Single-Nucleobase-Resolved Nanoruler Determines the Surface Energy Transfer Radius on the Living Cell Membrane.

Investigations about surface energy transfer radius (r0) are limited to the aqueous solution system, and it is quite limited on experimental values of r0 between dyes and the corresponding gold particle (AuNP) sizes, especially for living cell systems. Hence, the selection of suitable AuNP-dye pairs is restricted when designing nanometal surface energy transfer (NSET) strategies in analytical sciences. Here, we developed a single-nucleobase-resolved NSET strategy to in situ measure the r0 value between a specific dye and different-sized AuNPs on the living cell membrane. Using the aptamer-dye complex (XQ-2d-nTA-FAM) and antiCD71 antibody-coupled AuNP conjugate (Au@antiCD71) as two working elements to bind two different sites on CD71 receptors on living cell membranes, we modified the nTA spacer between FAM and the terminal of aptamer to change the distance (r) from FAM to AuNP center and further adjusted the quenching efficiency (Φ) between them. Different r0 values of various AuNP-FAM pairs in living cells are determined by this in situ detection strategy. Based on this single-nucleobase-resolved NSET strategy, we established a simple and efficient universal method for measuring r0 in the living cell system, which greatly expanded the selection range of AuNP-dye pairs during the construction of the NSET model at the nanoscale.

Allyl isothiocyanate induces DNA damage and inhibits DNA repair-associated proteins in a human gastric cancer cells in vitro.

Allyl isothiocyanate (AITC) is abundant in cruciferous vegetables and it present pharmacological activity including anticancer activity in many types of human cancer cells in vitro and in vivo. Currently, no available information to show AITC affecting DNA damage and repair-associated protein expression in human gastric cancer cells. Therefore, in the present studies, we investigated AITC-induced cytotoxic effects on human gastric cancer in AGS and SNU-1 cells whether or not via the induction of DNA damage and affected DNA damage and repair associated poteins expressions in vitro. Cell viability and morphological changes were assayed by flow cytometer and phase contrast microscopy, respectively, the results indicated AITC induced cell morphological changes and decreased total viable cells in AGS and SNU-1 cells in a dose-dependently. AITC induced DNA condensation and damage in a dose-dependently which based on the cell nuclei was stained by 4', 6-diamidino-2-phenylindole present in AGS and SNU-1 cells. DNA damage and repair associated proteins expression in AGS and SNU-1 cells were measured by Western blotting. The results indicated AITC decreased nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), glutathione, and catalase, but increased superoxide dismutase (SOD (Cu/Zn)), and nitric oxide synthase (iNOS) in AGS cells, however, in SNU-1 cells are increased HO-1. AITC increased DNA-dependent protein kinase (DNA-PK), phosphorylation of gamma H2A histone family member X on Ser139 (γH2AXpSer139 ), and heat shock protein 90 (HSP90) in AGS cells. AITC increased DNA-PK, mediator of DNA damage checkpoint protein 1 (MDC1), γH2AXpSer139 , topoisomerase II alpha (TOPIIα), topoisomerase II beta (TOPIIß), HSP90, and heat shock protein 70 (HSP70) in SNU-1 cells. AITC increased p53, p53pSer15 , and p21 but decreased murine double minute 2 (MDM2)pSer166 and O6 -methylguanine-DNA methyltransferase (MGMT) in AGS cells; however, it has a similar effect of AITC except increased ataxia telangiectasia and Rad3 -related protein (ATR)pSer428 , checkpoint kinase 1 (CHK1), and checkpoint kinase 2 (CHK2) in SNU-1 cells. Apparently, both cell responses to AITC are different, nonetheless, all of these observations suggest that AITC inhibits the growth of gastric cancer cells may through induction off DNA damage in vitro.

Record Resolution of Nanometal Surface Energy Transfer Optical Nanoruler Projects 3D Spatial Configuration of Aptamers on a Living Cell Membrane.

Decrypting the in situ three-dimensional spatial configuration of an aptamer is of considerable significance; however, suitable nanoscale resolution tools are lacking. Herein, we show that a new nanometal surface energy transfer (NSET) optical nanoruler has a record resolution, down to single-nucleobase levels. We labeled fluorophores on different T bases of XQ-2d, including 5', 3', 6T, 22T, 38T, and 52T positions. The NSET nanoruler in situ decrypted the base sequence-dependent distance projection on the nanogold surface, demonstrating that 5', 3', stem, and loop structures are symmetrical in three-dimensional spatial configuration. The orientation of the 5' and 3' stem was toward the antiCD71-binding site, whereas the loop was in the opposite direction at a considerable distance. Molecular docking simulation was performed to list all of the possible conformations; however, all base distance parameters projecting on the nanogold surface determined a single conformation of XQ-2d. The specific binding sites of XQ-2d were Lys477, Ser691, and Arg698 on the CD71 receptor.

Plasmon Resonance Energy Transfer Nanoruler for Pinpointing Molecular Distance and Interaction on the Living Cell Membrane.

Developing novel strategies to measure nanoscale distance and molecular interaction on a living cell membrane is of great significance but challenging. Here we develop a model of a linker-free plasmon resonance energy transfer, termed "PRET nanoruler", which is composed of a single-sized nanogold-antibody conjugates donor (G26@antiCD71) and a fluorophore-labeled XQ-2d aptamer receptor (XQ-2d-Cy3), that produces a separation distance (r) dependent energy transfer (ηPRET). Both the theoretical finite element simulation and experiments evidence the observable PRET between single G26NPs and XQ-2d-Cy3. Regardless of the size of ηPRET, we could confirm r is less than 5 nm, the separation of two binding sites is in the range of 13.0-18.0 nm. There is a competitive binding of Tf and XQ-2d-Cy3 on CD71 receptors. PRET nanoruler realizes the estimation of the nanoscale separation distance, and determines the molecular interaction and competitive binding. It is an alternative tool for observing nanoscale single molecular events in the future.

TGF-ß1 dominates stromal fibroblast-mediated EMT via the FAP/VCAN axis in bladder cancer cells.

BACKGROUND: Bladder cancer is one of the most common malignant tumors of the urinary system and is associated with a poor prognosis once invasion and distant metastases occur. Epithelial-mesenchymal transition (EMT) drives metastasis and invasion in bladder cancer. Transforming growth factor ß1 (TGF-ß1) and stromal fibroblasts, especially cancer-associated fibroblasts (CAFs), are positive regulators of EMT in bladder cancer. However, it remains unclear how TGF-ß1 mediates crosstalk between bladder cancer cells and CAFs and how it induces stromal fibroblast-mediated EMT in bladder cancer. We aimed to investigate the mechanism of TGF-ß1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. METHODS: Primary CAFs with high expression of fibroblast activation protein (FAP) were isolated from bladder cancer tissue samples. Subsequently, different conditioned media were used to stimulate the bladder cancer cell line T24 in a co-culture system. Gene set enrichment analysis, a human cytokine antibody array, and cytological assays were performed to investigate the mechanism of TGF-ß1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. RESULTS: Among the TGF-ß family, TGF-ß1 was the most highly expressed factor in bladder cancer tissue and primary stromal fibroblast supernatant. In the tumor microenvironment, TGF-ß1 was mainly derived from stromal fibroblasts, especially CAFs. In stimulated bladder cells, stromal fibroblast-derived TGF-ß1 promoted bladder cancer cell migration, invasion, and EMT. Furthermore, TGF-ß1 promoted the activation of stromal fibroblasts, inducing CAF-like features, by upregulating FAP in primary normal fibroblasts and a normal fibroblast cell line. Stromal fibroblast-mediated EMT was induced in bladder cancer cells by TGF-ß1/FAP. Versican (VCAN), a downstream molecule of FAP, plays an essential role in TGF-ß1/FAP axis-induced EMT in bladder cancer cells. VCAN may also function through the PI3K/AKT1 signaling pathway. CONCLUSIONS: TGF-ß1 is a critical mediator of crosstalk between stromal fibroblasts and bladder cancer cells. We revealed a new mechanism whereby TGF-ß1 dominated stromal fibroblast-mediated EMT of bladder cancer cells via the FAP/VCAN axis and identified potential biomarkers (FAP, VCAN, N-cadherin, and Vimentin) of bladder cancer. These results enhance our understanding of bladder cancer invasion and metastasis and provide potential strategies for diagnosis, treatment, and prognosis.

Clinicopathological characteristics, local treatment, and prognostic factors in IE/IIE primary breast lymphoma: a retrospective study of 67 patients.

INTRODUCTION: Primary breast lymphoma (PBL) is a rare disease, treatment of which excerpts does not reach a consensus. This retrospective study was conducted to analyze clinical features and survival outcomes of different therapeutic methods. MATERIALS AND METHODS: Records of 67 patients with stage IE/IIE primary breast lymphoma were reviewed from the medical record system. Survival information was gathered by searching the outpatient system. Clinicopathological characteristics were compared by chi-squared or Fisher's exact tests. A comparison of survival curves was performed by log-rank tests. The Cox proportional hazard model was applied for multivariate analysis. RESULTS: At the median follow-up time of 65.23 months (range, 9-150 months), there were 27 (40.3%) relapses, 28 (41.8%) distant metastases, and 21 (31.3%) deaths. The 5-year progression-free survival (PFS) and overall survival (OS) were 52.1% and 72.4%. Pathological types (DLBCL vs. non-DLBCL, p = 0.001) and rituximab use (p < 0.001) were statistically associated with longer PFS in patients with PBL. Nodal sites involved and radiotherapy administration were significant predictors for 5-year OS. Multivariate analysis suggested that nodal sites involved (p = 0.005) and radiotherapy administration (p < 0.003) were independent prognostic factors for OS in patients with PBL (p < 0.05). Radical surgery was not an independent factor for patients with PBL. CONCLUSIONS: Radiotherapy improved the survival of patients with PBL. Radical mastectomy offered no additional benefit in the treatment of PBL.

Stimuli-responsive composite biopolymer actuators with selective spatial deformation behavior.

Bioinspired actuators with stimuli-responsive and deformable properties are being pursued in fields such as artificial tissues, medical devices and diagnostics, and intelligent biosensors. These applications require that actuator systems have biocompatibility, controlled deformability, biodegradability, mechanical durability, and stable reversibility. Herein, we report a bionic actuator system consisting of stimuli-responsive genetically engineered silk-elastin-like protein (SELP) hydrogels and wood-derived cellulose nanofibers (CNFs), which respond to temperature and ionic strength underwater by ecofriendly methods. Programmed site-selective actuation can be predicted and folded into three-dimensional (3D) origami-like shapes. The reversible deformation performance of the SELP/CNF actuators was quantified, and complex spatial transformations of multilayer actuators were demonstrated, including a biomimetic flower design with selective petal movements. Such actuators consisting entirely of biocompatible and biodegradable materials will offer an option toward constructing stimuli-responsive systems for in vivo biomedicine soft robotics and bionic research.

Antifungal activities of a novel triazole fungicide, mefentrifluconazole, against the major maize pathogen Fusarium verticillioides.

Fusarium ear rot (FER) is a serious fungal disease occurring the late growth stage of maize. FER not only reduces the yield of maize but also causes mycotoxin contamination, which affects the quality of maize and threatens human and animal health. Fusarium verticillioides is the predominant causative pathogen of FER worldwide. At present, there is no registered fungicide for use against maize FER in China. The novel isopropyl alcohol-triazole fungicide mefentrifluconazole (MFZ) has been shown to be effective against several Fusarium spp., but little is known about its specific activity against F. verticillioides. MFZ exhibited strong antifungal activities against 50 strains of F. verticillioides collected from the major maize-growing areas in China. MFZ inhibited mycelial growth, conidium production, germination and germ tube elongation of F. verticillioides. MFZ treatment significantly reduced fumonisin production and the expression levels of fumonisin biosynthetic genes. Genome-wide transcriptional profiling of F. verticillioides in response to MFZ indicated that the expression of genes involved in ergosterol biosynthesis, including fungicide target genes (cyp51 genes), was significantly downregulated by MFZ. MFZ treatment resulted in reduced ergosterol production and increased glycerol and malonaldehyde production as well as relative conductivity in F. verticillioides. A 2-year field experiment showed a significant reduction in FER severity in maize after spraying with MFZ at the tasseling stage. This study evaluated the potential of MFZ to control FER in maize and provides insights into its antifungal activities and mechanism of action against F. verticillioides.

First report of Rice panicle blight caused by Fusarium sporotrichioides in China.

Rice (Oryza sativa L.) panicle blight, caused by various fungal and bacterial pathogens, is an emerging threat to rice production, due to the impact on rice yield and quality. In the autumn of 2020, a survey was conducted to understand the etiology of the disease in Liaoning province, an important rice growing area in northeastern China. Rice seeds with typical reddish or brown spots on the glumes were collected from various rice fields. Symptomatic seeds were sterilized with 5% sodium hypochlorite and 75% ethanol, rinsed in sterile distilled water, and placed on potato dextrose agar (PDA) plates. After 3 to 5 days of incubation at 25°C, suspected Fusarium strains showing cream to salmon colonies on PDA were purified by the single-spore isolation method. The identification of these strains were performed based on morphological and molecular characteristics. Fusarium incarnatum-equiseti species complex was the most frequently, followed by the members of Fusarium graminearum species complex and Fusarium fujikuroi species complex. However, one strain was identified as F. sporotrichioides Sherb. based on the following results: (I) Colonies on PDA produced dense mycelia and typical red pigment on the undersurface. Macroconidia were usually 3- to 5-septate, moderately curved to straight, and 27.46 ± 7.16 × 3.78 ± 0.8 µm (n = 50). Microconidia were ellipsoid to fusoid and 9.77 ± 2.29 × 2.99 ± 0.65 µm (n = 50). (II) Genomic DNA was extracted by AxyPrep Multisource Genomic DNA Miniprep Kit according to the manufacturer's instructions; the sequence analysis of partial translation elongation factor-1α (TEF-1α) and RNA polymerase II second largest subunit (RPB2) were accomplished with the primers EF1/2 and RPB5F/7CR, respectively. BLAST searches of the obtained sequences had 99-100% homology with several F. sporotrichioides strains from GenBank. DNA sequences of partial TEF-1α and RPB2 were deposited in GenBank as OQ068267 and OQ068269, respectively. (III) This strain can synthesis T-2, HT-2, diacetoxyscirpenol (DAS), and Neosolaniol (NEO) toxin at the concentration of about 5000, 600, 700 and 8000 µg/kg in rice culture, respectively, according to the previous culture and analysis methods (1,2). (IV) Pathogenicity tests were conducted with the rice variety Nanjing 9108 by spraying spore suspension (106 conidia/ml) on rice spikes (5 mL per spike) at the flowering stage. Control spikes were inoculated with sterile distilled water. Three weeks after inoculation, the inoculated rice glumes showed similar symptoms with the original samples in the field. No symptoms were observed on controls. Besides, F. sporotrichioides was successfully recovered from the inoculated rice spikes but not from controls. To our knowledge, this is the first report of F. sporotrichioides causing rice panicle blight in China and this disease appears to be a serious risk to food safety and human health. Funding: This work was supported by Jiangsu Agriculture Science and Technology (CX(21)1005). References: (1) J. J. Mateo et al. Int. J. Food Microbiol. 72:115, 2002. (2) J. Qiu et al. Plant Dis. 104:2193, 2020.

Recombinant human bone morphogenetic protein is a valid alternative to autologous bone graft for long bone non-unions: a systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of recombinant human bone morphogenetic proteins (rhBMPs) and autologous bone graft (ABG) on the healing of long bone non-union. METHODS: A systematic literature search was conducted on PubMed, Web of Science, Cochrane Library, and CNKI up to December 2021. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. A Meta-analysis was performed using state software (version 12.0). RESULTS: A total of 14 studies were included in this meta-analysis. Overall, there was no significant difference between the rhBMPs group and the ABG group in terms of healing rate (RR = 1.04, 95% CI = 0.96-1.12, p = 0.365) and healing time (SMD = -0.31, 95% CI = -0.76-0.14, p = 0.175). Subgroup analysis showed rhBMPs lead to higher healing rates (RR = 1.35, 95% CI = 1.17-1.56, p < 0.001), and shorter healing time (SMD = -0.65, 95% CI = -1.08 to -0.22, p = 0.003) in the subgroup of moderate-quality studies. Sensitivity analysis proved that our conclusions were relatively robust. No significant publication bias was recognized in all studies (Begg's test, p = 0.193; Egger's test, p = 0.307). CONCLUSIONS: RhBMPs or combined with allografts bone, inorganic bone was a valid alternative to ABG for the treatment of long bone non-union.

LncRNA CRNDE Exacerbates IgA Nephropathy Progression by Promoting NLRP3 Inflammasome Activation in Macrophages.

BACKGROUND: Activation of NLRP3 inflammasome in macrophages contributes greatly to IgA nephropathy (IgAN) progression. This study intended to investigate the underlying mechanism of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in the development of IgAN. METHODS: We examined the expression levels of colorectal neoplasia differentially expressed (CRNDE), NLRP3 inflammasome-related proteins in peripheral blood mononuclear cells (PBMCs) and J774A.1 cells and detected inflammatory cytokine levels in the serum of IgAN patients and cell supernatants of in vitro IgAN model. RNA pull-down and RNA immunoprecipitation (RIP) experiments were conducted to evaluate the interaction between CRNDE and NLRP3. Then, the ubiquitin level of NLRP3 and its binding ability to TRIM family member 31 (TRIM31) were determined. RESULTS: Compared with the control group, the expressions of CRNDE and NLRP3 inflammasome-related proteins in PBMCs and J774A.1 cells and levels of IL-1ß, TNF-α and IL-12 in serum of IgAN patients and cell supernatants of IgA-IC-induced J774A.1 cells were all increased. CRNDE silencing down-regulated NLRP3 inflammasome-related proteins and the levels of IL-1ß, TNF-α and IL-12 in cell supernatants, while NLRP3 overexpression reversed these effects. Additionally, CRNDE could interact with NLRP3 and promote NLRP3 expression. Furthermore, inhibition of CRNDE reduced NLRP3 protein level and promoted TRIM31-mediated NLRP3 ubiquitination and degradation. CONCLUSION: CRNDE exacerbates IgA nephropathy progression through restraining ubiquitination and degradation of NLRP3 and facilitating NLRP3 inflammasome activation in macrophages.

DNA methylation-mediated silencing of microRNA-204 enhances T cell acute lymphoblastic leukemia by up-regulating MMP-2 and MMP-9 via NF-κB.

T cell acute lymphoblastic leukaemia (T-ALL) is a highly aggressive haematological cancer of the bone marrow. The abnormal expression of microRNAs (miRNAs) is reportedly involved in T-ALL development and progression. Thus, we aimed to decipher the involvement of miR-204 silencing mediated by DNA methylation in the occurrence of T cell acute lymphoblastic leukaemia (T-ALL). miR-204 expression was determined in bone marrow and peripheral blood samples from T-ALL patients by real-time quantitative PCR (RT-qPCR) with its effect on cell proliferation evaluated by functional assays. In addition, bisulphite sequencing PCR was employed to detect the DNA methylation level of the miR-204 promoter region, and the binding site between miR-204 and IRAK1 was detected by luciferase assay. We found that miR-204 was down-regulated in T cells of T-ALL patients, which was caused by the increased DNA methylation in the promoter region of miR-204. Moreover, overexpression of miR-204 inhibited T-ALL cell proliferation while enhancing their apoptosis through interleukin receptor-associated kinase 1 (IRAK1), which enhanced the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 through activation of p-p65. Thus, miR-204 modulated MMP-2 and MMP-9 through IRAK1/NF-κB signalling pathway, which was confirmed by in vivo assay. Taken together, DNA methylation-mediated miR-204 silencing increased the transcription of IRAK1, thus activating the NF-κB signalling pathway and up-regulating the downstream targets MMP-2/MMP-9.

Melittin suppresses epithelial-mesenchymal transition and metastasis in human gastric cancer AGS cells via regulating Wnt/BMP associated pathway.

Gastric cancer has a poor prognosis; once cancer has metastasized, it can easily lead to patient death. Melittin is one of the major components extracted from the bee venom. It has been shown that melittin emerges antitumor activities against many human cancer cell lines. Our results indicated that melittin at 0.2-0.5 µm significantly reduced total cell viability in human gastric cancer AGS cells. At low concentrations (0.05-0.15 µm), melittin displayed antimetastasis effects and inhibited cell adhesion and colony formation. Besides, it inhibited cell motility and suppressed cell migration and invasion. Melittin inhibited the activities of MMP-2 and MMP-9 and the integrity of cell membrane in AGS cells. Furthermore, Western blotting results showed that melittin decreased the protein expressions of Wnt/BMP and MMP-2 signaling pathways. Based on these observations, melittin inhibited cell migration and invasion of AGS cells through multiple signaling pathways. It may be used to treat metastasized gastric cancers in the future.

Genistein enhances the effects of L-asparaginase on inducing cell apoptosis in human leukemia cancer HL-60 cells.

Genistein (GEN) has been shown to induce apoptotic cell death in various human cancer cells. L-asparaginase (Asp), a clinical drug for leukemia, has been shown to induce cell apoptosis in leukemia cells. No available information concerning GEN combined with Asp increased the cell apoptosis compared to GEN or Asp treatment alone. The objective of this study is to evaluate the anti-leukemia activity of GEN combined with Asp on human leukemia HL-60 cells in vitro. The cell viability, the distribution of cell cycle, apoptotic cell death, and the level of ΔΨm were examined by flow cytometric assay. The expressions of apoptosis-associated proteins were measured by western blotting. GEN combined with Asp revealed a more significant decrease in total viable cells and induced a higher percentage of G2/M phase arrest, DNA damage, and cell apoptosis than that of GEN or Asp treatment only in HL-60 cells. Furthermore, the combined treatments (GEN and Asp) showed a higher decrease in the level of ΔΨm than that of GEN or Asp treatment only. These results indicated that GEN combined with Asp induced mitochondria dysfunction by disrupting the mitochondrial membrane potential. The results from western blotting demonstrated that the treatment of GEN combined with Asp showed a higher increase in the levels of Bax and Bak (pro-apoptotic proteins) and an active form of caspase-3 and a higher decrease in Bcl-2 (anti-apoptotic protein) than that of GEN or Asp treatment alone. GEN significantly enhances the efficiency of Asp on cytotoxic effects (the induction of apoptosis) in HL-60 cells.

Effect of urinary tract infection on the risk of prosthetic joint infection: A systematic review and meta-analysis.

PURPOSE: Urinary tract infection (UTI) are very common in the general population, however it is unclear whether UTI is a risk factor of prosthetic joint infection (PJI). Our purposes were: (1) To determine whether UTI is a risk factor of PJI after joint replacement, and (2) to determine whether the microorganisms causing PJI and UTI are the same. METHODS: PubMed, Web of Science, the Cochrane Library, and EMBASE were searched systematically for studies. The effect sizes of RR were calculated for included studies that reported raw counts with 95% CIs. The aim 1 of the study is a meta-analysis; the aim 2 is a systematic review. RESULTS: The aim 1 indicated that the risk of PJI was significantly higher in the UTI group than in the control group (RR = 3.17; 95% CI, 2.19-4.59). The aim 2 indicated that the microorganisms of UTI and PJI were the same in the same patient, and these included Enterococcus faecalis, and Pseudomonas, which supports the theory of PJI occurring via the haematogenous route from the genitourinary tract that harbours bacteria in UTI. CONCLUSION: This study identified UTI as being significantly associated with PJI after joint arthroplasty and PJI occurring via the haematogenous route from the genitourinary tract harbouring bacteria in UTI. Therefore, postponing surgery and even treating patients with known UTI preoperatively are recommended.

Synthetic Iowaite Can Effectively Remove Inorganic Arsenic from Marine Extract.

For the removal of arsenic from marine products, iowaite was prepared and investigated to determine the optimal adsorption process of arsenic. Different chemical forms of arsenic (As(III), As(V)) with varying concentrations (0.15, 1.5, 5, 10, 15, and 20 mg/L) under various conditions including pH (3, 5, 7, 9, 11) and contact time (1, 2, 5, 10, 15, 30, 60, 120, 180 min) were exposed to iowaite. Adsorption isotherms and metal ions kinetic modeling onto the adsorbent were determined based on Langmuir, Freundlich, first- and second-order kinetic models. The adsorption onto iowaite varied depending on the conditions. The adsorption rates of standard solution, As(III) and As(V) exceeded 95% under proper conditions, while high complexity was noted with marine samples. As(III) and As(V) from Mactra veneriformis extraction all decreased when exposed to iowaite. The inclusion morphology and interconversion of organic arsenic limit adsorption. Iowaite can be efficiently used for inorganic arsenic removal from wastewater and different marine food products, which maybe other adsorbent or further performance of iowaite needs to be investigated for organic arsenic.

Kruppel-like factor 4 improves obesity-related nephropathy through increasing mitochondrial biogenesis and activities.

Obesity is positively linked to multiple metabolic complications including renal diseases. Several studies have demonstrated Kruppel-like factor 4 (KLF4) participated in renal dysfunction and structural disorders in acute kidney injuries, but whether it affected the process of chronic kidney diseases was unknown. Therefore, present study was to disclose the role of renal KLF4 in dietary-induced renal injuries and underlying mechanisms in obesity. Through utilizing high-fat diet-fed mice and human renal biopsies, we provided the physiological roles of KLF4 in protecting against obesity-related nephropathy. Decreased levels of renal KLF4 were positively correlated with dietary-induced renal dysfunction, including increased levels of creatinine and blood urea nitrogen. Overexpression of renal KLF4 suppressed inflammatory response in palmitic acid-treated mouse endothelial cells. Furthermore, overexpressed KLF4 also attenuated dietary-induced renal functional disorders, abnormal structural remodelling and inflammation. Mechanistically, KLF4 maintained renal mitochondrial biogenesis and activities to combat obesity-induced mitochondrial dysfunction. In clinical renal biopsies and plasma, the renal Klf4 level was negatively associated with circulating levels of creatinine but positively associated with renal creatinine clearance. In conclusions, the present findings firstly supported that renal KLF4 played an important role in combating obesity-related nephropathy, and KLF4/mitochondrial function partially determined the energy homeostasis in chronic kidney diseases.

Intraoperative hypotension is associated with shortened overall survival after lung cancer surgery.

BACKGROUND: Intraoperative hypotension is associated with increased morbidity and mortality after surgery. We hypothesized that intraoperative hypotension might also be associated with worse long-term survival after cancer surgery. Herein, we analyzed the correlation between intraoperative hyper-/hypotension and overall survival after lung cancer surgery. METHODS: In this retrospective cohort study, 676 patients who received lung cancer surgery between January 1, 2006 and December 31, 2009 were reviewed. Intraoperative hyper- and hypotension were defined according to their correlation with long-term survival. The primary endpoint was overall survival. The association between episodes of intraoperative hyper-/hypotension and overall survival was analyzed with multivariable Cox proportional hazard models. RESULTS: Long-term follow-ups were completed in 515 patients with a median duration of 5.2 years. The estimated 5-year survival rates were 66.5, 61.3, 56.5, and 41.2% in patients with only hypertension (systolic blood pressure > 140 mmHg for ≥5 min), with both hyper- and hypotension (systolic blood pressure < 100 mmHg for ≥5 min), with neither hyper- nor hypotension, and with only hypotension during surgery, respectively. After adjusting confounding factors, intraoperative hypotension was significantly associated with shortened overall survival (compared with patients with only intraoperative hypertension, those with both hyper- and hypotension: hazard ratio [HR]1.033, 95% confidence interval [CI] 0.709 to 1.507, p = 0.864; those with neither hyper- nor hypotension: HR 0.952, 95% CI 0.608 to 1.489, p = 0.829; those with only hypotension: HR 1.736, 95% CI 1.218 to 2.475, p = 0.002). CONCLUSIONS: For patients undergoing lung cancer surgery, intraoperative hypotension, but not hypertension, was associated with shortened overall survival.

Impact of pharmaceutical care in the orthopaedic department.

WHAT IS KNOWN AND OBJECTIVE: In the mid-1960s, clinical pharmacy developed in the USA, and as the demand for pharmaceutical services continued to grow, their impact began to be taken seriously. However, the participation of clinical pharmacists as members of the multidisciplinary team in the orthopaedic department is still in its infancy, although its role in orthopaedics has not been defined. The object of this study was to identify and discuss the impact of pharmaceutical care in the orthopaedic department. METHODS: A literature search was conducted on MEDLINE, PubMed, Web of Science, the Cochrane Library and CNKI (China National Knowledge Infrastructure) for papers published between 1998 and 2019, using the keywords pharmacy, pharmacist, and medication or drug combined with orthopaedic. Other available resources were also used to identify relevant articles. RESULTS AND DISCUSSION: Based on the available evidence in 74 articles, it was found that clinical pharmacists play an important role in all aspects of rational use of medications, medication review and reconciliation, monitoring adverse drug events, risk assessment, and medication education and counselling. In addition, clinical pharmacy services were developed to minimize medication errors, adverse drug events and medical costs, but clinical pharmacy is still in its early stages in orthopaedics. WHAT IS NEW AND CONCLUSION: A multidisciplinary approach should be adopted in the orthopaedic department, as pharmacist interventions can be vital for promoting the safety, effectiveness and cost-effectiveness of pharmacotherapy. Although pharmacists' contributions to orthopaedics are not yet fully recognized, pharmaceutical services can undoubtedly contribute to both clinical and societal outcomes.

Combinational treatment of 5-fluorouracil and casticin induces apoptosis in mouse leukemia WEHI-3 cells in vitro.

Leukemia is one of the major diseases causing cancer-related deaths in the young population, and its cure rate is unsatisfying with side effects on patients. Fluorouracil (5-FU) is currently used as an anticancer drug for leukemia patients. Casticin, a natural polymethoxyflavone, exerts anticancer activity against many human cancer cell lines in vitro, but no other reports show 5-FU combined with casticin increased the mouse leukemia cell apoptosis in vitro. Herein, the antileukemia activity of 5-FU combined with casticin in WEHI-3 mouse leukemia cells was investigated in vitro. Treatment of two-drug combination had a higher decrease in cell viability and a higher increase in apoptotic cell death, the level of DNA condensation, and the length of comet tail than that of 5-FU or casticin treatment alone in WEHI-3 cells. In addition, the two-drug combination has a greater production rate of reactive oxygen species but a lower level of Ca2+ release and mitochondrial membrane potential (ΔΨm ) than that of 5-FU alone. Combined drugs also induced higher caspase-3 and caspase-8 activities than that of casticin alone and higher caspase-9 activity than that of 5-FU or casticin alone at 48 hours treatment. Furthermore, 5-FU combined with casticin has a higher expression of Cu/Zn superoxide dismutase (SOD [Cu/Zn]) and lower catalase than that of 5-FU or casticin treatment alone. The combined treatment has higher levels of Bax, Endo G, and cytochrome C of proapoptotic proteins than that of casticin alone and induced lower levels of B-cell lymphoma 2 (BCL-2) and BCL-X of antiapoptotic proteins than that of 5-FU or casticin only. Furthermore, the combined treatment had a higher expression of cleaved poly (ADP-ribose) polymerase (PARP) than that of casticin only. Based on these findings, we may suggest that 5-FU combined with casticin treatment increased apoptotic cell death in WEHI-3 mouse leukemia cells that may undergo mitochondria and caspases signaling pathways in vitro.