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Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent lowgrade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment. [ABSTRACT FROM AUTHOR]

It is challenging to distinguish embryos with a balanced translocation karyotype from a normal karyotype by existing conventional genetic testing methods. However, in germ-cell gamete generation, chromosome exchange and separation through cell meiosis form a different proportion of unbalanced gametes. Adverse birth events may occur, such as repeated miscarriages and fetal birth defects. In this study, the exact breakpoints of structural variation (SV) from two balanced translocation carrier families by using Nanopore long reads sequencing technology were obtained, and haplotype analysis and Sanger verified the accuracy of the detection results, confirming the application value of the Nanopore sequencing technology in the detection of balanced translocation before embryo implantation. Nanopore long-read sequencing was performed to find the precise breakpoint of chromosome-balanced translocation carriers. The breakpoints were subsequently verified by designing primers across the breakpoints and Sanger sequencing. Haplotype linkage analysis of SNPs which can be linked by a read block of families around the breakpoint regions was followed. After frozen (-thawed) embryo transfer (FET), prenatal cytogenetic analysis of amniotic fluid cells confirmed the predicted karyotypes from the transferred embryos. The presence of breakpoints was detected in three embryos of patient 1. No breakpoints were detected in either embryo of patient 2. One balanced translocated embryo from patient 1 and one normal euploid embryo from patient 2 were transplanted back into the patients, and amniotic fluid cells were analyzed for the karyotype of fetuses. The results were entirely consistent with the fetal karyotype. And through late follow-up, both patients successfully had a live birth fetus. The breakpoint location of the balanced chromosome translocation can be accurately found by Nanopore sequencing. The haplotype of carriers can be successfully constructed by Nanopore and sanger sequencing confirmed that the results were accurate. This is very advantageous for preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) detection in the families without proband. [ABSTRACT FROM AUTHOR]

Objective: To determine whether non-invasive prenatal testing is an alternative testing option to preimplantation genetic testing (PGT) in pregnant patients. Methods: This was a retrospective study of the clinical outcomes of patients who underwent PGT and invasive or non-invasive pregnancy testing after euploid blastocyst transfer at our IVF centre between January 2017 and December 2022. Results: In total, 321 patients were enrolled in this study, 138 (43.0%) received invasive pregnancy testing, and 183 (57.0%) patients underwent non-invasive testing. The mean age of the patients in Group 2 was higher than that of the patients in Group 1 (35.64 ± 4.74 vs. 31.04 ± 4.15 years, P < 0.001). The basal LH and AMH levels were higher in Group 1 than in Group 2 (4.30 ± 2.68 vs. 3.40 ± 1.88, P = 0.003; 5.55 ± 11.22 vs. 4.09 ± 3.55, P = 0.012), but the clinical outcomes were not significantly different. Furthermore, the clinical outcomes of patients undergoing invasive testing were similar to those of patients undergoing non-invasive testing with the same PGT indication. Conclusion: Our results suggest that non-invasive pregnancy testing is a suitable alternative option for detecting the foetal chromosomal status in a PGT cycle. However, the usefulness of non-invasive testing in PGT-M patients is still limited. [ABSTRACT FROM AUTHOR]

Objective: Preimplantation genetic testing for monogenic disorders (PGT-M) has been used for over 20 years to detect many serious genetic conditions. However, there is still a lack of reference materials (RMs) to validate the test performance during the development and quality control of PGT-M. Method: Sixteen thalassemia cell lines from four thalassemia families were selected to establish the RMs. Each family consisted of parents with heterozygous mutations for α- and/or β-thalassemia and two children, at least one of whom carried a homozygous thalassemia mutation (proband). The RM panel consisted of 12 DNA samples (parents and probands in 4 families) and 4 simulated embryos (cell lines constructed from blood samples from the four nonproband children). Four accredited genetics laboratories that offer verification of thalassemia samples were invited to evaluate the performance of the RM panel. Furthermore, the stability of the RMs was determined by testing after freeze‒thaw cycles and long-term storage. Results: PGT-M reference materials containing 12 genome DNA (gDNA) reference materials and 4 simulated embryo reference materials for thalassemia testing were successfully established. Next-generation sequencing was performed on the samples. The genotypes and haplotypes of all 16 PGT-M reference materials were concordant across the four labs, which used various testing workflows. These well-characterized PGT-M reference materials retained their stability even after 3 years of storage. Conclusion: The establishment of PGT-M reference materials for thalassemia will help with the standardization and accuracy of PGT-M in clinical use. [ABSTRACT FROM AUTHOR]

This paper aims to provide the analytical solutions of the ground settlement for a space curved shield tunnel in the case of yaw construction. Settlement inducements include ground loss and construction loads, and two corresponding analytical models have been proposed in this study. Three-dimensional image theory has been adopted to calculate the ground settlement due to ground loss. Yawrelated parameters are introduced into the calculation model to deduce the relevant laws of the ground settlement. Based on modified Mindlin solutions, analytical models are established to calculate the ground settlement induced by construction loads, such as the frontal additional thrust, axial friction of shield shell, and the grouting pressure. The method of calculating the position of the shield machine in the ground is refined, and the influence area of construction loads from the shield machine is optimized. Subsequently, the obtained solutions are validated by a numerical model and field data. Besides, a comparison reveals that the proposed model is the composition of three classical analytical models, thus it excels them in solving the problem mentioned. Finally, parametric analyses of yaw are conducted to examine yaw angle and pitch angle on ground settlement. The proposed model can effectively predict ground settlement caused by the spatial linear shield tunneling process. [ABSTRACT FROM AUTHOR]

Background: The decline in the quantity and quality of mitochondria are closely associated with infertility, particularly in advanced maternal age. Transferring autologous mitochondria into the oocytes of infertile females represents an innovative and viable strategy for treating infertility, with no concerns regarding ethical considerations. As the donor cells of mitochondria, stem cells have biological advantages but research and evidence in this area are quite scarce. Methods: To screen out suitable human autologous ooplasmic mitochondrial donor cells, we performed comprehensive assessment of mitochondrial physiology, function and metabolic capacity on a varity of autologous adipose, marrow, and urine-derived mesenchymal stromal cells (ADSC, BMSC and USC) and ovarian germline granulosa cells (GC). Further, to explore the biosafety, effect and mechanism of stem cell-derived mitochondria transfer on human early embryo development, randomized in-vitro basic studies were performed in both of the young and aged oocytes from infertile females. Results: Compared with other types of mesenchymal stromal cells, USC demonstrated a non-fused spherical mitochondrial morphology and low oxidative stress status which resembled the oocyte stage. Moreover, USC mitochondrial content, activity and function were all higher than other cell types and less affected by age, and it also exhibited a biphasic metabolic pattern similar to the pre-implantation stage of embryonic development. After the biosafety identification of the USC mitochondrial genome, early embryos after USC mitochondrial transfer showed improvements in mitochondrial content, activity, and cytoplasmic Ca2+ levels. Further, aging embryos also showed improvements in embryonic morphological indicators, euploidy rates, and oxidative stress status. Conclusion: Autologous non-invasively derived USC mitochondria transfer may be an effective strategy to improve embryonic development and metabolism, especially in infertile females with advanced age or repeated pregnancy failure. It provides evidence and possibility for the autologous treatment of infertile females without invasive and ethical concerns. [ABSTRACT FROM AUTHOR]

Purpose: Poor ovarian response (POR) affects approximately 9% to 24% of women undergoing in vitro fertilization (IVF) cycles, resulting in fewer eggs obtained and increasing clinical cycle cancellation rates. The pathogenesis of POR is related to gene variations. Our study included a Chinese family comprising two siblings with infertility born to consanguineous parents. Poor ovarian response (POR) was identified in the female patient who had multiple embryo implantation failures occurring in subsequent assisted reproductive technology cycles. Meanwhile, the male patient was diagnosed with non-obstructive azoospermia (NOA). Methods: Whole-exome sequencing and rigorous bioinformatics analyses were conducted to identify the underlying genetic causes. Moreover, the pathogenicity of the identified splicing variant was assessed using a minigene assay in vitro. The remaining poor-quality blastocyst and abortion tissues from the female patient were detected for copy number variations. Results: We identified a novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings. Apart from NOA and POI, biallelic variants in HFM1 were also associated with recurrent implantation failure (RIF). Additionally, we demonstrated that splicing variants caused abnormal alternative splicing of HFM1. Using copy number variation sequencing, we found that the embryos of the female patients had either euploidy or aneuploidy; however, both harbored chromosomal microduplications of maternal origin. Conclusion: Our results reveal the different effects of HFM1 on reproductive injury in males and females, extend the phenotypic and mutational spectrum of HFM1, and show the potential risk of chromosomal abnormalities under the RIF phenotype. Moreover, our study provides new diagnostic markers for the genetic counseling of POR patients. [ABSTRACT FROM AUTHOR]

Cold production is a challenge in the case of heavy oil because of its high viscosity and poor fluidity in reservoir conditions. Alkali--cosolvent--polymer flooding is a type of microemulsion flooding with low costs and possible potential for heavy oil reservoirs. However, the addition of polymer may cause problems with injection in the case of highly viscous oil. Hence, in this study the feasibility of alkali--cosolvent (AC) flooding in heavy oil reservoirs was investigated via several groups of experiments. The interfacial tension between various AC formulations and heavy crude oil was measured to select appropriate formulations. Phase behavior tests were performed to determine the most appropriate formulation and conditions for the generation of a microemulsion. Sandpack flooding experiments were carried out to investigate the displacement efficiency of the selected AC formulation. The results showed that the interfacial tension between an AC formulation and heavy oil could be reduced to below 10-3 mN/m but differed greatly between different types of cosolvent. A butanol random polyether series displayed good performance in reducing the watereoil interfacial tension, which made it possible to form a Type III microemulsion in reservoir conditions. According to the results of the phase behavior tests, the optimal salinity for different formulations with four cosolvent concentrations (0.5 wt%, 1 wt%, 2 wt%, and 3 wt%) was 4000, 8000, 14000, and 20000 ppm, respectively. The results of rheological measurements showed that Type III microemulsion had a viscosity that was ten times that of water. The results of sandpack flooding experiments showed that, in comparison with waterflooding, the injection of a certain AC formulation slug could reduce the injection pressure. The pressure gradient during waterflooding and AC flooding was around 870 and 30e57 kPa/m, respectively. With the addition of an AC slug, the displacement efficiency was 30%e50% higher than in the case of waterflooding. [ABSTRACT FROM AUTHOR]

Isoginkgetin (ISO), a natural biflavonoid, exhibited cytotoxic activity against several types of cancer cells. However, its effects on hepatocellular carcinoma (HCC) cells and mechanism remain unclear. Here, we revealed that ISO effectively inhibited HCC cell proliferation and migration in vitro. LC3-II expression and autophagosomes were increased under ISO treatment. In addition, ISO-induced cell death was attenuated by treatment with chloroquine or knockdown of autophagy-related genes (ATG5 or ULK1). ISO significantly suppressed SLC2A1/GLUT1 (solute carrier family 2 member 1) expression and glucose uptake, leading to activation of the AMPK-ULK1 axis in HepG2 cells. Overexpression of SLC2A1/GLUT1 abrogated ISO-induced autophagy. Combining molecular docking with thermal shift analysis, we confirmed that ISO directly bound to the N terminus of CDK6 (cyclin-dependent kinase 6) and promoted its degradation. Overexpression of CDK6 abrogated ISO-induced inhibition of SLC2A1/GLUT1 transcription and induction of autophagy. Furthermore, ISO treatment significantly decreased the H3K27ac, H4K8ac and H3K4me1 levels on the SLC2A1/GLUT1 enhancer in HepG2 cells. Finally, ISO suppressed the hepatocarcinogenesis in the HepG2 xenograft mice and the diethylnitrosamine+carbon tetrachloride (DEN+CCl4)-induced primary HCC mice and we confirmed SLC2A1/GLUT1 and CDK6 as promising oncogenes in HCC by analysis of TCGA data and human HCC tissues. Our results provide a new molecular mechanism by which ISO treatment or CDK6 deletion promotes autophagy; that is, ISO targeting the N terminus of CDK6 for degradation inhibits the expression of SLC2A1/GLUT1 by decreasing the enhancer activity of SLC2A1/GLUT1, resulting in decreased glucose levels and inducing the AMPK-ULK1 pathway. [ABSTRACT FROM AUTHOR]

Photocatalytic degradation of organic pollutants in wastewater driven by solar energy is considered one of the effective means for environmental remediation. MIL-125(Ti) is a three-dimensional porous ordered metal-organic framework with Ti nodes, which has the advantages of porous structure, adjustable pore size, high chemical and thermal stability. However, the application of MIL-125(Ti) for photocatalysis is limited due to its limited light absorption and low carrier separation efficiency. Here, a novel AgI/MIL-125(Ti) composite was prepared by an ion precipitation exchange method to enhance the overcome of the above deficiencies. Characterization analysis reveals that AgI was uniformly loaded on the surface of MIL-125(Ti), forming a dense AgI/MIL-125(Ti) heterojunction. The light response range of AgI/MIL-125(Ti) composites was significantly improved, which promoted the generation of free radicals. In addition, the photogenerated electrons in the conduction band of AgI were transferred to MIL-125(Ti) by ligand-to-metal charge transfer (LMCT) mechanism under visible light, which avoids the recombination of e-h+ and prolongs the service life of the photocatalyst. Furthermore, as the main active substances, ·OH and ·O2- were generated in large quantities on the AgI surface, the presence of Ti3+-Ti4+ valence electron transfer band in the composite, significantly improved the photocatalytic performance. Therefore, the photocatalytic performance of AgI/MIL-125(Ti) composite for gentian violet degradation reached 95.7% in 120 minutes which was higher than that of the single component under visible light. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the potential bioactive compounds from Phyllanthus emblica L. fruit. Methods: Acetone extracts (60%) of P emblica fruit were dissolved in water and fractionated sequentially with light petroleum and ethyl acetate (EtOAc). The water fraction was separated using Sephadex LH-20 and the isolated compounds were purified by preparative high-performance liquid chromatography. The structures of the isolated compounds were determined through HR-ESI-MS and spectroscopic methods, including 1D- and 2D-NMR, and the antioxidant abilities of the isolates were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Results: Three new phenolic compounds, mucic acid 1-ethyl ester 3- O -gallate (1), mucic acid 6-methyl ester 3- O -gallate (2), and mucic acid 6-ethyl ester 2- O -gallate (3), together with 4 known compounds (4 - 7), were isolated from P emblica fruit. All phenolics exhibited potent antioxidant abilities (DPPH: IC50 7.5-13.2 µM; ABTS: 1.12-2.84 µM Trolox/µM; FRAP: 1.11-2.26 µM Fe2+/µM). Conclusions: Our research contributes to the growing body of evidence demonstrating the benefits of P emblica for health and supports the functional food and nutraceutical applications of the fruit. [ABSTRACT FROM AUTHOR]

To summarise the process of conversion of epidural labour analgesia to anaesthesia for caesarean delivery and explore the relationship between duration of labour analgesia and conversion. Parturients who underwent conversion from epidural labour analgesia to anaesthesia for caesarean delivery between May 2019 and April 2020 at the Chengdu Women's and Children's Central Hospital, Sichuan Maternal and Child Health Hospital, and Jinjiang District Maternal and Child Health Hospital were selected. If the position of the epidural catheter was correct and the effect was good, patients were converted to epidural surgical anaesthesia. If epidural labour analgesia was ineffective, spinal anaesthesia (SA) was administered immediately. For category-1 emergency caesarean sections, general anaesthesia (GA) was administered. A total of 1084 parturients underwent conversion. Of these, 19 (1.9%) received GA due to the initiation of category-1 emergency caesarean section. 704 (64.9%) were converted to epidural surgical anaesthesia, 2 (0.2%) had failed conversions and were administered GA before delivery, and 357 (32.9%) were converted to SA. Logistic regression analysis showed that prolonged duration of epidural labour analgesia ([Crude odds ratio (OR)=1.065; 95% confidence interval (CI), 1.037–1.094; p <.01]; [Adjusted OR = 1.060; 95% CI, 1.031–1.091; p <.01]) was an independent risk factor for conversion failure. A receiver operating characteristic curve constructed using duration of epidural labour analgesia showed that parturients with a duration of epidural labour analgesia ≥8 h, more frequently required a change of anaesthesia technique during conversion, and the relative risk of conversion failure was 1.54 (95% CI, 1.23–1.93; p <.01). Prolonged duration of epidural labour analgesia increases the possibility of having an invalid epidural catheter, resulting in an increased risk of conversion failure from epidural labour analgesia to epidural surgical anaesthesia. Further, this risk is higher when the time exceeds 8 h. Prolonged duration of epidural labour analgesia > 8 h is associated with conversion failure. If it is impossible to judge whether the conversion is successful immediately, spinal anaesthesia should be administered to minimise complications. [ABSTRACT FROM AUTHOR]

Purpose: Malignant pleural effusion (MPE) is an adverse prognostic factor in patients with osteoblastic osteosarcoma; however, the cellular contexts of MPE are largely unknown. Experimental design: We performed single‐cell RNA‐sequencing (scRNA‐seq) on 27 260 cells from seven MPE samples and 91 186 cells from eight osteosarcoma tissues, including one recurrent, one lung metastasis and six primary tumour (PT) samples, to characterize their tumour microenvironment. Results: Thirteen main cell groups were identified in osteosarcoma tumour and MPE samples. Immune cells dominate the cellular contexts in MPE with more T/NK cells and less osteoclasts compared to PT samples. Of T/NK cells, CD8+GNLY+, CD8+KLRC2+ T cells and FCGR3A+NK cells were enriched in MPE but CD4+FOXP3+ Tregs were enriched in PT samples. Naïve IGHD+ B and immune regulatory IGHA1+ B cells were largely identified in MPE, whereas bone metabolism‐related CLEC11A+ B cells were significantly enriched in osteosarcoma PT. M2‐type TAMs, including CLEC11A_TAM, C1QC_TAM and Prolif_TAMs, among myeloid cells were enriched in PT, which may suppress cytotoxicity activities of T cells through multiple ligand–receptor interactions. Mature LAMP3+ DCs were transformed from CD1C+ DC and CLEC9A+ DC sub‐clusters when exposure to tumour alloantigens, which may improve T cell cytotoxicity activities on tumour cells under anti‐PD‐L1 treatments. In further, immune cells from MPE usually present up‐regulated glycolysis and down‐regulated oxidative phosphorylation and riboflavin metabolism activities compared to those in PT samples. Conclusions: Our study provided a novel cellular atlas of MPE and PT in patients with advanced osteosarcoma, which may provide potential therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

The marine exhaust gas containing SO2 leads to serious impacts on human health and marine environments. Due to the strict emission standard of marine exhaust gas and the limited space of ships, desulphurization process intensification is urgent. Herein, a cross‐flow rotating packed bed (CF‐RPB) with a compact size was developed toward desulphurization of marine exhaust gas. According to the emission standards of different sea areas, the characteristics of simulated open seawater desulphurization (OSD) and closed alkali desulphurization (CAD) were systematically evaluated. The respective correlations for Kya of OSD and CAD were proposed to predict the height of CF‐RPB. The desulphurization efficiencies of 86% in the OSD and 97% in the CAD were achieved in a three‐stage CF‐RPB, satisfying the emission standard. Compared with the traditional spray tower, the CF‐RPB has a higher mass transfer coefficient with a smaller volume, which has great potential for desulphurization of marine exhaust gas. [ABSTRACT FROM AUTHOR]

Recent studies have suggested the potency of berberine (BBR) for multiple cancer treatments, including multiple myeloma (MM). However, the direct target and underlying mechanism of BBR remain largely understood in MM. Here, we demonstrated that BBR inhibited cell proliferation and acted synergistically with bortezomib in MM.1S cells. BBR treatment induced MM cell cycle arrest by downregulating several cell cycle-related proteins. Murine double minute 2 (MDM2) as a BBR-binding protein was identified by surface plasmon resonance image (SPRi) analysis and molecular docking. Overexpression of MDM2 is associated with MM progression and a poor prognosis. Knockdown MDM2 by siRNA transfection can repress MM malignant progression and attenuate the BBR sensitivity to MM.1S cells. BBR treatment induced the degradation of MDM2 through the ubiquitin–proteasome system and reactivated P53/P21 in MM cells. Overall, our data has illustrated that MDM2, as a binding protein of BBR for the first time, may serve as a potential therapeutic option for MM. [ABSTRACT FROM AUTHOR]

Objective: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treatment of refractory and relapsed acute leukemia, and the preconditioning methods before transplantationis one of the important factors affecting the survival of patients. Radiotherapy combined with chemotherapy is the most commonly used preconditioning method before transplantation. This study evaluated the safety and efficacy of total bone marrow combined with total lymphatic irradiation as a preconditioning method before hematopoietic stem cell transplantation. Methods: Seventeen patients with acute leukemia who were admitted to our center from 2016 to 2020 were selected. The median age was 17 years (8-35). The target area for TMLI includes the total bone marrow and total lymphatic space, and the organs at risk include the lens, lungs, kidneys, intestine, heart, and liver. The patients received a total bone marrow and lymphatic irradiation preconditioning regimen, the related acute adverse reactions were graded, and the prognosis of the patients after transplantation was observed. Results: During patient preconditioning, only grade 1-2 toxicity was observed, and grade 3-4 toxicity did not occur. Except for one patient whose platelets were not engrafted, all the other patients were successfully transplanted. The median time of neutrophil implantation was 14 d (9-15 d), and the median time of platelet implantation was 14 d (13-21 d). With a median follow-up of 9 months (2-48), 4 relapses occurred, 3 died, and 10 leukemia patients survived and were disease-free. One-year overall survival was 69.8%, cumulative recurrence was 19.5%, disease-free-survival was 54.2%. Conclusion: The Allo-HSCT pretreatment regimen of total bone marrow combined with total lymphatic irradiation is safe and effective in the treatment of malignant hematological diseases. Total bone marrow combined with total lymphatic irradiation may completely replace total body irradiation, and the clinically observed incidence of acute toxicity is not high. [ABSTRACT FROM AUTHOR]

The mutant form of the guanosine triphosphatase (GTPase) KRAS is a key driver in human tumors but remains a challenging therapeutic target, making KRASMUT cancers a highly unmet clinical need. Here, we report a class of bottlebrush polyethylene glycol (PEG)-conjugated antisense oligonucleotides (ASOs) for potent in vivo KRAS depletion. Owing to their highly branched architecture, these molecular nanoconstructs suppress nearly all side effects associated with DNA-protein interactions and substantially enhance the pharmacological properties of the ASO, such as plasma pharmacokinetics and tumor uptake. Systemic delivery to mice bearing human non-small-cell lung carcinoma xenografts results in a significant reduction in both KRAS levels and tumor growth, and the antitumor performance well exceeds that of current popular ASO paradigms, such as chemically modified oligonucleotides and PEGylation using linear or slightly branched PEG. Importantly, these conjugates relax the requirement on the ASO chemistry, allowing unmodified, natural phosphodiester ASOs to achieve efficacy comparable to that of chemically modified ones. Both the bottlebrush polymer and its ASO conjugates appear to be safe and well tolerated in mice. Together, these data indicate that the molecular brush-ASO conjugate is a promising therapeutic platform for the treatment of KRAS-driven human cancers and warrant further preclinical and clinical development. [ABSTRACT FROM AUTHOR]

Various structural defects deteriorate tunnel operation status and threaten public safety. Current tunnel inspection methods face problems of low efficiency, high equipment expense, and difficult data management. Combining the deep learning model and the 3D reconstruction method based on structure from motion (SfM), this paper proposes a novel SfM-Deep learning method for tunnel inspection. The high-quality 3D tunnel model is constructed by using images taken every 1 m along the longitudinal direction. The instance segmentation of leakage in longitudinal images is realized using the mask region-based convolutional neural network deep learning model. The SfM-Deep learning method projects the texture of the images after defect recognition to the 3D model and realizes the visualization of leakage defects. By projecting the model to the design cylindrical surface and expanding it, the tunnel leakage area is quantified. Through its practical application in a Shanghai metro shield tunnel, the reliability of the proposed method was verified. The novel SfM-Deep learning method can help engineers efficiently carry out intelligent tunnel detection. [ABSTRACT FROM AUTHOR]

Graphitic carbon nitride (g-C3N4), an appealing metal-free polymer, has featured in extensive research in heterogeneous Fenton-like reactions owing to its advantages of stable chemical and thermal properties, ease of structural regulation and unique redox ability. However, there are still some gaps in the understanding of the mechanism and fate of g-C3N4 and its derivatives in heterogeneous Fenton reaction degradation of contaminants. This paper gives systematic emphasis to the development and progress of g-C3N4 and its composites as catalysts in heterogeneous Fenton-like reactions. The main synthesis strategies of g-C3N4 composites are discussed, including calcination, hydrothermal method and self-assembly method. Then, the key catalytic properties of g-C3N4 in Fenton-like applications, including anchoring nanoparticles, increasing specific surface area and exposed active surface sites, as well as regulating charge transfer reactions, are highlighted. Special emphasis is placed on its multifunctional role in heterogeneous Fenton-like reactions and the mechanisms involved in the activation of hydrogen peroxide, persulfates, and photocatalytic activation of persulfate. Lastly, the existing challenges and possible development direction of g-C3N4-coupling Fenton reactions are proposed. It is believed that this paper will bring useful information for the development of graphitic carbon nitride in both laboratory studies and practical applications. [ABSTRACT FROM AUTHOR]

There was an investigation of the auxiliary role of convolutional neural network- (CNN-) based magnetic resonance imaging (MRI) image segmentation algorithm in MRI image-guided targeted drug therapy of doxorubicin nanomaterials so that the value of drug-controlled release in liver cancer patients was evaluated. In this study, 80 patients with liver cancer were selected as the research objects. It was hoped that the CNN-based MRI image segmentation algorithm could be applied to the guided analysis of MRI images of the targeted controlled release of doxorubicin nanopreparation to analyze the imaging analysis effect of this algorithm on the targeted treatment of liver cancer with doxorubicin nanopreparation. The results of this study showed that the upgraded three-dimensional (3D) CNN-based MRI image segmentation had a better effect compared with the traditional CNNbased MRI image segmentation, with significant improvement in indicators such as accuracy, precision, sensitivity, and specificity, and the differences were all statistically marked (p < 0.05). In the monitoring of the targeted drug therapy of doxorubicin nanopreparation for liver cancer patients, it was found that the MRI images of liver cancer patients processed by 3D CNN-based MRI image segmentation neural algorithm could be observed more intuitively and guided to accurately reach the target of liver cancer. The accuracy of targeted release determination of nanopreparation reached 80 ± 6.25%, which was higher markedly than that of the control group (66.6 ± 5.32%) (p < 0.05). In a word, the MRI image segmentation algorithm based on CNN had good application potential in guiding patients with liver cancer for targeted therapy with doxorubicin nanopreparation, which was worth promoting in the adjuvant treatment of targeted drugs for cancer. [ABSTRACT FROM AUTHOR]

Purpose: To provide a validated method to identify copy number variation (CNV) in regions of the Y chromosome of infertile men by next-generation sequencing (NGS). Methods: Semen analysis was used to determine the quality of semen and diagnose infertility. Deletion of the azoospermia factor (AZF) region in the Y chromosome was detected by a routine sequence-tagged-site PCR (STS-PCR) method. We then used the NGS method to detect CNV in the AZF region, including deletions and duplications. Results: A total of 326 samples from male infertility patients, family members, and sperm donors were studied between January 2011 and May 2017. AZF microdeletions were detected in 120 patients by STS-PCR, and these results were consistent with the results from NGS. In addition, of the 160 patients and male family members who had no microdeletions detected by STS-PCR, 51 cases were found to exhibit Y chromosome structural variations by the NGS method (31.88%, 51/160). No microdeletions were found in 46 donors by STS-PCR, but the NGS method revealed 11 of these donors (23.91%, 11/46) carried structural variations, which were mainly in the AZFc region, including partial deletions and duplications. Conclusion: The established NGS method can replace the conventional STS-PCR method to detect Y chromosome microdeletions. The NGS method can detect CNV, such as partial deletion or duplication, and provide details of the abnormal range and size of variations. [ABSTRACT FROM AUTHOR]

Background: Cryptic balanced translocations often evade detection by conventional cytogenetics. The preimplantation genetic testing (PGT) technique can be used to help carriers of balanced translocations give birth to healthy offspring; however, for carriers of cryptic balanced translocations, there is only one report about trying assisted reproduction using the PGT technique but with no pregnancy. Case presentation: A couple had 3 births out of 4 pregnancies, and all died very young, with two of them having both cerebral palsy and glaucoma. The husband with oligoasthenospermia was found to be a cryptic balanced translocation carrier for t (9,13) (p24.3, q31.3) with G-banding, FISH (fluorescence in-situ hybridization), and MicroSeq techniques; live birth of a healthy baby girl was achieved with PGT/NGS (next-generation sequencing) for the couple. Conclusion: Here, we report for the first time a successful live birth of a healthy baby through the PGT technique for a family in which the husband is a carrier of the cryptic balanced translocation t (9,13) (p24.3, q31.3), presumably causative for cerebral palsy and glaucoma. Our study showed that the PGT/NGS technique can effectively help families with a cryptic balanced translocation have healthy offspring. [ABSTRACT FROM AUTHOR]

Future Internet of Things (IoTs) networks will consist of a Hybrid Access Point (HAP) that powers devices via Radio Frequency (RF) signals. These devices harvest RF-energy and are tasked with monitoring target(s) such as vehicles at key locations. In order to maximize their expected targets monitoring time, this paper considers the problem of optimizing the HAP's transmit power, and the active time of devices. We formulate a Stochastic Program (SP) and solve it using the Sample Average Approximation method. We also present a sequential Monte-Carlo based reinforcement learning method or SMC-L to learn sensor activation time. Our results show that (i) the confidence interval upper bound of the solution derived by the SP is affected by the number of samples that represent targets appearance time, (ii) increasing the sensing range of devices affects the total expected target monitoring time, (iii) the learning speed of SMC-L is affected by its exploration rate, and (iv) SMC-L does not utilize the energy of devices fully under poor channel conditions. [ABSTRACT FROM AUTHOR]

In reviewing the evacuation problem of mass passenger flow in urban rail transit transfer stations, the cooperative evacuation strategy considering urban rail transit and emergency bus simultaneously is found to be an efficient way. In this work, firstly, the dynamic characteristics of mass passenger flow are analyzed based on the abstraction and simplification of major entities of urban rail transit, including passengers, stations and trains. Then, the operations of the urban rail transit system are modeled, including the boarding, landing and transferring processes of the passengers and the status updating flows of the trains and stations. To realize the cooperative evacuation, a multi-objective optimization model considering the evacuation speed, the number of passengers transferred, and the amount of emergency buses is proposed. The NSGA-II algorithm is adopted to solve the proposed model, which can balance the theoretical validity and computational convenience. Last, the proposed strategy is applied in a real-life case based on the Shanghai Metro line, and the results verify its effectiveness and efficiency. [ABSTRACT FROM AUTHOR]

Refining oil contaminants are complex and cause serious harm to the environment. Remediation of refining oil-contaminated soil is challenging but has significant impact in China. Two plant species Agropyron fragile (Roth) P. Candargy and Avena sativa L. and one bacterium Bacillus tequilensis ZJ01 were used to investigate their efficiency in remediating the refining oil-polluted soil sampled from an oil field in northern China. The simulated experiments of remediations by A. fragile or A. sativa alone and A. fragile or A. sativa combined with B. tequilensis ZJ01 for 39 days and by B. tequilensis ZJ01 alone for 7 days were performed in the laboratory, with B. tequilensis ZJ01 added before or after the germination of seeds. Seed germination rates and morphological characteristics of the plants, along with the varieties of oil hydrocarbons in the soil, were recorded to reflect the remediation efficiency. The results showed that the contamination was weakened in all experimental groups. A. sativa was more sensitive to the pollutants than A. fragile, and A. fragile was much more resistant to the oil hydrocarbons, especially to aromatic hydrocarbons. Adding B. tequilensis ZJ01 before the germination of seeds could restrain the plant growth while adding after the germination of A. fragile seeds notably improved the remediation efficiency. The degradation rate of oil hydrocarbons by B. tequilensis ZJ01 alone was also considerable. Together, our results suggest that the unitary remediation by B. tequilensis ZJ01 and the binary remediation by A. fragile combined with B. tequilensis ZJ01 added after the germination of seeds are recommended for future in situ remediations. [ABSTRACT FROM AUTHOR]

Background Subintimal plaque modification (SPM) is often performed to restore antegrade flow and facilitate subsequent lesion recanalization. This study aimed to compare the safety and efficacy of modified SPM with traditional SPM. Methods A total of 1454 consecutive patients who failed a chronic total occlusion percutaneous coronary intervention (CTO PCI) attempt and underwent SPM from January 2015 to December 2019 at our hospital were reviewed retrospectively. Fifty-four patients who underwent SPM finally were included in this study. We analyzed the outcomes of all the patients, and the primary endpoint was recanalization rate, which was defined as Thrombolysis in Myocardial Infarction (TIMI) grades 2-3 flow on angiography 30 to 90 days post-procedure. Results The baseline characteristics were similar between the two groups. In the follow-up, the recanalization rate was noticeably higher in the modified SPM group compared with the traditional SPM group (90.9% vs. 62.5%, P < 0.05). The proposed strategy in the modified group was more aggressive, including a larger balloon size (1.83 ± 0.30 vs. 2.48 ± 0.26 mm, P < 0.05) and longer subintimal angioplasty (0.59 ± 0.16 vs. 0.92 ± 0.12 mm, P < 0.05). Also, the common use of a Stingray balloon and guide catheter extension resulted in improvement of patients in the modified SMP group (12.5% vs. 100%, P < 0.05). Conclusion Modified SPM, which is associated with a high likelihood of successful recanalization, is an effective and safe CTO PCI bail out strategy. [ABSTRACT FROM AUTHOR]

In this paper, we consider a Hybrid Access Point (HAP) that supplies energy to sensor devices tasked with monitoring one or more mobile targets with a known trajectory. The HAP's goal is to maximize a Quality of Monitoring (QoM) metric that is a ratio of the following quantities: (i) distance between a sensor device and a target, and (ii) duration in which a target is monitored by a sensor device. We formulate a Mixed Integer Linear Program (MILP) and use it to determine the subset of sensor devices to be charged in each time slot, their activation time, and the transmission or charging power used by the HAP. We also propose a Cross-Entropy (CE) approach and a heuristic algorithm called Energy Reallocation Linear Programming Approximation (ERLPA) to select sensor devices for charging in large-scale networks. Our results show that (i) QoM is affected by the energy requirement of sensor devices, energy storage capacity, number of channels available to the HAP, sensor sensing radius and energy conversion efficiency of sensor devices, and (ii) both the CE method and ERLPA are capable of producing schedules that are near optimal. [ABSTRACT FROM AUTHOR]

The preparation of an amino-functionalized hybrid monolithic column (TEOS-co-AEAPTES) via one-pot co-condensation of tetraethoxysilane (TEOS) and N-(β-aminoethyl)-γ-aminopropyltriethoxysilane (AEAPTES) in a capillary is descibed. It was used as solid-phase microextraction (SPME) matrix followed by inductively coupled plasma-mass spectrometry (ICP-MS) for determination of trace metals. Under optimum conditions, the amino-functionalized SPME material can simultaneously retain Cu(II), Zn(II), Au(III), and Pb(II) with adsorption capacities of 148, 60, 81, and 64 μg m−1, respectively. Subsequently, these four metal ions can be quantitatively eluted using 1 mol L−1 HNO3 containing 1% thiourea. The retention mechanism of Cu(II), Zn(II), Au(III), and Pb(II) on the amino-functionalized hybrid monolith was explained as the combination of electrostatic and coordination interactions. With a 10-fold enrichment factor, the calibration curves were established in the range 0.5–100 μg L−1 with linear correlation coefficients above 0.9943 and the limits of quantitation were 0.05 μg L−1 for four target analytes. The limits of detection were 0.006, 0.012, 0.004, and 0.007 μg L−1 for Cu(II), Zn(II), Au(III), and Pb(II), respectively. The protocol was validated by analyzing Certified Reference Materials including standard sediment, soil, and nickel ore, and the results were in good agreement with their certified values. The relative standard deviations of the method were in the range 0.22–17.6%. The recoveries of the four metal ions in spiked samples were in the range 88.0–113.8%. Compared to direct ICP-MS determination, the proposed in-tube SPME procedure can effectively eliminate the interference from complex matrix, especially from those ores with very high content of main metal to improve the accuracy of analysis. Therefore the method is suitable for the simultaneous determination of ultra-trace Cu(II), Zn(II), Au(III), and Pb(II) in environmental and mineral samples. [ABSTRACT FROM AUTHOR]

Si-Wei-Qing-Gan-Tang (SWQGT) is a Chinese medicine formula that is widely used as a folk remedy of herbal tea for the treatment of chronic hepatitis, like non-alcoholic steatohepatitis (NASH), around Ganzhou City (Jiangxi province, China). However, the underlying mechanisms of this formula against NASH are still unknown. This study aimed to explore the effect and mechanisms of SWQGT against NASH. A network pharmacology approach was used to predict the potential mechanisms of SWQGT against NASH. Then a rat model of NASH established by feeding the methionine and choline deficient (MCD) diet was used to verify the effect and mechanisms of SWQGT on NASH in vivo. SWQGT (1 g/kg/d and 3 g/kg/d) were given by intragastric administration. Body weight, liver weight, serum biochemical indicators, liver triglyceride and total cholesterol were all measured. Tumor necrosis factor-α (TNF-α), Interleukin (IL)-1β, IL-6 levels in the livers were evaluated using ELISA. Hematoxylin and eosin (HE) and Oil Red O staining were used to determine histology, while western blot was used to assess the relative expression levels of the nuclear factor-κB (NF-κB) pathway- and autophagy-related proteins. Functional and pathway enrichment analyses revealed that SWQGT obviously influenced inflammation-related signal pathways in NASH. Furthermore, in vivo experiment showed that SWQGT caused a reduction in liver weight and liver index of MCD diet-fed rats. The formula also helped to reduce hepatomegaly and improve pathological liver changes and hepatic steatosis. SWQGT likewise reduced liver TNF-α, IL-1β, and IL-6 levels and down-regulated p-NF-κB p65, p-p38 MAPK, p-MEK1/2, p-ERK1/2, p-mTOR, and p62, while up-regulating p-ULK1 and LC3II protein expression levels. SWQGT could improve NASH in MCD diet-fed rats, and this effect may be associated with its down-regulation of NF-κB and activation of autophagy. [ABSTRACT FROM AUTHOR]

Background: Current therapies for multiple myeloma (MM) are associated with toxicity and resistance, highlighting the need for novel effective therapeutics. Berberine (BBR), a botanical alkaloid derived from several Berberis medicinal plants, has exhibited anti-tumor effects, including against multiple myeloma (MM); however, the molecular mechanism underlying the anti-MM effect has not been previously described. This study aimed to identify the target of berberine and related mechanisms involved in its therapeutic activity against MM. Results: Here, we demonstrated that BBR treatment killed MM cells in vitro and prolonged the survival of mice bearing MM xenografts in vivo. A screening approach integrating surface plasmon resonance (SPR) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified UHRF1 (ubiquitin-like with PHD and RING Finger domains 1) as a potential target of BBR. Combining molecular docking and SPR analysis, we confirmed UHRF1 as a BBR-binding protein and discovered that BBR binds UHRF1 in the tandem tudor domain and plant homeodomain (TTD-PHD domain). BBR treatment induced UHRF1 degradation via the ubiquitin-dependent proteasome system and reactivated p16INK4A and p73 in MM cells. Overexpression of UHRF1 promoted the MM cell proliferation and rendered MM cells more resistant to BBR, while silencing of UHRF1 with siRNA attenuated BBR-induced cytotoxicity. Conclusions: In summary, our study has identified UHRF1 as a direct target of BBR and uncovered molecular mechanisms involved in the anti-MM activity of BBR. Targeting UHRF1 through BBR may be a novel therapeutic strategy against MM. [ABSTRACT FROM AUTHOR]

To explore the interaction of alkylamine surfactants with kaolinite, the density functional theory (DFT) method was used to calculate the single adsorption of different methylamine cation on kaolinite basal surfaces and the competitive adsorption of methylamine cation and water molecule on kaolinite basal surfaces, respectively. Different methylamine cations can adsorb on kaolinite basal surfaces by electrostatic interaction and hydrogen bonds, and the methylamine cations more easily adsorbed on kaolinite Si-O surface. In the case of competitive adsorption with water molecule, the methylamine cation is capable of flushing out the surrounding water molecule to get rid of its steric effect and stably adsorbing on kaolinite basal surfaces, and the adsorption state of the competitive adsorption system is more stable. The adsorption mechanism of methylamine cation on kaolinite basal surface should be the result of electrostatic interaction and hydrogen bonds, and the electrostatic interaction plays the main role. [ABSTRACT FROM AUTHOR]

In order to solve the nonlinear uncertain system of ship heading control and deal with the influence of interference factors such as external environment and ship speed on ship heading control, this paper proposes a ship controller design method combining the backstepping technique and the adaptive control theory considering the robustness, at first, it describes the mathematical model for ship motion and proposes a nonlinear ship heading control system mathematical model considering the influence of external interference factors; Then, on this basis, the paper designs a ship heading adaptive nonlinear controller with robustness function and achieves the adaptive tracking of ship heading. Simulation results show that the heading control system with adaptive robustness can eliminate influence of certain interferences. The research results indicate that the study of this paper is of great significance for further promoting the development of ship heading nonlinear control theory. [ABSTRACT FROM AUTHOR]

Lonicera japonica flos (LJF) is widely used for different health benefits in various external preparations in traditional medicines, cosmetics and personal care products. However, its components that are absorbed via the skin remain poorly studied. In the present work, the skin permeability coefficient (log Kp) of known chemical components of LJF was computed using a linear free-energy relationship equation. The results showed that the potential skin-permeating components (SPCs) whose log Kp was suggested to exceed −7.0 included flavonoids, essential oils, phenols and phenolic acids, and triterpenoids, but only a few glycosides. It was further revealed that highly hydrophilic glycosyl groups produced a very adverse effect on the skin absorption of glycoside molecules. The SPCs of LJF methanol extract were collected via in vitro skin permeation experiments, and analysed by LC-MS/MS using an untargeted strategy. A total of 43 SPCs were found, including 13 compounds from the major component classes, namely 9 non-glycoside flavonoids, 1 organic acid (i.e., chlorogenic acid) and 3 iridoid glycosides. The chromatographic peak areas indicated that the detectable absorption of chlorogenic acid and iridoid glycosides with poor skin permeability was ascribed to their high contents in the plant. The experimental observations were in good agreement with the potential SPCs screened, which suggested that the skin permeability of compounds was not influenced by coexisting compounds in LJF. This was also confirmed by the fact that no significant change in skin electrical resistance was observed after the application of LJF methanol extract. To sum up the findings, the flavonoids and essential oils in LJF can enter the body through the skin in terms of good skin permeability and relatively high contents, presumably being effective components of the external preparations. On the other hand, the chlorogenic acids, iridoid glycosides and triterpenoids (mostly present as saponins) are delivered only marginally even when high doses are applied. [ABSTRACT FROM AUTHOR]

In this work, a novel carboxyl-functionalized organic–inorganic hybrid monolithic column (TMOS-co-CES) was prepared via one-pot co-condensation of carboxyethylsilanetriol sodium salt (CES) and tetramethoxysilane (TMOS). The TMOS-co-CES monolithic column was used as a needle-solid phase microextraction (SPME) matrix followed by using an inductively coupled plasma mass spectrometer (ICP-MS) for simultaneous speciation analysis of inorganic chromium and antimony. Various parameters of SPME operation and analytical performance were investigated systematically. Under the optimum conditions, the TMOS-co-CES column can selectively adsorb low-valent chromium (Cr(III)) and antimony (Sb(III)) without adsorbing high-valent species (Cr(VI) and Sb(V)) over a wide pH range (4.0–9.0). In the elution step, the captured Cr(III) and Sb(III) can be substantially completely eluted using 10% nitric acid (v/v) as the eluent. The TMOS-co-CES monolithic column based SPME protocol has the merits of facile preparation, low cost, selective adsorption and high adsorption capacity. In addition, the TMOS-co-CES column operates under milder elution conditions, offers higher recovery for antimony species, and is more compatible with the ICP-MS instrument, compared with a previously reported thiol-functionalized hybrid monolithic column taking speciation analysis of antimony as an example. Therefore, the developed TMOS-co-CES monolithic column is more suitable than the thiol-functionalized monolithic column for the speciation analysis of chromium and antimony in environmental waters. [ABSTRACT FROM AUTHOR]

The trans-Golgi network (TGN) is an essential tubular-vesicular organelle derived from the Golgi and functions as an independent sorting and trafficking hub within the cell. However, the molecular regulation of TGN biogenesis remains enigmatic. Here we identified an Arabidopsis mutant loss of TGN (lot) that is defective in TGN formation and sterile due to impaired pollen tube growth in the style. The mutation leads to overstacking of the Golgi cisternae and significant reduction in the number of TGNs and vesicles surrounding the Golgi in pollen, which is corroborated by the dispersed cytosolic distribution of TGN-localized proteins. Consistently, deposition of extracellular pectin and plasma membrane localization of kinases and phosphoinositide species are also impaired. Subcellular localization analysis suggests that LOT is localized on the periphery of the Golgi cisternae, but the mutation does not affect the localization of Golgi-resident proteins. Furthermore, the yeast complementation result suggests that LOT could functionally act as a component of the guanine nucleotide exchange factor (GEF) complex of small Rab GTPase Ypt6. Taken together, these findings suggest that LOT is a critical player for TGN biogenesis in the plant lineage. [ABSTRACT FROM AUTHOR]

The first-line treatment for metastatic esophageal squamous cell cancer (ESCC) is a platinum- or fluorouracil-based agent, followed by later treatment with taxanes or irinotecan. However, there is still no standard third-line treatment for patients with metastatic ESCC. We present a 62-year-old man initially diagnosed with locally advanced ESCC. After esophagectomy, the patient was administrated with six cycles of docetaxel and cisplatin combined with radiotherapy. After 8.0 months, computed tomography showed the left cervical lymph node metastasis. However, the metastatic lymph node was not significantly shrunk after locally palliative radiotherapy and the patient was intolerant of irinotecan as second-line systemic therapy. Then, the patient was rechallenged with six cycles of docetaxel combined with apatinib (an oral tyrosine kinase inhibitor to vascular endothelial growth factor receptor 2 [VEGFR2]), followed by single dose of apatinib as maintenance therapy. According to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard, partial response was achieved in this case after treating with docetaxel combined with apatinib. Now, the progression-free survival of this patient has been 7.5 months. After administrating with apatinib for 2 weeks, hypertension (grade III) was observed. Thus, the dose of apatinib was decreased from 850 to 500 mg and then the adverse effects were controllable and tolerable. In conclusion, apatinib with concurrent docetaxel provided potential efficacy as a salvage treatment for patients with metastatic ESCC. To our knowledge, this is the first case of ESCC who responded to apatinib combined with docetaxel. [ABSTRACT FROM AUTHOR]

Abstract: Background: Berberine downregulated miR‐19a/92a cluster expression in multiple myeloma (MM) cells. Methods: The cell viability of MM cells after berberine treatment was measured by CCK8 assay. qRT‐PCR assay validated miR‐19a/92a expression in multiple myeloma cells. TAM database analyzed miR‐19a/92a‐associated disease. miREnvironment database revealed that effects of environmental factors on the miR‐19a/92a cluster. By targeting the seed region in the miRNA, the role of t‐anti‐miR‐19a/92a cluster was evaluated by cell proliferation, migration, and colony formation. Results: Berberine inhibited the cell viability of MM cells and downregulated the expression of miR‐19a/92a. Seven kinds of hematological malignancies are closely associated with miR‐19a/92a expression. By targeting the seed region of the miRNA, t‐anti‐miR‐19a/92a significantly inhibits multiple myeloma cell proliferation, migration, and colony formation. Conclusion: Our findings may exhibit that miR‐19a/92a cluster is a therapeutic target for MM and provide new mechanistic insight into the anti‐MM effects of certain compounds in traditional Chinese herbal medicines. [ABSTRACT FROM AUTHOR]

Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C60 SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C60 SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs. [ABSTRACT FROM AUTHOR]