Further longitudinal designed studies are warranted to validate our findings.

Impact on lung function among children exposed to home new surface materials: The seven Northeastern Cities Study in China.

We conducted a cross-sectional study to investigate the associations between recent home renovation exposure and lung function in children. We randomly recruited 7326 school children residing in 24 districts from seven cities in northeastern China. We collected information about home renovations from parents using a questionnaire and lung function measurements from children using spirometer recordings gathered by trained professionals and expressed as the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), maximal mid-expiratory flow (MMEF), and peak expiratory flow (PEF). We identified higher odds of diminished lung function among these with home renovation in the previous 2 years compared to those without home renovation in the previous 2 years, for FVC (odds ratios [ORs] = 1.84 [95%CI: 1.58, 2.15]; FEV1: ORs = 2.82 [95%CI: 2.36, 3.36]; PEF: ORs = 1.51 [95%CI: 1.24, 1.83]; and MMEF: ORs = 1.90 [95%CI: 1.60, 2.24]). The associations were stronger among children exposed to new polyvinyl chloride (PVC) flooring compared to children exposed to other surface materials. Our results were consistent throughout the analysis of each type of renovation materials. In conclusion, recent home renovation exposure was associated with poor lung function among children. Strategies to protect home owners and their families from respiratory hazards during and after renovation are required.

Potential exposure to metals and health risks of metal intake from Tieguanyin tea production in Anxi, China.

The metal content of Tieguanyin tea from Anxi, Southeast China, was studied. Leaching experiments were designed based on the local tea-drinking habits, and tea infusions were prepared using three types of water and two methods of soaking tea. Twelve metals (Cd, As, Cr, Pb, Se, Sb, Ag, Tl, Cu, Zn, Be, and Ba) were measured by inductively coupled plasma mass spectrometry (ICP-MS), and a human health risk assessment was performed. The results showed that the quality of water used for steeping tea has a direct effect on the leaching concentrations of metals in the tea infusion and this effect can be reduced by using pure water or commercially available drinking water. Further, the two tea-soaking methods used by local residents can reduce the metal intake. The health risk assessment determined that the carcinogenic risk values of Cr, As, and Pb (Cr > Pb > As) were within an acceptable range (10-7-10-4); therefore, the concentrations of these metals in tea infusions do not pose substantial carcinogenic risk to tea drinkers. The results also indicate that the high concentrations of Tl in the tea infusions pose a substantial noncarcinogenic risk and may result from the dissolution characteristics of Tl and the water quality.

Long-term exposure to ambient air pollution (including PM1) and metabolic syndrome: The 33 Communities Chinese Health Study (33CCHS).

Little evidence exists about the effects of long-term exposure to ambient air pollution on metabolic syndrome (MetS). This study aimed to determine the association between long-term ambient air pollution and MetS in China. A total of 15,477 adults who participated in the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. MetS was defined based on the recommendation by the Joint Interim Societies. Exposure to air pollutants was assessed using data from monitoring stations and a spatial statistical model (including particles with diameters ≤ 1.0 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3)). Two-level logistic regression analyses were utilized to assess the associations between air pollutants and MetS. The prevalence of MetS was 30.37%. The adjusted odds ratio of MetS per 10 µg/m3 increase in PM1, PM2.5, PM10, SO2, NO2, and O3 were 1.12 (95% CI = 1.00-1.24), 1.09 (95% CI = 1.00-1.18), 1.13 (95% CI = 1.08-1.19), 1.10 (95% CI = 1.02-1.18), 1.33 (95% CI = 1.12-1.57), and 1.10 (95% CI = 1.01-1.18), respectively. Stratified analyses indicated that the above associations were stronger in participants with the demographic variables of males, < 50 years of age, and higher income, as well as with the behavioral characteristics of smoking, drinking, and consuming sugar-sweetened soft drinks frequently. This study indicates that long-term exposure to ambient air pollutants may increase the risk of MetS, especially among males, the young to middle aged, those of low income, and those with unhealthy lifestyles.

The ginsenoside metabolite compound K exerts its anti-inflammatory activity by downregulating memory B cell in adjuvant-induced arthritis.

CONTEXT: Compound K (CK, 20-O-d-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, is structurally a member of the dammarane-type triterpene saponins. Several studies have identified the anti-inflammatory activity of CK. Our previous study demonstrated that CK exerted its anti-inflammatory effect via inhibition of abnormal activation and differentiation of T cells. However, its mechanism of action on B cells remains unclear. OBJECTIVE: The objective of this study is to investigate the effect and underlying mechanisms of CK's effects on memory B cells in the setting of adjuvant-arthritis (AA). MATERIALS AND METHODS: Complete Freund's adjuvant was used to induce AA in rats. Rats were administered, either CK (10, 40, and 160 mg/kg), once daily for 15 d, or methotrexate (MTX; 0.5 mg/kg) once every 3 d, for a total of six times. To evaluate the anti-inflammatory effect of CK, a global assessment and a swollen joint count of AA rats were performed every 3 d. Spleen index and histopathology were examined. Subsets of B cells including CD45R(+)IgM(+) (total B cells) and CD45R(+)CD27(+) (memory B cells) and expression of CD40 and CD40L were assayed by flow cytometry. RESULTS: Compared with the AA rats, global assessment scores and swollen joint counts were significantly lower in the treated groups received CK (40 and 160 mg/kg; p < 0.05 and p < 0.01, respectively). CK (40 and 160 mg/kg) decreased the spleen index (p < 0.01), and alleviated hyperplasia of lymph nodes (p < 0.05 and p < 0.01, respectively) and marginal zone (p < 0.05) in the spleen. In addition, CK (40 and 160 mg/kg) suppressed memory B cell subsets (p < 0.05), and suppressed CD40L expression on T cells and CD40 expression on B cells (p < 0.05 and p < 0.01, respectively). DISCUSSION AND CONCLUSION: This study demonstrated that CK downregulated memory B cells in AA rats, and this down-regulation may be T-cell dependent.

Ginsenoside metabolite compound K suppresses T-cell priming via modulation of dendritic cell trafficking and costimulatory signals, resulting in alleviation of collagen-induced arthritis.

Ginsenoside metabolite compound K (CK; 20-O-d-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, belongs to the dammarane-type triterpene saponins, according to its structure. The anti-inflammatory activity of CK has been identified in several studies. Our study demonstrated that CK exerted an anti-inflammatory effect in collagen-induced arthritis (CIA) and adjuvant-induced arthritis animal models, and this effect was due to inhibition of the abnormal activation and differentiation of T cells. However, the mechanism of CK in suppressing T-cell activation remains unclear. In this study, CK had a therapeutic effect in mice with CIA, decreased the percentage of activated T cells and dendritic cells (DCs), and increased the percentage of naive T cells in lymph nodes. The inhibitory effect on T-cell activation of CK was related to suppression of accumulation of DCs in lymph nodes. CK decreased CCL21 levels in lymph nodes and CCR7 expression in DCs and suppressed CCL21/CCR7-mediated migration of DCs, thus reducing accumulation of DCs in lymph nodes. In addition, signals for T-cell activation including major histocompatibility complex class II and costimulatory molecules, such as CD80 and CD86, were suppressed by CK, and the proliferation of T cells induced by DCs was inhibited by CK. In conclusion, this study demonstrated that CK downregulated DC priming of T-cell activation in CIA, and suppression of CCL21/CCR7-mediated DC migration and signaling between T cells and DCs might be the potential mechanism. These results provide an interesting, novel insight into the potential mechanism by which CK contributes to the anti-inflammatory effect in autoimmune conditions.

Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis.

AIM: To investigate the anti-arthritis and immunomodulatory activities of ginsenoside compound K (C-K) in mice with collagen-induced arthritis (CIA). METHODS: DBA/1 mice with CIA were treated with C-K (28, 56 or 112 mg·kg(-1)·d(-1), ig) or the positive control methotrexate (2 mg/kg, ig, every 3 d) for 34 d. Splenic T and B lymphocytes were positively isolated using anti-CD3-coated magnetic beads or a pan B cell isolation kit. T lymphocyte subsets, and CD28, T cell receptor (TCR), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) expression in purified splenic T lymphocytes were analyzed using flow cytometry, Western blotting and laser confocal microscopy. RESULTS: C-K treatment significantly ameliorated the pathologic manifestations of CIA mice, remarkably inhibited T lymphocyte proliferation, and marginally inhibited the proliferation of B lymphocytes. C-K treatment significantly suppressed TNF-α and anti-CII antibody levels, and increased IFN-γ level in the joints of CIA mice, but did not alter IL-4 production. Treatment of CIA mice with C-K significantly decreased the percentages of activated T cells, co-stimulatory molecule-expressing T cells and effector memory T cells, and increased the frequencies of naive T cells and regulatory T cells. Furthermore, C-K treatment significantly decreased the expression of CD28 and TCR, whereas it increased the expression of CTLA-4 and PD-1 on T lymphocytes of CIA mice. Methotrexate treatment exerted comparable effects in all these experiments. CONCLUSION: C-K suppresses the progression of CIA through regulating TCR, CD28, CTLA-4 and PD-1 expression, thus inhibiting the abnormal activation and differentiation of T lymphocytes.

High-power single-frequency 1014.8 nm Yb-doped fiber amplifier working at room temperature.

A single-frequency 1014.8 nm Yb-doped fiber amplifier working at room temperature was investigated in detail with respect to gain fiber length, fiber geometry, and fiber host material, which can be frequency quadrupled to 253.7 nm for laser cooling of mercury. After optimization, an up to 8.06 W laser was achieved with a single-stage amplifier, and 19.3 W power was obtained with another boost amplifier, using polarization-maintaining Yb-doped single-mode fiber with a 10 µm core and 125 µm inner clad. The amplified spontaneous emission was 25 dB lower than the signal in the final output of the laser system. The laser has a linewidth of ~24 kHz without noticeable broadening after amplification. Further power scaling is limited by stimulated Brillouin scattering.

Ginsenoside metabolite compound K attenuates inflammatory responses of adjuvant-induced arthritis rats.

OBJECTIVE: To investigate the effects of ginsenoside metabolite compound K (CK) on adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on the function of immunocyte (B cell and macrophage) and effectors' cell (fibroblast-like synoviocyte, FLS). METHODS: Animals were divided randomly into nine groups including control, AA, CK (5, 10, 20, 40, 80, and 160 mg/kg, i.g.), and MTX (0.5 mg/kg, i.g.). The effects of CK on AA rats are evaluated by swelling of the paw, histopathology of joint, and inflammatory cytokine production in serum. To further investigate the effects of CK on the function of B cell, peritoneal macrophage, and FLS from AA rats, we examined the proliferation of B cell and FLS by [3H] thymidine incorporation, and the phagocytic function of peritoneal macrophage was measured by neutral red uptake. Cytokines and antibodies in serum and the supernatant from peritoneal macrophage and FLS were measured by ELISA kit. RESULTS: CK suppressed the severity of AA rats by attenuating the paw swelling and histopathology of joint. CK can inhibit the proliferation of B cell and autoantibody levels, and suppressed the phagocytic function of peritoneal macrophage and secreted pro-inflammatory cytokines TNF-α, IFN-γ, and IL-17 and up-regulated the level of protective cytokines IL-10. CK attenuated the proliferation of FLS, and balanced the ratio of RANKL to OPG in AA rats. CONCLUSION: Our results suggest that CK may attenuate the severity of AA rats, partially by influencing the function of immunocyte (B cell and macrophage) and effectors' cells (FLS) in AA.

Single-Mode Control and Individual Nanoparticle Detection in the Ultraviolet Region Based on Boron Nitride Microdisk with Whispering Gallery Mode.

Optical microcavities are known for their strongly enhanced light-matter interactions. Whispering gallery mode (WGM) microresonators have important applications in nonlinear optics, single-mode output, and biosensing. However, there are few studies on resonance modes in the ultraviolet spectrum because most materials with high absorption properties are in the ultraviolet band. In this study, the performance of a microdisk cavity based on boron nitride (BN) was simulated by using the Finite-difference time-domain (FDTD) method. The WGM characteristics of a single BN microdisk with different sizes were obtained, wherein the resonance modes could be regulated from 270 nm to 350 nm; additionally, a single-mode at 301.5 nm is achieved by cascading multiple BN microdisk cavities. Moreover, we found that a BN microdisk with a diameter of 2 µm has a position-independent precise sensitivity for the nanoparticle of 140 nm. This study provides new ideas for optical microcavities to achieve single-mode management and novel coronavirus size screening, such as SARS-CoV-2, in the ultraviolet region.

Drug-Loaded Bacillus Calmette-Guérin Bacteria for Immuno-Chemo Combo Therapy in Bladder Cancer.

Intravesical Bacillus Calmette-Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of patients still experience disease recurrence or progression. Although the combined intravesical instillation of various chemotherapeutic drugs is implemented in clinical trials to enhance the BCG therapy, the outcome is far from satisfying due to severe irritative effects and treatment intolerance at high doses. Therefore, it is adopted the "biotin-streptavidin strategy" to doxorubicin (DOX)-encapsulated nanoparticles within live BCG bacteria (DOX@BCG) to improve treatment outcomes. Adherence of BCG to the bladder epithelium helps precisely target DOX@BCG to the local tumor cells and simultaneously increases intratumoral transport of therapeutic drugs. DOX@BCG effectively inhibits cancer progression and prolongs the survival of rats/mice with orthotopic bladder cancer owing to synergism between BCG-immunotherapy, DOX-chemotherapy, and DOX-induced immunogenic tumor cell death; furthermore, it exhibits improved tolerance and biosafety, and establishes antitumor immunity in the tumor microenvironment. Therefore, the drug-loaded live BCG bacterial delivery system holds considerable potential for clinical translation in the intravesical treatment of bladder cancer.