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Background and Aim Methods Results Conclusions Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver‐related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD).This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB‐4). ΔLSM was defined as [(follow‐up LSM − baseline LSM)/baseline LSM × 100]. We recorded LREs and all‐cause mortality during a median follow‐up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression.Baseline FIB‐4, baseline LSM, ΔFIB‐4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00–1.07; 1.02, 95% CI, 1.01–1.03; 1.06, 95% CI, 1.03–1.09; 1.96, 95% CI, 1.63–2.35, 1.02, 95% CI, 1.01–1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time‐dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11).Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction. [ABSTRACT FROM AUTHOR]

Intelligent connected vehicles (ICVs) have played an important role in improving the intelligence degree of transportation systems, and improving the trajectory prediction capability of ICVs is beneficial for traffic efficiency and safety. In this paper, a real-time trajectory prediction method based on vehicle-to-everything (V2X) communication is proposed for ICVs to improve the accuracy of their trajectory prediction. Firstly, this paper applies a Gaussian mixture probability hypothesis density (GM-PHD) model to construct the multidimension dataset of ICV states. Secondly, this paper adopts vehicular microscopic data with more dimensions, which is output by GM-PHD as the input of LSTM to ensure the consistency of the prediction results. Then, the signal light factor and Q-Learning algorithm were applied to improve the LSTM model, adding features in the spatial dimension to complement the temporal features used in the LSTM. When compared with the previous models, more consideration was given to the dynamic spatial environment. Finally, an intersection at Fushi Road in Shijingshan District, Beijing, was selected as the field test scenario. The final experimental results show that the GM-PHD model achieved an average error of 0.1181 m, which is a 44.05% reduction compared to the LiDAR-based model. Meanwhile, the error of the proposed model can reach 0.501 m. When compared to the social LSTM model, the prediction error was reduced by 29.43% under the average displacement error (ADE) metric. The proposed method can provide data support and an effective theoretical basis for decision systems to improve traffic safety. [ABSTRACT FROM AUTHOR]

Background Ovarian cancer is the most frequent cause of death resulting from malignant gynecological tumors. After surgical intervention, cisplatin (DDP) is a major chemotherapy drug for ovarian cancer, but the ovarian cancer cells tend to develop DDP resistance in the clinical setting. Tumor cells are sensitive to low-dose radiation (LDR). However, how the LDR therapy improves the effects of chemotherapy drugs on ovarian cancer is not well understood. This study aimed to explore this issue. Methods The SKOV3/DDP cells were divided into 3 groups, including low-dose group, conventional-dose group, and control group (no radiation). Cell counting kit-8 assay was performed to measure cell proliferation. Flow cytometric analysis was then utilized to quantify the apoptosis with classical Annexin V/propidium iodide co-staining. And Real-time quantitative PCR and western blot were eventually used to analyze the mRNA and protein levels of excision repair cross complementing-group 1 (ERCC1), B-cell lymphoma 2 (Bcl-2), Survivin and Caspase-3, respectively. Results The IC50 value of DDP in the low-dose group was significantly lower compared with the other two groups. Compared with the conventional-dose group and control group, LDR treatment resulted in significantly more apoptosis. Besides, LDR treatment significantly decreased the mRNA and protein expression of ERCC1, Bcl-2, and Survivin, and enhanced the mRNA and protein expression of Caspase-3 compared with the other two groups. Conclusions LDR reversed DDP resistance in SKOV3/DDP cells possibly by suppressing ERCC1, Bcl-2, and Survivin expressions, and increasing Caspase-3 expression. [ABSTRACT FROM AUTHOR]

Background: Adipogenesis of adipocytes includes two stages: initiation and maturation. Growth hormone (GH) secretion is decreased in obese subjects and GH levels are inversely correlated with abdominal fat mass. The effects of growth hormone (GH) on lipids accumulation or maturation of adipocytes remains elusive. Methods: In the present study, effect of GH on lipid accumulation in vitro and in vivo was examined. cDNA microarray, quantitative real time-PCR (qPCR) and western blotting was used to analyze the expression of genes related to adipocyte lipid accumulation or degradation in pre- or mature 3T3-F442A adipocytes treated with GH and in epididymal adipose tissue of C57BL/6 mice administrated with GH. Level of adiponectin in supernatants of cultured F442A adipocytes was determined by enzyme-linked immune-sorbent assay. Results: We found that in 3T3-F442A especially 6 days post initiation of adipogenesis, GH intervention resulted in decreased expression of adipocyte maturation regulators (C/EBPα, PPARγ) and prominent genes related to lipid synthesis such as FAS and FABP, while the expression of UCP1 was markedly enhanced. cDNA microarray analysis and qPCR showed that the expression of SOCS2 and Adipor2 was increased under GH-treatment in mature 3T3-F442A adipocytes. GH treatment increased the mRNA expression of adiponectin and UCP1 in mature adipocytes. The above results were confirmed by in vivo study. Conclusions: GH potentially negatively modulates the maturation and accumulation of lipid in adipocytes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nickel acetylacetonate enhances the regression rate of HTPB by catalyzing its pyrolysis. • The catalytic effect is mainly induced by Ni2+ and NiO. • Ni(acac) 2 decreases the combustion heat and causes accumulation of decomposition products. The slow regression rate induced by the difficulty of pyrolysis has limited the practical application of hydroxyl-terminated polybutadiene (HTPB)-based fuels for hybrid rocket propulsion. A possible strategy is the use of suitable transition metal elements promoting polymer matrix thermal decomposition of fuels. This paper investigates the effects of nickel acetylacetonate, Ni(acac) 2 , on the thermal stability and combustion of HTPB-based fuel formulations. The presented experimental results show that the addition of Ni(acac) 2 can intensely decrease the thermal stability of HTPB thus enhancing the solid fuel regression rate even at a small additive mass fraction: under an oxygen mass flux of 50 kg/m2s, HTPB + 5 wt% Ni(acac) 2 shows a 25.5% increase over the non-loaded baseline. Kinetics analyses reveal that the catalytic effect is mainly induced by the Ni2+ in Ni(acac) 2 at the early stage of decomposition, and by the NiO produced from the oxidative decomposition of Ni(acac) 2 in the fuel final degradation stage. On the other hand, the addition of Ni(acac) 2 decreases the combustion heat of HTPB-based fuels significantly and implies the accumulation of its decomposition products (much metal Ni, moderate elemental C, and a little NiO.) at the fuel regressing surface. Eventually, when the content of Ni(acac) 2 exceeds 5 wt%, the growth of regression rate slows down rapidly, and a performance detriment occurs at 40 wt%. This study verifies the catalytic effect of Ni(acac) 2 on polymer matrix for HTPB based fuels showing the attractive regression rate performance of this additive. [ABSTRACT FROM AUTHOR]

Summary: Endophytes, found ubiquitous in all plant species in the world, contribute to their host plants by producing plenty of substances that provide protection and ultimately survival value to the plant. Many researches have proven that endophyte is a new and potential source of novel natural products for exploitation in modern medicine, agriculture and industry. So far, a great number of novel natural products possessing antimicrobial activities have been isolated from endophytes. It is believed that screening for antimicrobial compounds from endophytes is a promising way to overcome the increasing threat of drug resistant strains of human and plant pathogen. Antimicrobial metabolites isolated from endophytes belong to diverse structural classes, including: alkaloids, peptides, steroids, terpenoids, phenols, quinones, and flavonoids. In this review, many well-studied areas are presented and examples will be given to discuss the structure of compounds isolated from endophytes extracts with antimicrobial activities and show the wide variety of approaches taken within the field. These achievements would provide the opportunity to utilize endophytes as a new source for production of antibiotics. [ABSTRACT FROM AUTHOR]

Background: Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors. Methods: Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy. Results: From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1–77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6–14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3–83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3–4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with Tmax of 0.5–1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination. Conclusions: Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID. Trial Registration: ClinicalTrials.gov, NCT03781219. [ABSTRACT FROM AUTHOR]

Background: Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors. Methods: Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy. Results: From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1–77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6–14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3–83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3–4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with Tmax of 0.5–1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination. Conclusions: Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID. Trial Registration: ClinicalTrials.gov, NCT03781219. [ABSTRACT FROM AUTHOR]

• Sponge-like microvoids structure Al/PVDF fuel rich films were prepared. • These films exhibit excellent combustion performance and laser sensitivity. • The reactions ratios of Al-O 2 and Al-PVDF when burning were determined. • The released H 2 , H 2 O and AlF 3 gases from Al droplet reduce Al NPs sintering. The aluminum-fluorine reaction hold great potential in crippling Al pre-combustion sintering and agglomeration during combustion. Herein, the laser-sensitive Al/PVDF fuel rich films were prepared by employing a sponge-like microvoids structure through a phase inversion method coupled with micro-segmented flow, displaying the laser power threshold and ignition delay time by less than 4.8 J·cm−2 and 1.57 ms compared to unignited dense Al/PVDF pellet by a 19.6 J·cm−2 laser. The decreased Al atoms plasma electron temperature and a reduced F irons density with the increased Al content, imply a reduction of Al-F reaction ratio. This Al/PVDF films reveal 5 times higher flame propagation rate and mass consumption compared to the vacuum freeze-dried one, contributing to enhanced convective heat transfer in sponge-like microvoids channels. The ambient oxygen and released HF diffusion in microvoids, creating Al-F, Al-O competitive reaction path. The Al-O and Al-F reactions proportions of Al-30, Al-50 and Al-70 in open air were determined by 2:98, 41:59 and 74.5:22 after inferring evaporated AlF 3 combustion products and O 2 reactant by several assumption and calculation based on XPS results. The released gaseous H 2 and AlF 3 from Al droplet surface reduce nano-aluminum sintering. The different reaction paths of Al/PVDF films during combustion and thermal analysis were analyzed. [ABSTRACT FROM AUTHOR]

• A previously unreported porous layer mechanism of AlH 3 enhancing combustion was proposed. • A 50 μm thick porous layer when combustion was evaluated by SEM, thermo-analysis and a new simplified calculation method. • A new model predicting the overlapping process of AlH 3 dehydrogenation and Al oxidation in air atmosphere was developed. Although the motivation of AlH 3 enhancing combustion were recognized in many research, the promotion mechanism have been rarely explored. Herein, a previously unreported porous layer mechanism when combustion were determined in HTPB/AlH 3 fuels by SEM, thermo-analysis and a new simplified calculation method, owing to rapidly released gas phase H 2 from AlH 3 dehydrogenation exposing in melting layer. 5/10% 40–80 μm and 10% 80–200 μm AlH 3 -HTPB formulas show the regression rate increase by, 25.7%, 29.0% and 43.0% at Gox = 350 kg/m2·s, while by 57.2%, 42.0% and 44.2% enhancement at Gox = 150 kg/m2·s. The low AlH 3 content (≤ 10%) promotes the regression rate obviously, while excess AlH 3 content (≥ 20%) promotes slightly as a result of comprehensive factors combined by energy release, a certain porous layer mechanism, aggregated Al 2 O 3 attached on the burning surface and the blocking effect of the gaseous released H 2. A new model predicting the overlapping process of AlH 3 dehydrogenation and Al oxidation in air atmosphere was developed by superimposing AlH 3 dehydrogenation simulation and corresponding separated Al oxidation simulation. A 1.5th Avrami-Erofeev (A–E) simulation was proposed for Al passivation weight gain between 420 and 520 K with an activation energy of 124.92 kJ/mol and the pre-exponential of 10^12.35. [ABSTRACT FROM AUTHOR]

Abstract Hydroxyl-terminated polybutadiene (HTPB) is extensively used in propulsion; however, it's trapped in low regression rate, partly related to poor thermal transfer from combustion. Carbon nanotubes (CNT) act as an energy transfer media, potentially accelerating the heat transfer and combustion performance of HTPB. Herein, multiwall CNT (MWCNT)/HTPB composites were prepared by dispersing MWCNT and surfactant into HTPB and toluene solvent through ball milling. Low MWCNT content (≤1%) promoted combustion, and excess MWCNT (≥2%) depressed, despite MWCNT shifting the HTPB-O 2 reaction to higher temperatures. (0.5%, 1%, 2% and 3%) MWCNT/HTPB composites reinforced the instantaneous regression rate by 11.2%, 31.6%, −21.3%, and −39.7% at Gox = 365 kg/m2·s; by 27.0%, 25.0%, −26.4%, and −36.6% at Gox = 150 kg/m2·s; while strengthened the average regression rate by 0.9%, 8.5%, −17.4%, and −36.7% at Gox = 365 kg/m2·s; and by 5.4%, 8.9%, −8.3%, −22.6% at Gox = 100 kg/m2·s. Specifically, the optimal MWCNT level was 1%, as demonstrated by the optimized reinforced thermal conductivity and slightly reduced energy release, since excessive MWCNT (>2%) hinders combustion through heat dissipation, high viscosity of the melting layer, low energy release and an attached carbon layer on the burning surface blocking the energy transfer. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

At present, the COVID-19 pandemic still presents with outbreaks occasionally, and pedestrians in public areas are at risk of being infected by the viruses. In order to reduce the risk of cross-infection, an advanced pedestrian state sensing method for automated patrol vehicles based on multi-sensor fusion is proposed to sense pedestrian state. Firstly, the pedestrian data output by the Euclidean clustering algorithm and the YOLO V4 network are obtained, and a decision-level fusion method is adopted to improve the accuracy of pedestrian detection. Then, combined with the pedestrian detection results, we calculate the crowd density distribution based on multi-layer fusion and estimate the crowd density in the scenario according to the density distribution. In addition, once the crowd aggregates, the body temperature of the aggregated crowd is detected by a thermal infrared camera. Finally, based on the proposed method, an experiment with an automated patrol vehicle is designed to verify the accuracy and feasibility. The experimental results have shown that the mean accuracy of pedestrian detection is increased by 17.1% compared with using a single sensor. The area of crowd aggregation is divided, and the mean error of the crowd density estimation is 3.74%. The maximum error between the body temperature detection results and thermometer measurement results is less than 0.8°, and the abnormal temperature targets can be determined in the scenario, which can provide an efficient advanced pedestrian state sensing technique for the prevention and control area of an epidemic. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of death worldwide. Especially, non-small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efficient biomarkers for detection, diagnosis and prognosis. To find high efficient biomarkers for clinical diagnosis of NSCLC patients, we used gene differential expression and gene ontology (GO) to define a set of 26 tumor suppressor (TS) genes. The 26 TS genes were down-expressed in tumor samples in cohorts GSE18842, GSE40419, and GSE21933 and at stages 2 and 3 in GSE19804, and 15 TS genes were significantly down-expressed in tumor samples of stage 1. We used S-scores and N-scores defined in correlation networks to evaluate positive and negative influences of these 26 TS genes on expression of other functional genes in the four independent cohorts and found that SASH1, STARD13, CBFA2T3 and RECK were strong TS genes that have strong accordant/discordant effects and network effects globally impacting the other genes in expression and hence can be used as specific biomarkers for diagnosis of NSCLC cancer. Weak TS genes EXT1, PTCH1, KLK10 and APC that are associated with a few genes in function or work in a special pathway were not detected to be differentially expressed and had very small S-scores and N-scores in all collected datasets and can be used as sensitive biomarkers for diagnosis of early cancer. Our findings are well consistent with functions of these TS genes. GSEA analysis found that these 26 TS genes as a gene set had high enrichment scores at stages 1, 2, 3 and all stages. [ABSTRACT FROM AUTHOR]

Objective: Cisplatin is the first‐line chemotherapy for ovarian cancer. However, cisplatin resistance is severely affecting the treatment efficacy. FOXO3a has been reported to be involved in reversing chemotherapy resistance. However, whether low‐dose fraction radiation therapy (LDFRT) can reverse cisplatin resistance remains unclear. This study aimed to explore the effect of LDFRT on cisplatin resistance and its relation with FOXO3a expression in vitro. Methods: The toxicity of cisplatin on SKOV3/DDP cells was evaluated by CCK8 assay and cell apoptosis was measured by Annexin V‐FITC staining as well as Hoechst33342 staining. The expression of FOXO3a and other relative proteins was measured by western blot. Results: Our study found that LDFRT enhanced cisplatin‐induced apoptosis of SKOV3/DDP cells and promoted the expression of FOXO3a and pro‐apoptotic protein PUMA. In addition, overexpression of FOXO3a promoted PUMA activity and toxicity of cisplatin on SKOV3/DDP cells. Conclusion: LDFRT reverses cisplatin resistance of SKOV3/DDP cells possibly by upregulating the expression of FOXO3a and its downstream target PUMA, suggesting that LDFRT might be a potent chemosensitizer for the treatment of ovarian cancer.LDFRT reverses cisplatin resistance of SKOV3/DDP cells possibly by upregulating the expressions of FOXO3a and its downstream target PUMA, suggesting that LDFRT might be a potent chemosensitizer for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Programming by demonstration (PBD) transforms the robot programming from the code level to automated interface between robot and human, promoting the flexibility of robotized automation. In this paper, we focus on programming the industrial robot for assembly tasks by parsing the human demonstration into a series of assembly skills and compiling the skill to the robot executables. To achieve this goal, an identification system using multimodal information to recognize the assembly skill, called MASD, is proposed including: 1) an initial learning stage using a hierarchical model to recognize the action by considering the features from action-object effect, gesture, and trajectory and 2) a retrospective thinking stage using a segmentation method to cut the continuous demonstrations into multiple assembly skills optimally. Using MASD, the demonstration of assembly tasks can be explained with high accuracy in real time, driving a hypothesis that a PBD system on the top of MASD can be extended to more realistic assembly tasks beyond pure positional moving and picking. In experiments, the skill identification module is used to recognize the five kinds of assembly skills in demonstrations of both single and multiple assembly skills, and outperforms the comparative action identification methods. Besides integrated with the MASD, the PBD system can generate the program based on the demonstration and successfully enable an ABB industrial robotic arm simulator to assemble a flashlight and a switch, verifying the initial hypothesis. Note to Practitioners—In the conventional robotized automation, the key role of the robot mainly owes to its capacity for repeating a wide variety of tasks with high speed and accuracy in long term, with a cost of days to months of programming for deployment. On the other hand, the new trend of customization brings the new characteristics: production in short cycle and small volume. This irreversible momentum urges the robot to switch from task to task efficiently. The biggest bottleneck here is the tedious programming, which also has high prerequisites for most practitioners in manufacturing. This situation motivates the development of a PBD system that can understand the assembly skills performed by the human experts in the demonstration and accordingly generate the program for robot’s execution of the taught task. In this paper, we present a skill decoding system to parse the observational raw demonstration into symbolic sequences, which is the crucial bridge to enable the automatic programming. The system achieves high performance in recognition and is tailored for the PBD in assembly tasks by considering both advantages and disadvantages in the background of assembly, such as controllable environment and limited computational resources. It is particularly useful for assembly tasks with modularized actions based on a set of standard parts. At the perspective of industrial application, the PBD upon the proposed system is a promising solution to improve the flexibility of manufacture, which is expected to be true in midterm but an important step toward this goal. [ABSTRACT FROM AUTHOR]

Intrinsic or acquired resistance to oxaliplatin (L-OHP) is a major reason of treatment failure in gastric cancer and limits therapeutic success. Here we generated an oxaliplatin resistant gastric cancer cell line, BGC823/L-OHP, to investigate the effect of a hepatoprotective compound, polyene phosphatidylcholine (PPC), on conquest of oxaliplatin resistance. BGC823/L-OHP cells showed less sensitive to L-OHP directed growth inhibition than the parental BGC823 cells. PPC treatment significantly increased anti-proliferative activity of L-OHP on resistant cells and promoted L-OHP triggered apoptosis, indicating that drug resistance was overcome. Mechanistically, L-OHP incubation stimulated upregulation of an ABC family protein, ABCF2, and the expression was inhibited by PPC. Moreover, expression levels of the stemness factor Nanog and its regulator TLR4 were notably enhanced in BGC823/L-OHP cells and reduced by PPC treatment. To conclude, PPC can overcome oxaliplatin resistance in gastric cancer cells via promoting apoptosis, inhibiting ABCF2, as well via reducing cancer stem cell-like features. The combination therapeutic strategy could serve to increase oxaliplatin effectiveness in the clinic. [ABSTRACT FROM AUTHOR]

Urinary calculus is a common and recurrent condition that affects kidney function. The present study evaluated the use of digital tomosynthesis (DTS) and Kidneys-Ureters-Bladder (KUB) radiography as methods of diagnosing urinary calculi. Unenhanced multidetector computed tomography (UMDCT) was used in the diagnosis of calculi. KUB radiography and DTS procedures were conducted on patients prior to and following bowel preparation to detect kidney, ureteral and bladder calculi. Differences in diagnostic performance of KUB radiography and DTS imaging on prepared and unprepared bowel were evaluated using the Χ² test. The consistency of diagnostic results between two examining physicians was analyzed using the κ test. A total of 138 calculi from 80 patients were detected via UMDCT. The calculi detection rates of KUB prior to and following bowel preparation were 47.8 and 66.7% respectively, and the calculi detection rate of DTS prior to and following bowel preparation were 94.2 and 96.4%, respectively. The detection rates of calculi >5 mm via KUB prior to and following bowel preparation were 56.6 and 73.5% respectively, and in DTS they were 100% prior to and following bowel preparation. Economically, DTS performed on the unprepared bowel was the most cost effective, followed by DTS on the prepared bowel, KUB on the unprepared bowel and KUB on the prepared bowel. Therefore, the current study concluded that DTS may be an appropriate first-line imaging technique in patients with urinary calculi. [ABSTRACT FROM AUTHOR]

Targeted cell delivery to lesion sites via minimally invasive approach remains an unmet need in regenerative medicine to endow satisfactory therapeutic efficacy and minimized side-effects. Here, we rationally designed a pathology-targeted cell delivery strategy leveraging injectable micro-scaffolds as cell-loading capsule and endogenous tissue transglutaminase (TGase) at lesion site as adhesive. Up-regulated TGase post-liver injury catalyzed chemical bonding between the glutamine and lysine residues on liver surface and micro-scaffolds both ex vivo and in vivo , facilitating sufficient adhesion on the pathological liver. Upon intraperitoneal injection, Mesenchymal Stem Cell-loaded capsules, exhibiting cell protection from shear-induced damage and post-transplantation anoikis, adhered to the CCl 4 -treated liver with a hundred-fold improvement in targeting efficiency (70.72%) compared to free-cell injection, which dramatically improved mice survival (33.3% vs. 0% for free-cell therapy) even with low-dosage treatment. This unique and widely-applicable cell delivery mechanism and strategy hold great promise for transforming cell therapy for refractory diseases. [ABSTRACT FROM AUTHOR]

Checkpoint with FHA and Ring Finger (CHFR) is a checkpoint protein that reportedly initiates a cell cycle delay in response to microtubule stress during prophase in mitosis, which has become an interesting target for understanding cancer pathogenesis. Recently, aberrant methylation of the CHFR gene associated with gene silencing has been reported in several cancers. In the present study, we examined the expression of CHFR in B-cell non-Hodgkin lymphoma (B-NHL) in vitro and in vivo. Our results showed that the expression level of CHFR mRNA and protein was reduced in B-NHL tissue samples and B cell lines. Furthermore, CHFR methylation was detected in 39 of 122 B-NHL patients, which was not found in noncancerous reactive hyperplasia of lymph node (RH) tissues. CHFR methylation correlated with the reduced expression of CHFR, high International Prognostic Index (IPI) scores and later pathologic Ann Arbor stages of B-NHL. Treatment with demethylation reagent, 5-Aza-dC, could eliminate the hypermethylation of CHFR, enhance CHFR expression and cell apoptosis and inhibit the cell proliferation of Raji cells, which could be induced by high expression of CHFR in Raji cells. Our results indicated that aberrant methylation of CHFR may be associated with the pathogenesis, progression for B-NHL, which might be a novel molecular marker as prognosis and treatment for B-NHL. [ABSTRACT FROM AUTHOR]

Inhibition of c-MYC has been considered as a potential therapy for lymphoma treatment. We explored a lentiviral vector-mediated small interfering RNA (siRNA) expression vector to stably reduce c-MYC expression in B cell line Jijoye cells and investigated the effects of c-MYC downregulation on cell growth, cell cycle, and apoptosis in vitro. The expression of c-MYC mRNA and protein levels were inhibited significantly by c-MYC siRNA. The c-MYC downregulation resulted in the inhibition of cell proliferation and cell cycle arrest at G2/M phase, which was associated with decreased expression of cyclin B and cyclin-dependent kinase 1 (CDK1) and increased expression of CDK inhibitor p21 proteins. In addition, downregulation of c-MYC induced cell apoptosis characterized by DNA fragmentation and caspase-3 activation. Taken together, these results suggest that lentiviral vector-mediated siRNA for c-MYC may be a promising approach for targeting c-MYC in the treatment of Burkitt lymphoma. [ABSTRACT FROM AUTHOR]

Background: With a wide range of applications, titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO2 nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. Methods: In this study, mice were injected intravenously with a single dose of TiO2 NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. Results: Death of mice in the highest dose (1387 mg/kg) group was observed at day two after TiO2 NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC) count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW) coefficients, and lower liver and kidney coefficients in the TiO2 NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO2 NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO2 NPs treated mice. Conclusions: Intravenous injection of TiO2 NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed. [ABSTRACT FROM AUTHOR]

Objective: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We evaluate serum Angiopoietin-2(Ang-2) and β human chorionic gonadotropin (β-hCG) in women who had undergone a medical abortion as markers of prolonged uterine bleeding (PUB). Methods: Prospective trial involving 2843 women attending an gynecology outpatient clinic who following a medical abortion with mifepristone and misoprostol, the study cohort was divided into women with duration of uterine bleeding >14 days (PUB) and women with duration of uterine bleeding ≤14 days (normal uterine bleeding, NUB). Serum determinations of Ang-2 levels by ELISA and β-hCG levels by electrochemiluminiscence immunoassay. Receiver Operating Characteristics (ROC) analyses were calculated and plotted for the diagnostic accuracy of serum β-hCG and Ang-2 concentration to discriminate PUB and NUB. Results: Baseline characteristics for both groups were similar, Only duration of bleeding showed a significant difference between the PUB group and NUB group. Ang-2 serum levels moderately correlated with serum β-hCG levels with statistically significant correlation coefficients of 0.536. Serum β-hCG and Ang-2 levels on day 7 and on day 14 after medical abortion were signifcantly higher in PUB group than in NUB group. Plotted as ROC curves, β-hCG area under curve (AUC) was 0.65 (95% CI, 0.53–0.76) on day 7, rising to AUC = 0.83 (95% CI, 0.75–0.92) on day 14. Using Ang-2 on day 7 and day 14 as predictive parameter resulted in an analogous AUC (AUC = 0.61 on day 7, AUC = 0.78 on day 14). Conclusions: Both parameters are clinically useful as a diagnostic test in predicting PUB after medical abortion, and can be helpful in uncertain clinical situations, but should be considered as supplementary to a general clinical evaluation. [ABSTRACT FROM AUTHOR]

A peripherally inserted central catheter (PICC) provides an important access for patients requiring prolonged intravenous infusion. However, intravascular migration and subsequent malposition of a PICC may be caused by its flexibility and thinness and by changes in intrathoracic pressure and body position. In this report, we describe one case of persistent hiccup whose PICC migrated to and was bent and folded in the right subclavian vein. [ABSTRACT FROM AUTHOR]