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.

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.

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.

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.

Whole transcriptome sequencing and integrated network analysis elucidates the effects of 3,8-Di-O-methylellagic acid 2-O-glucoside derived from Sanguisorba offcinalis L., a novel differentiation inducer on erythroleukemia cells.

Acute erythroid leukemia (AEL) is a rare and aggressive hematologic malignancy with no specific treatment. Sanguisorba officinalis L. (S. officinalis), a well-known traditional Chinese medicine, possesses potent anticancer activity. However, the active components of S. officinalis against AEL and the associated molecular mechanisms remain unknown. In this study, we predicted the anti-AML effect of S. officinalis based on network pharmacology. Through the identification of active components of S. officinalis, we found that 3,8-Di-O-methylellagic acid 2-O-glucoside (DMAG) not only significantly inhibited the proliferation of erythroleukemic cell line HEL, but also induced their differentiation to megakaryocytes. Furthermore, we demonstrated that DMAG could prolong the survival of AEL mice model. Whole-transcriptome sequencing was performed to elucidate the underlying molecular mechanisms associated with anti-AEL effect of DMAG. The results showed that the total of 68 miRNAs, 595 lncRNAs, 4030 mRNAs and 35 circRNAs were significantly differentially expressed during DMAG induced proliferation inhibition and differentiation of HEL cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed miRNAs, lncRNAs, mRNAs and circRNAs were mainly involved in metabolic, HIF-1, MAPK, Notch pathway and apoptosis. The co-expression networks showed that miR-23a-5p, miR-92a-1-5p, miR-146b and miR-760 regulatory networks were crucial for megakaryocyte differentiation induced by DMAG. In conclusion, our results suggest that DMAG, derived from S. officinalis might be a potent differentiation inducer of AEL cells and provide important information on the underlying mechanisms associated with its anti-AEL activity.

Image-matching assisted dual-frequency phase-sensitive optical time domain reflectometry.

An image-matching assisted dual-frequency phase-sensitive optical time domain reflectometry (Φ-OTDR) is proposed and demonstrated. Compared to the conventional dual-frequency Φ-OTDR, which retrieves data via curve matching, the proposed scheme can effectively improve the temporal resolution and measurement precision while keeping the spatial resolution without additional hardware. In the experiments, with a 10 s temporal window, the proposed scheme realized the same measurement precision as the conventional method that used a 40 s window, suggesting a fourfold improvement of temporal resolution. When both used the 10 s temporal window, the measurement error was suppressed from 21.4% to 1.2% in the sensing for a 2 m hot zone at the end of a 90-m fiber.

Programming changes in GLUT1 mediated the accumulation of AGEs and matrix degradation in the articular cartilage of female adult rats after prenatal caffeine exposure.

Osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal glucose metabolism. Our laboratory previously reported that prenatal caffeine exposure (PCE) can induce intrauterine maternal glucocorticoid (GC) overexposure in IUGR offspring and increase susceptibility to osteoarthritis after birth. In the present study, we demonstrated the essential role of glucose transporter 1 (GLUT1) programming changes in the increased matrix degradation of articular cartilage and susceptibility to osteoarthritis in female PCE adult offspring. In vivo, we found that PCE decreased the matrix content but did not significantly change the expression of matrix degradation-related genes in the articular cartilage of female fetal rats. The decreased expression of IGF1 and GLUT1 and the content of advanced-glycation-end-products (AGEs) were also detected. At different postnatal stages (2, 6, and 12 weeks), the cartilage matrix content decreased while the degradation-related genes expression increased in the PCE group. Meanwhile, the expression of IGF1 and GLUT1 and AGEs content in the local cartilage increased. In vitro, the expression levels of IGF1 and GLUT1 were inhibited by corticosterone but remained unchanged under caffeine treatment. Exogenous IGF1 can reverse the corticosterone-induced decrease in GLUT1 expression and promote AGEs production, while mifepristone (a glucocorticoid receptor inhibitor) reversed the corticosterone-induced low expression of IGF1 and GLUT1. Exogenous AGEs can increase the expression of inflammatory factors (IL-6 and TNF-α) and degradation-related genes, and decrease the matrix synthesis-related genes expression in chondrocyte. In conclusion, the GC-IGF1-GLUT1 axis mediated intrauterine dysplasia of articular cartilage, increased accumulation of AGEs and matrix degradation after birth in PCE female offspring, thereby increasing their susceptibility to osteoarthritis in adulthood.

[Qualitative and quantitative analysis of quassinoid diterpenoids from Eurycoma longifolia by UPLC-Q-TOF-MS combined with UPLC-QQQ-MS/MS].

In this work, a sensitive and efficient method was established and validated for qualitative and quantitative analysis of major quassinoid diterpenoids constituents from the extract of Eurycoma longifolia by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometry(UPLC-QQQ-MS/MS). The UPLC-Q-TOF-MS analysis was performed on an Agilent Eclipse Plus C_(18) RRHD(2.1 mm×100 mm,1.8 µm) column with acetonitrile and 0.1% formic acid water as mobile phase by gradient elution. The UPLC-QQQ-MS/MS analysis was performed on an Agilent Eclipse Plus C_(18) RRHD(2.1 mm×50 mm, 1.8 µm)column with acetonitrile and 0.1% formic acid water as mobile phase by gradient elution. The data was collected by electrospray ionization in positive mode. According to the contrast of the reference standards and the accurate masses of molecules, a total of 32 quassinoid diterpenoids in E. longifolia extract were identified by UPLC-Q-TOF-MS. For quantitative the linear range of 4 detected quassinoid diterpenoids were good(r≥0.999 6), and the overall recoveries ranged from 90.35% to 106.4%, with the RSD ranging from 1.8% to 3.6%. The method was accurate, reliable and efficient, and could comprehensively reflect the chemical constituents and content of E. longifolia, and could provide a reference for further elucidating its pharmacological basis and quality control.

LncRNA PVT1 regulates VEGFC through inhibiting miR-128 in bladder cancer cells.

Long noncoding RNA PVT1 is considered to be an oncogene in multiple cancers. Our previous studies indicated that PVT1 levels were higher in bladder cancer tissue and correlated with clinical progression and poor prognosis in bladder cancer patients. A bioinformatics analysis showed that PVT1 may regulate VEGFC expression through miR-128 as a competing endogenous RNA (ceRNA). In this study, we demonstrated that PVT1 expression levels affect the proliferation and migration ability of bladder cancer cells. Moreover, PVT1 knockdown significantly decreased the proliferation capacity of bladder cancer cells in nude mice. Luciferase assays and RNA-binding protein immunoprecipitation were performed to investigate the potential mechanism of ceRNAs in the regulation of PVT1 and VEGFC. The results showed that the increased number of PVT1 transcripts interacted directly with miR-128 to decrease miR-128 binding to the VEGFC 3'-untranslated region. This effect suppressed VEGFC mRNA degradation by miR-128. In conclusion, these results indicated that PVT1 might play a critical role in bladder cancer tumorigenesis via miR-218 and VEGFC. Therefore, PVT1 could be a new biomarker for bladder cancer diagnosis and therapy.

Analysis of the effect of green roof substrate amended with biochar on water quality and quantity of rainfall runoff.

Green roofs are becoming a popular ecological alternative in urban areas worldwide. In this study, we constructed two modular green roofs (commercial substrate green roof and biochar substrate green roof) and analyzed the effects that the green roof substrate amended with biochar on the runoff retention capacity, water quality, pollutants releasing characteristic, and pollution load by simulating rainfall experiment (rainfall levels 10~80 mm). Results showed that the mean retention ratio was no significant differences between the commercial substrate (72.54%) and the biochar substrate (72.08%). Both the two kinds of substrates showed that the concentrations of total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (COD), and iron (Fe) decreased gradually with the extension of rainfall time. Electrical conductivity (EC) and pH, as well as mean concentrations of TN, COD, TP, total suspended solids (TSS), and Fe, showed no differences between the green roof runoff of two kind of substrate. However, the neutralizing capacity of biochar substrate for the pH of green roof runoff was stronger than the commercial substrate, and the mean concentration of the TN and COD in the commercial substrate (16.14 mg/L and 171.79 mg/L, respectively) was about two times higher than the biochar substrate (9.85 mg/L and 97.31 mg/L, respectively). Similarly, the pollution load of TN and COD in the commercial substrate was significantly higher than that in the biochar substrate. Therefore, the biochar substrate could effectively reduce the pollution load of TN and COD in the runoff of green roof. Consequently, we suggest that the biochar could be applied to green roof substrates in order to reduce the impact of city non-point pollution on receiving water bodies.

A novel technique for en bloc kidney transplantation from infant donors with extremely low body weight by using the distal abdominal aorta as an outflow tract.

Pediatric kidney donors remain underutilized due to the high risk of postoperative thrombosis. To address this problem, we developed a novel en bloc kidney transplantation technique using donor thoracic aorta and the distal abdominal aorta as inflow and outflow tracts, respectively. Briefly, eight kidneys from deceased infant donors under five months old and with low body weight (1.9-4.9 kg) were transplanted en bloc into four pediatric and four adult patients. The donor's common iliac artery or external iliac artery was anastomosed to the recipient's distal external iliac artery or inferior epigastric artery, respectively, as an outflow tract. Recipients received basiliximab or antithymocyte globulin as induction therapy followed by tacrolimus, mycophenolate mofetil, and prednisone but without prophylactic anticoagulation. Delayed graft function was observed in one patient but was reversed at 90 days posttransplant. Two patients had urine leakage, which was cured by conservative treatment. Two recipients developed lung infections that eventually cleared. No patients experienced posttransplant vascular thrombosis. After 1-1.5 years of follow-up, all patients are well and have normal serum creatinine levels. In conclusion, this novel en bloc kidney transplantation technique using a modified arterial inflow and outflow tract can prevent vascular thrombosis and provide adequate graft function.

Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor.

Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor.

Design, synthesis and biological evaluation of novel benzo-α-pyrone containing piperazine derivatives as potential BRAFV600E inhibitors.

The increasingly acquired resistance to vemurafenib and side effects of known inhibitors motivate the search for new and more effective anti-melanoma drugs. In this Letter, virtual screening and scaffold growth were combined together to achieve new molecules as BRAFV600E inhibitors. Along with docking simulation, a primary screen in vitro was performed to filter the modifications for the lead compound, which was then substituted, synthesized and evaluated for their inhibitory activity against BRAFV600E and several melanoma cell lines. Out of the obtained compounds, derivative 3l was identified as a potent BRAFV600E inhibitor and exerted an anticancer effect through BRAFV600E inhibition. The following biological evaluation assays confirmed that 3l could induce cell apoptosis and marked DNA fragmentation. Furthermore, 3l could arrest the cell cycle at the G0/G1 phase in melanoma cells. The docking simulation displayed that 3l could tightly bind with the crystal structure of BRAFV600E at the active site. Overall, the biological profile of 3l suggests that this compound may be developed as a potential anticancer agent.

Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors.

A series of novel pyrazole-nitroimidazole derivatives had been arranged and evaluated for their EGFR/HER-2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on four kinds of cancer cell lines (MCF-7, Hela, HepG2, B16-F10). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activity, with the IC50 values ranging from 0.13µM to 128.06µM in four tumor cell lines. Among them, compound 5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26µM/0.51µM, respectively, comparable to the positive control erlotinib (IC50=0.41µM for HER-2 and IC50=0.20µM for EGFR) and lapatinib (IC50=0.54µM for HER-2 and IC50=0.28µM for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity of the proposed compounds and activity relationship (SAR) of these pyrazole-nitroimidazole derivatives.

Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse.

To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P < 0.05). High-risk category was associated with just lower PFS, but not OS. In multivariate analysis, complete resection and desmoplastic pathology were independently predictive factors of improved PFS and OS. In adult medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes.

Sulfonamide derivatives containing dihydropyrazole moieties selectively and potently inhibit MMP-2/MMP-9: Design, synthesis, inhibitory activity and 3D-QSAR analysis.

New series of sulfonamide derivatives containing a dihydropyrazole moieties inhibitors of MMP-2/MMP-9 were discovered using structure-based drug design. Synthesis, antitumor activity, structure-activity relationship and optimization of physicochemical properties were described. In vitro the bioassay results revealed that most target compounds showed potent inhibitory activity in the enzymatic and cellular assays. Among the compounds, compound 3i exhibited the most potent inhibitory activity with IC50 values of 0.21 µM inhibiting MMP-2 and 1.87 µM inhibiting MMP-9, comparable to the control positive compound CMT-1 (1.26 µM, 2.52 µM). Docking simulation was performed to position compound 3i into the MMP-2 active site to determine the probable binding pose. Docking simulation was further performed to position compound 3i into the MMP-2 active site to determine the probable binding model the 3D-QSAR models were built for reasonable design of MMP-2/MMP-9 inhibitors at present and in future.

Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors.

Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized, and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In vitro biological evaluation against three human tumor cell lines revealed that most target compounds showed antiproliferative activities. Among the compounds, compound 48 exhibited the most potent and selective COX-2 inhibitor (COX-2 IC50=0.33 µM; COX-1 IC50=68.49 µM) relative to the reference drugs celecoxib (IC50=0.052 µM). Docking simulation was performed to position compound 48 into the COX-2 active site and the result showed that compound 48 could bind well at the COX-2 active site and it indicated that compound 48 could be a potent and selective COX-2 inhibitor.

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.

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.