Proteomics Identifies Circulating TIMP-1 as a Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, although disease stratification using in-depth plasma proteomics has not been performed to date. By measuring more than 1000 proteins in the plasma of 147 DLBCL patients using data-independent acquisition mass spectrometry and antibody array, DLBCL patients were classified into four proteomic subtypes (PS-I-IV). Patients with the PS-IV subtype and worst prognosis had increased levels of proteins involved in inflammation, including a high expression of metalloproteinase inhibitor-1 (TIMP-1) that was associated with poor survival across two validation cohorts (n = 180). Notably, the combination of TIMP-1 with the international prognostic index (IPI) identified 64.00% to 88.24% of relapsed and 65.00% to 80.49% of deceased patients in the discovery and two validation cohorts, which represents a 24.00% to 41.67% and 20.00% to 31.70% improvement compared to the IPI score alone, respectively. Taken together, we demonstrate that DLBCL heterogeneity is reflected in the plasma proteome and that TIMP-1, together with the IPI, could improve the prognostic stratification of patients.

Rapid Oxidative Detoxification of Mustard Simulant by the Multisite Synergistic Catalytic Action of {PMoVI11MoVO40CuI8} Units.

Under hydrothermal and solvent-thermal conditions, we synthesized two novel polyoxometalate (POM)-based hybrids: [CuI4(Pz)2(H2O)8(PMoVI11MoVO40)]·3.5H2O (1, Pz = pyrazine) and [(C2H8N)5(HPMoVI9MoV3O40)]·DMF·4H2O (2). Single-crystal X-ray diffraction indicates that compound 1 is a three-dimensional structure consisting of Cu (I), {PMo12} anions, Pz, and water, where Cu (I) can be considered as Lewis acid sites. Furthermore, both compounds 1 and 2 possess favorable catalysis activity in catalyzing the conversion of chemical warfare agent simulant 2-chloroethylethyl sulfide (CEES) to nontoxic production of 2-chloroethylethyl sulfoxide (CEESO) under ambient temperature. Significantly, 1 could realize 98% conversion and 100% selectivity of CEES owing to the multisite synergy in the {PMoVI11MoVO40CuI8} units in which the tricoordinated Cu (I) could interact with S and O atoms from CEES and H2O2, respectively. This interaction not only decreases the distance of CEES from peroxomolybdenum species formed by H2O2 but also activates CEES.

Exploring Electron Transfer Mechanism in Synergistic Interactional Reduced Polyoxometalate-Based Cu(I)-Organic Framework for Photocatalytic Removal of U(VI).

Photocatalytic reduction of U(VI) is a promising method for removing uranium containing pollutants. However, using polyoxometalate-based metal-organic frameworks (POMOFs) for photoreduction of U(VI) is rare, and the relevant charge transfer pathway is also not yet clear. In this article, we demonstrate a highly efficient strategy and revealed a clearly electron transfer pathway for the photoreduction of U(VI) with 99% removal efficiency by using a novel POMOF, [Cu(4,4'-bipy)]5·{AsMo4VMo6VIV2VO40(VIVO)[VIVO(H2O)]}·2H2O (1), as catalyst. The POMOF catalyst was constructed by the connection of reduced {AsMo10V4} clusters and Cu(I)-MOF chains through Cu-O coordination bonds, which exhibits a broader and stronger light absorption capacity due to the presence of reduced {AsMo10V4} clusters. Significantly, the transition of electrons from Cu(I)-MOF to {AsMo10V4} clusters (Cu → Mo/V) greatly inhibits the recombination of photogenerated carriers, thereby advancing electron transfer. More importantly, the {AsMo10V4} clusters are not only adsorption sites but also catalytically active sites. This causes the fast transfer of photogenerated electrons from Mo/V to UO22+(Mo/V → O → U) via the surface oxygen atoms. The shorter electron transmission distance between catalytic active sites and UO22+ achieves faster and more effective electron transport. All in all, the highly effective photocatalytic removal of U(VI) using the POMOF as a catalyst is predominantly due to the synergistic interaction between Cu(I)-MOFs and reduced {AsMo10V4} clusters.

Phytohormones-mediated strategies for mitigation of heavy metals toxicity in plants focused on sustainable production.

KEY MESSAGE: In this manuscript, authors reviewed and explore the information on beneficial role of phytohormones to mitigate adverse effects of heavy metals toxicity in plants. Global farming systems are seriously threatened by heavy metals (HMs) toxicity, which can result in decreased crop yields, impaired food safety, and negative environmental effects. A rise in curiosity has been shown recently in creating sustainable methods to reduce HMs toxicity in plants and improve agricultural productivity. To accomplish this, phytohormones, which play a crucial role in controlling plant development and adaptations to stress, have emerged as intriguing possibilities. With a particular focus on environmentally friendly farming methods, the current review provides an overview of phytohormone-mediated strategies for reducing HMs toxicity in plants. Several physiological and biochemical activities, including metal uptake, translocation, detoxification, and stress tolerance, are mediated by phytohormones, such as melatonin, auxin, gibberellin, cytokinin, ethylene, abscisic acid, salicylic acid, and jasmonates. The current review offers thorough explanations of the ways in which phytohormones respond to HMs to help plants detoxify and strengthen their resilience to metal stress. It is crucial to explore the potential uses of phytohormones as long-term solutions for reducing the harmful effects of HMs in plants. These include accelerating phytoextraction, decreasing metal redistribution to edible plant portions, increasing plant tolerance to HMs by hormonal manipulation, and boosting metal sequestration in roots. These methods seek to increase plant resistance to HMs stress while supporting environmentally friendly agricultural output. In conclusion, phytohormones present potential ways to reduce the toxicity of HMs in plants, thus promoting sustainable agriculture.

Analysis of the incidence and risk factors of blood transfusion in total knee revision: a retrospective nationwide inpatient sample database study.

OBJECTIVE: This study sought to determine the incidence and risk factors of blood transfusion among patients undergoing total knee revision (TKR) using a nationwide database. METHODS: A retrospective data analysis was conducted based on the Nationwide Inpatient Sample (NIS), enrolling patients who underwent TKR from 2010 to 2019 with complete information. The patients were divided into two groups based on whether they received blood transfusion or not. The demographic characteristics (race, sex, and age), length of stay (LOS), total charge of hospitalization, hospital characteristics (admission type, insurance type, bed size, teaching status, location, and region of hospital), hospital mortality, comorbidities, and perioperative complications were analyzed. Finally, we conducted univariate and multivariate logistic regression to identify factors that were associated with TKR patients to require blood transfusion. RESULTS: The NIS database included 115,072 patients who underwent TKR. Among them, 14,899 patients received blood transfusion, and the incidence of blood transfusion was 13.0%. There was a dramatic decrease in the incidence over the years from 2010 to 2019, dropping from 20.4 to 6.5%. TKR patients requiring transfusions had experienced longer LOS, incurred higher total medical expenses, utilized Medicare more frequently, and had increased in-hospital mortality rates (all P < 0.001). Independent predictors for blood transfusion included advanced age, female gender, iron-deficiency anemia, rheumatoid disease, chronic blood loss anemia, congestive heart failure, coagulopathy, uncomplicated diabetes, lymphoma, fluid and electrolyte disorders, metastatic carcinoma, other neurological diseases, paralysis, peripheral vascular disorders, pulmonary circulation disorders, renal failure, valvular disease, and weight loss. In addition, risk factors for transfusion in TKR surgery included sepsis, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, gastrointestinal bleeding, heart failure, renal insufficiency, pneumonia, wound infection, lower limb nerve injury, hemorrhage/seroma/hematoma, wound rupture/non healing, urinary tract infection, acute renal failure, and postoperative delirium. CONCLUSIONS: Our findings highlight the importance of recognizing the risk factors of blood transfusion in TKR to reduce the occurrence of adverse events.

Clinical Value of Serum miR-106a in the Diagnosis and Prognosis of Human Papillomavirus-Positive Cervical Cancer.

INTRODUCTION: Cervical cancer (CC) is a prevailing malignant tumor in women, mainly caused by human papillomavirus (HPV) infection. This study investigated miR-106a expression in the serum of HPV-positive CC patients and estimated its value in diagnosis and prognosis. METHODS: We enrolled 120 CC patients as study subjects, with another 80 healthy women as controls. Clinical baseline data and clinicopathological indexes including age, tumor size, differentiation degree, FIGO stage, lymph node metastasis, and squamous cell carcinoma antigen (SCC-Ag) were recorded. Serum miR-106a expression was measured using reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve was employed to estimate the efficacy of miR-106a in diagnosing CC or HPV-positive CC. Under a 5-year follow-up, patient survival was recorded, and the impact of miR-106a on overall survival rate was analyzed by the Kaplan-Meier method. The logistic regression model was used to analyze whether miR-106a was an independent prognostic factor for HPV infection in CC patients. RESULTS: Serum miR-106a was upregulated in CC patients and the level >1.365 assisted the CC diagnosis. miR-106a expression in HPV-positive CC patients was elevated relative to HPV-negative CC patients, and serum miR-106a level >1.300 distinguishing HPV positive and HPV negative. HPV positivity was linked with tumor differentiation degree, FIGO stage, lymph node metastasis, and SCC-Ag in CC patients, but not with age and tumor size. High expression of miR-106a in HPV-positive CC patients increased the risk of poor prognosis, and miR-106a expression is an independent prognostic factor for HPV infection in CC patients. CONCLUSION: High expression of miR-106a assists in the diagnosis of HPV-positive CC and predicts poor prognosis.

Two 3D Two-Fold Interpenetrated Dia-Like Polyoxometalate-Based Metal-Organic Frameworks: Synthesis and Sulfide Selective Oxidation Activity.

Two new three-dimensional (3D) polyoxometalate-based metal-organic frameworks (POMOFs), [M2(btap)4(H2O)4(HPMo10VI Mo2VO40)] (M = Co (1) and Cd (2); btap = 3, 5-bis(1', 2', 4'-triazol-1'-yl)pyridine), have been synthesized under mild hydrothermal conditions and characterized in detail. Single-crystal X-ray diffraction (SXRD) analysis indicates that 1 and 2 are isostructural. In complexes 1 and 2, the metal ion is coordinated with the ligand to form two different left and right helical one-dimensional chains, which are alternately connected in a twisted form to build a two-fold interpenetrated three-dimensional structure, and the polyoxometalate is encapsulated into in the pores generated by the interpenetrating structure. It is noteworthy that 1 and 2, as recyclable catalysts, possess favorable heterogeneous catalytic activity and excellent sulfoxide selectivity in sulfide oxidation reactions, with H2O2 as an oxidant. By reason of the high dispersion of polyoxometalate with good intrinsic activity in the skeleton structure, the title complex has high activity. In addition, no obvious decrease of sulfoxide yield is observed after at least five cycles. These results indicate the excellent catalytic activity and sustainability of 1 and 2.

Synergistic toxicity of some food additives used in non-alcoholic beverages on renal tubular epithelial cells.

Evidences supported many food additives (FAs) possess toxicity to human health due to chronic excessive exposure. Global hygienic standards strictly limit the dosage of each FA and mixture of the same functional FAs. However, the synergetic effects caused by the combination of FAs with different functions require careful evaluation. In the present study, the content of each FA in beverages was determined by HPLC-UV-Vis detection. The cytotoxic effects of selected typical FAs alone or their combination were evaluated in human renal tubular epithelial cells. Mathematical Modeling and bioinformatics methods were employed to evaluate the toxicity of FAs and to predict the key target proteins of FAs on renal tubular cell toxicity, which were verified by western blot. The results indicated above 5 FAs were used in each surveyed beverage. The content of each FA and the respective ratios of the same functional FAs in each beverage did not exceed the maximum permitted level. But it was intensively shown that the significant synergistic cytotoxicity for the combination of FAs with lower concentration. The intercellular signaling transduction pathways including JNK/STAT, PI3P/AKT, and MAPK pathways, which could also be activated by PDGF signaling, were predicted to be involved in Fas-induced cytotoxicity. The increased expression of p-STAT3, p-JNK and p-AKT was associated with renal tubular injury. The current study implied the synergistic cytotoxic effect caused by multiple FAs at no toxic dosages via activated cellular transduction pathways regulating cell survival and apoptosis function, which warning of the synergistic toxic effects of different types of FAs.

Factor structure and measurement invariance of the 8-item CES-D: a national longitudinal sample of Chinese adolescents.

BACKGROUND: The 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) has been widely used to measure depressive symptoms in many large-scale surveys. Due to its brevity, it can lower costs, relieve respondent burdens, and ensure data quality. However, its factor structure and measurement invariance across gender and time among adolescents have not been adequately evaluated. This study investigated its factor structure and measurement invariance across gender and time among adolescents. METHODS: The data was drawn from the China Family Panel Studies (CFPS) conducted in 2018 and 2020, with 3099 participants (46.82% girls) aged 11 to 18 in 2018. First, exploratory and confirmatory factor analyses were used to examine the factor structure of the CES-D 8. Next, multi-group confirmatory factor analysis was conducted to test its measurement invariance across gender and time. Finally, a longitudinal cross-gender test was conducted to further confirm the stability of the scale. RESULTS: A two-factor structure was identified among the adolescents, including Negative Symptoms and Diminished Happiness Feeling. Measurement invariance across gender and time, as well as the longitudinal cross-gender invariance, was supported, with configural, factor loadings, thresholds and residual invariance. CONCLUSIONS: The factor structure of the CES-D 8 remains stable across gender and time among adolescents, indicating that it is a promising instrument for measuring depressive symptoms, especially in large-scale and longitudinal surveys.

Effects of Chitosan and Cellulose Derivatives on Sodium Carboxymethyl Cellulose-Based Films: A Study of Rheological Properties of Film-Forming Solutions.

Bio-based packaging materials and efficient drug delivery systems have garnered attention in recent years. Among the soluble cellulose derivatives, carboxymethyl cellulose (CMC) stands out as a promising candidate due to its biocompatibility, biodegradability, and wide resources. However, CMC-based films have limited mechanical properties, which hinders their widespread application. This paper aims to address this issue by exploring the molecular interactions between CMC and various additives with different molecular structures, using the rheological method. The additives include O-carboxymethylated chitosan (O-CMCh), N-2-hydroxypropyl-3-trimethylammonium-O-carboxymethyl chitosan (HTCMCh), hydroxypropyltrimethyl ammonium chloride chitosan (HACC), cellulose nanocrystals (CNC), and cellulose nanofibers (CNF). By investigating the rheological properties of film-forming solutions, we aimed to elucidate the influencing mechanisms of the additives on CMC-based films at the molecular level. Various factors affecting rheological properties, such as molecular structure, additive concentration, and temperature, were examined. The results revealed that the interactions between CMC and the additives were dependent on the charge of the additives. Electrostatic interactions were observed for HACC and HTCMCh, while O-CMCh, CNC, and CNF primarily interacted through hydrogen bonds. Based on these rheological properties, several systems were selected to prepare the films, which exhibited excellent transparency, wettability, mechanical properties, biodegradability, and absence of cytotoxicity. The desirable characteristics of these selected films demonstrated the strong biocompatibility between CMC and chitosan and cellulose derivatives. This study offers insights into the preparation of CMC-based food packaging materials with specific properties.

[The role of PERK-eIF2α-ATF4-CHOP pathway in the apoptosis of TM4 cells induced by bisphenol A].

OBJECTIVE: To investigate the effects of bisphenol A(BPA) on the proliferation and apoptosis of mouse testicular sertoli cells(TM4 cells) and the role of PERK-eIF2α-ATF4-CHOP pathway. METHODS: TM4 cells were treated with different concentrations of BPA(0, 25, 50, 100 µmol/L) and 100 µmol/L BPA combined with protein kinase R-like ER kinase(PERK) inhibitor GSK2656157 for 24 h, and the apoptosis of TM4 cells was observed by TUNEL staining. The expression levels of Bax, Bcl-2, cleaved Caspase-3, GRP78 and PERK-eIF2α-ATF4-CHOP pathway-related proteins were detected by Western blot. RESULTS: The apoptosis rate of TM4 cells in 25, 50 and 100 µmol/L BPA exposed groups was increased to 3.31%±0.34%, 7.51%±1.10% and 14.58%±0.91%, respectively, which was significantly higher than that in control group(0.73%±0.03%, P<0.05). Compared with the control group(1.00), cleaved Caspase-3 protein expression of TM4 cells in the 25, 50 and 100 µmol/L BPA exposed groups increased to 1.49±0.11, 1.59±0.12, 2.42±0.24, respectively; the ratio of Bax/Bcl-2 increased to 2.06±0.19, 3.94±0.034, 6.14±0.71, respectively; the protein expression of GRP78 increased to 1.29±0.06, 1.39±0.06, 1.92±0.17, respectively; the expression of p-PERK protein was increased to 1.64±0.03, 2.52±0.09, 2.80±0.11, respectively; the expression of p-eIF2α protein was increased to 1.79±0.05, 2.48±0.10, 4.77±0.32, respectively; ATF4 protein expression was increased to 2.51±0.03, 3.24±0.14 and 7.45±0.51, respectively; CHOP protein expression was increased to 1.44±0.01, 3.20±0.11 and 3.80±0.11, respectively, and all the differences were statistically significant(P<0.05). Compared to 100 µmol/L BPA group, the expression level of p-PERK, p-eIF2α, ATF4, CHOP, cleaved Caspase-3 protein and the ratio of Bax/Bcl-2 in 100 µmol/L BPA+10 µmol/L GSK2656157 group were decreased to 2.17±0.11, 1.81±0.13, 1.71±0.23, 2.18±0.22, 1.43±0.03, 2.22±0.13, respectively; the apoptosis rate of TM4 cells was also decreased to 7.28%±0.47%, all the differences were statistically significant(P<0.05). CONCLUSION: BPA can induce apoptosis of TM4 cells by activating endoplasmic reticulum stress and regulating PERK-eIF2α-ATF4-CHOP pathway.

[KEAP1/PGAM5/AIFM1 mediated oxeiptosis pathway in TDCIPP-induced reduction of TM4 cell viability].

OBJECTIVE: To investigate the toxic effects and potential mechanisms of tri(1, 3-dichloro-2-propyl) phosphate(TDCIPP) exposure on the mouse testicular supporting cell line(TM4 cells). METHODS: TM4 cells were treated with different concentrations of TDCIPP(0, 12.5, 25 and 50 µmol/L), or 50 µmol/L TDCIPP combined with antioxidant N-acetylcysteine(NAC) for 24 h. Cell viability was assessed using the CCK8 assay, intracellular ROS levels were detected using the DCFH-DA probe, and the protein levels of oxeiptosis-related proteins, such as KEAP1, PGAM5, AIFM1 and phosphorylated AIFM1(p-AIFM1), were detected using Western blot. RESULTS: TDCIPP dose-dependently reduced TM4 cell viability(P<0.05). ROS levels in TM4 cells treated with 12.5, 25 and 50 µmol/L TDCIPP were 9.44±1.42, 17.25±1.81 and 18.38±2.66, respectively, significantly higher than the control group's 5.08±0.90(P<0.05). ROS levels in the 5 mmol/L NAC+50 µmol/L TDCIPP group were 14.70±0.50, significantly lower than the corresponding TDCIPP group's 26.44±0.73(P<0.05). The activity of TM4 cells in KEAP1siRNA+TDCIPP group and PGAM5siRNA+TDCIPP group were 77.00±1.73 and 76.67±1.53, respectively, significantly higher than TDCIPP group 68.67±1.53(P<0.05). The relative expression of KEAP1 protein in TM4 cells treated with 25 and 50 µmol/L TDCIPP were 0.77±0.04 and 0.82±0.02, respectively, significantly higher than the control group's 0.57±0.01(P<0.05). The relative expression of PGAM5 protein in TDCIPP-treated TM4 cells were 1.17±0.04, 1.38±0.03 and 1.41±0.03, respectively, significantly higher than the control group's 0.81±0.02(P<0.05). The relative expression of AIFM1 protein were 0.42±0.01, 0.63±0.01 and 0.68±0.02, respectively, significantly higher than the control group's 0.34±0.02(P<0.05). The relative expression of p-AIFM1 protein were 1.73±0.02, 1.52±0.02 and 0.73±0.01, respectively, significantly lower than the control group's 2.25±0.02(P<0.05). In the 5 mmol/L NAC+50 µmol/L TDCIPP group, the relative expression of KEAP1, PGAM5 and AIFM1 proteins in TM4 cells were 0.61±0.01, 0.58±0.01 and 0.48±0.03, respectively, significantly lower than the TDCIPP group's 0.86±0.12(P<0.05), 0.74±0.02(P<0.05) and 0.92±0.01(P<0.05). The relative expression of p-AIFM1 protein in the 5 mmol/L NAC+50 µmol/L TDCIPP group was 0.45±0.11, significantly higher than the TDCIPP group's 0.23±0.01(P<0.05). CONCLUSION: The reduction of TM4 cell viability induced by TDCIPP may be related to ROS-mediated regulation of the KEAP1/PGAM5/AIFM1 pathway, leading to oxeiptosis.

CircRTN4 aggravates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.

Circular RNAs (circRNAs) are regulators of gene expression that can regulate cell proliferation and programmed cell death and serve as biomarkers in renal diseases. However, the specific traits and underlying mechanisms of circRNAs in the progression of lupus nephritis (LN) have not been elucidated. In the present study, we clarified that hsa_circ_0054595 (circRTN4) was upregulated in human renal mesangial cells (HRMCs). In cultured HRMCs, circRTN4 could enhance FN expression by directly interacting with miR-513a-5p. High circRTN4 expression in monocytes disseminated into HRMCs in an exosomal manner, thereby accelerating cell proliferation and extracellular matrix deposition. In addition, knockdown of circRTN4 in the kidney or peripheral blood alleviated renal damage in MRL/lpr and BALB/c mice. Clinically, high levels of circRTN4 were found in peripheral blood mononuclear cells and kidney tissues of LN patients, hence serving as an effective biomarker for LN detection and a novel therapeutic target. Our findings indicated that circRTN4 exacerbates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.

Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy.

BACKGROUND: Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. METHOD: Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). RESULTS: Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). CONCLUSION: This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

TRIM27 contributes to glomerular endothelial cell injury in lupus nephritis by mediating the FoxO1 signaling pathway.

Tripartite motif-containing 27 (TRIM27) belongs to the triple motif (TRIM) protein family, which plays a role in a variety of biological activities. Our previous study showed that the TRIM27 protein was highly expressed in the glomerular endothelial cells of patients suffering from lupus nephritis (LN). However, whether TRIM27 is involved in the injury of glomerular endothelial cells in lupus nephritis remains to be clarified. Here, we detected the expression of the TRIM27 protein in glomerular endothelial cells in vivo and in vitro. In addition, the influence of TRIM27 knockdown on endothelial cell damage in MRL/lpr mice and cultured human renal glomerular endothelial cells (HRGECs) was explored. The results revealed that the expression of TRIM27 in endothelial cells was significantly enhanced in vivo and in vitro. Downregulating the expression of TRIM27 inhibited the breakdown of the glycocalyx and the injury of endothelial cells via the FoxO1 pathway. Moreover, HRGECs transfected with the WT-FoxO1 plasmid showed a reduction in impairment caused by LN plasma. Furthermore, suppression of the protein kinase B (Akt) pathway could attenuate damage by mediating the expression of TRIM27. Thus, the present study showed that TRIM27 participated in the injury of glomerular endothelial cells and served as a potential therapeutic target for the treatment of lupus nephritis.

Hollow Lindqvist-like-Shaped {V6} Cluster-Based Metal-Organic Framework for the Highly Efficient Detoxification of Mustard Gas Simulant.

A polyoxovanadate-based nickel-organic framework, [Ni(bib)2]{V2O6}({V6}-MOF, bib = 1,4-bis(1H-imidazoly-1-yl)benzene), was facilely prepared under gentle hydrothermal conditions and structurally characterized. Single-crystal X-ray diffraction analysis indicates that the {V6} cluster in the {V6}-MOF is constructed of two VO5 tetragonal pyramids and four VO4 tetrahedrons via the apex sharing of O atoms, presenting a hollow Linqvist-like structure, which is different from these reported hexanuclear vanadium clusters. The {V6}-MOF not only expands the structure of polyoxovanadates (POVs) but also catalyzes the rapid detoxification of mustard gas simulant (2-chloroethyl ethyl sulfide, CEES) at 25 °C. The catalytic results were determined by means of GC, GC-MS, and 1H NMR. Using {V6}-MOF as a heterogeneous catalyst, CEES underwent catalyzed oxidation to only nontoxic product 2-chloroethyl ethyl sulfoxide (CEESO) within 40 min, and the conversion and selectivity were almost 100%. In addition, {V6}-MOF exhibits high sustainability, and no obvious reductions in conversion and selectivity are observed after five runs.

HMGB1 protein promotes glomerular mesangial matrix deposition via TLR2 in lupus nephritis.

Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus. Patients with LN mostly die of sclerosing glomerulonephritis and renal failure. The inhibition of glomerular mesangial matrix deposition is an efficient method to restrict the progress of renal injury. By recognizing and binding extracellular and intracellular ligands, Toll-like receptor 2 (TLR2) contributes to the pathogenesis of most immune diseases. However, the relationship between TLR2 and LN is still unknown. Our previous studies confirmed that high-mobility group box 1 (HMGB1), an important ligand of TLR2, promotes the progression of LN by inducing the proliferation of glomerular mesangial cells. However, whether or not HMGB1 participates in the pathogenesis of glomerular mesangial matrix deposition in LN remains unknown. In this study, we observed the upregulated expression of TLR2 in the glomeruli of LN patients and MRL/lpr mice. The inhibition of either TLR2 or HMGB1 inhibited the release of fibronectin and the activation of the MyD88/NF-κB pathway in mesangial cells cultured with LN plasma. In addition, both TLR2- and HMGB1-deficient mice showed reduced 24 hr urine protein levels and improved glomerular histological changes and sclerosis levels. These results indicate that TLR2 regulates glomerular mesangial matrix deposition in LN through the activation of the MyD88/NF-κB pathway by binding to HMGB1.

Anti-p53 autoantibody in blood as a diagnostic biomarker for colorectal cancer: A meta-analysis.

Serum autoantibodies against tumour-associated antigens are promising biomarkers for diagnosis of cancer. This review summarizes the available evidence pertaining to the diagnostic potential of autoantibodies studied in the context of colorectal cancer (CRC). A systematic literature search was conducted in three databases (PubMed, Cochrane Library and Embase). Data pertaining to a total of 145 autoantibodies published in 80 articles were reviewed. Of these, anti-p53 antibody was the most commonly studied autoantibody; thus, we performed a meta-analysis on anti-p53 antibody in 24 articles. According to the cut-off values used to determine positivity for anti-p53 antibody, we divided the included studies into five groups. Owing to the presence of threshold effect in groups 4 and 5 and non-threshold effect in groups 1 and 2, pooled analysis focused on group 3 using a fixed-effects model (Mantel-Haenszel). Group 3, determining the cut-off value based on the value of p53 antibody titre index, was comprised of five articles including 733 patients with CRC and 172 controls (126 healthy individuals and 46 benign diseases). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and summary area under the receiver operating characteristic curves were 0.21, 0.99, 12.26, 0.80, 15.46 and 0.87, respectively. Serum anti-p53 autoantibody may potentially help distinguish CRC from healthy controls or benign diseases; however, it should be used in combination with other indicators due to the low sensitivity. Our study provides insights for further exploration of the optimal combination of different tumour-associated antigens or autoantibodies for diagnosis of CRC.

A new method of ultra-performance liquid chromatography/tandem mass spectrometry for determination of chlorogenic acid in human plasma and urine.

RATIONALE: Chlorogenic acid (CA) is well known for its various biological activities. Here, a clinical study was performed in patients with advanced malignant cancer to explore its therapeutic effects. We aimed to develop a method to quantify CA in human plasma and urine to assist the clinical pharmacokinetic study. METHODS: Ultra-performance liquid chromatography (UPLC) coupled with a triple quadruple mass spectrometry was used to separate and detect CA, with puerarin serving as the internal standard. RESULTS: The method presents an excellent linearity ranging from 5 to 2000 ng/mL for plasma analysis and 50 to 20 000 ng/mL for urine analysis. Intra- and inter-day precision and accuracy were both less than 15% for plasma and urine. CONCLUSIONS: These results showed that the novel UPLC method was robust and sensitive, and fulfilled the requirements for a clinical pharmacokinetic study of CA in patients with advanced cancer.

Knockdown of TRIM27 expression suppresses the dysfunction of mesangial cells in lupus nephritis by FoxO1 pathway.

TRIM27 (tripartite motif-containing 27) is a member of the TRIM (tripartite motif) protein family and participates in a variety of biological processes. Some research has reported that TRIM27 was highly expressed in certain kinds of carcinoma cells and tissues and played an important role in the proliferation of carcinoma cells. However, whether TRIM27 takes part in the progression of lupus nephritis (LN) especially in cells proliferation remains unclear. Our study revealed that the overexpression of TRIM27 was observed in the kidneys of patients with LN, lupus mice and mesangial cells exposed to LN plasma which correlated with the proliferation of mesangial cells and ECM (extracellular matrix) deposition. Downregulation of TRIM27 expression suppressed the proliferation of mesangial cells and ECM accumulation in MRL/lpr mice and cultured human mesangial cells (HMCs) by regulating the FoxO1 pathway. Furthermore, the overexpression of FoxO1 remarkably decreased HMCs proliferation level and ECM accumulation in LN plasma-treated HMCs. In addition, the protein kinase B (Akt) signal pathway inhibitor LY294002 significantly reduced the expression of TRIM27 and inhibited the dysfunction of mesangial cells. These above data suggested that TRIM27 mediated abnormal mesangial cell proliferation in kidney of lupus and might be the potential target for treating mesangial cell proliferation of lupus nephritis.