Exogenous 24-Epibrassinolide Enhanced Drought Tolerance and Promoted BRASSINOSTEROID-INSENSITIVE2 Expression of Quinoa.

Brassinosteroids (BRs) are involved in the regulation of biotic and abiotic stresses in plants. The molecular mechanisms of BRs that alleviate the drought stress in quinoa have rarely been reported. Here, quinoa seedlings were treated with 24-epibrassinolide (EBR) and we transiently transferred CqBIN2 to the quinoa seedlings' leaves using VIGS technology to analyze the molecular mechanism of the BR mitigation drought stress. The results showed that EBR treatment significantly increased the root growth parameters, the antioxidant enzyme activities, and the osmolyte content, resulting in a decrease in the H2O2, O2∙-, and malondialdehyde content in quinoa. A transcriptome analysis identified 8124, 2761, and 5448 differentially expressed genes (DEGs) among CK and Drought, CK and EBR + Drought, and Drought and EBR + Drought groups. WGCNA divided these DEGs into 19 modules in which these characterized genes collectively contributed significantly to drought stress. In addition, the EBR application also up-regulated the transcript levels of CqBIN2 and proline biosynthesis genes. Silenced CqBIN2 by VIGS could reduce the drought tolerance, survival rate, and proline content in quinoa seedlings. These findings not only revealed that exogenous BRs enhance drought tolerance, but also provided insight into the novel functions of CqBIN2 involved in regulating drought tolerance in plants.

PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/ß-catenin axis.

BACKGROUND: PIEZO1 works differently in different cancers and at different stages of development. The objective of the current study was to explore the function and underlying mechanism of PIEZO1 in lung adenocarcinoma (LUAD) cells. METHODS: Different LUAD cell lines were treated with PIEZO1 inhibitor (GsMTx4) and agonist (Yoda1), and the expression of PIEZO1 in LUAD cells was detected using real-time quantitative PCR (RT-qPCR) and western blotting. The effects of PIEZO1 on invasion, migration and epithelial-mesenchymal transition (EMT) markers protein expression of LUAD cells were detected using the MTT assay, flow cytometry, transwell assay, wound-healing assay, and western blotting. Reactive oxygen species (ROS) agonists (BAY 87-2243) and inhibitors (NAC) and Wnt/ß-catenin pathway inhibitors (iCRT3) were selected to treat A549 cells to investigate the mechanism of PIEZO1 on ROS production and Wnt/ß-catenin expression in A549 cells. RESULTS: In A549, NCI-H1395, and NCI-H1975 cells, GsMTx4 promoted cell proliferation, invasion, migration, upregulated EMT-related marker protein expression, and inhibited cell apoptosis, while Yoda1 exerted effects opposite to those of GsMTx4. In A549 cells, GsMTx4 can reduce ROS production, it also inhibited ROS production, apoptosis, and downregulated proapoptotic markers induced by BAY 87-2243. Importantly, BAY 87-2243 blocked the effect of GSMTX4-induced Wnt/ß-catenin overexpression. Similarly, Yoda1 can reduce the effect of NAC. In addition, iCRT3 can block the upregulation of EMT-related marker proteins by GsMTx4, and increase apoptosis and decrease cell invasion and migration. CONCLUSION: In summary, PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/ß-catenin axis, providing a new perspective on the role of mechanosensitive channel proteins in cancer.

Efficacy of mFOLFOX6 plus bevacizumab regimen in advanced colorectal cancer after deep hyperthermia: a single-center retrospective study.

Background: This study aimed to explore the clinical efficacy and safety of a modified FOLFOX6 (oxaliplatin + leucovorin + 5-fluorouracil) plus bevacizumab regimen after deep hyperthermia in advanced colorectal cancer. Methods: A total of 80 colorectal cancer patients treated at our hospital were selected as research subjects. According to the random number table method, patients were divided into a control group (mFOLFOX6 plus bevacizumab) and a combination group (mFOLFOX6 plus bevacizumab after deep hyperthermia treatment), with 40 patients in each group. After six cycles of treatment, the objective response rate (ORR), disease control rate (DCR), levels of serum tumor markers carcinoembryonic antigen (CEA), vascular epidermal growth factor (VEGF), Karnofsky performance status (KPS) scores, and the occurrence of adverse events were compared between the two groups. Results: After six cycles of treatment, the ORR in the combination group was higher than that in the control group, but the difference was not statistically significant (P>0.05). The DCR in the combination group was significantly higher than that in the control group (P<0.05). The serum CEA levels in the control and combination groups after treatment were significantly lower than those before treatment, and the serum CEA and VEGF levels in the combination group were significantly lower than those in the control group (all P<0.001). The KPS scores in both groups after treatment were higher than those before treatment, and the KPS scores in the combination group after treatment were significantly higher than those in the control group (all P<0.001). The incidence of fatigue and pain in the combination group was significantly lower than that in the control group (P<0.05). Conclusion: mFOLFOX6 plus bevacizumab after deep hyperthermia is effective in advanced colorectal cancer patients, which can effectively improve their quality of life, and the adverse events are controllable and tolerable. A randomized or prospective trial will be required to further prove these data and explore its potentiality, especially if compared to conventional treatment.

Differential Photoaging Effects on Colored Nanoplastics in Aquatic Environments: Physicochemical Properties and Aggregation Kinetics.

Nanoplastics (NPs) have different colors, which could affect their photoaging processes in aquatic environments. This study investigated the effects of irradiation on physicochemical properties and aggregation kinetics of five colored NPs. Photodegradation rates and photooxidation degrees ranked white ≈ yellow > red > blue ≈ black NPs, indicating that NPs with longer color wavelengths photoaged faster. The discoloration process followed color fading (2-14 days, except for white NPs), yellowing (10-16 days), yellow fading (18 days), and turning transparent (20-22 days). White NPs exhibited a different photoaging sequence (C-H → C-OH → C═O → O-C═O) from others. Photodegradation was mainly controlled by singlet oxygen, producing 13 chemicals that were mostly organic acids. The overall colloidal stability of pristine NPs ranked blue > yellow > red > black > white. Irradiation for 16 days retarded aggregation of white and other NPs in NaCl solution, raising the critical coagulation concentration (CCC) by 82.14 and 0.85-7.90%, respectively. Contrarily, irradiation promoted aggregation in CaCl2 solution by reducing the CCC of white (67.37%) and other (33.33-37.58%) NPs. The findings demonstrate that colored NPs underwent photoaging processes different from white/transparent NPs, which were focused by previous work, highlighting the important role of color in their environmental fate and transport.

Saikosaponin d modulates the polarization of tumor-associated macrophages by deactivating the PI3K/AKT/mTOR pathway in murine models of pancreatic cancer.

The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) poses a major obstacle to traditional and immunomodulatory cancer therapies and is closely associated with macrophage polarization. Saikosaponin d (SSd), a major active component of triterpene saponins derived from Bupleurum falcatum, has anti-inflammatory and antitumor activities. However, whether SSd can regulate immune cells during the development of the TME in PDAC remains unknown. In the present study, we aimed to analyze the role of SSd in regulating immune cells in the PDAC TME, especially the polarization of macrophages, and examine the related mechanisms. An orthotopic PDAC cancer model was used to investigate the antitumor activities and the regulation of immune cells in vivo. In vitro, bone marrow mononuclear (BM-MNC) cells and RAW 264.7 cells were used to induce the M2 macrophage phenotype and examine the effects and molecular mechanism of SSd on M2 macrophage polarization. The results revealed that SSd could directly inhibit the apoptosis and invasion of pancreatic cancer cells, modulate the immunosuppressive microenvironment and reactivate the local immune response, especially by decreasing the shift toward M2 macrophage polarization by downregulating phosphorylated STAT6 levels and the PI3K/AKT/mTOR signaling pathway. Furthermore, 740-Y-P (PI3K activator) was used to verify that SSd inhibited M2 polarization in RAW264.7 cells via the PI3K/AKT/mTOR signaling pathway. In conclusion, this study provided experimental evidence of the antitumor effect of SSd, especially in the regulation of M2 macrophage polarization, and demonstrated that SSd may be a promising therapeutic agent in PDAC.

Efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment in HER-2 negative advanced gastric cancer.

Aim: To observe the efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment for patients with human epidermal growth factor receptor 2 (HER-2) negative advanced gastric cancer. Methods: 80 eligible patients with HER-2 negative advanced gastric cancer admitted to Jingjiang People's Hospital Affiliated with Yangzhou University-from March 2021 to March 2022 were selected, and they were divided into the control group (n = 40, apatinib) and experimental group (n = 40, apatinib plus deep hyperthermia) on the basis of random number table method. The levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and vascular endothelial growth factor (VEGF) were monitored, and the efficacy of the two groups was analyzed by referring to Karnofsky performance status (KPS), overall survival (OS) and disease control rate (DCR) before and after treatment. Results: The levels of CEA, CA199, and VEGF in both groups were lower after treatment than before (p < 0.05), and lower (CEA: 8.85 ± 1.36 vs. 12.87 ± 1.23, CA199: 34.19 ± 4.68 vs. 50.11 ± 5.73, VEGF: 124.8 ± 18.03 vs. 205.9 ± 19.91) in the experimental group than in the control group (p < 0.05). The DCR and KPS of the patients in the experimental group were significantly higher (DCR: 62.50% vs. 40.00%; KPS: 83.25 ± 1.15 vs. 76.25 ± 1.17) than in the control group (p < 0.05). In survival analysis, patients with control group had shorter OS than the experimental group. (median 5.65 vs. 6.50 months; hazard ratio [HR], 1.63 [95% confidence interval (CI) 1.02-2.60], p = 0.0396). Conclusion: The application of low-dose apatinib plus deep hyperthermia for patients with HER-2 negative gastric cancer who failed second-line treatment should be a promising option.

S1P/S1PR2 promote pancreatic stellate cell activation and pancreatic fibrosis in chronic pancreatitis by regulating autophagy and the NLRP3 inflammasome.

Sphingosine-1-phosphate (S1P) is a bioactive lipid molecule that governs various functions by embedding its receptor, S1PR, in different cells. Chronic pancreatitis (CP) is characterized by pancreatic fibrosis via activation of pancreatic stellate cells (PSCs). However, the effect of S1P on CP and PSC activation is still unknown. Here, we conducted a series of experiments to explore the effect of S1P on a CP rat model and primary cultured PSCs. In vivo, CP was induced by intravenous injection of dibutyltin dichloride. S1P was administered at a dosage of 200 µg/kg body weight per day by intraperitoneal injection. After 4 weeks, serum, plasma and pancreas samples were collected for molecular analysis and histological detection. In vitro, PSCs were isolated and cultured for treatment with different doses of S1P. 3MA and MCC950 were used to determine the effect of S1P on PSC activation by regulating autophagy and the NLRP3 inflammasome. JTE013 and Si-S1PR2 were applied to verify that the functions of S1P were realized by combining with S1PR2. Cells were collected for RT‒PCR, western blotting and immunofluorescence. The results showed that S1P was increased in the plasma and pancreatic tissue of CP rats. When S1P was administered to CP rats, the function and histomorphology of the pancreas were severely impaired. In addition, S1P promoted PSC activation, heightened autophagy and enhanced the NLRP3 inflammasome in vivo and in vitro. Moreover, S1PR2 mediated the effect of S1P on PSC activation by regulating autophagy and the NLRP3 inflammasome sequentially. In conclusion, S1P binding to S1PR2 promoted PSC activation and pancreatic fibrosis in CP by regulating autophagy and the NLRP3 inflammasome. These findings provide a theoretical basis for targeting S1P/S1PR2 to treat pancreatic fibrosis and further suggest that considering the role of autophagy and the NLRP3 inflammasome may help with the treatment pancreatic fibrosis.

Combined exposure to polystyrene nanoplastics and bisphenol A induces hepato- and intestinal-toxicity and disturbs gut microbiota in channel catfish (Ictalurus punctatus).

The widespread consumption of nanoplastics (NPs) and bisphenol A (BPA) affected the aquatic ecosystem and imposed risks to the safety of aquatic organisms. This study was aimed at assessing the ecotoxicological effects of single and combined exposure to BPA and polystyrene nanoplastics (PSNPs) on the channel catfish (Ictalurus punctatus). A total of 120 channel catfish were separated into four groups with triplicate (each contains 10 fish) and exposed to chlorinated tap water (control group), PSNP single exposure (0.3 mg/L), BPA single exposure (500 µg/L) and PSNPs (0.3 mg/L) + BPA (500 µg/L) co-exposure for 7 days. Our results showed a relatively higher intestinal accumulation of PSNPs in co-exposure group, compared to PSNP single exposure group. Histopathological analysis showed that single exposure to PSNPs and BPA caused breakage of intestinal villi and swelling of hepatocytes in channel catfish, while the co-exposure exacerbated the histopathological damage. In addition, co-exposure significantly increased SOD, CAT activities and MDA contents in the intestine and liver, inducing oxidative stress. In terms of immune function, the activities of ACP and AKP were significantly decreased. The expressions of immune-related genes such as IL-1ß, TLR3, TLR5, hepcidin and ß-defensin were significantly up-regulated, and the expression of IL-10 was down-regulated. Additionally, the co-exposure significantly altered the composition of the intestinal microbiota, leading to an increase in the Shannon index and a decrease in the Simpson index. In summary, this study revealed that mixture exposure to PSNPs and BPA exacerbated toxic effects on histopathology, oxidative stress, immune function and intestinal microbiota in channel catfish. It emphasized the threat of NPs and BPA to the health of aquatic organisms and human food safety, with a call for effective ways to regulate the consumption of these anthropogenic chemicals.

Xuanfei Baidu Decoction suppresses complement overactivation and ameliorates IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway.

BACKGROUND: The significant clinical efficacy of Xuanfei Baidu Decoction (XFBD) is proven in the treatment of patients with coronavirus disease 2019 (COVID-19) in China. However, the mechanisms of XFBD against acute lung injury (ALI) are still poorly understood. METHODS: In vivo, the mouse model of ALI was induced by IgG immune complexes (IgG-IC), and then XFBD (4g/kg, 8g/kg) were administered by gavage respectively. 24 h after inducing ALI, the lungs were collected for histological and molecular analysis. In vitro, alveolar macrophages inflammation models induced by IgG-IC were performed and treated with different dosage of XFBD-containing serum to investigate the protective role and molecular mechanisms of XFBD. RESULTS: The results revealed that XFBD mitigated lung injury and significantly downregulated the production of pro-inflammatory mediators in lung tissues and macrophages upon IgG-IC stimulation. Notably, XFBD attenuated C3a and C5a generation, inhibited the expression of C3aR and C5aR and suppressed the activation of JAK2/STAT3/SOCS3 and NF-κB signaling pathway in lung tissues and macrophages induced by IgG-IC. Moreover, in vitro experiments, we verified that Colivelin TFA (CAF, STAT3 activator) and C5a treatment markedly elevated the IgG-IC-triggered inflammatory responses in macrophages and XFBD weakened the effects of CAF or C5a. CONCLUSION: XFBD suppressed complement overactivation and ameliorated IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway. These data contribute to understanding the mechanisms of XFBD in COVID-19 treatment.

Synergistic removal of sulfamethoxazole and dimethyl phthalate by five constructed wetland substrates.

Frequent detection and joint toxicity of sulfonamides (SAs) and phthalate acid esters (PAEs) in water environment have caused serious health and safety problems that can be reduced by vertical flow constructed wetland (VFCW). However, it remains unclear what kind of substrate used in VFCW can synergistically remove SAs and PAEs. In this study, it was determined if biochar, zeolite, vermiculite, peat and sand synergistically removed sulfamethoxazole (SMX) and dimethyl phthalate (DMP) as representatives of SAs and PAEs by using batch and column experiments. The batch experiments showed that pseudo-second-order and intraparticle diffusion kinetics and Freundlich isotherm could better describe the synergistic adsorption of SMX and DMP on each substrate. SMX promoted hydrophobic interaction between DMP and each substrate so that low concentration DMP almost was adsorbed completely at neutral pH. Both neutral and alkaline pH conditions were favorable for synergistic adsorption of SMX and DMP on each substrate. The column experiments showed that removal of SMX or DMP in VFCW by substrate adsorption alone was limited with run time increasing, but SMX and DMP were effectively removed with run time increasing when loaded with simulated wastewater, SMX and DMP. The VFCW not only removed 94.7% SMX and 91.8% DMP after running 50 d, but also improved total nitrogen removal. In conclusion, these results strongly suggest that biochar, zeolite, vermiculite, peat and sand filled in VFCW can synergistically remove SMX and DMP.

The optimum particle size of anaerobic ammonia oxidation granular sludge under different substrate concentrations.

The nitrogen removal performance of anaerobic ammonia oxidation granular sludge (AnGS) varies widely among particle sizes. In this paper, the nitrogen removal performance, extracellular polymeric substances (EPS) secretion level and microbial community of AnGS with different particle sizes were investigated to select the optimal particle size for different substrate concentrations. The results showed that the optimal particle size migrated from 0.6-1.6 mm to 1.6-2.5 mm and then to 2.5-3.2 mm as the substrate concentration increased. When the influent concentration of NH4+-N was 110 mg/L, granular sludge with particle size of 1.6-2.5 mm showed excellent nitrogen removal performance with the highest EPS secretion, while the highest EPS secretion gradually migrated to smaller particles as the substrate concentration decreased. The nitrogen removal performance of AnGS with different particle sizes depends on different proportions of anaerobic ammonium-oxidizing (anammox) bacteria (Candidates_Jettenia, Candidates_Kuenenia, Candidatus_Brocadia), heterotrophic nitrification aerobic denitrifying bacteria (Acinetobacter) and denitrifying bacteria (Denitratisoma). The optimum particle size range for AnGS has been clarified for different influent nitrogen concentrations, which can provide some new understanding for the application of anammox reactors.

Prevalence and relevant factors of physical and emotional abuse by parents among children with autism spectrum disorder / 中国学校卫生

Objective@#To explore the prevalence and relevant factors of physical and emotional abuse by parents among children with autism spectrum disorder (ASD), so as to provide basis for intervention program of children abuse.@*Methods@#A total of 221 ASD children from 3 special education institutions in Tangshan were investigated from March to October in 2021, 395 non ASD children from two kindergartens in urban and rural areas were selected by convenient sampling. Parents of these children were invited for online and on site questionnaire survey. The self designed violence questionnaire, Childhood Autism Rating Scale and Patient Health Questionnaire-9 were used to assess violence, severity of autism, depression of parents. Chi square test, Fisher s exact probability method and Logistic regression were used to analyze the influencing factors of violence.@*Results@#About 81.9% of children with ASD and 72.9% of non ASD children experienced violence( P <0.05). The reported rates of physical and emotional violence in ASD children were 74.2% and 73.8% respectively, which in non ASD children were 58.7% and 65.8% respectively. There were significant differences in the 3 types of violence rate between the two groups ( P <0.05). Multivariate Logistic regression analysis showed that boys ( OR =1.70, 95% CI =1.12-2.60), annual per capita income <10 000 yuan( OR =2.43, 95% CI =1.45- 4.08 ), and parental depression ( OR mild =11.01, 95% CI =5.38-22.49; OR moderate =69.97，95% CI =24.25-201.93) were the risk factors for child violence exposure; ASD disease ( OR=1.96，95%CI =1.32-2.92), older age ( OR=1.19, 95%CI =1.01-1.41) and parental depression( OR mild =7.83, 95% CI =3.67-16.74; OR moderate =14.37，95% CI =6.17-33.46) were risk factors for physical violence; boys ( OR =1.62, 95% CI =1.11-2.36), mothers who work in manual labor ( OR=1.68, 95%CI =1.09-2.59) and parental depression ( OR mild =7.69, 95% CI =3.74-15.81; OR moderate =25.37, 95% CI =10.80-59.63) were risk factors for emotional violence( P < 0.05 ).@*Conclusion@#The reported rate of parental violence against children with ASD is high. Mental health promotion and social support for families with ASD should be strengthened.

Effective removal of nanoplastics from water by cellulose/MgAl layered double hydroxides composite beads.

Micro/nanoplastic pollution is an emerging concern all over the world as it has a certain impact on the eco-environment and human health. In this study, cellulose/MgAl layered double hydroxides (LDHs) composite beads were prepared for the removal of polystyrene nanoparticles by utilizing the porous properties of cellulose and the unique positive charge of LDHs. The effects of pH, contact time, initial concentration, temperature, humic acid, and ionic strength on the attachment of nanoplastics were studied. The microstructure characteristics of the beads were also analyzed before and after the attachment of nanoplastics. The results indicate that nanoplastic attachment probably involves pore diffusion, hydrogen bonding, and electrostatic interactions. The attachment behavior can be successfully explained using the pseudo-second-order kinetic model (R2 = 0.964), Webber-Morris (intra-particle diffusion) model, and Langmuir isotherm model (R2 = 0.978). The maximum attachment capacity can reach 6.08 mg/g. Therefore, the cellulose/LDHs composite beads can be a promising adsorbent for removing micro/nanoplastics.

The antitumor activity of hPRDX5 against pancreatic cancer and the possible mechanisms.

Recombinant human peroxiredoxin-5 (hPRDX5), isolated from anti-cancer bioactive peptide (ACBPs), shows a homology of 89% with goat peroxiredoxin-5 (gPRDX5) and is reported to display anti-tumor activity in vivo. Herein, we explored the effect of hPRDX5 and the responsible mechanism in treating pancreatic cancer. Tumor-bearing mice were randomly divided into normal PBS group and treatment group (n=5; 10 mg/kg hPRDX5). Flow cytometry was employed to examine lymphocytes, myeloid-derived suppressor cell subsets, and the function proteins of natural killer (NK) cells in peripheral blood, spleen, and tumor tissues of mice. Western blot was used to measure the protein expressions of the key nodes in TLR4-MAPK-NF-κB signaling pathway. The rate of tumor suppression was 57.6% at a 10 mg/kg dose in orthotopic transplanted tumor mice. Moreover, the population of CD3+CD4+T cells, NK cells, and CD3+CD8+T cells was significantly increased in the tumor tissue of the hPRDX5 group, while the proportion of granulocytic-myeloid-derived suppressor cells decreased slightly. In addition, after treatment with hPRDX5, the percentage of NK cells in blood increased more than 4-fold. Our findings indicated that hPRDX5 effectively suppressed pancreatic cancer possibly via the TLR4-MAPK-NF-κB signaling cascade; hence hPRDX5 could be a prospective immunotherapy candidate for treating pancreatic cancer.

Plasma cfDNA for the Diagnosis and Prognosis of Colorectal Cancer.

Objective: To evaluate the value of cell-free DNA (cfDNA) for the diagnosis and prognosis of colorectal cancer (CRC). Methods: Peripheral blood specimens of 120 CRC patients and 90 healthy volunteers (as a control cohort) were extracted. A quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the cfDNA expression. Following correlation analyses for cfDNA and clinical endpoints, a receiver operator characteristic (ROC) curve was established to assess the sensitivity and specificity of cfDNA, CEA, VEGF, and CA125 and for evaluating the disease-free survival (DFS) of patients. Results: The plasma cfDNA level of colorectal cancer patients was significantly higher than that of healthy subjects (P < 0.05), and after chemotherapy, cfDNA level was significantly lower than that before chemotherapy (P < 0.05). CA125/CEA/VEGF expression significantly correlated with cfDNA level, but not with cfDNA integrity. There was also a significant correlation between tumor differentiation and the cfDNA level. cfDNA has a higher ROC value than the current tumor biomarkers. Survival analysis showed that the DFS of the low cfDNA expression group was longer (29.99 ± 0.78 months) than that of the high cfDNA expression group (27.66 ± 1.05 months, P=0.031). Conclusion: The blood cfDNA is associated with the pathological features of CRC clinical cases and represents a possible indicator for CRC diagnosis and prognosis.

Syringaresinol Resisted Sepsis-Induced Acute Lung Injury by Suppressing Pyroptosis Via the Oestrogen Receptor-ß Signalling Pathway.

Acute lung injury (ALI) is a common lung disease characterized by severe acute inflammatory lung injury in patients with sepsis. Syringaresinol (SYR) has been reported to have anti-apoptotic and anti-inflammatory effects, but whether it could prevent pyroptosis to improve sepsis-induced ALI remains unclear. The purpose of this work was to examine the impact of SYR on sepsis-induced ALI and investigate the underlying mechanisms. The ALI model was induced by caecal ligation and puncture (CLP) in C57BL/6 mice, structural damage in the lung tissues was determined using haematoxylin and eosin (HE) staining, and the levels of related inflammatory cytokines and macrophage polarization were examined by enzyme-linked immunosorbent assays (ELISAs) and flow cytometry, respectively. The activation of the NLRP3 inflammasome and the protein levels of TLR4, NF-κB and MAPKs was measured by western blotting. The results demonstrated that SYR pretreatment significantly reduced lung tissue histological damage, inhibited the production of proinflammatory cytokines and albumin in bronchoalveolar lavage fluid (BALF), and decreased myeloperoxidase (MPO) levels, thereby alleviating lung tissue injury. Meanwhile, septic mice treated with SYR displayed a higher survival rate and lower percentage of M1 macrophages in the BALF and spleen than septic mice. In addition, lung tissues from the CLP + SYR group exhibited downregulated protein expression of NLRP3, ASC, GSDMD caspase-1 p20 and TLR4, along with decreased phosphorylated levels of NF-κB, ERK, JNK and P38, indicating that SYR administration effectively prevented CLP-induced pyroptosis in the lung. SYR also suppressed LPS-induced pyroptosis in RAW 264.7 cells by inhibiting the activation of the NLRP3 inflammasome, which was abolished by an oestrogen receptor-ß (ERß) antagonist (PHTPP). In conclusion, SYR exerted protective effects on CLP-induced ALI via the oestrogen receptor-ß signalling pathway.

The antitumor activity of hPRDX5 against pancreatic cancer and the possible mechanisms

Recombinant human peroxiredoxin-5 (hPRDX5), isolated from anti-cancer bioactive peptide (ACBPs), shows a homology of 89% with goat peroxiredoxin-5 (gPRDX5) and is reported to display anti-tumor activity in vivo. Herein, we explored the effect of hPRDX5 and the responsible mechanism in treating pancreatic cancer. Tumor-bearing mice were randomly divided into normal PBS group and treatment group (n=5; 10 mg/kg hPRDX5). Flow cytometry was employed to examine lymphocytes, myeloid-derived suppressor cell subsets, and the function proteins of natural killer (NK) cells in peripheral blood, spleen, and tumor tissues of mice. Western blot was used to measure the protein expressions of the key nodes in TLR4-MAPK-NF-κB signaling pathway. The rate of tumor suppression was 57.6% at a 10 mg/kg dose in orthotopic transplanted tumor mice. Moreover, the population of CD3+CD4+T cells, NK cells, and CD3+CD8+T cells was significantly increased in the tumor tissue of the hPRDX5 group, while the proportion of granulocytic-myeloid-derived suppressor cells decreased slightly. In addition, after treatment with hPRDX5, the percentage of NK cells in blood increased more than 4-fold. Our findings indicated that hPRDX5 effectively suppressed pancreatic cancer possibly via the TLR4-MAPK-NF-κB signaling cascade; hence hPRDX5 could be a prospective immunotherapy candidate for treating pancreatic cancer.

Saikosaponin D Attenuates Pancreatic Injury Through Suppressing the Apoptosis of Acinar Cell via Modulation of the MAPK Signaling Pathway.

Chronic pancreatitis (CP) is a progressive fibro-inflammatory syndrome. The damage of acinar cells is the main cause of inflammation and the activation of pancreatic stellate cells (PSCs), which can thereby possibly further aggravate the apoptosis of more acinar cells. Saikosaponind (SSd), a major active ingredient derived from Chinese medicinal herb bupleurum falcatum, which exerted multiple pharmacological effects. However, it is not clear whether SSd protects pancreatic injury of CP via regulating the apoptosis of pancreatic acinar cells. This study systematically investigated the effect of SSd on pancreatic injury of CP in vivo and in vitro. The results revealed that SSd attenuate pancreatic damage, decrease the apoptosis and suppress the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2, and p38 MAPK) significantly in the pancreas of CP rats. In addition, SSd markedly reduced the apoptosis and inflammation of pancreatic acinar AR42J cells induced by cerulein, a drug induced CP, or Conditioned Medium from PSCs (PSCs-CM) or the combination of PSCs-CM and cerulein. Moreover, SSd significantly inhibited the activated phosphorylation of JNK1/2, ERK1/2, and p38 MAPK induced by cerulein or the combination of PSCs-CM and cerulein in AR42J cells. Furthermore, SSd treatment markedly decreased the protein levels of p-JNK and p-p38 MAPK caused by PSCs-CM alone. In conclusion, SSd ameliorated pancreatic injury, suppressed AR42J inflammation and apoptosis induced by cerulein, interrupted the effect of PSCs-CM on AR42J cells inflammation and apoptosis, possibly through MAPK pathway.

Impact of MicroRNAs in Interaction With Environmental Factors on Autism Spectrum Disorder: An Exploratory Pilot Study.

Background: This study aimed to explore the main effects of environmental risk factors as well as their interaction effects with miRNA on the risk of autism spectrum disorder (ASD). Methods: One hundred fifty-nine ASD children (ASD group) and 159 healthy children (control group), aged 2-6 years, were included in this study. ASD diagnoses were based on DSM-5 criteria. The extensive medical and demographic characterization of the two groups were recorded. MicroRNAs (miRNAs) in serum were detected by qRT-PCR. Results: Compared with the control group, the ASD group had significantly higher rates of maternal stress during pregnancy (p < 0.001), maternal drinking during pregnancy (p = 0.006), threatened abortion (p = 0.011), pregnancy-induced hypertension (p = 0.032), gestational diabetes (p = 0.039), maternal anemia during pregnancy (p < 0.001), umbilical cord knot (p < 0.001), neonatal jaundice (p < 0.001), family psychiatric history (p = 0.001), and much lower birth weight (p = 0.012). Furthermore, the ASD group had much lower expression levels of hsa-miR-181b-5p (p < 0.001) and hsa-miR-320a (p < 0.001) and significantly higher levels of hsa-miR-19b-3p (p < 0.001). The interactions of hsa-miR-320a and maternal stress during pregnancy (OR = 39.42, p < 0.001), hsa-miR-19b-3p and neonatal jaundice (OR = 2.44, p < 0.001), and hsa-miR-181b-5p and family psychiatric history (OR = 8.65, p = 0.001) could increase ASD risk. Conclusions: The dysregulation of hsa-miR-181b-5p, hsa-miR-320a, and hsa-miR-19b-3p could interact with environmental factors, such as maternal stress during pregnancy, neonatal jaundice, and family psychiatric history, to impact the risk of ASD.

Grouping strategies in numerosity perception between intrinsic and extrinsic grouping cues.

The number of items in an array can be quickly and accurately estimated by dividing the array into subgroups, in a strategy termed "groupitizing." For example, when memorizing a telephone number, it is better to do so by divide the number into several segments. Different forms of visual grouping can affect the precision of the enumeration of a large set of items. Previous studies have found that when groupitizing, enumeration precision is improved by grouping arrays using visual proximity and color similarity. Based on Gestalt theory, Palmer (Cognit Psychol 24:436, 1992) divided perceptual grouping into intrinsic (e.g., proximity, similarity) and extrinsic (e.g., connectedness, common region) principles. Studies have investigated groupitizing effects on intrinsic grouping. However, to the best of our knowledge, no study has explored groupitizing effects for extrinsic grouping cues. Therefore, this study explored whether extrinsic grouping cues differed from intrinsic grouping cues for groupitizing effects in numerosity perception. The results showed that both extrinsic and intrinsic grouping cues improved enumeration precision. However, extrinsic grouping was more accurate in terms of the sensory precision of the numerosity perception.