Effect of abamectin on osmoregulation in red swamp crayfish (Procambarus clarkii).

As a widely used pesticide, abamectin could be a threat to nontarget organisms. In this study, the toxic mechanism of abamectin on osmoregulation in Procambarus clarkii was explored for the first time. The results of this study showed that with increasing abamectin concentration, the membrane structures of gill filaments were damaged, with changes in ATPase activities, transporter contents, biogenic amine contents, and gene expression levels. The results of this study indicated that at 0.2 mg/L abamectin, ion diffusion could maintain osmoregulation. At 0.4 mg/L abamectin, passive transport was inhibited due to damage to the membrane structures of gill filaments, and active transport needed to be enhanced for osmoregulation. At 0.6 mg/L abamectin, the membrane structures of gill filaments were seriously damaged, and the expression level of osmoregulation-related genes decreased, but the organisms were still mobilizing various transporters, ATPases, and biogenic amines to address abamectin stress. This study provided a theoretical basis for further study of the effects of contaminations in aquatic environment on the health of crustaceans.

Ultra-broadband multi-tone frequency measurement based on the recirculating frequency shift of a frequency modulated continuous wave.

We proposed an ultra-broadband multi-tone frequency measurement (FM) approach based on frequency modulated continuous wave (FMCW). This work aims to achieve wide-range multi-tone FM without image interference, using electrical components with narrow bandwidth and low sampling rate, while maintaining high FM accuracy. The FM range is largely increased by extending the bandwidth of the optical FMCW through a recirculating frequency shift (RFS) loop, from 0.001 GHz-16 GHz to 0.001 GHz-437.5 GHz. The bandwidth-extended optical FMCW coherently beats with a continuous wave (CW) light modulated by the signal under test (SUT) at the balanced photodetector (BPD). The following low-pass filter (LPF) outputs pulses at the time when the frequencies of FMCW and SUT are equal, constructing frequency-to-time mapping (FTTM). Owing to the zero-intermediate-frequency (zero-IF) architecture, image interference is avoided. In addition, the up- and down-chirps of FMCW are used to achieve self-reference, avoiding the utilizing of reference signals, which realizes high FM accuracy. In the experiment, a FM within 0.1 GHz-43.5 GHz is demonstrated using an available microwave generator (MG) with a maximum output frequency of 43.5 GHz. The FM errors are kept within ±10 MHz for all frequencies with a mean and standard deviation of -0.3 MHz and 3.17 MHz, respectively. The multi-tone resolution is about 60 MHz at the FMCW chirp rate of 3.1998 G H z/µ s, which is consistent with the theoretical result. According to the theoretical derivation, the multi-tone resolution can be improved to 1 MHz by lowering the FMCW chirp rate.

CD72 is an inhibitory pattern recognition receptor that recognizes ribosomes and suppresses production of anti-ribosome autoantibody.

B cell responses to nucleic acid-containing self-antigens that involve intracellular nucleic acid sensors play a crucial role in autoantibody production in SLE. CD72 is an inhibitory B cell co-receptor that down-regulates BCR signaling, and prevents the development of SLE. We previously showed that CD72 recognizes the RNA-containing self-antigen Sm/RNP, a target of SLE-specific autoantibodies, and induces B cell tolerance to Sm/RNP by specifically inhibiting B cell response to this self-antigen. Here, we address whether CD72 inhibits B cell response to ribosomes because the ribosome is an RNA-containing self-antigen and is a target of SLE-specific autoantibodies as well as Sm/RNP. We demonstrate that CD72 recognizes ribosomes as a ligand, and specifically inhibits BCR signaling induced by ribosomes. Although conventional protein antigens by themselves do not induce proliferation of specific B cells, ribosomes induce proliferation of B cells reactive to ribosomes in a manner dependent on RNA. This proliferative response is down-regulated by CD72. These results suggest that ribosomes activate B cells by inducing dual signaling through BCR and intracellular RNA sensors and that CD72 inhibits B cell response to ribosomes. Moreover, CD72-/- but not CD72+/+ mice spontaneously produce anti-ribosome autoantibodies. Taken together, CD72 induces B cell self-tolerance to ribosomes by recognizing ribosomes and inhibiting RNA-dependent B cell response to this self-antigen. CD72 appears to prevent development of SLE by inhibiting autoimmune B cell responses to multiple RNA-containing self-antigens. Because these self-antigens but not protein self-antigens induce RNA-dependent B cell activation, self-tolerance to RNA-containing self-antigens may require a distinct tolerance mechanism mediated by CD72.

Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/ß-catenin pathway.

Background: Tolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However, whether MMPs are involved in the functional reprogramming of DCs is unknown. The study aims to investigate the role of MMPs in sepsis-induced DCs tolerance and the potential mechanisms. Methods: A murine model of late sepsis was induced by cecal ligation and puncture (CLP). The expression levels of members of the MMP family were detected in sepsis-induced tolerogenic DCs by using microarray assessment. The potential roles and mechanisms underlying MMP8 in the differentiation, maturation and functional reprogramming of DCs during late sepsis were assessed both in vitro and in vivo. Results: DCs from late septic mice expressed higher levels of MMP8, MMP9, MMP14, MMP19, MMP25 and MMP27, and MMP8 levels were the highest. MMP8 deficiency significantly alleviated sepsis-induced immune tolerance of DCs both in vivo and in vitro. Adoptive transfer of MMP8 knockdown post-septic bone marrow-derived DCs protected mice against sepsis-associated lethality and organ dysfunction, inhibited regulatory T-cell expansion and enhanced Th1 response. Furthermore, the effect of MMP8 on DC tolerance was found to be associated with the nuclear factor kappa-B p65/ß-catenin pathway. Conclusions: Increased MMP8 levels in septic DCs might serve as a negative feedback loop, thereby suppressing the proinflammatory response and inducing DC tolerance.

Risk model for predicting mortality in patients with necrotizing soft tissue infections in the intensive care unit.

BACKGROUND: The goal of this study is to look into the factors that lead to death in patients with necrotizing soft tissue infections（NSTIs） in the intensive care unit and create a mortality risk model. METHODS: The clinical data of 106 patients with necrotizing soft tissue infections admitted to intensive care unit(ICU) of the First Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2021 were retrospectively analyzed. Univariate analysis and multivariate analysis were performed to evaluate the risk factors impacting patient mortality. The regression coefficient in binary logistic regression analysis was converted into the item score in the model, and then the model score of each patient was calculated. Finally, an ROC curve was constructed to evaluate the efficiency of the model for predicting mortality. Thirteen patients with NSTIs admitted to ICU between January 2022 and November 2022 were used to validate the model. RESULTS: The death group had 44 patients, while the survival group had 62 patients. The overall mortality was 41.5%. Binary logistic regression analysis showed that risk factors for mortality were age≥ 60 years(OR:4.419; 95%CI:1.093-17.862; P = 0.037), creatinine ≥ 132µmol/L(OR:11.166; 95%CI:2.234-55.816; P = 0.003), creatine kinase ≥ 1104 U/L(OR:4.019; 95%CI:1.134-14.250; P = 0.031), prothrombin time ≥ 24.4 s(OR:11.589; 95%CI:2.510-53.506; P = 0.002), and invasive mechanical ventilation (OR:17.404; 95%CI:4.586-66.052; P＜0.000). The AUC of the model for predicting mortality was 0.940 (95% CI:0.894-0.986). When the cut-off value for the model was 4 points, the sensitivity was 95.5% and the specificity was 83.9%. CONCLUSION: The death risk model in this study for NSTIs patients in the intensive care unit shows high sensitivity and specificity. Patients with a score of ≥ 4 points have a higher risk of mortality.

Extended endoscopic endonasal approach to the chiasmatic cistern: An anatomical study of the arachnoid.

This paper studied the arachnoid of the chiasmatic cistern (CC) and the methods for increasing the exposure of the CC from an endoscopic perspective. Eight anatomical specimens with vascular injection were used for endoscopic endonasal dissection. The anatomical characteristics of the CC were studied and documented, and anatomical measurements were collected. The CC is an unpaired five-walled arachnoid cistern located between the optic nerve, optic chiasm, and the diaphragma sellae. The average exposed area of the CC before the anterior intercavernous sinus (AICS) was transected was 66.67 ± 33.76 mm2 . After the AICS was transected and the pituitary gland (PG) was mobilized, the average exposed area of the CC was 95.90 ± 45.48 mm2 . The CC has five walls and a complex neurovascular structure. It is located in a critical anatomical position. The transection of the AICS and mobilization of the PG or the selective sacrifice of the descending branch of the superior hypophyseal artery can improve the operative field.

Photonic-assisted fast broadband microwave vector network analyzer based on FMCW.

In the paper, we propose a photonic-assisted fast broadband microwave vector network analyzer (FB-VNA) based on frequency modulated continuous wave (FMCW). A photonic recirculating frequency shift (RFS) loop is used to extend the bandwidth of optical FMCW. The bandwidth-extended optical FMCW beats with the continuous wave (CW) light to generate the broadband electrical FMCW, which serves as the incident signal of the device under test (DUT). The response signals of the DUT are modulated on the bandwidth-extended optical FMCW to perform de-chirping. After coherently beating the de-chirped light with the CW light, the broadband response signals of DUT are down-converted to a single-tone intermediate frequency (IF) signal carrying the frequency response of DUT, and the scattering parameters of DUT can be obtained. The single-tone IF signal relaxes the demand on the bandwidth and sampling rate of the electrical backend. Thanks to the RFS loop and the short period of FMCW, the measurement frequency range is highly extended and measurement speed is greatly accelerated at the same time, which can be applied in monitoring sudden changes of DUT features. A bandwidth multiplication of the FMCW from 6-18 GHz to 6-498 GHz is experimentally implemented. With available photodetectors (PDs) and Mach-Zehnder modulators (MZMs), a 6-54 GHz FB-VNA is demonstrated, and the S parameters of a 25-GHz low-pass filter (LPF) is measured within 6 µs. The sudden changes of S21 parameter of DUT simulated by fast adjusting the bias voltage of the MZM used for de-chirping are also characterized by the proposed FB-VNA. The sudden changes as short as 0.01 µs can be captured.

Efficacy and safety of transarterial chemoembolization combined with lenvatinib, programmed death-1 inhibitor, and iodine-125 seed brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND: Therapy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is still controversial. This study was performed to evaluate the efficacy and safety of the combination therapy comprising transarterial chemoembolization (TACE), lenvatinib (L), programmed death-1 inhibitor (P), and iodine-125 seed (I125) brachytherapy relative to TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy and TACE plus lenvatinib therapy. METHODS: The data of HCC patients with PVTT from July 2017 to August 2022 were assessed in this single-center retrospective study. Primary study outcomes were progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were disease control rate (DCR), objective response rate (ORR), and treatment-related adverse events. RESULTS: We enrolled 150 patients totally, including 50 patients treated with TACE plus lenvatinib therapy (TACE+L group), 45 patients treated with TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy (TACE+L+P group), and 55 patients treated with the combination therapy of TACE along with I125 brachytherapy, lenvatinib, and programmed death-1 inhibitor therapy (TACE+L+P+I125 group). The median OS in the TACE+L+P+I125 group (21.0; 95% confidence interval [CI]: 18.4∼23.5 months) was significantly longer than that in the TACE+L group (10; 95% CI: 7.8∼12.1months) (p = 0.006), while it was insignificantly longer than that in the TACE+L+P group (14.0; 95% CI: 10.7∼17.2months) (p = 0.058). The median PFS in the TACE+L+P+I125 group (13.0; 95% CI: 10.2∼15.7 months) was significantly longer than that in the TACE+L group (5.0; 95% CI: 4.2∼5.7 months) (p = 0.014) and the TACE+L+P group (9.0; 95% CI: 6.7∼11.2 months) (p = 0.048). Statistically significant differences between groups were found in DCR (p = 0.015). There were no significant between-group differences in treatment-related adverse events (p > 0.05). CONCLUSIONS: A combination therapy of TACE, lenvatinib, programmed death-1 inhibitor, and I125 seed brachytherapy significantly improve OS, PFS, and DCR and show better survival prognosis for HCC patients accompanied by PVTT.

SUPPLEMENTATION WITH NICOTINAMIDE RIBOSIDE ATTENUATES T CELL EXHAUSTION AND IMPROVES SURVIVAL IN SEPSIS.

ABSTRACT: T cell exhaustion is the main cause of sepsis-induced immunosuppression and is associated with the poor prognosis. Nicotinamide adenine dinucleotide (NAD + ) is well known for its anti-aging effect, but its role in sepsis-induced T cell exhaustion remains to be elucidated. In the present study, using a classic septic animal model, we found that the levels of NAD + and its downstream molecule, which is sirtuins 1 (SIRT1), in T cells in sepsis were decreased. Supplementation with nicotinamide ribose (NR), the precursor of NAD + , right after cecal ligation and puncture significantly increased the levels of NAD + and SIRT1. Supplementation with NR alleviated the depletion of mononuclear cells and T lymphocytes in spleen in sepsis and increased the levels of CD3 + CD4 + and CD3 + CD8 + T cells. Interestingly, both Th1 and Th2 cells were expanded after NR treatment, but the balance of Th1/Th2 was partly restored. Nicotinamide ribose also inhibited the regulatory T cells expansion and programmed cell death 1 expression in CD4 + T cells in sepsis. In addition, the bacteria load, organ damage (lung, heart, liver, and kidney), and the mortality of septic mice were reduced after NR supplementation. In summary, these results demonstrate the beneficial effect of NR on sepsis and T cell exhaustion, which is associated with NAD + /SIRT1 pathway.

Mutual promotion of mitochondrial fission and oxidative stress contributes to mitochondrial-DNA-mediated inflammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) is one of the main causes of death in patients with paraquat (PQ) poisoning. This study aimed to evaluate the relationship between mitochondrial fission and oxidative stress in PQ-induced epithelial-mesenchymal transition (EMT) and PF. METHODS: C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) staining. Mitochondrial morphology was detected by MitoTracker® Deep Red FM or transmission electron microscopy (TEM). Western blotting and immunofluorescence were used to determine the expression of protein. The migration ability of the cells was detected by the cell scratch test. Mitochondrial DNA (mtDNA) levels were assessed by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was applied to detect cytokine levels. Superoxide dismutase (SOD) activity and the levels of glutathione (GSH) and malondialdehyde (MDA) were detected by chemichromatometry. RESULTS: PQ exposure caused EMT and PF in vivo and in vitro. PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1 (Drp1), which were accompanied by oxidative stress. Inhibiting mitochondrial fission using mitochondrial division inhibitor-1 (Mdivi-1), a selective inhibitor of Drp1, attenuated PQ-induced EMT and oxidative damage. Treatment with N-acetyl-L-cysteine (NAC), an antioxidant, reduced Drp1 expression, attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF. Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release, the expression of Toll-like receptor 9 (TLR9) and phosphorylation (P)-NF-κB p65 as well as cytokines (interleukin 6 [IL-6], interleukin-1ß [IL-1ß], and tumor necrosis factor-α [TNF-α]) production. CONCLUSION: Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF, which is associated with the mtDNA/TLR9/NF-κB pathway.

Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization.

Background: The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib. Methods: In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. Results: We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029). Conclusions: A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.

Safety and efficacy of biliary stenting combined with iodine-125 seed strand followed by hepatic artery infusion chemotherapy plus lenvatinib with PD-1 inhibitor for the treatment of extrahepatic cholangiocarcinoma with malignant obstructive jaundice.

Objectives: To evaluate the efficacy and safety of biliary stenting implantation with iodine-125 seed strand (SI) followed by hepatic artery infusion chemotherapy (HAIC) plus lenvatinib (Len) with programmed death-1 (PD-1) inhibitor for patients diagnosed with extrahepatic cholangiocarcinoma (ECC) and malignant obstructive jaundice (MOJ). Methods: In this single-center retrospective study, the data of ECC patients with MOJ from March 2015 to January 2023 was assessed. Using probability score matching (PSM), the selection bias of patients was reduced. Primary study outcomes included overall survival (OS) and progression-free survival (PFS). The OS and PFS were performed using the Kaplan-Meier method and evaluated with the log-rank test. Results: A total of 104 patients were enrolled finally, including 52 patients treated with interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor (SI+HAIC+Len+P group) and 52 patients treated with interventional therapy (SI+HAIC) plus lenvatinib (SI+HAIC+Len group). 26 pairs of patients were matched after PSM analysis. After PSM analysis, the median OS and PFS in the SI+HAIC+Len+P group were significantly longer compared to those in the SI+HAIC+Len group (OS:16.6 vs. 12.3 months, P = 0.001; PFS:12.6 vs 8.5 months, P = 0.004). The DCR was significantly different between groups (P = 0.039), while ORR not (P = 0.548). The addition of PD-1 inhibitor was generally well tolerated without treatment-associated mortality. Conclusion: Interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor was effective for ECC patients accompanied by MOJ with a manageable safety profile.

Effects of metformin on modulating the expression of brain-related genes of APP/PS1 transgenic mice based on Single Cell Sequencing.

BACKGROUND: Alzheimer's disease is the most common form of dementia, affecting millions of people worldwide. METHODS: Here, we analyzed the effects of metformin on APP/PS1 transgenic mice by behavioral test and single-cell sequencing. Results showed that metformin can improve the spatial learning, memory function, and anxiety mood of APP/PS1 transgenic mice. We identified transcriptionally distinct subpopulations of nine major brain cell types. Metformin increased the differentiation of stem cells, decreased the proportion of cells in the G2 phase, enhanced the generation of neural stem cells and oligodendrocyte progenitor cells, and the tendency of neural stem cells to differentiate into astrocytes. Notably, 253 genes expressed abnormally in APP/PS1 transgenic mice and were reversed by metformin. Ttr, Uba52, and Rps21 are the top 3 genes in the cell-gene network with the highest node degree. Moreover, histochemistry showed the expressions of RPS15, UBA52, and RPL23a were consistent with the data from single-cell sequencing. Pathway and biological process enrichment analysis indicated metformin was involved in nervous system development and negative regulation of the apoptotic process. CONCLUSION: Overall, metformin might play an important role in the differentiation and development and apoptotic process of the central nervous system by regulating the expression of Ttr, Uba52, Rps21, and other genes to improve cognition of APP/PS1 transgenic mice. These results provided a clue for elaborating on the molecular and cellular basis of metformin on AD.

The influence of stigma and disability acceptance on psychosocial adaptation in patients with stoma: A multicenter cross-sectional study.

Background: The stoma can cause serious physical and psychological distress to the patient, leading to an inability to live a normal life; although it effectively improves the 5-year survival rate of patients. Objective: The purpose of this study is to explore the status of stigma and disability acceptance of patients with stoma and their influences on psychosocial adaptation. Design: A multicenter cross-sectional study. Methods: A total of 259 patients with stoma in 6 hospitals from southeast China were enrolled. And this research adhered to the STROBE guideline and approved by the Ethics Committee of Fu Jian Provincial Hospital. The ostomy adjustment inventory-20、acceptance of disability scale and social impact scale were used to collect data. The hypothetical path model was tested using the SPSS version 22.0 software and AMOS version 26.0 software. Results: Stigma, disability acceptance and psychosocial adaptation was associated. The sense of stigma was severe (72.76 ± 12.73), the acceptance of disability was medium (179.24 ± 32.29) and the psychosocial adaptation was poor (38.06 ± 8.76). Also, the hypothesis model of this study fitted the data well (AGFI = 0.967>0.08; χ 2/df = 1.723, p = 0.08 > 0.05), and the results showed that disability acceptance positively affected psychosocial adaptation; while stigma negatively affected psychosocial adaptation, and disability acceptance mediated between stigma and psychosocial adaptation (p < 0.01). Conclusion: The stigma and disability acceptance of patients with stoma are serious problems that are closely related to their psychosocial adaptation. Medical staff should take some interventions based on different paths to reduce stoma patients' stigma and guide them to improve disability acceptance, thus to improve the level of psychosocial adaptation of patients with stoma.

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.

Toll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. L. reuteri treatment was carried out in vivo and vitro study. Compared with wild-type mice, AP and AP-associated gut injury were exacerbated in TLR4ΔIEC mice in a gut microbiota-dependent manner. The relative abundance of Lactobacillus and number of Paneth cells remarkably decreased in TLR4ΔIEC mice. The KEGG pathway analysis derived from RNA sequencing suggested that genes affected by intestinal TLR4 deletion were related to the activation of nod-like receptor pathway. Furthermore, L. reuteri treatment could significantly improve the pancreatic and intestinal injury in TLR4ΔIEC mice through promoting Paneth cells in a NOD2-dependent manner. Loss of intestinal epithelial TLR4 exacerbated pancreatic and intestinal damage during AP, which might be attributed to the gut microbiota dysbiosis especially the exhausted Lactobacillus. L. reuteri might maintain intestinal homeostasis and alleviate AP via Paneth cells modulation.Abbreviations: AP Acute pancreatitis, TLR4 Toll-like receptor 4, IL-1ß Interleukin-1ß, IL-6 Interleukin-6, TNF-α Tumor necrosis factor-α, SIRS Systematic inflammatory response syndrome, LPS Lipopolysaccharides, SPF Specific pathogen-free, ZO-1 Zonula occludens-1, CON Control, H&E Hematoxylin and eosin, FISH Fluorescence in situ hybridization, DAPI 4',6-diamidino-2-phenylindole, PCoA Principal co-ordinates analysis, SCFA Short chain fatty acid, LEfSe Linear discriminant analysis Effect Size, ANOVA Analysis of variance, F/B Firmicutes/Bacteroidetes, PCA Principal component analysis, NOD2 Nod-like receptor 2, ABX antibiotics, PCNA proliferating cell nuclear antigen.

The role of B cells in cancer development.

B cells play a critical role in adaptive immune responses mainly due to antigen presentation and antibody production. Studies about the tumor-infiltrating immune cells so far demonstrated that the function of B cells in tumor immunity is quite different among various tumor types. The antigen presentation of B cells is mainly anti-tumoral, while the role of antibody production is controversial. Moreover, the immunosuppressive regulatory B cells are detrimental to anti-tumor immunity via the secretion of various anti-inflammatory cytokines. This review briefly summarizes the different roles of B cells classified by the primary function of B cells, antigen presentation, antibody production, and immunity regulation. Further, it discusses the potential therapeutic target of B cells in tumor immunity.

Capabilities and mechanisms of microalgae on nutrients and florfenicol removing from marine aquaculture wastewater.

The regulations governing the discharge of marine aquaculture wastewater are becoming increasingly stringent, and the problems of nitrogen and phosphorus pollution and antibiotic residues in wastewater are serious. Microalgae-based treatment with the dual benefits of wastewater purification and microalgae resource recycling was regarded as the most promising technology in aquaculture wastewater treatment. Isochrysis galbana and Chlorella sp. were chosen to investigate antibiotic and nutrient removal mechanisms from aquaculture wastewater. FLO addition stimulated microalgae growth at low FLO concentrations (0.1 and 1 mg/L) but inhibited growth at 10 mg/L. The removal efficiency of DIN by Chlorella sp. and I. galbana after 7 days of cultivation was 66.4% and 25.8%, respectively. Linear curves were obtained between DIN concentration and cultivation duration, remove constant (k) increased as FLO concentration increased from 0 to 10 mg/L, and the highest value of k was obtained in both the Chlorella sp. and I. galbana groups at 10 mg/L. DIP concentrations in FLO-contained simulated aquaculture wastewater decreased sharply with the cultivation of Chlorella sp. and I. galbana, and DIP removal rate increased as FLO concentration increased. When the initial concentration of FLO was 0.1 mg/L, biodegradation by I. galbana accounted for 86.67% of FLO removal. In contrast, FLO removal with biodegradation and biosorption by Chlorella sp. was 89.74% and 3.72%, respectively. Furthermore, Chlorella sp. grown in MPBR demonstrated superior capability for antibiotic-containing marine aquaculture wastewater purification, with average removal rates of DIN and DIP of 81.2% and 100%, respectively. The high removal rate is related to membranes which can improve microalgae performance by decoupling SRT and HRT. For microalgae-based aquaculture wastewater, ammonia was the most crucial nitrogen source, followed by nitrate. These findings serve as a theoretical foundation for developing microalgae-based aquaculture wastewater treatment technology and eliminating antibiotics in aquaculture.

Vesicle transport related protein Synaptotagmin-1 mediates paraquat transport to antagonize paraquat toxicity.

In this study, A549/PQ cells with moderate resistance to paraquat (PQ) were obtained by treating A549 cells with PQ, their growth rate was slowed down, the accumulation concentration of PQ and the levels of growth inhibition, injury and early apoptosis induced by PQ were significantly lower than those of parental A549 cells. Microarray screening and RT-qPCR detection found that Synaptotagmin-1 (SYT1) expression in drug-resistant cells was significantly increased, and PQ further enhanced its expression. After inhibiting SYT1 expression in A549/PQ cells, cell viability, intracellular PQ concentration and the expression of Bcl-2, SNAP25 and RAB26 were significantly reduced, while the mortality, early apoptosis rate and Bax expression were significantly increased. In vivo experiments also further showed that PQ promoted the expression of SYT1, SNAP25 and RAB26 in PQ-poisoned mice; when inhibiting SYT1 expression, PQ concentration in lung tissues was significantly increased, and the levels of lung injury and apoptosis were also significantly enhanced, while the expression of SNAP25 and RAB26 was significantly reduced. This indicates that PQ poisoning leads to compensatory up-regulation of vesicle transport related proteins such as SYT1 in vivo, thereby promoting PQ transmembrane transport, and then reducing the pulmonary accumulation of PQ and PQ-caused lung injury.

CD71+ Erythroid Cell Expansion in Adult Sepsis: Potential Causes and Role in Prognosis and Nosocomial Infection Prediction.

BACKGROUND: Immune suppression contributes to nosocomial infections (NIs) and poor prognosis in sepsis. Recent studies revealed that CD71+ erythroid cells had unappreciated immunosuppressive functions. This study aimed to investigate the values of CD71+ erythroid cells (CECs) in predicting NIs and prognosis among adult septic patients. The potential factors associated with the expansion of CECs were also explored. METHODS: In total, 112 septic patients and 32 critically ill controls were enrolled. The frequencies of CD71+ cells, CD71+CD235a+ cells, and CD45+ CECs were measured by flow cytometry. The associations between CECs and NIs and 30-day mortality were assessed by ROC curve analysis and Cox and competing-risk regression models. Factors associated with the frequency of CECs were identified by linear regression analysis. RESULTS: The percentage of CD71+ cells, CECs, and CD45+ CECs were higher in septic patients than critically ill controls. In septic patients, the percentages of CD71+ cells, CECs, and CD45+ CECs were associated with NI development, while CD71+ cells and CECs were independently associated with 30-day mortality. Linear regression analysis showed that the levels of interleukin (IL)-6 and interferon (IFN)-γ were positively associated with the frequencies of CD71+ cells, CECs, and CD45+ CECs, while IL-10 was negatively associated with them. Additionally, the levels of red blood cells (RBCs) were negatively associated with the percentage of CD45+ CECs. CONCLUSIONS: CECs were expanded in sepsis and can serve as independent predictors of the development of NI and 30-day mortality. Low levels of RBCs and high levels of IL-6 and IFN-γ may contribute to the expansion of CECs in sepsis. TRIAL REGISTRATION: ChiCTR, ChiCTR1900024887. Registered 2 August 2019, http://www.chictr.org.cn/showproj.aspx?proj=38645.

Protein antigen conjugated with cholesteryl amino-pullulan nanogel shows delayed degradation in dendritic cells and augmented immunogenicity.

Carriers that augment delivery, immunogenicity or both are crucial in the development of vaccines especially component vaccines as components of pathogens are often poorly immunogenic. Cholesteryl pullulan (CHP) that forms nano-sized hydrogel (nanogel) and encapsulates proteins was shown to be useful in the delivery of vaccines. Here we demonstrate that subcutaneous immunization of mice with bovine serum albumin (BSA) chemically conjugated to NH2-CHP nanogel induces strong antibody production. This augmented antibody production requires covalent conjugation between BSA and CHP, but does not require nanogel formation. Conjugation of NH2-CHP nanogel induces persistence of BSA in dendritic cells (DCs) in vivo. As resistance to lysosomal degradation was previously shown to augment antigen presentation by DCs, conjugation of antigens with CHP nanogel may enhance antibody production to antigens by delaying lysosomal degradation. Therefore, delayed degradation of antigens by covalent conjugation with nanoparticles may be a good strategy for the development of effective vaccines.