Effect of tumor-derived extracellular vesicle-shuttled lncRNA MALAT1 on proliferation, invasion and metastasis of triple-negative breast cancer by regulating macrophage M2 polarization via the POSTN/Hippo/YAP axis.

OBJECTIVES: Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated the mechanism of TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis. METHODS: BC-associated targeted EV-derived lncRNAs were screened. Tumor tissues/tissues adjacent to cancer of TNBC patients, and blood samples of all subjects were collected. MALAT1/POSTN mRNA levels in tumor tissues/tissues adjacent to cancer, and MALAT1 expression in EVs and its correlation with TNBC patient overall survival were assessed by RT-qPCR/Kaplan-Meier survival analysis/log-rank test. TNBC patient M2 infiltration was detected by flow cytometry. MALAT1/POSTN levels in EVs/macrophages were regulated by transfection. Hippo/YAP activation was determined by Western blot. Nude mouse xenograft model was established and metastasis was detected by H&E staining. RESULTS: MALAT1/POSTN were up-regulated and correlated with M2 infiltration/poor prognosis in TNBC patients. TNBC-derived EVs induced M2 polarization. MALAT1 was highly expressed in TNBC-derived EVs and could be transferred to macrophages via EVs to induce M2 polarization. POSTN overexpression diminished the inhibitory effect of MALAT1 knockdown on M2 markers. EVs activated the Hippo/YAP pathway in macrophages. The Hippo/YAP pathway inhibition abrogated the effect of POSTN overexpression on M2 marker expression. TNBC-EV-derived MALAT1 facilitated M2 polarization, and thus promoting occurrence and metastasis of TNBC in vitro and in vivo. CONCLUSIONS: TNBC-EV-derived MALAT1 activated the Hippo/YAP axis by up-regulating POSTN, thereby inducing M2 polarization to promote TNBC occurrence and metastasis in vivo.

Orbital Adipose Tissue: The Optimal Control for Back-Table Fluorescence Imaging of Orbital Tumors.

Control tissue is essential for ensuring the precision of semiquantitative analysis in back-table fluorescence imaging. However, there remains a lack of agreement on the appropriate selection of control tissues. To evaluate the back-table fluorescence imaging performance of different normal tissues and identify the optimal normal tissue, a cohort of 39 patients with orbital tumors were enrolled in the study. Prior to surgery, these patients received indocyanine green (ICG) and following resection, 43 normal control tissues (34 adipose tissues, 3 skin tissues, 3 periosteal tissues, and 3 muscle tissues) were examined using back-table fluorescence imaging. The skin tissue demonstrated significantly elevated fluorescence intensity in comparison to the diseased tissue, whereas the muscle tissue exhibited a broad range and standard deviation of fluorescence signal intensity. Conversely, the adipose and periosteum displayed weak fluorescence signals with a relatively consistent distribution. Additionally, no significant correlations were found between the signal-to-background ratio (SBR) of adipose tissue and patients' ages, genders, weights, disease duration, tumor origins, dosing of administration of ICG infusion, and the time interval between ICG infusion and surgery. However, a positive correlation was observed between the SBR of adipose tissue and its size, with larger adipose tissues (>1 cm) showing an average SBR 27% higher than smaller adipose tissues (≤1 cm). In conclusion, the findings of this study demonstrated that adipose tissue consistently exhibited homogeneous hypofluorescence during back-table fluorescence imaging, regardless of patient clinical variables or imaging parameters. The size of the adipose tissue was identified as the primary factor influencing its fluorescence imaging characteristics, supporting its utility as an ideal control tissue for back-table fluorescence imaging.

N6-methyladenosine modification of linc-OIP5 confers paclitaxel resistance in breast cancer through a DDX5-dependent mechanism.

Chemoresistance is a significant obstacle in the treatment of breast cancer (BC). Due to its diverse composition, the causes of chemoresistance in BC are complex and have not been completely understood. In this article, we explored the mechanism of N6-methyladenosine (m6A)-modified long intervening noncoding RNA (linc)-OIP5 in BC chemoresistance. We successfully constructed drug-resistant cell lines MCF-7/P and MDA-MB-231/P by exposing parental MDA-MB-231 and MCF-7 cells to escalating doses of paclitaxel (PTX) and revealed multiple m6A methylation modification sites on linc-OIP5 according to the predictive analysis of the SRAMP database. Linc-OIP5 expression and m6A modification were up-regulated in PTX-resistant BC cells. Inhibition of m6A modification or linc-OIP5 knockdown facilitated PTX-resistant and parental BC cell apoptosis and repressed proliferation and migration. Mechanistically, linc-OIP5 bound to TRIM5 and reduced the ubiquitination of DDX5, thus stabilizing the DDX5 protein. Additionally, DDX5 overexpression partly abrogated the suppressing effects of inhibited m6A modification or si-linc-OIP5 on cell proliferation, migration and PTX resistance. These findings indicate that m6A-modified linc-OIP5 reduced DDX5 ubiquitination and enhanced DDX5 stability by binding to TRIM5, thereby promoting BC cell proliferation, migration and PTX resistance, and inhibiting apoptosis.

Superior oxidase-mimetic activity of FeCo-NC dual-atom nanozyme for smartphone-based visually colorimetric assay of organophosphorus pesticides.

A colorimetric analysis platform has been successfully developed based on FeCo-NC dual-atom nanozyme (FeCo-NC DAzyme) for the detection of organophosphorus pesticides (OPPs). The FeCo-NC DAzyme exhibited exceptional oxidase-like activity (OXD), enabling the catalysis of colorless TMB to form blue oxidized TMB (oxTMB) without the need for H2O2 involvement. By combining acid phosphatase (ACP) hydrolase with FeCo-NC DAzyme, a "FeCo-NC DAzyme + TMB + ACP + SAP" colorimetric system was constructed, which facilitated the rapid detection of malathion. The chromogenic system was applied to detect malathion using a smartphone-based app and an auxiliary imaging interferogram device for colorimetric measurements, which have a linear range of 0.05-4.0 µM and a limit of detection (LOD) as low as 15 nM in real samples, comparable to UV-Vis and HPLC-DAD detection methods. Overall, these findings present a novel approach for convenient, rapid, and on-site monitoring of OPPs.

Edge-oriented growth of cadmium sulfide nanoparticles on nickel metal-organic framework nanosheets for photocatalytic hydrogen evolution.

In this study, a directional loading of cadmium sulfide (CdS) nanoparticles (NPs) was achieved on the opposite edges of nickel metal-organic framework (Ni-MOF) nanosheets (NSs) by adjusting the weight ratio of CdS NPs in the reaction process to produce effective visible light photocatalysts. The close contact between the zero-dimensional (0D) and two-dimensional (2D) regions and the matching positions of the bands promoted charge separation and heterojunction formation. The optimal CdS NPs loading of composite material was 40 wt%. At this ratio, CdS NPs grew primarily at the opposite edges of the Ni-MOF NSs rather than on their surfaces. When lactic acid was used as the sacrificial agent, the hydrogen production rate of the 40 %-CdS/Ni-MOF heterojunction under visible light irradiation was 19.6 mmol h-1 g-1, making a 20-fold enhancement compared to the original CdS NPs sample (1.0 mmol h-1 g-1). The charge carriers generated in CdS NPs were transferred to Ni-MOF NSs through heterojunctions, where Ni-MOF NSs also served as cocatalysts to improve hydrogen production. The combination of the two materials improved the light absorption ability. In particular, the 40 %-CdS/Ni-MOF heterojunction exhibited good photostability, effectively preventing the photocorrosion of CdS NPs. This study introduces an approach for constructing efficient and stable photocatalysts for visible light-driven photocatalytic hydrogen production.

LncRNA MCM3AP-AS1 promotes chemoresistance in triple-negative breast cancer through the miR-524-5p/RBM39 axis.

Triple-negative breast cancer (TNBC) is the most lethal subtype of BC, with unfavorable treatment outcomes. Evidence suggests the engagement of lncRNA MCM3AP-AS1 in BC development. This study investigated the action of MCM3AP-AS1 in chemoresistance of TNBC cells. Drug-resistant TNBC cell lines SUM159PTR and MDA-MB-231R were constructed by exposure to increasing concentrations of doxorubicin/docetaxel (DOX/DXL). MCM3AP-AS1 and miR-524-5p expression levels were determined by RT-qPCR. RNA binding motif 39 (RBM39) level was measured using Western blot. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The targeted binding of miR-524-5p with MCM3AP-AS1 or RBM39 was predicted by ECORI database and validated by dual-luciferase assays. The gain-and-loss of function assays were conducted in cells to investigate the interactions among MCM3AP-AS1, miR-524-5p, and RBM39. TNBC xenograft mouse models were established through subcutaneous injection of MCM3AP-AS1-silencing MDA-MB-231R cells and intraperitoneally administrated with DOX/DXL to verify the role of MCM3AP-AS1 in vivo. MCM3AP-AS1 was upregulated in drug-resistant TNBC cells, and MCM3AP-AS1 silencing could sensitize drug-resistant TNBC cells to chemotherapeutic drugs by promoting apoptosis. MCM3AP-AS1 targeted miR-524-5p. After DOX/DXL treatment, miR-524-5p inhibition partially reversed the effect of MCM3AP-AS1 silencing on inhibiting chemoresistance and promoting apoptosis of drug-resistant TNBC cells. miR-524-5p targeted RBM39. Silencing MCM3AP-AS1 promoted apoptosis via the miR-524-5p/RBM39 axis, thereby enhancing chemosensitivity of drug-resistant TNBC cells. MCM3AP-AS1 knockdown upregulated miR-524-5p, downregulated RBM39, and restrained tumor development in vivo. MCM3AP-AS1 silencing potentiates apoptosis of drug-resistant TNBC cells by upregulating miR-524-5p and downregulating RBM39, thereby suppressing chemoresistance in TNBC.

[Matrix solid-phase dispersion extraction of organophosphorus flame retardants in soil based on response surface methodology].

Organophosphorus flame retardants (OPFRs) are widely used in commercial products owing to their exceptional flame-retarding and plasticizing properties. However, OPFRs are also well recognized as emerging persistent organic pollutants (POPs) because of their environmental persistence, biological concentration, and potential toxicity. Thus, the accurate detection of OPFRs in environmental media is critical for analyzing their fate, transport, and ecological risk. However, very few OPFR detection methods are currently available, and the types of OPFRs detected may vary from site to site. In this study, matrix solid-phase dispersion extraction (MSPD), a simple, rapid, and versatile technique for preparing solid, semisolid, liquid, and viscous samples, was combined for the first time with gas chromatography-tandem mass spectrometry (GC-MS/MS) to analyze 10 OPFRs in soil, namely, tripropyl phosphate (TPrP), tri-n-butyl phosphate (TnBP), tri-iso-butyl phosphate (TiBP), tris(2-chloroisopropyl) phosphate (TCIPP), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPP), triphenylphosphine oxide (TPPO), and trimethylphenyl phosphate (TCP). The GC-MS/MS system was equipped with a Bruker-5MS capillary column coupled with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode. Prior to detection, a mixed standard solution was fortified with 10 ng of13C-PCB208 as an internal standard. The optimal conditions under which MSPD could achieve high selectivity for OPFRs were determined. In addition, single-factor analysis was used to examine the influence of the sorbent (i. e., C18, PSA, Florisil, GCB, and multiwalled carbon nanotubes (MWCNTs)) as well as the dosage, type, and volume of the eluent on the extraction efficiency of the method for the 10 OPFRs. When GCB and ethyl acetate were used as the adsorbent and solvent, respectively, during elution, high extraction recoveries for the OPFRs were achieved. Optimization via response surface methodology (RSM) was adopted to further analyze the impact of three key factors, namely, the adsorbent dosage, eluent volume, and grinding time, as well as their interactions, on OPFR recoveries. Under the optimal conditions of 0.3 g of GCB as the adsorbent, 10 mL of ethyl acetate as the eluent, and 5 min of grinding time, the relative average recovery of the OPFRs was 87.5%. Furthermore, the 10 OPFRs showed good linear relationships under five concentration gradients, with correlation coefficients greater than 0.998. The limits of detection (LODs) and quantification (LOQs) were calculated as signal-to-noise ratios (S/N) of 3 and 10, respectively, and found to be in the ranges of 0.006-0.161 and 0.020-0.531 ng/g, respectively. The performance of the proposed method was verified by determining the recoveries and relative standard deviations (RSDs) of the OPFRs in soils spiked at low, medium, and high levels (10, 20, and 100 ng/g, respectively). The recoveries of the OPFRs ranged from 70.4% to 115.4%, with RSDs ranging from 0.7% to 6.7%. Compared with the conventional accelerated solvent extraction (ASE) method, MSPD presents higher efficiency, simpler operation, and less solvent requirements. The developed method was applied to determine OPFRs in soil samples collected from different sites in Suzhou, including an electronics factory, an auto-repair factory, a paddy field, and a school field. The results revealed that the contents of OPFRs in the soils from the electronics and auto-repair factories were significantly higher than those in the soils from the paddy and school fields. The main pollutants in the soil samples collected from the electronics and auto-repair factories were TCIPP, TPPO, TCEP, and TDCPP. Moreover, the contents of these compounds were 5.30, 4.44, 4.54, and 4.20 ng/g, in soils from the electronics factory and 2.70, 3.93, 7.60, and 5.04 ng/g, in soils from the auto-repair factory. To the best of our knowledge, this study is the first to determine high concentrations of TPPO in industrial soils. Thus, the combination of MSPD and GC-MS/MS adopted in this study can provide useful insights into the detection of the 10 OPFRs in soil.

CTRP13 Mitigates Endothelial Cell Ferroptosis via the AMPK/KLF4 Pathway: Implications for Atherosclerosis Protection.

BACKGROUND C1q/tumor necrosis factor-related protein 13 (CTRP13) preserves endothelial function and possesses anti-oxidation activity. However, its effects on ferroptosis of human umbilical vein endothelial cells (HUVECs) remain unclear. We investigated the effects of CTRP13 on HUVEC ferroptosis induced by oxidized low-density lipoprotein (ox-LDL) and explored the underlying mechanisms of CTRP13 against ferroptosis via the AMPK/KLF4 pathway. MATERIAL AND METHODS Cell Counting Kit-8 assay was used to evaluate cell viability. Lactate dehydrogenase activity and malondialdehyde content analysis were performed to evaluate the cell membrane integrity and lipid peroxidation. Mito-Tracker, JC-1, and 2',7'-dichlorofluorescein di-acetate were used to evaluate the biological activity of mitochondria, mitochondrial membrane potential, and reactive oxygen species (ROS) in endothelial cells. The ferroptosis indicator expressions, recombinant solute carrier family 7, member 11, glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long-chain family member 4 were examined using real-time reverse transcription-polymerase chain reaction and Western blot. Immunofluorescence staining detected GPX4 location in endothelial cells. RESULTS The results demonstrate that CTRP13 (450 ng/mL) prevented HUVEC ferroptosis by inhibiting ROS overproduction and mitochondrial dysfunction, and CTRP13 accelerated antioxidant enzyme expression levels, such as heme oxygenase 1, superoxide dismutase 1, and superoxide dismutase 2, compared with the ox-LDL (100 µg/mL) group for 48 h. Additionally, CTRP13 treatment increased p-AMPK/AMPK expression by 47.65% (P<0.05) while decreasing Krüppel-like factor 4 expression by 37.43% (P<0.05) in ox-LDL-induced HUVECs and elucidated the protective effect on endothelial dysfunction from ferroptosis. CONCLUSIONS These findings provide new insights for understanding the effects and mechanism of CTRP13 on preventing endothelial cell ferroptosis.

Comparing the distal pancreatectomy fistula risk score (D-FRS) and DISPAIR-FRS for predicting pancreatic fistula after distal pancreatectomy.

BACKGROUNDS: Distal pancreatectomy fistula risk score (D-FRS) and DISPAIR-FRS has not been widely validated for predicting postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). METHODS: We retrospectively analysed 104 patients undergoing DP. The predictive value of the D-FRS and DISPAIR-FRS were compared. Risk factors associated with POPF were investigated by multivariate analysis. RESULTS: Of the 104 patients, 23 (22.1%) were categorized into the POPF group (all grade B). The areas under the ROC (AUCs) of the D-FRS (preoperative), D-FRS (intraoperative), and DISPAIR-FRS were 0.737, 0.809, and 0.688, respectively. Stratified by the D-FRS (preoperative), the POPF rates in low-risk, intermediate-risk, and high-risk groups were 5%, 22.6%, and 36.4%, respectively. By the D-FRS (intraoperative), the POPF rates in low-risk, intermediate-risk, and high-risk groups were 8.8%, 47.1%, and 47.4%, respectively. By the DISPAIR-FRS, the POPF rates in low-risk, intermediate-risk, and extreme-high-risk groups were 14.8%, 23.8% and 62.5%, respectively. Body mass index and main pancreatic duct diameter were independent risk factors of POPF both in preoperative (P = 0.014 and P = 0.033, respectively) and intraoperative (P = 0.015 and P = 0.039) multivariate analyses. CONCLUSION: Both the D-FRS (preoperative), D-FRS (intraoperative), and DISPAIR-FRS has good performance in POPF prediction after DP. The risk stratification was not satisfactory in current Asian cohort.

Programmed Intermittent Bolus for Erector Spinae Plane Block Versus Intercostal Nerve Block With Patient-controlled Intravenous Analgesia in Video-assisted Thoracoscopic Surgery: A Randomized Controlled Noninferiority Trial.

OBJECTIVE: Postoperative analgesia is crucial after video-assisted thoracoscopic surgery (VATS). This study was designed to investigate whether the analgesic effect of programmed intermittent bolus (PIB) erector spinae plane block (ESPB) is noninferior to that of intercostal nerve block with patient-controlled intravenous analgesia (ICNB-PCIA) for VATS. METHODS: The study was a single-center, open labeled, randomized noninferiority trial. A total of 80 patients (American Society of Anesthesiologists I to III) undergoing elective video-assisted thoracoscopic lobectomy or bulla resection were randomly allocated to the ICNB-PCIA (n=40) or the ESPB (n=40) group using a PIB injection. The primary outcome was pain intensity at movement at 4 hours postoperatively using the Numeric Rating Scale (NRS). Secondary outcomes included pain scores at rest and movement in the recovery room, at 8, 24, and 48 hours postoperatively, perioperative analgesics, adverse effects, hospital stay, and patient satisfaction. RESULTS: The mean difference in NRS scores at movement at 4 hours postoperatively between the ESPB (n=39) and the ICNB-PCIA (n=37) groups was under the noninferiority margin. NRS scores were significantly higher in the ICNB-PCIA group than the ESPB group at movement postoperatively. At rest, NRS scores were significantly elevated in the ICNB-PCIA at 4, 8, and 24 hours. The postoperative opioids consumption was decreased in the ESPB group. No difference was found in rescue analgesics, hospital stay, and patient satisfaction. DISCUSSION: ESPB using a PIB injection offers noninferior analgesia to ICNB-PCIA after VATS.

The expression of Ki-67 and Glypican -3 in hepatocellular carcinoma was evaluated by comparing DWI and 18F-FDG PET/CT.

Objective: The value of DWI and 18F-FDG PET/CT in evaluating the expression of Ki-67 and GPC-3 in HCC was compared. Materials and methods: Ninety-four patients with primary HCC confirmed by pathology were retrospectively divided into high- and low-Ki-67-expression groups and positive- and negative- GPC-3 groups. The ADC and SUVmax values of the lesions in both groups were measured. ROC curves were used to evaluate the identification efficiency of parameters with significant differences for each group of lesions, and AUCwas calculated. The combined ADC and SUVmax values were analyzed by binary logistic regression. The Delong test was used to compare the AUC values of the combined and single parameters. Pearson (in line with normal distribution) or Spearman (in line with abnormal distribution) correlation analysis was used to analyze the correlation. Results: The ADC value of the high-Ki-67-expression group was lower than that of the low-Ki-67-expression group (P<0.05), and the SUVmax value of the high-expression group was higher than that of the low-expression group (P<0.05). The ADC value of the positive-GPC-3 group was lower than that of the negative group (P<0.0.tive group (P<0.05). The combined ADC and SUVmax values in the GPC-3 group were better than those of a single parameter (P<0.05). There was a strong negative correlation between the SUVmax value and ADC value in the Ki-67 group (R=-0.578, P<0.001) and a weak negative correlation between the SUVmax value and ADC value in the GPC-3 group (R=-0.279, P=0.006). The SUVmax value was strongly positively correlated with the Ki-67 expression index (R=0.733, P<0.001), while the ADC value was strongly negatively correlated with the Ki-67 expression index (R=-0.687, P<0.001). Conclusion: DWI and 18F-FDG PET/CT can be used to evaluate the expression of Ki-67 and GPC-3 in HCC, and there is a certain correlation between the ADC value and SUVmax. Combined DWI and 18F-FDG PET/CT is superior to a single technique in evaluating the expression of GPC-3 in HCC patients. However, the combined model did not benefit the Ki-67 group.

RIPK1 polymorphisms and expression levels: impact on genetic susceptibility and clinical outcome of epithelial ovarian cancer.

BACKGROUND: The aim of this study was to explore the associations of RIPK1 polymorphisms, plasma levels and mRNA expression with susceptibility to epithelial ovarian cancer (EOC) and clinical outcome. METHODS: Three hundred and nineteen EOC patients included in a 60-month follow-up program and 376 controls were enrolled. Two tag SNPs (rs6907943 and rs9392453) of RIPK1 were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Plasma levels of RIPK1 and RIPK1 mRNA expression in white blood cells were determined by ELISA and qPCR, respectively. RESULTS: For rs9392453, significantly increased EOC risk was found to be associated with C allele (P = 0.002, OR = 1.49, 95%CI 1.15-1.92), and with CT/CC genotypes in the dominant genetic model (P = 0.006, OR = 1.54, 95%CI 1.12-2.08). CC haplotype (rs6907943-rs9392453) was associated with increased EOC susceptibility. CC genotype of rs6907943 and CT/CC genotypes of rs9392453 were associated with early onset (age ≤ 50 years) of EOC (OR = 2.5, 95%CI 1.03-5.88, and OR = 1.64, 95%CI 1.04-2.63, respectively). AC genotype of rs6907943 was associated with better overall survival of EOC patients in the over-dominant genetic model (P = 0.035, HR = 0.41, 95%CI 0.18-0.94). Multivariate survival analysis identified the AC genotype of rs6907943 as an independent protective factor for survival of early onset patients (P = 0.044, HR = 0.12, 95%CI 0.02-0.95). Compared to controls, significantly increased plasma levels of RIPK1 and reduced RIPK1 mRNA expression were observed in patients. CONCLUSIONS: Our results suggest that tag SNPs of RIPK1, increased plasma levels of RIPK1 protein and reduced RIPK1 mRNA expression in white blood cells, may influence the susceptibility to EOC. SNP rs6907943 may be a useful marker to distinguish EOC patients with high risk of death.

[Correlation between Expression Patterns of CD117/CD200 in Plasma Cells and Molecular Genetic Prognostic Parameters in Multiple Myeloma].

OBJECTIVE: To investigate the correlation between the expression of CD117 and CD200 in plasma cells and molecular genetic abnormalities in patients with multiple myeloma (MM). METHODS: 100 newly diagnosed MM patients were selected, and fresh bone marrow fluid was collected from the patients. The immunophenotypes and chromosomal structural variations of plasma cells were detected by flow cytometry (FCM) and fluorescence in situ hybridization (FISH). RESULTS: The positive expression frequencies of CD117 and CD200 in abnormal plasma cells of all MM patients were 44.0% and 44.0%, respectively. At least one molecular genetic abnormality was detected in 53 of the 75 patients who underwent FISH testing, and the overall detection rate was 70.7% (53/75). The detection rates of 1q21 (CKS1B ) duplication, 1p32 (CDKN2C ) deletion, p53 deletion and IgH rearrangement were 48.6% (36/74), 10.6% (7/66), 11.1% (8/72) and 32.9% (24/73), respectively. The incidence of IgH rearrangement in CD117+ patients was significantly lower than that in CD117- patients (P<0.05), and the proportion of 1p32 (CDKN2C ) deletion in CD200- patients was significantly lower than that in CD200+ patients (P<0.05). According to the expressions of CD117 and CD200, the patients were divided into 4 groups: CD117+CD200+, CD117+CD200-, CD117-CD200+ and CD117-CD200-. Further analysis showed that the incidence of IgH rearrangement in the CD117+CD200- group was significantly lower than that in the CD117-CD200+ group (P<0.05), and the deletion rate of 1p32 (CDKN2C ) gene in CD117+CD200- group was significantly lower than that in CD117+CD200+ group and CD117-CD200+ group (P<0.05). CONCLUSION: The difference in the expression patterns of CD117 combined with CD200 shows important value in judging the prognosis of MM patients, and the MM patients with CD117-CD200+ expression patterns in abnormal plasma cells have a worse prognosis.

Pancreaticoduodenectomy performed for a patient with prepancreatic postduodenal portal vein: a case report and literature review.

Introduction: Prepancreatic postduodenal portal vein (PPPV) is a rare congenital variation, with only 17 cases reported in the literature and five of them undergoing pancreaticoduodenectomy (PD). Of these, four were L-shaped PPPV with a thin wall that was difficult to isolate, while only one normal-shaped PPPV was reported previously. For patients undergoing PD, recognizing this variation is important to prevent PPPV injury, which could lead to liver ischemia or intraoperative hemorrhage. We here present a case of normal-shaped PPPV who underwent PD. Case presentation: A 68-year-old woman underwent PD for bile duct carcinoma at our hospital. Preoperative enhanced CT revealed that the portal vein was located anterior to the pancreas and posterior to the duodenum, and the L-shaped splenic vein was longitudinally located posterior to the pancreatic neck. During surgery, there was a loose tissue area between the PPPV and the pancreatic head, and the PPPV could be isolated safely. The morphology of PPPV was similar to normal portal vein. Due to the presence of the PPPV, a superior mesenteric artery (SMA)-first approach from the anterior was at high risk of vascular injury, and the pancreatic neck could not be dissected at the dorsal face of PV. Therefore, the SMA was revealed by the classic right posterior approach after transection of the pancreatic neck on the dorsal surface of L-shaped spleen vein, and the specimen was successfully resected without significant intraoperative bleeding. The patient was discharged 18 days after surgery without complications. The final pathology was bile duct carcinoma with R0 resection. Conclusion: PPPV is a rare variant that can be diagnosed by preoperative imaging. In PD procedure, knowledge of PPPV helps in surgical decision-making, approach selection and avoid major bleeding due to PPPV injury. The origin of normal-shaped and L-shaped PPPV might be different. Normal-shaped PPPV can be safely isolated in this case.

Mechanistic illustration on lipid-metabolism disorders induced by triclosan exposure from the viewpoint of m6A-RNA epigenetic modification.

As a typically anthropogenic contaminant, the toxicity effects of triclosan (TCS) were investigated in-depth from the viewpoint of m6A-pre-miRNAs modification. Based on miRNAs high-throughput sequencing, we unravelled the underlying molecular mechanisms regarding TCS-induced lipid-metabolism functional disorders. TCS exposure caused severe lipid accumulation in 120 hpf zebrafish liver and reduced their locomotor activity. Both bioinformatics analysis and experimental validation verified that TCS targeted miR-27b up-regulation to further trigger lipid-metabolism disorders and developmental malformations, including shortened body length, yolk cysts, curved spine and delayed yolk absorption. TCS exposure and miR-27b upregulation both caused the enhanced levels of triglyceride and total cholesterol. Knockdown and overexpression of miR-27b regulated the expression changes of several functional genes related to downstream lipid metabolism of miR-27b, and most downstream target genes of miR-27b were suppressed and enriched in the AMPK signaling pathway. The experiments of pathway inhibitors and agonists further evidenced that TCS caused lipid-metabolism disorders by suppressing the AMPK signaling pathway. In upstream of miR-27b, TCS decreased total m6A-RNA level by targeting upregulation of demethylase and downregulation of methylase reader ythdf1. Molecular docking and ythdf1 siRNA interference further confirmed that TCS targeted the expression change of ythdf1. Under ythdf1 knockdown in upstream of miR-27b, both abnormal lipid metabolism and miR-27b upregulation highlighted that TCS-induced lipid-metabolism disorders were attributable to the decreasing m6A-RNA methylation levels in vivo. These perspectives provide an innovative idea for prevention and treatment of the lipid metabolism-related diseases and these findings open a novel avene for TCS's risk assessment and early intervention of the contaminant.

Study on fast algorithm of neutron radiation field under complex terrain scenario based on ensemble learning approach.

In this study a prediction algorithm has been proposed to rapidly figure out neutron radiation field for nuclear explosion under complex terrain scenario based on ensemble learning approach, which could be an impossibility for traditional radiation transport simulation methodology. By analyzing the influence of complex surface morphology on the radiation field, a series of characteristic parameters which could characterize the topographic features and their influence on the transport of neutrons and secondary gamma in the atmosphere have been extracted with the application of DEM, and the sample sethas been constructedwith the MC simulation results of terrain samples generated by random algorithm, to be used to train the prediction model for the neutron radiation field of nuclear explosion. In order to verify the actual prediction performance of the model, the study has implemented the prediction for the neutron flux, neutron tissue dose and secondary gamma tissue dose under the authentic urban and mountainous terrain scenarios, and analyzed and compared the results from fast prediction and MC simulation in different evaluation dimensions. The comparisons suggest that both of the results are in good agreement with each other, demonstrating that the fast prediction models preliminarily possess the engineering application value. In addition, a feasible approach to improve the generalization performance of the prediction model for various radiation scenarios has been proposed, which could be deemed as a reference for further research.

[Research progress on regulation of N6-adenylate methylation modification in lipid metabolism disorders].

Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N6-adenylate methylation (m6A) on RNA represents a new "post-transcriptional" regulation mode. m6A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m6A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m6A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.

A pretreatment method combined matrix solid-phase dispersion with dispersive liquid-liquid micro-extraction for polybrominated diphenyl ethers in vegetables through quantitation of gas chromatography-tandem mass spectrometry (GC-MS).

Herein, a novel pretreatment method for extraction of polybrominated diphenyl ethers (PBDEs) using matrix solid phase dispersion (MSPD) and depth purification using dispersive liquid-liquid micro-extraction (DLLME) from vegetables was designed. The vegetables included three leafy vegetables (Brassica chinensis, Brassica rapa var. glabra Regel and Brassica rapa L.), two root vegetables (Daucus carota and Ipomoea batatas (L.) Lam.), and Solanum melongena L. First, the freeze-dried powders of vegetables and sorbents were evenly ground to a mixture, which was then loaded into a solid phase column containing two molecular sieve spacers, one positioned at the top and the other at the bottom. The PBDEs were eluted with a small amount of solvent, concentrated, redissolved in acetonitrile, and then mixed with extractant. Next, 5 mL water was added to form an emulsion and centrifuged. Finally, the sedimentary phase was collected and injected into a gas chromatography-tandem mass spectrometry (GC-MS) system. The main factors such as the type of adsorbent, ratio of sample mass and adsorbents, volume of elution solvent used in the MSPD process, as well as the types and volume of dispersant and the, extractant used in DLLME were all evaluated using the single factor method. Under optimal conditions, the proposed method showed good linearity (R2 > 0.999) within the range of 1 to 1000 g kg-1 for all PBDEs and satisfactory recoveries of spiked samples (82.9-113.8%, except for BDE-183 (58.5-82.5%)) and matrix effects (-3.3-18.2%). The limits of detection and the limits of quantification were in the range of 1.9-75.1 g kg-1 and 5.7-25.3 g kg-1, respectively. Moreover, the total pretreatment and detection time was within 30 min. This method proved to be a promising alternative to other high-cost and time-consuming and multi-stage procedures for determination of PBDEs in vegetables.

A smartphone-based ratiometric fluoroprobe based on blue-red dual-emission signals of thiochrome and copper nanoclusters for sensitive assay of metam-sodium in cucumbers.

It is of great importance to develop the highly efficient fluorescence strategy for rapid/sensitive detection of metam-sodium (MES) in evaluating its residual safety, especially in fresh vegetables. Herein, we prepared an organic fluorophore (thiochrome, TC) and glutathione-capped copper nanoclusters (GSH-CuNCs), and their combination (TC/GSH-CuNCs) was sucessfully employed as a ratiometric fluoroprobe by means of the blue-red dual emission. The fluorescence intensities (FIs) of TC decreased upon the addition of GSH-CuNCs via the fluorescence resonance energy transfer (FRET) process. When fortified at the constant levels of GSH-CuNCs and TC, MES substantially reduced the FIs of GSH-CuNCs, while this was not the case in the FIs of TC except for the prominent red-shift of ∼30 nm. Compared to the previous fluoroprobes, the TC/GSH-CuNCs based fluoroprobe supplied wider linear range of 0.2-500 µM, lower detection limit (60 nM), and satisfactory fortification recoveries (80-107%) for MES in the cucumber samples. Based on the fluorescence quenching phenomenon, a smartphone application was used to output RGB values of the captured images for the colored solution. The smartphone-based ratiometric sensor could be utilized for the visual fluorescent quantitation of MES by virtue of the R/B values in cucumbers, which gave linear range (1-200 µM) and LOD (0.3 µM). By means of blue-red dual-emission fluorescence, the smartphone-based fluoroprobe provides a cost-effective, portable and reliable avenue for the on-site, rapid and sensitive assay of MES's residues in complex vegetable samples.

CD8A is a Promising Biomarker Associated with Immunocytes Infiltration in Hyperoxia-Induced Bronchopulmonary Dysplasia.

Background: Bronchopulmonary dysplasia (BPD) refers to a chronic lung disease which is commonly observed in preterm infants. It can usually be caused by several pathological processes that endanger the long-term lung development, such as inflammation and immune dysfunction. Methods: In this study, a bioinformatics approach was applied to identify the differentially expressed immune-related genes (DEIRGs). We downloaded the transcriptional profiles (GSE32472 dataset) from the Gene Expression Omnibus (GEO) database and performed gene set enrichment analysis (GSEA). Cell type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT), microenvironment cell populations counter (MCPcounter), and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were used for the analysis of the immune cell infiltration landscape of BPD. A weighted co-expression network was subsequently constructed using weighted gene co-expression network analysis (WGCNA) to screen candidate differentially expressed immune related genes (DEIRGs). Results: GSEA results indicated that immune-related pathways were mainly involved in BPD. Ten significantly different immune cell types were observed between BPD and normal groups. A total of 228 DEGs in the turquoise module were identified, and 31 DEIRGs were further identified. Cluster of the differentiation 8 alpha (CD8A) expression was down-regulated in BPD, and its expression was validated by the GSE25286, GSE25293, GSE99633 datasets and qRT-PCR. In addition, CD8A expression was closely associated with immune cells infiltration, especially T cells CD8 and neutrophil. Conclusion: A distinct immune cell infiltration landscape was found between BPD and normal group. CD8A can be a novel candidate biomarker for BPD, which plays an essential role in the onset and progress of hyperoxia-related BPD via the disruption of immune cell functions.