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Due to the progress in light detection and ranging (LiDAR) technology, the collection of road point cloud data containing depth information and spatial coordinates has become more accessible. Consequently, utilizing point cloud data for pavement distress detection and quantification emerges as a crucial approach to improving the precision and reliability of road maintenance procedures. This paper aims to automatically detect and visualize pavement distress using LiDAR, deep learning-based 3D object detection method, and building information modeling (BIM). A pavement distress data set is first established using the point cloud data obtained from LiDAR. Then, the 3D object detection network, namely PointPillar, is employed for pavement distress detection, and the detection results will be quantified at a region-level. Finally, pavement BIM model integrating parametrically modeled distress families is built to visually manage the detected distress. After training and validating the model with the pavement distress data set, a detection performance index of recall is 78.5%, mean average precision (mAP) is 62.7%, which is better than other compared point cloud-based methods though the detection performance can be further improved. In addition, a newly untrained section of road is applied for the experiment. The detected distress is integrated in BIM environment for a visual management, providing a better maintenance guidance. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor T cell (CAR-T) therapy has demonstrated significant success in B-cell lymphoma. The combination with autologous stem cell transplantation (ASCT) further enhances the efficacy of CAR-T cell therapy, although its impact on adverse reactions remains inconclusive. This study examined 147 patients who received CAR-T alone and 145 patients who underwent ASCT combined with CAR-T for B-cell lymphoma. The combined group had a higher incidence of overall and grade 1–2 CRS, but the risk of grade 3–4 CRS and CRES was not elevated. A univariate logistic regression analysis revealed that females had a lower incidence of grade 3–4 CRS but a higher incidence of severe CRES. The involvement of the central nervous system also correlated with increased CRES occurrence. The findings suggest that combining ASCT with CAR-T does not heighten the risk of severe adverse effects post-infusion. However, further validation through multicenter, prospective clinical studies is necessary to establish CAR-T combined with ASCT as a superior treatment paradigm. (1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with r/r B-cell lymphoma received either CAR-T therapy alone or in combination with ASCT at our institution. We evaluated the incidence of CRS and CRES and utilized a logistic regression model to identify factors contributing to severe CRS (grade 3–4) and CRES (grade 3–4). (3) Results: The overall incidence of CRS and CRES was 78.9% and 8.2% in 147 patients receiving CAR-T alone, and 95.9% and 15.2% in 145 patients receiving CAR-T combined with ASCT, respectively. The incidence of overall CRS (p < 0.0001) and mild CRS (grade 1–2) (p = 0.021) was elevated in the ASCT combined with CAR-T group. No significant difference was observed in severe CRS and CRES between the groups. Among the 26 cases of lymphoma involving the central nervous system (CNS), 96.2% (25/26) developed CRS (15.4% grade 3–4), and 34.6% (9/26) manifested CRES (7.7% grade 3–4). Female patients had a lower incidence of severe CRS but a higher incidence of severe CRES. Lymphomas with CNS involvement demonstrated a higher risk of CRES compared to those without central involvement. (4) Conclusions: The combination of ASCT with CAR-T demonstrated a preferable option in r/r B-cell lymphoma without an increased incidence of severe CRS and CRES. [ABSTRACT FROM AUTHOR]

New energy sources such as solar energy have been developed and utilized due to the shortage of non-renewable energy, and photoelectric materials have attracted more attention, accordingly. Moreover, flexible optoelectronic devices are crucial in the fields of wearable artificial intelligence, portable energy, and smart medical care. At present, photoelectric devices based on traditional perovskite cobalt oxide rigid films have problems such as inability to bend and deformation, which limits their application environment. Here, natural mica with atomically flat surface, high thermal stability, high transparency and good mechanical flexibility was selected as the substrate for preparing a series of LaCoO 3 flexible photoelectric films. These films exhibit excellent photoelectric properties and flexible properties. More importantly, the flexible film still has fast response speed and reproducible light response after 500 bending cycles. It reveals that all-inorganic perovskite LaCoO 3 is a promising candidate for designing high-performance, flexible and wearable optoelectronic devices. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. Methods: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. Results: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07–11.27) and 13.17 months (95% CI 2.78–23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. Conclusions: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment. [ABSTRACT FROM AUTHOR]

We are concerned with solutions of the following quasilinear Schrödinger equations − div ( φ 2 ( u ) ∇ u ) + φ ( u ) φ ′ ( u ) | ∇ u | 2 + λ u = f ( u ) , x ∈ R N with prescribed mass ∫ R N u 2 d x = c , where N ⩾ 3, c > 0, λ ∈ R appears as the Lagrange multiplier and φ ∈ C 1 ( R , R + ). The nonlinearity f ∈ C ( R , R ) is allowed to be mass-subcritical, mass-critical and mass-supercritical at origin and infinity. Via a dual approach, the fixed point index and a global branch approach, we establish the existence of normalized solutions to the problem above. The results extend previous results by L. Jeanjean, J. J. Zhang and X.X. Zhong to the quasilinear case. [ABSTRACT FROM AUTHOR]

Seeking new cathode chemistry with high onset potential and compatibility with electrolytes has become a challenge for aqueous Zn ion batteries. Anion intercalation in graphite (4.5 V vs Li+/Li) possesses the potentiality but usually shows a competitive relationship with oxygen evolution reaction (OER) in aqueous solutions. Herein, a decoupled design is proposed to optimize a full utilization of perchlorate ion intercalation in graphite cathode by pH adjustment. Benefiting from the decoupled design, high Coulombic efficiency is obtained by decelerating the kinetic of OER in acidic media. The decoupled Zn‐graphite battery exhibits a wide potential window of 2.01 V, as well as an attractive energy density of 231 Wh kg−1. In addition, a Zn‐graphite battery with SO42−${\mathrm{SO}}_4^{2 - }$ insertion is assembled, which demonstrates the capability of the proposed decoupled strategy to integrate novel electrode chemistries for high‐performance aqueous Zn‐based energy storage systems. [ABSTRACT FROM AUTHOR]

Background: MCD (MYD88L265P/CD79Bmut) diffuse large B‐cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL. Aims: This study aimed to analyse the efficacy and safety of Bruton's tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut. Materials and Methods: Twenty‐three newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) or rituximab + lenalidomide (R2). A control group of 17 patients with MYD88mut and/or CD79Bmut DLBCL who received the standard R‐CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression‐free survival (PFS) of the two groups. Results: The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R‐CHOP, and five elderly DLBCL patients were treated with BTKi + R2. Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1‐year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R‐CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R‐CHOP group had better PFS than patients in the control group. In the BTKi + R‐CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi‐type subgroups exhibited statistically significant differences in 1‐year PFS (p = 0.028). There were no significant differences in grade 3–4 haematological toxicity (p = 1) and grade 3–4 non‐haematological toxicity (p = 0.49) between the BTKi + R‐CHOP and R‐CHOP treatment groups. In the BTKi + R2 group, the ORR was 100%, the CRR was 80%, and the 1‐year PFS rate was 80%. The incidences of grade 3–4 haematologic toxicity and non‐haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients. Discussion: The efficacy of BTKi combined with R‐CHOP was similar to previous reports, which was significantly better than R‐CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R‐CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non‐GCB, DEL or high‐IPI‐score DLBCL patients with MYD88mut and/or CD79Bmut. In our study, five elderly DLBCL patients with MYD88mut and/or CD79Bmut were achieved better ORR, CRR, PFS than the historical data of R‐miniCHOP treatment and Ibrutinib + R2 treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size. Conclusion: This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real‐world clinical data. [ABSTRACT FROM AUTHOR]

Modulation of the microenvironment on the electrode surface is one of the effective means to improve the efficiency of electrocatalytic carbon dioxide reduction (eCO2RR). To achieve high conversion rates, the phase boundary at the electrode surface should be finely controlled to overcome the limitation of CO2 solubility in the aqueous electrolyte. Herein, we developed a simple and efficient method to structure electrocatalyst with a superhydrophobic surface microenvironment by one‐step co‐electrodeposition of Cu and polytetrafluoroethylene (PTFE) on carbon paper. The super‐hydrophobic Cu‐based electrode displayed a high ethylene (C2H4) selectivity with a Faraday efficiency (FE) of 67.3 % at −1.25 V vs. reversible hydrogen electrode (RHE) in an H‐type cell, which is 2.5 times higher than a regular Cu electrode without PTFE. By using PTFE as a surface modifier, the activity of eCO2RR is enhanced and water (proton) adsorption is inhibited. This strategy has the potential to be applied to other gas‐conversion electrocatalysts. [ABSTRACT FROM AUTHOR]

Modulation of the microenvironment on the electrode surface is one of the effective means to improve the efficiency of electrocatalytic carbon dioxide reduction (eCO2RR). To achieve high conversion rates, the phase boundary at the electrode surface should be finely controlled to overcome the limitation of CO2 solubility in the aqueous electrolyte. Herein, we developed a simple and efficient method to structure electrocatalyst with a superhydrophobic surface microenvironment by one‐step co‐electrodeposition of Cu and polytetrafluoroethylene (PTFE) on carbon paper. The super‐hydrophobic Cu‐based electrode displayed a high ethylene (C2H4) selectivity with a Faraday efficiency (FE) of 67.3 % at −1.25 V vs. reversible hydrogen electrode (RHE) in an H‐type cell, which is 2.5 times higher than a regular Cu electrode without PTFE. By using PTFE as a surface modifier, the activity of eCO2RR is enhanced and water (proton) adsorption is inhibited. This strategy has the potential to be applied to other gas‐conversion electrocatalysts. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a persistent, lifelong inflammation of the digestive system. Dextran sulfate sodium is commonly used to induce colitis in experimental animal models, which causes epithelial damage, intestinal inflammation, mucin depletion, and dysbiosis of the gut microbiota. Various prebiotics, polysaccharides, and polypeptides are used for IBD treatment. In this study, we used a murine model utilizing BALB/c mice, with 10 mice per group, to investigate the treatment effect of sea conch peptide hydrolysate (CPH) on DSS-induced colitis mice. Colitis was induced through the administration of 2.5% DSS in drinking water over a seven-days period. Furthermore, on the eighth day of the experiment, sea conch peptide hydrolysate (CPH) at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, which were continued for 14 days, were assessed for medicinal purposes in DSS-induced colitis mice. Our results showed that CPH treatment significantly alleviated the severity and symptoms of colitis. The epithelial integrity and histological damage were improved. Intestinal inflammation and inflammatory cell infiltration were improved. Furthermore, the expression of pro-inflammatory cytokines was reduced, and intestinal barrier integrity was restored by elevating the tight junction proteins. Moreover, 16s RNA sequencing revealed dysbiosis of the gut microbiota was observed upon DSS treatment, which was reinstated after CPH treatment. An increased level of Firmicutes and Lactobacillus was observed in the treatment groups. Finally, our results suggest that CPH would be recommended as a functional food source and also have the potential to be used as a medicinal product for different gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

γδT cells are important innate immune cells that are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis (LN) is a serious complication of SLE, characterized by the accumulation of immune cells (including γδT cells) in the target organs to participate in the disease process. Therefore, clarifying how γδT cells chemotactically migrate to target organs may be a key to developing therapeutic methods against LN. Enzyme‐linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in LN patients and healthy controls. Real‐time polymerase chain reaction (RT‐PCR) and flow cytometry were used to measure the expression of chemokine receptors on the surface of γδT cells. The chemotactic migration ability of γδT cells was detected by Transwell assay. Signalling pathway activation of γδT cells was detected by Automated Capillary Electrophoresis Immunoassay and flow cytometry. The serum levels of chemokines, including monocyte chemoattractant protein‐1 (MCP‐1) in LN patients, were significantly increased. CCR2, the receptor of MCP‐1, was also highly expressed on the surface of peripheral γδT cells in LN patients. In addition, the exogenous addition of MCP‐1 can enhance chemotactic migration of γδT cells in LN patients. MCP‐1 could activate STAT3 signalling in LN patients' peripheral γδT cells. γδT cells might participate in the pathogenesis of LN through MCP‐1/CCR2 axis. This finding provides new opportunities for developing treatment methods against LN by targeting MCP‐1/CCR2 axis. [ABSTRACT FROM AUTHOR]

Background: Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted. Methods: We systematically searched four major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAI treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration's risk of bias tool as described in the updated version 1 of the Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of topics. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAIs. Results: Forty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAIs were included in the network meta-analyses. The vast majority of patients with an acute physiology and chronic health evaluation II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cefepime plus metronidazole was more effective than tigecycline and ceftolozane/tazobactam plus metronidazole (odds ratio [OR] = 1.96, 95% credibility interval [CrI] 1.05 ~ 3.79; OR = 3.09, 95% CrI 1.02 ~ 9.79, respectively). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates. Cefepime plus metronidazole had lower risk of all-cause mortality than tigecycline (OR = 0.22, 95% CrI 0.05 ~ 0.85). Statistically significant trends were observed favoring cefotaxime plus metronidazole, which exhibited fewer discontinuations because of adverse events (AEs) when compared with eravacycline, meropenem and ceftolozane/tazobactam plus metronidazole (OR = 0.0, 95% CrI 0.0 ~ 0.8; OR = 0.0, 95% CrI 0.0 ~ 0.7; OR = 0.0, 95% CrI 0.0 ~ 0.64, respectively). Compared with tigecycline, eravacycline was associated with fewer discontinuations because of AEs (OR = 0.17, 95% CrI 0.03 ~ 0.81). Compared with meropenem, ceftazidime/avibactam plus metronidazole had a higher rate of discontinuation due to AEs (OR = 2.09, 95% CrI 1.0 ~ 4.41). In pairwise meta-analyses, compared with ceftriaxone plus metronidazole, ertapenem and moxifloxacin (one trial, OR = 1.93, 95% CI 1.06 ~ 3.50; one trial, OR = 4.24, 95% CI 1.18 ~ 15.28, respectively) were associated with significantly increased risks of serious AEs. Compared with imipenem/cilastatin, tigecycline (four trials, OR = 1.57, 95%CI 1.07 ~ 2.32) was associated with a significantly increased risk of serious AEs. According to the surface under the cumulative ranking curve, Cefepime plus metronidazole was more likely to be optimal among all treatments in terms of efficacy and safety, tigecycline was more likely to be worst regimen in terms of tolerability, and eravacycline was more likely to be best tolerated. Conclusion: This study suggests that cefepime plus metronidazole is optimal for empirical treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering the safety and tolerability concerns. However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer is by far the most lethal gynecological malignancy. The exploration of promising immunomarkers to predict prognosis in ovarian cancer patients remains challenging. In our research, we carried out an integrated bioinformatic analysis of genome expressions and their immune characteristics in the ovarian cancer microenvironment with validation in different experiments. We filtrated 332 differentially expressed genes with 10 upregulated hub genes from the Gene Expression Omnibus database. These genes were closely related to ovarian tumorigenesis. Subsequently, the survival and immune infiltration analysis demonstrated that the upregulation of five candidate genes, ITGB2, VEGFA, CLDN4, OCLN, and SPP1, were correlated with an unfavorable clinical outcome and increased immune cell infiltration in ovarian cancer. Of these genes, ITGB2 tended to be the gene most correlated with various immune cell infiltrations and had a strong correlation with significant M2 macrophages infiltration (r = 0.707, p = 4.71 × 10−39), while it had a moderate correlation with CD4+/CD8+ T cells and B cells. This characteristic explains why the high expression of ITGB2 was accompanied by immune activation but did not reverse carcinogenesis. Additionally, we confirmed that ITGB2 was over-expressed in ovarian cancer tissues and was mainly located in cytoplasm, detected by Western blotting and the immunohistochemical method. In summary, ITGB2 may serve as a prognostic immunomarker for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8+ T and NKT (natural killer T) cells and inhibiting CD25+ Foxp3+ Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/β-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the efficacy of intensive rosuvastatin therapy plus 7-day dual antiplatelet therapy (DAPT) in reducing stroke recurrence for patients with acute ischemic stroke (AIS) and compared subgroups of patients. Methods: We enrolled patients with AIS whose time of onset to medication was ≤ 72 h, and the baseline scores of NIHSS (bNIHSS) were 0–10. The patients received intensive rosuvastatin therapy plus 7-day DAPT with aspirin and clopidogrel (study group) or rosuvastatin plus single antiplatelet therapy (SAPT, control group). The primary outcomes were recurrence of ischemic stroke, bleeding, statin-induced liver injury, and statin-associated myopathy (SAM) within 90 days. We also performed a subgroup analysis to assess the heterogeneity of the two therapy regimens in reducing recurrent stroke. Results: Recurrent stroke occurred in 10 patients in the study group and 42 patients in the control group (hazard ratio [HR], 0.373, 95% confidence interval [CI], 0.178–0.780; P = 0.009). Bleeding events occurred in 9 patients in the study group and 14 patients in the control group (HR, 1.019; 95%CI, 0.441–2.353; P = 0.966). Statin-induced liver injury and SAM were not recorded. Intensive rosuvastatin plus 7-day DAPT was generally effective in reducing the risk of recurrent stroke, except in the subgroup with bNIHSS ≤ 2. The therapy was particularly efficient in the elderly, male, high-bNIHSS, and hypertension, diabetes, and hyperlipidemia subgroups, with P < 0.02. Conclusions: Without increasing bleeding and statin-associated adverse events, intensive rosuvastatin therapy plus 7-day DAPT significantly reduced the risk of recurrent stroke, especially for subgroups with high-risk factors. Clinical trial registration. China Clinical Trial Registration Center (ChiCTR1800017809). [ABSTRACT FROM AUTHOR]

Immunotherapeutic strategies are recognized as promising treatment methods for colorectal cancer (CRC). αβT cell-mediated cytotoxicity is tolerated by cancer cells with low MHC class I expression; therefore, γδT cell-based cancer immunotherapy has generated increasing interest as a potential treatment option. To enhance the potency of γδT cell-based immunotherapy, the key factors involved in the regulation of γδT cells in CRC need to be identified along with devising ways to overcome potential hurdles. In this study, we observed that leukemia inhibitory factor (LIF), the serum level of which was highly increased in those with solid tumors, could specifically attenuate the cytotoxic function of peripheral γδT cells in patients with CRC. We observed that in patients with CRC, the expression levels of perforin and granzyme were significantly decreased in the recombinant human LIF (rhLIF)-treated peripheral γδT cells, whereas that of the LIF receptor (LIFR) was higher. The regulation of the cytotoxic function of the γδT cells by rhLIF was effected mainly through the STAT3 signaling pathway, which caused an increase in the expression levels of interleukin (IL)-17, COX-2, and prostaglandin E2 (PGE2). Our results revealed that rhLIF could impair the function of γδT cells in CRC patients by reducing the cytotoxic function and increasing the expression of tumor-promoting molecules, such as IL-17, COX-2, and PGE2. [ABSTRACT FROM AUTHOR]

Obesity is closely related to a poor prognosis in patients with advanced colorectal cancer (CRC), but the mechanisms remain unclear. Ferroptosis is a form of nonapoptotic cell death characterized by lipid reactive oxygen species (ROS) accumulation and iron dependency and is associated with the chemoresistance of tumors. Here, it is shown that adipose‐derived exosomes reduce ferroptosis susceptibility in CRC, thus promoting chemoresistance to oxaliplatin. It is found that microsomal triglyceride transfer protein (MTTP) expression is increased in the plasma exosomes of CRC patients with a high body fat ratio, serving as an inhibitor of ferroptosis and reducing sensitivity to chemotherapy. Mechanistically, the MTTP/proline‐rich acidic protein 1 (PRAP1) complex inhibited zinc finger E‐box binding homeobox 1 expression and upregulated glutathione peroxidase 4 and xCT, leading to a decreased polyunsaturated fatty acids ratio and lipid ROS levels. Moreover, experiments are carried out in organoids, and a tumor implantation model is established in obese mice, demonstrating that the inhibition of MTTP increases the sensitivity to chemotherapy. The results reveal a novel intracellular signaling pathway mediated by adipose‐derived exosomes and suggest that treatments targeting secreted MTTP might reverse oxaliplatin resistance in CRC. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the fastest growing malignancies in morbidity and mortality, and current therapies are in general not sufficiently effective for this deadly disease. This study characterizes the anticancer effects of glaucocalyxin A (GLA) and explores the underlying mechanisms using human non‐small cell lung carcinoma (NSCLC) cells. First, our data showed that GLA suppressed the viability of cancer cells, whereas no effect was observed in the normal bronchial epithelial cell BEAS‐2B cells. Second, GLA inhibited colony formation, induced apoptosis of cancer cells. Third, GLA downregulated the expression of B‐cell lymphoma‐2 (Bcl‐2) protein; upregulated the expression of Bcl2‐associated X protein (Bax), and strengthened cleavage of caspase 3 and polyadenyl diphosphate ribose polymerase (PARP). Fourth, GLA also diminished mitochondrial membrane potential and inhibited phosphatidylinositol 3‐kinase (PI3K)/Akt/ glycogen synthase kinase‐3β (GSK3β) pathway. In addition, injection of GLA (20 mg/kg) every 2 days significantly inhibited A549 xenograft tumour growth, accompanied by increased apoptosis and decreased proliferation. Together, our study provides evidence that the anticancer effect of GLA in NSCLC is mediated by inducing apoptosis through inhibiting PI3K/Akt/GSK3β pathway and suggests that GLA may be used as a promising natural medicine for NSCLC therapy. [ABSTRACT FROM AUTHOR]

Objective: To compare the survival outcomes and adverse events of patients with locally advanced cervical cancer (LACC) who received platinum monotherapy with concurrent chemoradiation therapy (CCRT) versus platinum-based dual drug therapy with CCRT. Method: All relevant literature was screened form the PubMed, EMBASE, Web of Science, The Cochrane Library and other databases from their establishment to October 2020. The main endpoint indicators included overall survival (OS) and progression-free survival (PFS). Grade 3 and above adverse events induced by chemotherapy were also compared. Results: This study involved 17 literature and 4,106 patients. There were 2,066 patients treated with CCRT with platinum-based dual drug therapy and 2,040 patients received CCRT with platinum monotherapy. Meta-analysis results showed that, compared to CCRT with platinum monotherapy, OS (HR = 0.68, 95% CI 0.58–0.79) and PFS (HR = 0.67, 95% CI 0.58–0.77) of LACC patients were significantly improved by CCRT with platinum-based dual drug therapy. In addition, CCRT with platinum-based dual drug therapy led to more adverse reactions such as neutropenia (OR = 4.92, 95% CI 3.55–6.84), anemia (OR = 1.99, 95% CI 1.17–3.39), diarrhea (OR = 1.70, 95% CI 1.30–2.22), leukopenia (OR = 2.42, 95%CI 1.84–3.17), thrombocytopenia (OR = 2.87, 95%CI 1.44–5.72), etc. Conclusion: CCRT with platinum-based dual drug therapy improved OS and PFS of LACC patients relative to the CCRT with platinum monotherapy. But it also increased the adverse reactions caused by multiple chemotherapy drugs. Thus, it is crucial to select a proper chemotherapy regimen based on the actual tolerance of patients in clinical practice. [ABSTRACT FROM AUTHOR]

Cell invasion is an initiating event during tumor cell metastasis and an essential process during development. A screen of C. elegans orthologs of genes overexpressed in invasive human melanoma cells has identified several components of the conserved DNA pre-replication complex (pre-RC) as positive regulators of anchor cell (AC) invasion. The pre-RC genes function cell-autonomously in the G1-arrested AC to promote invasion, independently of their role in licensing DNA replication origins in proliferating cells. While the helicase activity of the pre-RC is necessary for AC invasion, the downstream acting DNA replication initiation factors are not required. The pre-RC promotes the invasive fate by regulating the expression of extracellular matrix genes and components of the PI3K signaling pathway. Increasing PI3K pathway activity partially suppressed the AC invasion defects caused by pre-RC depletion, suggesting that the PI3K pathway is one critical pre-RC target. We propose that the pre-RC, or a part of it, acts in the postmitotic AC as a transcriptional regulator that facilitates the switch to an invasive phenotype. Cell invasion is an initiating event during tumor cell metastasis and an essential process during development. This study in the nematode Caenorhabditis elegans shows that the DNA pre-replication complex plays a cell cycle-independent role in promoting cell invasion. [ABSTRACT FROM AUTHOR]

In this paper, a generalized fuzzy barycentric Lagrange interpolation method is proposed to solve two-dimensional fuzzy fractional Volterra integral equations. Firstly, we use the generalized Gronwall inequality and iterative methods to demonstrate the existence and uniqueness of solutions to the original equation. Secondly, combining the generalized fuzzy interpolation method and the fuzzy Gauss-Jacobi quadrature formula to discretize the original equation into corresponding algebraic equations in fuzzy environment. Then, the convergence of the proposed method is analyzed, and an error estimate is given based on the uniform continuity modulus. Finally, some numerical experiments show that the proposed method has high numerical accuracy for both smooth and non-smooth solutions. [ABSTRACT FROM AUTHOR]

Translation ambiguous words are lexical items with one-to-many equivalents in another language. Some of these equivalents are more dominant (i.e., more frequently used) than others. The aim of the present study is to explore non-target language activation of translation ambiguous words among Chinese–English bilinguals.The implicit priming paradigm was used in three experiments to explore the activation of primary and secondary first language (L1) translations when bilinguals process second language (L2) translation ambiguous words (Experiment 1); the effect of L1 translation repetition on the processing of semantically related words in an L2 (Experiment 2); and whether such patterns are observed in the reverse direction, that is, whether L2 primary translations are activated when processing L1 translation ambiguous words (Experiment 3).We use repeated measures analyses of variance (ANOVAs) to analyse the data.Experiment 1 showed that when processing pairs of semantically unrelated (SU) L2 words, primary L1 translation equivalents are activated, but not secondary L1 translation equivalents. Experiment 2 found that when the target L2 words were semantically related, performance was facilitated when their translation equivalents were the same L1 word (i.e., implicitly repeated). Similarly, Experiment 3 showed that when processing L1 words, the L2 translation equivalents are automatically activated. Moreover, under semantically related conditions, implicit repetition of the non-target L2 translation facilitated L1 judgements, while under SU conditions, L2 implicit repetition hampered L1 judgements.Most research on cross-language activation has examined L1 activation during L2 processing. However, few have investigated the reverse and findings from these few studies are inconsistent. Moreover, research on cross-language activation has mainly investigated the activation of primary translation equivalents, with very little focus on secondary translations. The present study uses the implicit priming paradigm to address these gaps in the literature.The findings support interactive theories of bilingual processing. [ABSTRACT FROM AUTHOR]

This paper proposes a discrete collocation method based on the fuzzy Lagrange interpolation and the fuzzy Gauss-Legendre quadrature formula for solving two-dimensional linear and nonlinear fuzzy Volterra integral equations. Firstly, the existence and uniqueness of the solution of the original equation are proved by using a two-dimensional Gronwall inequality and an iterative method. Secondly, the discrete collocation method is utilized to convert the linear and nonlinear fuzzy Volterra integral equations into the corresponding linear and nonlinear systems of algebraic equations. Finally, the error estimation and convergence analysis of the proposed numerical method are discussed in terms of the uniform modulus of continuity. Some numerical experiments illustrate that the scheme possesses a higher accuracy and yields a better approximation when compared with other known methods. [ABSTRACT FROM AUTHOR]

The structural details of carbon materials directly affect their properties as an electrode material, such as specific capacitance and coulomb efficiency. Therefore, the structural analysis of carbon materials has always been an important step in the mechanistic insight into their roles in electrochemical energy storage. Raman spectroscopy, as molecular spectroscopy technique, has been widely used in understanding the lattice vibration mechanics of carbon materials and providing information on the chemical structure at molecular level, as well as microstructure analysis of carbon materials. In addition, the development of correlative‐Raman technology enables clarifying more comprehensive and accurate structural information for carbon‐based materials. With this information, it is of great significance to guide the construction of advanced carbon‐based electrode materials for energy storage. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity.In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c‐MET, VEGFR1, c‐KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti–PD‐L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression‐free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response.Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%–32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment‐related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35–5.68 months) and 5.98 months (95% CI, 3.71–8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%–83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%–89.10%) in patients with HCC.Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy‐refractory patients with advanced ESCC and HCC. [ABSTRACT FROM AUTHOR]

[Display omitted] Two dimensional (2D) materials, with ideal interlayer spacing for ion intercalation/de-intercalation, are quite appealing for hybrid supercapacitors (HSCs) in the pursuit of harvesting promising electrochemical performance. Integrating different 2D materials together is one effective strategy to achieve such goals. However, preserving the ion diffusion channel and accelerating electron transfer should be considered during the compositing process. Herein, we propose a two-step strategy to efficiently composite cobalt hydroxide (Co(OH) 2) and Ni-based MOF (Ni-MOF-24), in which a vertically oriented Ni-MOF@Co(OH) 2 array on nickel foam is obtained. The maximum specific capacitance of 1448 Fg−1 (2 Ag−1) is delivered by Ni-MOF@Co(OH) 2. Accordingly, a hybrid Ni-MOF@Co(OH) 2 //AC HSC is thereof assembled, which outputsa high specific power of 22,400 W kg−1 and a considerable specific energy of 45.7 Wh kg−1. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether the gap-balancing technique with patient-specific instrumentation (PSI) and a new balancing device in total knee arthroplasty (TKA) can improve knee function to a greater extent than can the measured resection technique. Materials and methods: Data from 150 patients who underwent TKA from August 2014 to June 2016 were studied retrospectively. The gap-balancing technique assisted by PSI and the new balancing device was used in 80 patients (82 knees), and the measured resection technique was used in 70 patients (70 knees). The surgical, imaging, and knee function data were compared. Results: The gap-balancing technique assisted by PSI and the new balancing device was found to be feasible in all operated knees and reliable. In total, 150 patients (152 knees) of ages ranging from 52 to 78 years (mean 67 years) underwent TKA during the study period. The follow-up period ranged from 35 to 52 months (mean 45 months). Only one patient, who was included in the gap-balancing group, underwent a revision surgery at 2 years postoperatively due to infection. There were no differences in the incidence of anterior knee pain between the two groups. The mean flexion angle, KSS scores, and VAS scores did not significantly differ between the measured resection group and gap-balancing group at 12 weeks or 36 weeks postoperatively. The average joint line displacement was 1.3 ± 1.1 mm (range 0–3) proximally in the GB (gap-balancing) group and 1.2 ± 1.4 mm in the MR (measured-resection) group. No outliers >5 mm in either group were recorded. The mean leg axis deviation from the neutral mechanical axis was 1.8°±1.5° varus (range 0°–3°varus) versus the neutral mechanical axis in the GB group and 1.4°±1.2°(range 0°–3°)in the MR group. No outliers with >3° deviation in either group were recorded. Conclusions: The gap-balancing technique performed with the new balancing device and PSI can yield accurate femoral component alignment as well as outcomes similar to those of measured resection at 3 years. The new balancing device can be taken into consideration by surgeons who prefer performing the gap-balancing technique with PSI. [ABSTRACT FROM AUTHOR]

In this study, a series of transparent ceramics with chemical composition of La 1+x Yb 1+y Zr 2 O 7 (x, y = 0.1−0.5) were successfully prepared by vacuum sintering using combustion synthesized powders. The effects of excess contents on the phase composition, microstructure and in-line transmittance have been studied. The detailed results indicate that the in-line transmittance increases at first and then decreases as La content be elevated. It was also determined that the highest in-line transmittance of La 1+x Yb 1+y Zr 2 O 7 (x, y = 0.1−0.5) ceramics is 84.1 % at 1100 nm when the excess amount of co-doped La-Yb is 30 %. Compared with stoichiometric LaYbZr 2 O 7 ceramic, the nonstoichiometric La 1+x Yb 1+y Zr 2 O 7 (x, y = 0.1−0.5) ceramics exhibit much higher transparency. In addition, the high excess amount of La, Yb and co-doped La-Yb also shows effects on the phase composition and crystal structure. [ABSTRACT FROM AUTHOR]

Metal organic frameworks (MOFs) with numerous potential pseudocapacitive sites are quite appealing to supercapacitors with high specific and areal capacitances. However, MOFs suffer from a low conductivity nature, resulting in a mediocre electrochemical performance. Herein, we propose a template-growth strategy of MOF to enhance both specific and areal capacitances of MOF as the electrode material for supercapacitor. As the loading mass of MOF increases from 2 to 5 mg, the specific capacitance also increases from 937 to 2387 Fg−1 (431 to 1098 Cg−1) and areal capacitance 1.87 to 11.94 Fcm−2 (0.86 to 5.49 Ccm−1). Accordingly, a hybrid MOF//AC supercapacitor can deliver a maximum energy density of 67 Wh kg−1 and a maximum power density of 6000 W kg−1. These results point to a way to fabricate MOF electrode of supercapacitor with high specific and areal capacitance, which leads them to a more practical future. [ABSTRACT FROM AUTHOR]

Dual-ion batteries (DIBs) suffer potential matching problem of anode and cathode, which originates from the contrasting size difference between the corresponding small metal cations and large polyatomic anions from metallic salt solution electrolyte. With wide voltage window and high stability, ionic liquid (IL) can provide larger cations occupying similar radius with anions, which can be a facile solution for unbalanced match of both electrodes. Thus, searching for electrode materials with large interlayer space for IL is in a great demand. MXene, a 2D transition metal nitride or carbide with high conductivity, provides large layer distance to accommodate large ions of ILs. The electrochemical intercalation behavior of EMIm+ cations and MXene has been investigated and a delicate design of an IL-based DIB is proposed. On the basis of size match on both anode and cathode, the DIB also shows promising energy-power characteristic and excellent cycling stability. [ABSTRACT FROM AUTHOR]

The ultrasensitive detection of hepatitis C virus (HCV) nucleic acid is crucial for the early diagnosis of hepatitis C. In this study, by combining Ag@Au core/shell nanoparticle (Ag@AuNP)-based surface-enhanced Raman scattering (SERS) tag with hybridization chain reaction (HCR), a novel SERS-sensing method was developed for the ultrasensitive detection of HCV nucleic acid. This SERS-sensing system comprised two different SERS tags, which were constructed by modifying Ag@AuNP with a Raman reporter molecule of 4-ethynylbezaldehyde, two different hairpin-structured HCR sequences (H1 or H2), and a detection plate prepared by immobilizing a capture DNA sequence onto the Ag@AuNP layer surface of the detection wells. When the target nucleic acid was present, the two SERS tags were captured on the surface of the Ag@AuNP-coated detection well to generate many "hot spots" through HCR, forming a strong SERS signal and realizing the ultrasensitive detection of the target HCV nucleic acid. The limit of detection of the SERS-sensing method for HCV nucleic acid was 0.47 fM, and the linear range was from 1 to 105 fM. [ABSTRACT FROM AUTHOR]

A novel AIEgen molecular probe (N-3QL) with typical AIE effects, good biocompatibility, lysosome targeting, pH activation, excellent photostability, and high brightness was synthesized using two simple synthetic steps. Spectroscopic and cytotoxicity experiments indicate that N-3QL can not only be used for the dynamic monitoring of cancer cell lysosomes, but also for photodynamic therapy (PDT) ablation of cancer cells. [ABSTRACT FROM AUTHOR]

Since the Economic Recession in the late 2000s, many neighbourhood coffee bars in Northern and Central Italy have been taken over by Chinese immigrants. This article investigates why neighbourhood bars, which are thought to be at the heart of Italian urban culture, have become a new business niche for Chinese immigrants in spite of overwhelmingly anti‐immigrant discourse. By elucidating the political economy of Italy's coffee bar industry and restructuring of its Chinese ethnic economy, it shows how the formation of this new immigrant business niche is a form of historical contingency embedded in a set of structural transformation processes. The broader purpose of the article is to contribute to an understanding of the structural mechanisms of embedded immigrant entrepreneurship and immigrants' economic incorporation, as well as to debates on the roles of immigrants in the new urban economy and related local cultures of a multi‐ethnic European nation‐state. [ABSTRACT FROM AUTHOR]

Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest. Author summary: Cells invasion is a fundamental biological process that allows cells to cross compartment boundaries and migrate to new locations. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. We have investigated how a specialized cell in the Nematode C. elegans, the so-called anchor cell, can invade into the adjacent epithelium during normal development. Our work has identified an oncogenic transcription factor that controls the expression of specific target genes necessary for cell invasion, and at the same time inhibits the proliferation of the invading anchor cell. These findings shed light on the mechanisms, by which cells decide whether to proliferate or invade. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic. Methods: Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential. Results: Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. Conclusions: The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC. [ABSTRACT FROM AUTHOR]

Objective: To explore the effects of miR-193b on cell proliferation, migration, invasion and tumourigenicity of renal cell carcinoma, and the underlying molecular mechanisms. Methods: The expression of miR-193b and IGF1R was detected by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay was used to detect cell viability. The migration and invasion abilities were measured by transwell assay. Western blot was used to detect the protein expression of IGF1R. Murine xenograft model was established using Caki-1cells transfected with miR193b. Results: The expression of miR-193b was significantly down-regulated in renal cell carcinoma tissues and cells while the expression of IGF1R was obvious increased in tissues. Overexpression miR-193b or knockdown of IGF1R significantly inhibited the abilities of cells proliferation, migration and invasion in renal cell carcinoma. MiR-193b directly targeted IGF1R and inhibited its expression in vitro and vivo. Up-regulation miR-193b inhibits cells proliferation, migration and invasion of renal cell carcinoma by targeting IGF1R. In addition, overexpression miR-193b significantly inhibited tumour growth in nude mice. Conclusion: miR-193b can inhibit the growth and metastasis of renal cell carcinoma by targeting decreasing IGF1R expression, which provides a new target for the prevention and treatment of renal cell carcinoma. [ABSTRACT FROM AUTHOR]

In this paper, a piecewise fuzzy polynomial interpolation method is proposed to approximate the solutions of fuzzy delay integral equations with weakly singular kernels. Firstly, the existence and uniqueness of the solutions of these fuzzy delay integral equations are proved by using the Gronwall inequality and an iterative method. Then, the fuzzy weakly singular delay integral equations are discretized into related algebraic equations by using piecewise fuzzy polynomial interpolation and the fuzzy Gauss-Jacobi quadrature formula. Moreover, the convergence of the numerical method is investigated and an error estimate is provided. Finally, the accuracy and efficiency of the proposed method are verified by some numerical experiments. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • DINP exposure could induce marked increase in blood pressure. • DINP exposure resulted in the increase of ACE and AT1R expression. • DINP exposure inhibit the eNOS expression and NO production. • ACEI treatment effectively alleviated the increase in blood pressure level. Abstract Recent epidemiological studies have found that diisononyl phthalate (DINP) is associated with an increase in blood pressure. However, this correlation had not been clarified, nor has the underlying mechanism been characterized. In this study, C57/BL6 mice were exposed to DINP doses of 0.15 mg/kg/day, 1.5 mg/kg/day or 15 mg/kg/day for 6 weeks. Dexamethasone (DEXA) was used to build the hypertension model. After DINP exposure and 1 mg/kg/day DEXA treatment, the levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) were determined, and any histopathological changes in hypertension targeted organs of the mice were investigated. The results suggest that DINP exposure and DEXA treatment induced marked increases in SBP, DBP, and MBP, and that 15 mg/kg/day DINP exposure could also increase the HR level. Along with the blood pressure increase, DINP exposure induced pathological changes to the heart, aorta, and kidney. To explore the underlying mechanism, we measured the expression of angiotensin converting enzyme (ACE), angiotensin-II type 1 receptor (AT1R) and endothelial nitric oxide synthase (eNOS) in the aorta, as well as the nitric oxide (NO) concentration in serum. The data suggest that DINP exposure and DEXA treatment enhance the expression of ACE and AT1R, and inhibit eNOS expression and NO production. Interestingly, treatment with 5 mg/kg/day ACE inhibitor (ACEI) alleviated the increase in blood pressure induced by DINP exposure and DEXA treatment. These findings expand our understanding of how DINP exposure impacts the development of hypertension, and elucidates the underlying mechanisms. [ABSTRACT FROM AUTHOR]

• Utilize attention mechanism to quickly lock key disturbance areas and reduce unnecessary noise. • Different to Lp-norm based metrics, we use multi-standard metrics to reflect human perception. • Experiments show that the attention mechanism can reduce the disturbance amount while maintaining the attack success rate. Recently, research on adversarial attack and adversarial defense received more and more attention. Because although deep neural networks (DNNs) outperform humans in many tasks, studies have shown that they are easily fooled by human invisible disturbances. Identifying vulnerabilities in existing networks and further improving the robustness of the network is critical to the application of DNNs in real life. In this paper, a spatial transformed attack method based on the attention mechanism is proposed. The attention mechanism based on gradient-weighted class activation mapping (Grad-CAM) is used to find an meaningful attack area and the spatial transformation is performed on the this area to achieve adversarial attack. The experimental results show that the obtained method can reduce the magnitude of the disturbances needed to achieve the attack while ensuring the effectiveness. The adversarial examples generated by the obtained method shows smaller difference from the original sample under several different metrics. [ABSTRACT FROM AUTHOR]

Abstract Dodecahedral NaBH 4 -reduced Co 3 O 4 (R-Co 3 O 4) was successfully prepared via a conformal transformation method. Such facile procedure leads to abundance of electrochemically active sites of Co2+ ions. The as-prepared R-Co 3 O 4 affords the material an improved specific capacitance of 329 F/g, which is triply that of the pristine Co 3 O 4. In addition, an enhanced cycling stability is also achieved for the R-Co 3 O 4. Thus, we develop a novel but simple route for large-scale industrial production of electrochemically active materials via NaBH 4 reduction. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggest a positive relationship between phthalate exposure and diabetes. However, little is known about the impact of dibutyl phthalate (DBP) exposure on the development of diabetes. To determine the role of DBP exposure on the development of type 2 diabetes, mice were orally exposed to DBP dosages of 0.5, 5, 50 mg/kg/day for 7 weeks, combined with a high fat diet and injections of a low dose of streptozotocin (STZ). The results showed that exposure to 50 mg/kg/day DBP alone induced a marked decrease in insulin secretion and glucose intolerance, but had no influence on insulin resistance. However, combined with a high fat diet and STZ treatment, DBP exposure markedly aggravated glucose intolerance, insulin tolerance and insulin resistance and induced lesions in the pancreas and kidney. Investigation of the role of DBP on the insulin signaling pathway, we found that DBP exposure could disrupt the PI3K expression and AKT phosphorylation, and decrease the level of GLUT-2 in the pancreas. Administering demethylasterriquinone B1, significantly increased the level of PI3K, AKT phosphorylation and GLUT-2 expression, effectively inhibiting the aggravation of diabetes. Our results suggested that DBP aggravated type 2 diabetes by disrupting the insulin signaling pathway and impairing insulin secretion. [ABSTRACT FROM AUTHOR]

Diisodecyl phthalate (DIDP) is considered to be one of the less toxic phthalates. However epidemiological studies suggest that DIDP is associated with the occurrence of asthma. The effect of DIDP exposure on allergic asthma and the underlying mechanism have not been fully elucidated. Here, mice were exposed to DIDP and sensitization with OVA. The results demonstrated that DIDP exposure aggravated allergic asthma. Exposure to 15 mg/kg/day DIDP markedly exacerbated airway remodeling and promoted airway hyperresponsiveness (AhR). The study suggests that exposure to DIDP not only promotes a predominant Th2 response, but also induces Th17-type immunity. The induced allergic asthma was accompanied by elevation of IgE, an increase in TSLP expression and exacerbation of oxidative stress. Inhibition of oxidative stress by Vitamin E effectively alleviated the airway remodeling and AhR induced by DIDP and OVA sensitization. Treatment with Vitamin E inhibited the Th2 response and the production of TSLP. Blocking the activation of p38 MAPK by SB203580 prevented elevation of IL-1β and IL-17A induced by DIDP and OVA sensitization and effectively alleviated Th17 type asthmatic lesions. These results suggest that exposure to DIDP exacerbates the Th2 and Th17 response through aggravating oxidative stress and activation of the p38 MAPK pathway. [ABSTRACT FROM AUTHOR]

Abstract: Metal organic frameworks (MOFs) are considered as promising candidates for supercapacitors because of high specific area and potential redox sites. However, their shuffled orientations and low conductivity nature lead to severely‐degraded performance. Designing an accessibly‐manipulated and efficient method to address those issues is of outmost significance for MOF application in supercapacitors. It is the common way that MOFs scarify themselves as templates or precursors to prepare target products. But to reversely think it, using target products to prepare MOF could be the way to unlock the bottleneck of MOFs' performance in supercapacitors. Herein, a novel strategy using Co(OH)2 as both the template and precursor to fabricate vertically‐oriented MOF electrode is proposed. The electrode shows a double high specific capacitance of 1044 Fg−1 and excellent rate capability compared to MOF in powder form. An asymmetric supercapacitor was also fabricated, which delivers a maximum energy density of 28.5 W h kg−1 at a power density of 1500 W kg−1, and the maximum of 24000 W kg−1 can be obtained with a remaining energy density of 13.3 W h kg−1. Therefore, the proposed strategy paves the way to unlock the inherent advantages of MOFs and also inspires for advanced MOF synthesis with optimum performance. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) consist of molecules acting on the defense systems of numerous organisms toward tumor and multiple pathogens, such as bacteria, fungi, viruses, and parasites. Compared to traditional antibiotics, AMPs are more stable and have lower propensity for developing resistance through functioning in the innate immune system, thus having important applications in the fields of medicine, food and so on. However, despite of their high economic values, the low yield and the cumbersome extraction process in AMPs production are problems that limit their industrial application and scientific research. To conquer these obstacles, optimized heterologous expression technologies were developed that could provide effective ways to increase the yield of AMPs. In this review, the research progress on heterologous expression of AMPs using Escherichia coli , Bacillus subtilis, Pichia pastoris and Saccharomyces cerevisiae as host cells was mainly summarized, which might guide the expression strategies of AMPs in these cells. [ABSTRACT FROM AUTHOR]

The pivotal characteristics of Alzheimer's disease (AD) are irreversible memory loss and progressive cognitive decline, eventually causing death from brain failure. In the various proposed hypotheses of AD, oxidative stress is also regarded as a symbolic pathophysiologic cascade contributing to brain diseases. Using Chinese herbal medicine may be beneficial for treating and preventing AD. As a rare and valuable animal medicine, Moschus possesses antioxidant and antiapoptotic efficacy and is extensively applied for treating unconsciousness, stroke, coma, and cerebrovascular diseases. We aim to evaluate whether Moschus protects PC12 cells from hydrogen peroxide (H 2 O 2)-induced cellular injury. The chemical constituents of Moschus are analyzed by GC-MS assay. The cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) levels, oxidative stress-related indicators, and apoptotic proteins are determined. Through GC-MS analysis, nineteen active contents were identified. The cell viability loss, lactate dehydrogenase releases, MMP levels, ROS productions, and Malondialdehyde (MDA) activities decreased, and BAX, Caspase-3, and Kelch-like ECH-associated protein 1 expression also significantly down-regulated and heme oxygenase 1, nuclear factor erythroid-2-related factor 2 (Nrf-2), and quinine oxidoreductase 1 expression upregulated after pretreatment of Moschus. The result indicated Moschus has neuroprotective activity in relieving H 2 O 2 -induced cellular damage, and the potential mechanism might be associated with regulating the Nrf-2/ARE signaling pathway. A more in-depth and comprehensive understanding of Moschus in the pathogenesis of AD will provide a fundamental basis for in vivo AD animal model research, which may be able to provide further insights and new targets for AD therapy. [Display omitted] • H2O2 mimics the in vitro AD oxidative injured model. • H2O2 neurotoxicity causes apoptosis and oxidative damage. • The potential mechanism of oxidative damage may be associated with the Nrf-2/ARE signaling pathways. • Moschus possesses efficiency of neuroprotection, anti-apoptotic, and anti-oxidant in H2O2-induced PC12 cells. • Moschus ameliorates H2O2-induced injury in PC12 cells via regulating the Nrf-2/ARE signaling pathway [ABSTRACT FROM AUTHOR]

Objectives:Our aim was to retrospectively investigate the data from our institute the response rate and outcome in patients with primary mediastinal B-cell lymphoma (PMBL) who received the rituximab in combination with CHOP (RCHOP) followed by autologous stem cell transplantation (ASCT) or RCHOP followed by involved field radiation therapy (IFRT). Methods:Sixty five patients with PMBL received RCHOP as first-line chemotherapy between January 2005 and December 2010. Forty of the 65 patients completed the planned subsequent IFRT after initial chemotherapy. Thirteen of the 65 patients received the front-line ASCT after RCHOP. Twelve patients received RCHOP alone. Results:Thirty two of the 40 patients who received the RCHOP followed by IFRT have complete remission (CR) or CRu (CR/unconfirmed). All patients have CR or CRu after the ASCT. The progression free survival (PFS) and the estimated overall survival (OS) rate at 5 years for 32 CR/CRu patients in the RCHOP followed by IFRT group were 57 and 65%, respectively, as compared to RCHOP/ASCT group who were 94 and 100%, respectively. Twelve patients who received RCHOP alone had the same PFS and OS rate as the 40 patients who received RCHOP/IFRT (5-year PFS:62 vs. 65%,p = 0.068; 5-year OS:57 vs. 67%,p = 0.058). For all 65 patients, the age-adjusted international prognostic index (aaIPI) score remained the only predictor of a worse outcome. Conclusion:The PFS and OS rate of RCHOP/IFRT were found to be unsatisfied. RCHOP/ASCT showed a satisfactory PFS and OS rate. [ABSTRACT FROM PUBLISHER]

The conventional enhancement in capacitive performance that only relies on electrode materials is limited. Here, based on the system-level design principle, we explore the possibility of enhancing capacitance through both electrode and electrolyte. A novel and ultrahigh-performance asymmetric supercapacitor has been fabricated using two redox electrode systems. The positive electrode system consists of graphene supported Co(OH) 2 nanosheet (Co(OH) 2 /GNS) electrode and mixed KOH and K 3 Fe(CN) 6 aqueous electrolyte. And the negative electrode system comprises carbon fiber paper supported activated carbon (AC/CFP) electrode in mixed KOH and p-phenylenediamine (PPD) aqueous electrolyte. The novel asymmetric supercapacitor exhibits a significantly improved capacitive performance (specific capacitance of 204.5 Fg −1 , operational voltage of 2.0 V) in comparison with that of the conventional asymmetric supercapacitor (66.8 Fg −1 , 1.5 V) fabricated without redox electrolyte. The improvement is attributed high reversibility and conductivity of electrode materials and redox electrolyte, as well as the synergistic effect between the two electrode systems, resulting in a ultrahigh energy density (114.5 Whkg −1 at a power density of 1000 Wkg −1 ), excellent power density (4000 Wkg −1 at an energy density of 31.6 Whkg −1 ) and long-term cycling stability (after 20000 cycles, initial capacitance remains well). These encouraging results afford a facile and efficient way to fabricate ultrahigh-performance supercapacitors for the increasing demands on the energy storage devices. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify novel microRNAs for potential use in the diagnosis of pancreatic cancer (PaC). Methods: A total of 1063 serum samples from 303 patients with PaC were collected, and the expression level of miR-25 was measured using quantitative real-time PCR (qRT-PCR). Results: We found that miR-25 had significant diagnostic value for the differential diagnosis of PaC in normal controls with an AUC (the area under the ROC curve) of 0.915 (95% CI: 0.893-0.937) that was significantly higher compared with an AUC of 0.725 for serum tumor marker carcinoembryonic antigen (CEA) and an AUC of 0.844 for CA19-9. Conclusions: These data suggest that serum miR-25 has strong potential as a novel biomarker for the early detection of PaC. [ABSTRACT FROM AUTHOR]

Determination of endogenous brassinosteroids (BRs) in limited sample amount is vital to elucidating their tissue- and even local tissue-specific signaling pathway and physiological effects on plant growth and development. In this work, an ultra-sensitive quantification method was established for endogenous BRs in milligram fresh plant by using pipette-tip solid-phase extraction coupled with ultra-performance liquid chromatography tandem mass spectrometry (PT-SPE-UPLC-MS/MS), in which a quaternary ammonium phenyl boronic acid, 4-borono- N,N,N -trimethylbenzenaminium iodide (BTBA) was first developed for chemical derivatization of BRs. Due to the cationic quaternary ammonium group of BTBA, the ionization efficiencies of the BRs chelates with BTBA (BTBA-BRs) were enhanced by 1190–448785 times, which is the highest response enhancement factor among all derivatization reagents reported for BRs. In addition, PT-SPE packed with C18 sorbent was first used for purifying BRs from plant extracts, so the required sample amount was minimized, and recoveries higher than 91% were achieved. Under the optimized conditions, the minimal detectable amounts (MDA) of five target BRs were in the range of 27–94 amol, and the correlation coefficients (R 2 ) were >0.9985 over four orders of magnitude. The relative recoveries of 75.8–104.9% were obtained with the intra- and inter-day relative standard deviations (RSDs) less than 18.7% and 19.6%, respectively. Finally, three BRs were successfully quantified in only 5 mg fresh rice plant samples, and 24-epiBL can even be detected in only 0.5 mg FW rice leaf segments. It is the first time that the BRs content in sub-milligram fresh plant sample has been quantified. [ABSTRACT FROM AUTHOR]