Nanosensor detection of reactive oxygen and nitrogen species leakage in frustrated phagocytosis of nanofibres.

Exposure to widely used inert fibrous nanomaterials (for example, glass fibres or carbon nanotubes) may result in asbestos-like lung pathologies, becoming an important environmental and health concern. However, the origin of the pathogenesis of such fibres has not yet been clearly established. Here we report an electrochemical nanosensor that is used to monitor and quantitatively characterize the flux and dynamics of reactive species release during the frustrated phagocytosis of glass nanofibres by single macrophages. We show the existence of an intense prolonged release of reactive oxygen and nitrogen species by single macrophages near their phagocytic cups. This continued massive leakage of reactive oxygen and nitrogen species damages peripheral cells and eventually translates into chronic inflammation and lung injury, as seen during in vitro co-culture and in vivo experiments.

A Combination of EGFR Inhibitors and AE-PDT Could Synergistically Suppress Breast Cancer Progression.

BACKGROUND: Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancerrelated deaths in women. Activation of EGFR by EC-secreted EGFR ligands promotes breast cancer progression. Current treatments provide limited benefits in triple-negative breast cancer (TNBC). Photodynamic therapy (PDT) has been proven effective for the treatment of TNBC through the EGFR pathway, but the underlying mechanism is still unclear. PURPOSE: The purpose of this study was to determine the role of the EGFR pathway in the treatment of PDT on TNBC in a co-culture system. METHODS: MB-231 and HUVEC were co-cultured for experiments (HU-231). Cell viability and ROS production were detected after AE-PDT, a combination of EGFR inhibitors (AEE788)with PDT to test angiogenesis, apoptosis, and pyroptosis. WB detects expression of EGFR. EGFR, P-EGFR, VEGF, caspase-1, capase-3, and GSDMD . RESULTS: AE-PDT inhibited HU-231 cell proliferation and tumor angiogenesis, and induced cell apoptosis and pyroptosis by promoting ROS production. AEE788, an inhibitor of the EGFR, enhanced HU-231 cell killing after AE-PDT. CONCLUSION: Our study suggested that the combination of EGFR inhibitors and AE-PDT could synergistically suppress breast cancer progression, providing a new treatment strategy.

Erratum: [Corrigendum] Lidocaine inhibits the invasion and migration of TRPV6­expressing cancer cells by TRPV6 downregulation.

[This corrects the article DOI: 10.3892/ol.2016.4709.].

MOFs-based Fe@YAU-101/GCE electrochemical sensor platform for highly selective detecting trace multiplex heavy metal ions.

The construction of sensors with specific recognition functions can easily, sensitively and efficiently detect heavy metal ions, which is a demand in the field of electrochemical sensing and an important topic in the detection of environmental pollutants. An electrochemical sensor based on MOFs composites was developed for sensing of multiplex metal ions. The large surface area, adjustable porosities and channels in MOFs facilitate successful loading of sufficient quantities highly active units. The active units and pore structures of MOFs are regulated and synergetic with each other to enhance the electrochemical activity of MOFs composites. Thus, the selectivity, sensitivity and reproducibility of MOFs composites have been improved. Fortunately, after characterization, Fe@YAU-101/GCE sensor with strong signal was successfully constructed. In the presence of target metal ions in solution, the Fe@YAU-101/GCE can efficiently and synchronously identify Hg2+, Pb2+, and Cd2+. The detection limits (LOD) are 6.67 × 10-10 M(Cd2+), 3.33 × 10-10 M(Pb2+) and 1.33 × 10-8 M (Hg2+), and are superior to the permissible limits set by the National Environmental Protection Agency. The electrochemical sensor is simple without sophisticated instrumentation and testing processes, hence promising for practical applications.

Deficient chaperone-mediated autophagy in macrophage aggravates inflammation of nonalcoholic steatohepatitis by targeting Nup85.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.

The ALK1­Smad1/5­ID1 pathway participates in tumour angiogenesis induced by low­dose photodynamic therapy.

Photodynamic therapy (PDT) is an effective and low­invasive tumour therapy. However, it can induce tumour angiogenesis, which is a main factor leading to tumour recurrence and metastasis. Activin receptor­like kinase­1 (ALK1) is a key factor regulating angiogenesis. However, it remains unclear whether ALK1 plays an unusual role in low­dose PDT­induced tumour angiogenesis. In the present study, human umbilical vein endothelial cells (HUVECs) co­cultured with breast cancer MDA­MB­231 cells (termed HU­231 cells) were used to construct an experimental model of tumour angiogenesis induced by low­dose PDT. The viability, and the proliferative, invasive, migratory, as well as the tube­forming ability of the HU­231 cells were evaluated following low­dose PDT. In particular, ALK1 inhibitor and and an adenovirus against ALK1 were used to further verify the role of ALK1 in low­dose PDT­induced tumour angiogenesis. Moreover, the expression of ALK1, inhibitor of DNA binding 1 (ID1), Smad 1, p­Smad1/5, AKT and PI3K were detected in order to verify the underlying mechanisms. The findings indicated that low­dose PDT enhanced the proliferative ability of the HU­231 cells and reinforced their migratory, invasive and tube formation capacity. However, these effects were reversed with the addition of an ALK1 inhibitor or by the knockdown of ALK1 using adenovirus. These results indicated that ALK1 was involved and played a critical role in tumour angiogenesis induced by low­dose PDT. Furthermore, ALK1 was found to participate in PDT­induced tumour angiogenesis by activating the Smad1/5­ID1 pathway, as opposed to the PI3K/AKT pathway. On the whole, the present study, for the first time, to the best of our knowledge, demonstrates that ALK1 is involved in PDT­induced tumour angiogenesis. The inhibition of ALK1 can suppress PDT­induced tumour angiogenesis, which can enhance the effects of PDT and may thus provide a novel treatment strategy for PDT.

Ginseng-derived panaxadiol ameliorates STZ-induced type 1 diabetes through inhibiting RORγ/IL-17A axis.

Retinoic-acid-receptor-related orphan receptor γ (RORγ) is a major transcription factor for proinflammatory IL-17A production. Here, we revealed that the RORγ deficiency protects mice from STZ-induced Type 1 diabetes (T1D) through inhibiting IL-17A production, leading to improved pancreatic islet ß cell function, thereby uncovering a potential novel therapeutic target for treating T1D. We further identified a novel RORγ inverse agonist, ginseng-derived panaxadiol, which selectively inhibits RORγ transcriptional activity with a distinct cofactor recruitment profile from known RORγ ligands. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for panaxadiol in the RORγ ligand-binding pocket. Despite its inverse agonist activity, panaxadiol induced the C-terminal AF-2 helix of RORγ to adopt a canonical active conformation. Interestingly, panaxadiol ameliorates mice from STZ-induced T1D through inhibiting IL-17A production in a RORγ-dependent manner. This study demonstrates a novel regulatory function of RORγ with linkage of the IL-17A pathway in pancreatic ß cells, and provides a valuable molecule for further investigating RORγ functions in treating T1D.

Tranexamic versus aminocaproic acids in patients with total hip arthroplasty: a retrospective study.

BACKGROUND: Recently, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been applied in total hip arthroplasty (THA). However, doubts in clinicians' minds about which medicine is more efficient and economical in THA need to be clarified. Therefore, this study compared the efficacy and cost of the intraoperative administration of TXA and EACA per surgery in decreasing perioperative blood transfusion rates in THA. METHODS:  This study enrolled patients who underwent THA between January 2019 to December 2020. A total of 295 patients were retrospectively divided to receive topical combined with intravenous TXA (n = 94), EACA (n = 97) or control (n = 104). The primary endpoints included transfusions, estimated perioperative blood loss, cost per patient and the drop in the haemoglobin and haematocrit levels. RESULTS: Patients who received EACA had greater total blood loss, blood transfusion rates, changes in HGB levels and mean cost of blood transfusion per patient (P < 0.05) compared with patients who received TXA. In addition, both TXA and EACA groups had significantly fewer perioperative blood loss, blood transfusion, operation time and changes in haemoglobin and haematocrit levels than the control group (P < 0.05). Cost savings in the TXA and EACA groups were 736.00 RMB and 408.00 RMB per patient, respectively. CONCLUSIONS: The application of perioperative antifibrinolytics notably reduces the need for perioperative blood transfusions. What's more, this study demonstrated that TXA is superior to EACA for decreasing blood loss and transfusion rates while at a lower cost per surgery. These results indicate that TXA may be the optimum antifibrinolytics for THA in Chinese area rather than EACA.

Transcripts related with ammonium use and effects of gibberellin on expressions of the transcripts responding to ammonium in two invasive and native Xanthium species.

Soil nitrogen forms are important for exotic plant invasions. However, little effort has been made to study the molecular mechanisms underlying the utilization of different N forms in co-occurring invasive and native plants. The invasive plant Xanthium strumarium prefers nitrate relative to ammonium, and mainly invades nitrate-dominated environments, while it co-occurring native congener X. sibiricum prefers ammonium. Here, we addressed the genetic bases for the interspecific difference in ammonium use and the effects of gibberellin (GA). Twenty-six transcripts related with GA biosynthesis and ammonium utilization were induced by ammonium in X. sibiricum, while only ten in X. strumarium and none for ammonium uptake. XsiAMT1.1a, XsiGLN1.1 and XsiGLT1b may be crucial for the strong ability to absorb and assimilate ammonium in X. sibiricum. All tested transcripts were significantly up-regulated by GA1 and GA4 in X. sibiricum. XsiGA3OX1a, which was also induced by ammonium, may be involved in this regulation. Consistently, glutamine synthetase activity increased significantly with increasing ammonium-N/nitrate-N ratio for X. sibiricum, while decreased for X. strumarium. Our study is the first to determine the molecular mechanisms with which invasive and native plants use ammonium differently, contributing to understanding the invasion mechanisms of X. strumarium and its invasion habitat selection.

Effectiveness of peripheral defocus spectacle lenses in myopia control: a Meta-analysis and systematic review.

AIM: To evaluate the effectiveness of peripheral defocus spectacle lenses (PDLs) in myopia control. METHODS: Literature retrieval on PubMed, Cochrane Library, Embase, and Web of Science databases, and the search time limit was from the establishment of each database to December 29, 2021 were conducted. Change of spherical equivalent refraction (SER) and axial change (AL) were extracted from the literatures that met the inclusion criteria, and RevMan5.3 software was used for Meta-analysis. RESULTS: A total of 4 randomized controlled trials (RCTs) were included in this Meta-analysis, involving 770 myopic children. The results showed that PDLs could delay the progression of myopia in children with myopia compared with single vision spectacle lenses (SVLs; WMD=0.21 D, 95%CI: 0.01, 0.41, P=0.04). However, there was no significant difference in controlling the growth of axial length (AL) in myopic children (WMD=-0.10 mm, 95%CI: -0.21, 0.01, P=0.07). The results of the effectiveness of myopia control between the two spectacle lenses showed that PDLs were more effective in controlling the progression of myopia (OR=5.73, 95%CI: 2.58, 12.70, P<0.001) and delaying the growth of AL (OR=44.25, 95%CI: 8.84, 221.58, P<0.001) than SVLs, and the differences were statistically significant. CONCLUSION: PDLs can control the progression of myopia compared with SVLs, but cannot delay the growth of AL, and the effectiveness of PDLs in myopia control better than SVLs.

Homeostasis inside Single Activated Phagolysosomes: Quantitative and Selective Measurements of Submillisecond Dynamics of Reactive Oxygen and Nitrogen Species Production with a Nanoelectrochemical Sensor.

Reactive oxygen and nitrogen species (ROS/RNS) are generated by macrophages inside their phagolysosomes. This production is essential for phagocytosis of damaged cells and pathogens, i.e., protecting the organism and maintaining immune homeostasis. The ability to quantitatively and individually monitor the four primary ROS/RNS (ONOO-, H2O2, NO, and NO2-) with submillisecond resolution is clearly warranted to elucidate the still unclear mechanisms of their rapid generation and to track their concentration variations over time inside phagolysosomes, in particular, to document the origin of ROS/RNS homeostasis during phagocytosis. A novel nanowire electrode has been specifically developed for this purpose. It consisted of wrapping a SiC nanowire with a mat of 3 nm platinum nanoparticles whose high electrocatalytic performances allow the characterization and individual measurements of each of the four primary ROS/RNS. This allowed, for the first time, a quantitative, selective, and statistically robust determination of the individual amounts of ROS/RNS present in single dormant phagolysosomes. Additionally, the submillisecond resolution of the nanosensor allowed confirmation and measurement of the rapid ability of phagolysosomes to differentially mobilize their enzyme pools of NADPH oxidases and inducible nitric oxide synthases to finely regulate their homeostasis. This reveals an essential key to immune responses and immunotherapies and rationalizes its biomolecular origin.

FXR: structures, biology, and drug development for NASH and fibrosis diseases.

The nuclear receptor farnesoid-X-receptor (FXR) plays an essential role in bile acid, glucose, and lipid homeostasis. In the last two decades, several diseases, such as obesity, type 2 diabetes, nonalcoholic fatty liver disease, cholestasis, and chronic inflammatory diseases of the liver and intestine, have been revealed to be associated with alterations in FXR functions. FXR has become a promising therapeutic drug target, particularly for enterohepatic diseases. Despite the large number of FXR modulators reported, only obeticholic acid (OCA) has been approved for primary biliary cholangitis (PBC) therapy as FXR modulator. In this review, we summarize the structure and function of FXR, the development of FXR modulators, and the structure-activity relationships of FXR modulators. Based on the structural analysis, we discuss potential strategies for developing future therapeutic FXR modulators to overcome current limitations, providing new perspectives for enterohepatic and metabolic diseases treatment.

Spatiotemporal characteristics of PM2.5 and ozone concentrations in Chinese urban clusters.

Despite China's public commitment to emphasise air pollution investigation and control, trends in PM2.5 and ozone concentrations in Chinese urban clusters remain unclear. This study quantifies the spatiotemporal variations in PM2.5 and surface ozone at the scale of Chinese urban clusters by using a long-term integrated dataset from 2015 to 2020. Nonlinear Granger causality testing was used to explore the spatial association patterns of PM2.5 and ozone pollution in five megacity cluster regions. The results show a significant downward trend in annual mean PM2.5 concentrations from 2015 to 2020, with a decline rate of 2.8 µg m-3 yr-1. By contrast, surface ozone concentrations increased at a rate of 2.1 µg m-3 yr-1 over the 6 years. The annual mean PM2.5 concentrations in urban clusters show significant spatial clustering characteristics, mainly in Beijing-Tianjin-Hebei (BTH), Fenwei Plain (FWP), Northern slope of Tianshan Mountains urban cluster (NSTM), Sichuan Basin urban cluster (SCB), and Yangtze River Delta (YRD). Surface ozone shows severe summertime pollution and distributional variability, with increased ozone pollution in major urban clusters. The highest increases were observed in BTH, Yangtze River midstream urban cluster (YRMR), YRD, and Pearl River Delta (PRD). Nonlinear Granger causality tests showed that PM2.5 was a nonlinear Granger cause of ozone, further supporting the literature's findings that PM2.5 reduction promoted photochemical reaction rates and stimulated ozone production. The nonlinear test statistic passed the significance test in magnitude and statistical significance. FWP was an exception, with no significant long-term nonlinear causal link between PM2.5 and ozone. This study highlights the challenges of compounded air pollution caused primarily by ozone and secondary PM2.5. These results have implications for the design of synergistic pollution abatement policies for coupled urban clusters.

[α-lipoic acid ameliorates liver injury in rats with type 2 diabetes mellitus via activating AMPK/mTOR pathway].

OBJECTIVE: To investigate the effect of α-lipoic acid in ameliorating liver injury in rats with type 2 diabetes mellitus via activating adenosine 5'-monophosphate-activate protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. METHODS: The T2DM rat models were established by feeding with high-fat, high-sucrose diet and intraperitoneal injection of 27.5 mg/(kg·d) streptozotocin. The 32 rats with T2DM were randomly divided into 4 groups: T2DM group, α-lipoic acid group (LA), Compound C group (Comp C, an inhibitor of AMPK) and LA+Comp C group, with 8 rats in each group. Additionally, 8 Sprague-Dawlay (SD) rats without diabetes were set as normal control. The rats received α-lipoic acid at a dosage of 100 mg/(kg·d) or Compound C at a dosage of 20 mg/(kg·d) by intraperitoneal injection for 8 weeks as needed. The levels of relevant biochemical indexes were detected. The weight of liver was recorded to calculate liver weight index (LWI), and the pathological changes of liver tissues were detected by light and electron microscopy. The levels of AMPK, p-AMPK, mTOR, p-mTOR in rat liver were detected by Western blot. RESULTS: Compared with control group, the levels of LWI, homeostasis model assessment of insulin resistance, fasting blood glucose, alanine transaminase, aspartate transaminase, gamma glutamyl transferase and triglyceride in T2DM group were increased significantly (all P＜0.05). The liver tissue lesions were more serious and hepatic steatosis grade was higher. The expression of p-AMPK was decreased (P＜0.05) and the expression of p-mTOR was increased significantly(P＜0.05). α-lipoic acid could reverse the above-mentioned changes, ameliorate insulin resistance (all P＜0.05), protect the structure and function of liver, and activate the AMPK/mTOR pathway (P＜0.05). The protection of α-lipoic acid was weakened by the inhibition of AMPK with Compound C (P＜0.05). CONCLUSION: α-lipoic acid could protect the liver of rats with T2DM by activating AMPK/mTOR pathway.

Medical services for sports injuries and illnesses in the Beijing 2022 Olympic Winter Games.

BACKGROUND: Beijing 2022 Olympic Winter Games was the second Games held amid the COVID-19 pandemic. To a certain extent, it has altered the way sporting activities operate. There is a lack of knowledge on injury risk and illness occurrence in elite winter sport athletes amid the COVID-19 pandemic. This study aimed to describe the incidence of injuries and illnesses sustained during the XXIV Olympic Winter Games in Beijing from February 4 to 20, 2022. METHODS: We recorded the daily number of injuries and illnesses among athletes reported by Beijing 2022 medical staff in the polyclinic, medical venues, and ambulance. We calculated injury and illness incidence as the number of injuries or illnesses occurring during competition or training, respectively, with incidence presented as injuries/illnesses per 100 athlete-days. RESULTS: In total, 2,897 athletes from 91 nations experienced injury or illness. Beijing 2022 medical staff reported 326 injuries and 80 illnesses, equaling 11.3 injuries and 2.8 illnesses per 100 athletes over the 17-day period. Altogether, 11% of the athletes incurred at least one injury and nearly 3% incurred at least one illness. The number of injured athletes was highest in the skating sports (n=104), followed by alpine skiing (n=53), ice track (n=37), freestyle skiing (n=36), and ice hockey (n=35), and was the lowest in the Nordic skiing disciplines (n=20). Of the 326 injuries, 14 (4.3%) led to an estimated absence from training or competition of more than 1 week. A total of 52 injured athletes were transferred to hospitals for further care. The number of athletes with illness (n=80) was the highest for skating (n=33) and Nordic skiing (n=22). A total of 50 illnesses (62.5%) were admitted to the department of dentistry/ophthalmology/otolaryngology, and the most common cause of illness was other causes, including preexisting illness and medicine (n=52, 65%). CONCLUSION: Overall, 11% of athletes incurred at least one injury during the Games, which is similar to the findings during the Olympic Winter Games in 2014 and 2018. Regarding illness, 2% of athletes were affected, which is approximately one-third of the number affected in the 2018 Olympic Winter Games.

Medical services for sports injuries and illnesses in the Beijing 2022 Olympic Winter Games / 世界急诊医学杂志（英文）

BACKGROUND: Beijing 2022 Olympic Winter Games was the second Games held amid the COVID-19 pandemic. To a certain extent, it has altered the way sporting activities operate. There is a lack of knowledge on injury risk and illness occurrence in elite winter sport athletes amid the COVID-19 pandemic. This study aimed to describe the incidence of injuries and illnesses sustained during the XXIV Olympic Winter Games in Beijing from February 4 to 20, 2022. METHODS: We recorded the daily number of injuries and illnesses among athletes reported by Beijing 2022 medical staff in the polyclinic, medical venues, and ambulance. We calculated injury and illness incidence as the number of injuries or illnesses occurring during competition or training, respectively, with incidence presented as injuries/illnesses per 100 athlete-days. RESULTS: In total, 2,897 athletes from 91 nations experienced injury or illness. Beijing 2022 medical staff reported 326 injuries and 80 illnesses, equaling 11.3 injuries and 2.8 illnesses per 100 athletes over the 17-day period. Altogether, 11％ of the athletes incurred at least one injury and nearly 3％ incurred at least one illness. The number of injured athletes was highest in the skating sports (n=104), followed by alpine skiing (n=53), ice track (n=37), freestyle skiing (n=36), and ice hockey (n=35), and was the lowest in the Nordic skiing disciplines (n=20). Of the 326 injuries, 14 (4.3％) led to an estimated absence from training or competition of more than 1 week. A total of 52 injured athletes were transferred to hospitals for further care. The number of athletes with illness (n=80) was the highest for skating (n=33) and Nordic skiing (n=22). A total of 50 illnesses (62.5％) were admitted to the department of dentistry/ophthalmology/otolaryngology, and the most common cause of illness was other causes, including preexisting illness and medicine (n=52, 65％). CONCLUSION: Overall, 11％ of athletes incurred at least one injury during the Games, which is similar to the findings during the Olympic Winter Games in 2014 and 2018. Regarding illness, 2％ of athletes were affected, which is approximately one-third of the number affected in the 2018 Olympic Winter Games.

[Extraction, Characterization and Immune Effect Analysis of Listeria Monocytogenes Membrane Vesicles].

OBJECTIVE: To establish a method for extracting Listeria monocytogenesmembrane vesicles (LM-MVs) and to analyze the characteristics of LM-MVs and their ability to induce innate immune effect in vitro so as to lay the foundation for research into using LM-MVs as vaccine carrier and drug delivery platform. METHODS: The membrane vesicles secreted by Listeria monocytogenes were extracted through a continuous process, including culturing, centrifugation, filtration, ultrafiltration concentration and ultracentrifugation. The morphological characteristics of LM-MVs were observed with transmission electron microscope, and particle size distribution were measured by dynamic light scattering analysis. SDS-PAGE and Western blot were used to analyze the protein composition of LM-MVs. CCK-8 cell proliferation and toxicity determination experiments were done to analyze their effect on the proliferation of innate immune cells, and qPCR was used to analyze their ability to induce innate immune responses. RESULTS: A method for extracting LM-MVs was successfully established. Under the transmission electron microscope, LM-MVs presented a nearly circular film-like structure, and dynamic light scattering analysis showed that their sizes were between 65 and 190 nm. SDS-PAGE and Western blot showed that LM-MVs contained proteins, including listeriolysin O (LLO). CCK-8 cell proliferation and toxicity experiment showed that after intervention with 10, 20 and 50 µg/mL of LM-MVs for 24 hours, the proliferation rate of DC 2.4 mouse dendritic cell line was higher than that of non-interventional DC 2.4 cells ( P<0.05); after intervention with 0.1, 1, 10, 20 and 50 µg/mL of LM-MVs for 24 hours, the proliferation rate of RAW 264.7 cells was higher than that of non-interventional RAW 264.7 cells ( P<0.01). The results of qPCR showed that, after intervention with 50 µg/mL of LM-MVs, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 in RAW 264.7 cells were higher than those of non-intervention control cells ( P<0.05). CONCLUSIONS: The method established in the study can be used to extract LM-MVs. The extracted LM-MVs have a diameter of 65-190 nm and a nearly circular membrane-like structure. They can secrete a variety of protein components and stimulate innate immune responses.

[Heterogeneity of growth and maturity of Larimichthys polyactis in the offshore waters of southern Zhejiang, China]. / 浙江南部近海小黄鱼生长和性成熟特征的异质性.

The variations of life history traits have been observed for many fish species, which gains much concerns in the study of aquatic biology and ecology. In this study, the biological characteristics were explored for yellow croaker (Larimichthys polyactis) in the offshore waters of southern Zhejiang, based on 4920 individuals collected from 13 fishery-independent seasonal surveys from autumn 2015 to autumn 2018. Linear mixed effects models were used to estimate the growth, maturity characteristics, and their heterogeneity. The body length of yellow croaker samples ranged from 13 to 215 mm with the dominant body of 110 to 154 mm. The body weight ranged from 0.5 to 182.2 g, with the dominant body weight from 20 to 55 g. The results showed that the linear mixed effects models with random effects from season, gender, and year performed best for length-weight relationship, with the lowest AIC and RMSE values. The effects of season were much larger than those of genders and years. When the length exceeded 160 mm, the weight gain rate of yellow croaker was faster in spring and summer, lower in autumn and winter, while the male individuals gained more weight than the females with the same body length. Among 4841 individuals of specimens with gonadal data, the individuals at maturity Ⅱ stage occupied 50.4%, and the individuals at maturity stage contributed to 19.6%. The results from the best linear mixed effects model showed that season had the most significant influence on the maturity of yellow croaker. The 50% maturity length (L50%) was much lower in winter (124.6 mm) with no much difference between other seasons, indicating that yellow croaker matures earlier in winter. Our results indicated that linear mixed effect model could reflect the biological heterogeneity of yellow croaker conveniently and that the growth and maturity of yellow croaker had significantly sexual and temporal variations, which should be considered in the stock assessment and fishery management for yellow croaker.

Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection.

While Baccillus Calmette-Guerin (BCG) is used worldwide, tuberculosis (TB) is still a global concern due to the poor efficacy of BCG. Novel vaccine candidates are therefore urgently required. In this study, two attenuated recombinant Listeria strains, LMΔ-msv and LIΔ-msv were constructed by deletion of actA and plcB and expression of a fusion protein consisting of T cell epitopes from four Mycobacterium tuberculosis (Mtb) antigens (Rv2460c, Rv2660c, Rv3875, and Rv3804c). The safety and immunogenicity of the two recombinant strains were evaluated in C57BL/6J mice. After intravenous immunization individually, both recombinant strains entered liver and spleen but eventually were eliminated from these organs after several days. Simultaneously, they induced antigen-specific cell-mediated immunity, indicating that the recombinant Listeria strains were immunogenic and safe in vivo. LMΔ-msv immunization induced stronger cellular immune responses than LIΔ-msv immunization, and when boosted with LIΔ-msv, antigen-specific IFN-γ CD8+ T cell responses were notably magnified. Furthermore, we evaluated the protection conferred by the vaccine candidates against mycobacterial infection via challenging the mice with 1 × 107 CFU of BCG. Especially, we tested the feasibility of application of them as heterologous BCG supplement vaccine by immunization of mice with BCG firstly, and boosted with LMΔ-msv and LIΔ-msv sequentially before challenging. Combination immune strategy (LMΔ-msv prime-LIΔ-msv boost) conferred comparable protection efficacy as BCG alone. More importantly, BCG-vaccinated mice acquired stronger resistance to Mycobacterial challenge when boosted with LMΔ-msv and LIΔ-msv sequentially. Our results inferred that heterologous immunization with Listeria-based recombinant strains boosted BCG-primed protection against pulmonary mycobacterial infection.

Erratum: DR2 blocker thioridazine: A promising drug for ovarian cancer therapy.

[This corrects the article DOI: 10.3892/ol.2017.7184.].