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Over the past decade, the concept of a circular economy has increasingly gained attention as a framework for guiding businesses and policymakers. Given its significant environmental impact, the building industry plays a pivotal role in the transition toward a circular economy. To address this, our review proposes a bio-based building material, specifically straw bale, which elaborates on the circularity of bio-based buildings based on the 3R principles of a circular economy: reduce, reuse, and recycle. In terms of the "reduce" principle, straw-bale buildings can reduce construction waste, the environmental impact, energy requirements, and carbon emissions. Regarding the "reuse" principle, straw-bale buildings utilize agricultural waste resources and are easily disassembled due to their prefabrication. As for the "recycle" principle, straw-bale buildings can undergo physical, biological, and biochemical conversion processes (thermochemical conversion), yielding both wooden composite boards and potential biogas and biomass fuels for electricity and heating. This study evaluates the contribution of straw packaging construction and the use of straw as a raw material, using the 3R principles to determine future research opportunities for the construction industry to achieve a circular economy. The results of this study offer circular economy solutions and interdisciplinary research insights for researchers and practitioners interested in the building environment. [ABSTRACT FROM AUTHOR]

A high porosity micropore arrayed parylene membrane is a promising device that is used to capture circulating and exfoliated tumor cells (CTCs and ETCs) for liquid biopsy applications. However, its fabrication still requires either expensive equipment or an expensive process. Here, we report on the fabrication of high porosity (>40%) micropore arrayed parylene membranes through a simple reactive ion etching (RIE) that uses photoresist as the etching mask. Vertical sidewalls were observed in etched parylene pores despite the sloped photoresist mask sidewalls, which was found to be due to the simultaneous high DC-bias RIE induced photoresist melting and substrate pedestal formation. A theoretical model has been derived to illustrate the dependence of the maximum membrane thickness on the final pore-to-pore spacing, and it is consistent with the experimental data. A simple, yet accurate, low number (<50) cell counting method was demonstrated through counting cells directly inside a pipette tip under phase-contrast microscope. Membranes as thin as 3 μm showed utility for low number tumor cell capture, with an efficiency of 87–92%. [ABSTRACT FROM AUTHOR]

Multi-layer lightweight composite structures are widely used in the field of aviation and aerospace during the processes of manufacturing and use, and, as such, they inevitably produce defects, damage, and other quality problems, creating the need for timely non-destructive testing procedures and the convenient repair or replacement of quality problems related to the material. When using terahertz non-destructive testing technology to detect defects in multi-layer lightweight composite materials, due to the complexity of their structure and defect types, there are many signal characteristics of terahertz waves propagating in the structures, and there is no obvious rule behind them, resulting in a large gap between the recognition results and the actual ones. In this study, we introduced a U-Net-BiLSTM network that combines the strengths of the U-Net and BiLSTM networks. The U-Net network extracts the spatial features of THz signals, while the BiLSTM network captures their temporal features. By optimizing the network structure and various parameters, we obtained a model tailored to THz spectroscopy data. This model was subsequently employed for the identification and quantitative analysis of defects in multi-layer lightweight composite structures using THz non-destructive testing. The proposed U-Net-BiLSTM network achieved an accuracy of 99.45% in typical defect identification, with a comprehensive F1 score of 99.43%, outperforming the CNN, ResNet, U-Net, and BiLSTM networks. By leveraging defect classification and thickness recognition, this study successfully reconstructed three-dimensional THz defect images, thereby realizing quantitative defect detection. [ABSTRACT FROM AUTHOR]

The thermomechanical properties of carbon fiber reinforced silicon carbide ceramic matrix composites (Cf/SiC CMCs) were studied up to 2000 °C using high-temperature in situ flexural testing in argon. The CMC specimens were fabricated using an ultrahigh concentration (66 vol%) aqueous slurry containing nano-sized silicon carbide powder. The SiC powder compacts were obtained by drying the slurry and were densified using the precursor impregnation and pyrolysis (PIP) method with field assisted sintering technology/spark plasma sintering (FAST/SPS). The high relative density of the SiC green body (77.6%) enabled densification within 2.5 days using four PIP cycles. In contrast, conventional PIP processes take over 7 days. The in situ flexural strength of the Cf/SiC CMC was 434 MPa at 1750 °C, which was 84% higher than the room temperature value. The value further increased to 542 MPa at 2000 °C. Possible mechanisms to explain the excellent strength of the CMC at elevated temperatures are discussed. [ABSTRACT FROM AUTHOR]

The road traffic state is usually analyzed from a temporal and macroscopic perspective; however, traffic flow parameters, such as density and spacing, can explain the evolution of traffic states from the microscopic perspective and the spatial distribution of vehicles in lanes. In this paper, we attempt to take both temporal and spatial characteristics into consideration simultaneously, and a parameter is defined as the traffic spatiotemporal state of urban road sections to represent the operational status of road traffic, using advanced prediction techniques to estimate its short-term trends. An estimation method is constructed for the traffic spatiotemporal state considering travel times, speeds, and queuing situations from temporal and spatial perspectives. Then, based on Takens' theorem and the single variable phase space, the phase space of multiple traffic parameters is reconstructed and the chaotic characteristics are analyzed. Next, an LSTM prediction model is constructed based on the phase space reconstruction of multiple variables, and the traffic parameters are predicted by empirical analysis. The results show the proposed estimation method has a significantly improved accuracy. Finally, combined with RFID data, the traffic spatiotemporal state of the case section is calculated, which provides a theoretical basis and practical reference for road traffic state evaluations. [ABSTRACT FROM AUTHOR]

Simple Summary: The objective of this study was to investigate the association between IL-8 rs4073, rs2227306, rs2227543, and rs1126647 genotypes and the risk of colorectal cancer (CRC) in the Taiwanese population. Our findings reveal that the A allele and AA genotype of IL-8 rs4073 are significantly associated with an increased susceptibility to CRC in Taiwan. This observation provides further evidence of the complex interplay between inflammation and carcinogenesis in CRC development. Furthermore, individuals with the AA genotype exhibit significantly higher levels of serum IL-8 expression. Combining IL-8 rs4073 genotyping with the assessment of IL-8 levels may have potential benefits in terms of the precise risk evaluation and early detection of CRC among patients. Interleukin-8 (IL-8), a pro-inflammatory cytokine, is upregulated in CRC and plays an important role in its development and progression. Genetic variants in the IL-8 gene may impact the risk of CRC by modulating IL-8 levels. Our primary objective was to investigate the role of IL-8 genotypes in the development of CRC. To accomplish this, we employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze the genotypes of IL-8 rs4017, rs2227306, rs2227543, and rs1126647 in 362 CRC patients and 362 controls. Additionally, we evaluated the interactions between these genotypes and factors such as age, gender, smoking, alcohol consumption, and body mass index (BMI) status in relation to the risk of CRC. Furthermore, we utilized quantitative reverse transcription-PCR to measure the serum IL-8. The results demonstrated a significant difference in the distribution of rs4017 genotypes between the control and case groups (p for trend = 0.0059). Logistic regression analysis revealed that individuals with variant AA genotype had a 1.92-fold higher CRC risk (95% confidence interval [CI] = 1.28–2.89, p = 0.0023). Moreover, carriers of the IL-8 rs4017 AT + AA genotypes exhibited a significant association with CRC risk (odds ratio [OR] = 1.39, 95% CI = 1.02–1.91, p = 0.0460). Additionally, individuals with IL-8 rs4017 AA genotype displayed significantly elevated serum IL-8 compared to those with TT genotype at a 1.73–fold level (p < 0.0001), indicating a correlation between genotype and phenotype. In conclusion, the genotypes of IL-8 rs4017, along with their associated expression levels, can potentially serve as predictive markers for the risk of CRC. [ABSTRACT FROM AUTHOR]

Objective: We performed a systematic review and meta-analysis of the efficacy and safety of nusinersen and risdiplam in the treatment of spinal muscular disease (SMA). Methods: We screened the literature published in Pubmed, Web of Science, Embase, and Cochrane before July 2023 to conduct randomized controlled trials to test the treatment of SMA patients with nusinersen and risdiplam. The data were analyzed using Review Manager 5.4 software and Stata version 15.0 software. Results: A total of six randomized controlled trials were included, involving 728 SMA patients, to synthesize evidence. It is reported that nusinersen treatment was beneficial for increasing the score of the Hammersmith Functional Motor Scale—Expanded (HFMSE) (WMD: 4.90; 95% CI: 3.17, 6.63; p < 0.00001), Revised Upper Limb Module (RULM) (WMD: 3.70; 95% CI: 3.30, 4.10; p < 0.00001), and Hammersmith Infant Neurological Evaluation Section 2 (HINE-2) (WMD: 5.21; 95% CI: 4.83, 5.60; p < 0.00001). In addition, the risdiplam treatment group also showed statistically significant improvements in the HFMSE score (WMD:0.87; 95% CI: 0.05, 1.68; p = 0.04), the 32-item Motor Function Measure (MFM32) (WMD:1.48; 95% CI: 0.58, 2.38; p = 0.001), and (WMD: 1.29; 95% CI: 0.57, 2.01; p = 0.0005). Nusinersen and risdiplam did not cause a statistically significant increase in the RULM score for adverse events (OR: 0.93; 95% CI: 0.51, 1.7; p = 0.82) and for severe adverse events (OR: 0.77; 95% CI: 0.47, 1.27; p = 0.31). Conclusion: Our analysis found that nusinersen and risdiplam treatment showed clinically meaningful improvement in motor function and a similar incidence rate of adverse events compared with the placebo. Further research should be carried out to provide a direct comparison between the two drugs in terms of safety and efficacy. [ABSTRACT FROM AUTHOR]

Background and Objectives: The modification of histone acetylation plays a vital role in regulating tumor occurrence and development, but the interaction between histone acetylation modulator genes and the liver hepatocellular carcinoma (LIHC) microenvironment, as well as immunotherapy, has not been investigated. Materials and Methods: Analysis of all statistical data was carried out using R software (Version 4.2.0) and the online tool Sangerbox. Comprehensive bioinformatics analysis, including signature construction and validation, functional analyses, immune and genomic features analyses, and immunotherapy prediction analyses, were performed to explore the prognostic and therapeutic role of histone acetylation modulator genes in LIHC development and progression. Results: The LIHC cohort from The Cancer Genome Atlas (TCGA) database was selected as the training cohort; the GSE76427 cohort from the Gene Expression Omnibus (GEO) database and the LIRI-JP cohort from the International Cancer Genome Consortium (ICGC) database were selected as the validation cohorts. The histone acetylation modulator gene-based prognostic signature was constructed and validated successfully. Immune infiltration analysis showed that most immune cells and immune functions were enriched in patients with high histone acetylation risk scores (HARS). Additionally, high levels of checkpoint inhibitors (ICIs) and human leukocyte antigens (HLAs) were also observed in high HARS patients. Meanwhile, TIDE algorithm analysis was conducted to explore the relationship between HARS and immunotherapy response, and submap algorithm analysis was used for the verification of the results, from which we found that high HAPS patients were more likely to respond to immunotherapy. Conclusions: Our findings revealed that the histone acetylation modulator genes, particularly for KAT21, SIRT6, and HAT1, may have the potential to function as a new prognostic marker and therapeutic target for LIHC. [ABSTRACT FROM AUTHOR]

We aimed to investigate the association between genotypes for mir146a and mir196a-2 and the risk of developing colorectal cancer (CRC). We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the mir146a rs2910164 and mir196a-2 rs11614913 genotypes in 362 CRC patients and 362 controls. We also assessed the interactions between these genotypes and age, gender, smoking, alcohol consumption, and BMI status on CRC risk. Additionally, the serum expression level of mir196a-2 was quantified using quantitative reverse transcription-PCR. Our findings demonstrated that among the controls, the proportions of TT, CT, and CC genotypes of mir196a-2 rs11614913 were 32.3%, 48.1%, and 19.6%, respectively. As for the cases, the proportions were 24.6%, 45.0%, and 30.4%, respectively. Logistic regression analysis revealed that the CC genotype carriers had a 2.04-fold increased risk (95% confidence interval [CI] = 1.36–3.06, p = 0.0008). Furthermore, carriers of the CT + CC genotypes also exhibited a significant association with CRC risk (odds ratio [OR] = 1.46, 95% CI = 1.06–2.03, p = 0.0261). Moreover, carriers of the CC genotype had significantly higher serum levels of mir196a-2 compared to those with the TT genotype (p < 0.0001), indicating a genotype-phenotype correlation. No association was found regarding mir146a rs2910164. In conclusion, mir196a-2 rs2910164 genotypes, along with their associated expression, can serve as predictive markers for CRC risk. [ABSTRACT FROM AUTHOR]

The development of regenerative medicine provides new options for the treatment of end-stage liver diseases. Stem cells, such as bone marrow mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells (iPSCs), are effective tools for tissue repair in regenerative medicine. iPSCs are an appropriate source of hepatocytes for the treatment of liver disease due to their unlimited multiplication capacity, their coverage of the entire range of genetics required to simulate human disease, and their evasion of ethical implications. iPSCs have the ability to gradually produce hepatocyte-like cells (HLCs) with homologous phenotypes and physiological functions. However, how to induce iPSCs to differentiate into HLCs efficiently and accurately is still a hot topic. This review describes the existing approaches for inducing the differentiation of iPSCs into HLCs, as well as some challenges faced, and summarizes various parameters for determining the quality and functionality of HLCs. Furthermore, the application of iPSCs for in vitro hepatoprotective drug screening and modeling of liver disease is discussed. In conclusion, iPSCs will be a dependable source of cells for stem-cell therapy to treat end-stage liver disease and are anticipated to facilitate individualized treatment for liver disease in the future. [ABSTRACT FROM AUTHOR]

Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype–phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity. [ABSTRACT FROM AUTHOR]

Herpetin, an active compound derived from the seeds of Herpetospermum caudigerum Wall., is a traditional Tibetan herbal medicine that is used for the treatment of hepatobiliary diseases. The aim of this study was to evaluate the stimulant effect of herpetin on bone marrow mesenchymal stem cells (BMSCs) to improve acute liver injury (ALI). In vitro results showed that herpetin treatment enhanced expression of the liver-specific proteins alpha-fetoprotein, albumin, and cytokeratin 18; increased cytochrome P450 family 3 subfamily a member 4 activity; and increased the glycogen-storage capacity of BMSCs. Mice with ALI induced by carbon tetrachloride (CCl4) were treated with a combination of BMSCs by tail-vein injection and herpetin by intraperitoneal injection. Hematoxylin and eosin staining and serum biochemical index detection showed that the liver function of ALI mice improved after administration of herpetin combined with BMSCs. Western blotting results suggested that the stromal cell-derived factor-1/C-X-C motif chemokine receptor 4 axis and the Wnt/β-catenin pathway in the liver tissue were activated after treatment with herpetin and BMSCs. Therefore, herpetin is a promising BMSC induction agent, and coadministration of herpetin and BMSCs may affect the treatment of ALI. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99–2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46–3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype–phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA. [ABSTRACT FROM AUTHOR]

Accurate estimation of crop evapotranspiration (ETc) is crucial for effective irrigation and water management. To achieve this, support vector regression (SVR) was applied to estimate the daily ETc of spring maize. Random forest (RF) as a data pre-processing technique was utilized to determine the optimal input variables for the SVR model. Particle swarm optimization (PSO) was employed to optimize the SVR model. This study used data obtained from field experiments conducted between 2017 and 2019, including crop coefficient and daily meteorological data. The performance of the innovative hybrid RF–SVR–PSO model was evaluated against a standalone SVR model, a back-propagation neural network (BPNN) model and a RF model, using different input meteorological variables. The ETc values were calculated using the Penman–Monteith equation, which is recommended by the FAO, and used as a reference for the models' estimated values. The results showed that the hybrid RF–SVR–PSO model performed better than all three standalone models for ETc estimation of spring maize. The Nash–Sutcliffe efficiency coefficient (NSE), root mean square error (RMSE), mean absolute error (MAE) and coefficient of determination (R2) ranges were 0.956–0.958, 0.275–0.282 mm d−1, 0.221–0.231 mm d−1 and 0.957–0.961, respectively. It is proved that the hybrid RF–SVR–PSO model is appropriate for estimation of daily spring maize ETc in semi-arid regions. [ABSTRACT FROM AUTHOR]

Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to alleviate acute liver injury (ALI). Herpetfluorenone (HPF), as an active ingredient in the dried, mature seeds Herpetospermum caudigerum Wall, used in Tibetan medicine, has been proven to effectively alleviate ALI. Therefore, the purpose of this study was to determine whether HPF can promote the differentiation of BMSCs into HLCs and promote ALI recovery. Mouse BMSCs were isolated, and the BMSCs' differentiation into HLCs was induced by HPF and hepatocyte growth factor (HGF). Under the induction of HPF and HGF, the expression of hepatocellular specific markers and the accumulation of glycogen and lipids in the BMSCs increased, indicating that BMSCs successfully differentiated into HLCs. Then, the ALI mouse model was established, using carbon tetrachloride, followed by an intravenous injection of BMSCs. Then, only HPF was injected intraperitoneally, in order to verify the effect of HPF in vivo. In vivo imaging was used to detect the homing ability of HPF–BMSCs, and it was detected that HPF–BMSCs significantly increased the levels of serum AST, ALT and ALP in the liver of ALI mice, and alleviated liver cell necrosis, oxidative stress and liver pathology. In conclusion, HPF can promote the differentiation of BMSCs into HLCs and promote the recovery of ALI in mice. [ABSTRACT FROM AUTHOR]

Simple Summary: The innate immune system of insects can recognize various pathogens that invade insects and make rapid immune responses. However, excessive immune activation is detrimental to the survival of insects. Nub gene of the OCT/POU family plays an important role in regulating the intestinal IMD pathway. In this study, an important horticultural pest, Bactrocera dorsalis, was adopted to study its high adaptability in complex habitats. Through NCBI database analysis, we found that the BdNub gene of B. dorsalis produced two transcription isoforms, BdNubX1 and BdNubX2. After Gram-negative bacterium Escherichia coli with system infection, the immunoeffector genes of Imd signaling pathway, antimicrobial peptides Diptcin (Dpt), Cecropin (Cec), AttcinA (AttA), AttcinB (AttB) and AttcinC (AttC) were significantly up-regulated. The expression levels of antimicrobial peptide genes Dpt, Cec, AttA, AttB, and AttC were significantly up-regulated at 6 h and 9 h after intestinal infection with the Gram-negative bacterium Providencia rettgeri. RNAi showed that the silencing of the BdNubX1 and BdNubX2 genes could make the gut more sensitive to Providencia rettgeri infection, reduce the survival rate significantly, and cause changes in the gut microbiota's structure. These results suggest that the maintenance of immune balance plays an important role in B. dorsalis high invasiveness. Insects face immune challenges posed by invading and indigenous bacteria. They rely on the immune system to clear these microorganisms. However, the immune response can be harmful to the host. Therefore, fine-tuning the immune response to maintain tissue homeostasis is of great importance to the survival of insects. The Nub gene of the OCT/POU family regulates the intestinal IMD pathway. However, the role of the Nub gene in regulating host microbiota remains unstudied. Here, a combination of bioinformatic tools, RNA interference, and qPCR methods were adopted to study BdNub gene function in Bactrocera dorsalis gut immune system. It's found that BdNubX1, BdNubX2, and antimicrobial peptides (AMPs), including Diptcin (Dpt), Cecropin (Cec), AttcinA (Att A), AttcinB (Att B) and AttcinC (Att C) are significantly up-regulated in Tephritidae fruit fly Bactrocera dorsalis after gut infection. Silencing BdNubX1 leads to down-regulated AMPs expression, while BdNubX2 RNAi leads to increased expression of AMPs. These results indicate that BdNubX1 is a positive regulatory gene of the IMD pathway, while BdNubX2 negatively regulates IMD pathway activity. Further studies also revealed that BdNubX1 and BdNubX2 are associated with gut microbiota composition, possibly through regulation of IMD pathway activity. Our results prove that the Nub gene is evolutionarily conserved and participates in maintaining gut microbiota homeostasis. [ABSTRACT FROM AUTHOR]

Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The TERT-CLMPT1L locus on 5p15.33, the 4q23 ADH1B locus, and the LAMC3 locus on 9q34.12 were also consistent in the Taiwanese. We found two new independent loci on 6p21.32, rs401775 in SKIV2L gene and rs9267798 in TNXB gene. We also found two suggestive novel Taiwanese-specific loci near the TPRS1 gene on 8q23.3 and in the TMED3 gene on 15q25.1. This study identified both common and unique oral cancer susceptibility loci in the Taiwanese as compared to populations of European descent and shed significant light on the etiology of oral cancer in Taiwan. [ABSTRACT FROM AUTHOR]

LiDAR placement and field of view selection play a role in detecting the relative position and pose of vehicles in relocation maps based on high-precision map automatic navigation. When the LiDAR field of view is obscured or the LiDAR position is misplaced, this can easily lead to loss of repositioning or low repositioning accuracy. In this paper, a method of LiDAR layout and field of view selection based on high-precision map normal distribution transformation (NDT) relocation is proposed to solve the problem of large NDT relocation error and position loss when the occlusion field of view is too large. To simulate the real placement environment and the LiDAR obstructed by obstacles, the ROI algorithm is used to cut LiDAR point clouds and to obtain LiDAR point cloud data of different sizes. The cut point cloud data is first downsampled and then relocated. The downsampling points for NDT relocation are recorded as valid matching points. The direction and angle settings of the LiDAR point cloud data are optimized using RMSE values and valid matching points. The results show that in the urban scene with complex road conditions, there are more front and rear matching points than left and right matching points within the unit angle. The more matching points of the NDT relocation algorithm there are, the higher the relocation accuracy. Increasing the front and rear LiDAR field of view prevents the loss of repositioning. The relocation accuracy can be improved by increasing the left and right LiDAR field of view. [ABSTRACT FROM AUTHOR]

Brain-computer interface (BCI) can be used as a real-time bidirectional information gateway between the brain and machines. In particular, rapid progress in invasive BCI, propelled by recent developments in electrode materials, miniature and power-efficient electronics, and neural signal decoding technologies has attracted wide attention. In this review, we first introduce the concepts of neuronal signal decoding and encoding that are fundamental for information exchanges in BCI. Then, we review the history and recent advances in invasive BCI, particularly through studies using neural signals for controlling external devices on one hand, and modulating brain activity on the other hand. Specifically, regarding modulating brain activity, we focus on two types of techniques, applying electrical stimulation to cortical and deep brain tissues, respectively. Finally, we discuss the related ethical issues concerning the clinical application of this emerging technology. [ABSTRACT FROM AUTHOR]

The bonding structure is affected by environmental loads during use, causing internal stress in the adhesive layer, which leads to the debonding and expansion of the bonding layer. Therefore, it is important to accurately measure the stress distribution of the bonding layer to assess the life of the bonding structure. In this study, based on the transmission and reflection terahertz time-domain spectroscopy (THz-TDS) technique, the stress optical coefficients of a silicone adhesive were measured, and the calculation models of the transmission and reflection stress optical coefficients were derived. In the reflection calculation model, the caliper THz thickness measurement method was proposed to compensate for the thickness change of the silicone adhesive, under tensile stress. Under the transmission THz-TDS stress optical coefficient calculation model, the stress optical coefficient C of the silicone adhesive is 0.1142 ± 0.0057 MPa−1, and the stress optical coefficient C of the reflective system is 0.1135 ± 0.0051 MPa−1. The test results show that the reflective THz-TDS can also be used to measure the optical stress coefficient of the material, which compensates for the shortcomings of the traditional transmission measurement method, and lays a foundation for the characterization of the internal stress of the adhesive layer of the adhesive structure. [ABSTRACT FROM AUTHOR]

An astigmatic optical profilometer with a commercial optical pickup head provides benefits, such as high resolution, compact size, and low cost. To eliminate artifacts caused by complex materials with different reflectances, a z-axis modulation mode is proposed to obtain quantitative surface morphology by measuring S curves on all image pixels. Moreover, the slope of the linear region in the S curve shows a positive relationship with the surface reflectance. However, the slope was calculated using an offline curve fitting method, which did not allow real-time reflectance imaging. Furthermore, quantitative reflectance data were unavailable because of the lack of calibration. In this study, we propose a novel method for real-time reflectance imaging by measuring the amplitude of a focus error signal (FES). The calibration results displayed a linear relationship between the FES amplitude and reflectance. The reflectance image of a grating sample with chrome patterns on a glass substrate demonstrates accurate reflectance measurements with a micrometer spatial resolution. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a rare and highly lethal disease with few effective treatment options. Cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) are non-psychedelic components extracted from cannabis. These non-psychoactive compounds have shown anti-proliferative potential in other tumor models; however, the efficacy of CBD and CBG in CCA is unknown. Furthermore, two cell death pathways are implicated with CBD resulting in autophagic degeneration and CBG in apoptosis. HuCC-T1 cells, Mz-ChA-1 cells (CCA cell lines) and H69 cells (immortalized cholangiocytes), were treated with CBD and CBG for 24 to 48 h. The influence of these cannabinoids on proliferation was assessed via MTT assay. Apoptosis and cell cycle were evaluated via Annexin-V apoptosis assay and propidium iodide, respectively. The expression of proliferation biomarker Ki-67, apoptosis biomarker BAX, and autophagic flux biomarkers LC3b and LAMP1 were evaluated via immunofluorescence. Cell migration and invasion were evaluated via wound healing assay and trans-well migration invasion assays, respectively. The colony formation was evaluated via colony formation assay. In addition, the expression of autophagy gene LC3b and apoptosis genes BAX, Bcl-2, and cleaved caspase-3 were evaluated via Western blot. CBD and CBG are non-selective anti-proliferative agents yielding similar growth curves in CCA; both cannabinoids are effective, yet CBG is more active at lower doses. Low doses of CBD and CBG enhanced immortalized cholangiocyte activity. The reduction in proliferation begins immediately and occurs maximally within 24 h of treatment. Moreover, a significant increase in the late-stage apoptosis and a reduction in the number of cells in S stage of the cell cycle indicates both CBD and CBG treatment could promote apoptosis and inhibit mitosis in CCA cells. The fluorescent expression of BAX and LC3b was significantly enhanced with CBD treatment when compared to control. LAMP1 and LC3b colocalization could also be observed with CBD and CBG treatment indicating changes in autophagic flux. A significant inhibition of migration, invasion and colony formation ability was shown in both CBD and CBG treatment in CCA. Western blot showed an overall decrease in the ratio of anti-apoptotic protein Bcl-2 with respect to pro-apoptotic protein BAX with CBG treatment. Furthermore, CBD treatment enhanced the expression of Type II cell death (autophagic degeneration) protein LC3b, which was reduced in CBG-treated CCA cells. Meanwhile, CBG treatment upregulated Type I cell death (programmed apoptosis) protein cleaved caspase-3. CBD and CBG are effective anti-cancer agents against CCA, capable of inhibiting the classic hallmarks of cancer, with a divergent mechanism of action (Type II or Type I respectively) in inducing these effects. [ABSTRACT FROM AUTHOR]

During terahertz (THz) non-destructive testing (NDT), multiple echoes from the sample interface reflection signals are mixed with the detection signals, resulting in signal distortion and affecting the accuracy of the THz NDT results. Combined with the frequency property of multiple echoes, an improved wavelet multi-scale analysis is put forth in this paper to correct multiple echoes, allowing the maximum retention of detailed signal information in contrast with the existing echo correction methods. The results showed that the improved wavelet multi-scale analysis enhanced the continuity and smoothness of the image at least twice in testing adhesive layer thickness, prevented missing judgments and misjudgments in identifying characteristic defects, and ensured accurate detection results. Hence, it is of great significance for evaluating the THz NDT results. [ABSTRACT FROM AUTHOR]

Recently, predicting multivariate time-series (MTS) has attracted much attention to obtain richer semantics with similar or better performances. In this paper, we propose a tri-partition alphabet-based state (tri-state) prediction method for symbolic MTSs. First, for each variable, the set of all symbols, i.e., alphabets, is divided into strong, medium, and weak using two user-specified thresholds. With the tri-partitioned alphabet, the tri-state takes the form of a matrix. One order contains the whole variables. The other is a feature vector that includes the most likely occurring strong, medium, and weak symbols. Second, a tri-partition strategy based on the deviation degree is proposed. We introduce the piecewise and symbolic aggregate approximation techniques to polymerize and discretize the original MTS. This way, the symbol is stronger and has a bigger deviation. Moreover, most popular numerical or symbolic similarity or distance metrics can be combined. Third, we propose an along–across similarity model to obtain the k-nearest matrix neighbors. This model considers the associations among the time stamps and variables simultaneously. Fourth, we design two post-filling strategies to obtain a completed tri-state. The experimental results from the four-domain datasets show that (1) the tri-state has greater recall but lower precision; (2) the two post-filling strategies can slightly improve the recall; and (3) the along–across similarity model composed by the Triangle and Jaccard metrics are first recommended for new datasets. [ABSTRACT FROM AUTHOR]

Freeway travel time is influenced by many factors including traffic volume, adverse weather, accidents, traffic control, and so on. We employ the multiple source data-mining method to analyze freeway travel time. We collected toll data, weather data, traffic accident disposal logs, and other historical data from Freeway G5513 in Hunan Province, China. Using the Support Vector Machine (SVM), we proposed the travel time predicting model founded on these databases. The new SVM model can simulate the nonlinear relationship between travel time and those factors. In order to improve the precision of the SVM model, we applied the Artificial Fish Swarm algorithm to optimize the SVM model parameters, which include the kernel parameter σ, non-sensitive loss function parameter ε, and penalty parameter C. We compared the new optimized SVM model with the Back Propagation (BP) neural network and a common SVM model, using the historical data collected from freeway G5513. The results show that the accuracy of the optimized SVM model is 17.27% and 16.44% higher than those of the BP neural network model and the common SVM model, respectively. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins, cell death, cell apoptosis, ROS generation and the ATP/AMPK pathway in Sertoli cells. The role of ROS, ER stress and the ATP/AMPK pathway in ZEA-induced cell-cycle arrest and cell apoptosis was explored by using the antioxidant NAC, ER stress inhibitor 4-PBA and the AMPK inhibitor dorsomorphin, respectively. The results revealed that ZEA inhibited the cell proliferation, influenced the distribution of the cell cycle and induced cell apoptosis through the ATP/AMPK pathway. The ATP/AMPK pathway was regulated by ER stress that was induced by ROS generation after exposure to ZEA. Taking these together, this study provided evidence that ROS regulated the process of ZEA-induced cell cycle arrest and cell apoptosis through ER stress and the ATP/AMPK signal ways. [ABSTRACT FROM AUTHOR]

DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10−4 and 9 sites with P < 10−5 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa. [ABSTRACT FROM AUTHOR]

Improving the tumor targeting of docetaxel (DTX) would not only be favored for the chemotherapeutic efficacy, but also reduce its side effects. However, the regulation of the tumor microenvironment could further inhibit the growth of tumors. In this study, we introduced a system consisting of hypoxia-engineered bone marrow mesenchymal stem cells (H-bMSCs) and DTX micelles (DTX-M) for breast cancer treatment. First, the stem cell chemotherapy complex system (DTX@H-bMSCs) with tumor-targeting ability was constructed according to the uptake of DTX-M by hypoxia-induced bMSCs (H-bMSCs). DTX micellization improved the uptake efficiency of DTX by H-bMSCs, which equipped DTX@H-bMSCs with satisfactory drug loading and stability. Furthermore, the migration of DTX@H-bMSCs revealed that it could effectively target the tumor site and facilitate the drug transport between cells. Moreover, in vitro and in vivo pharmacodynamics of DTX@H-bMSCs exhibited a superior antitumor effect, which could promote the apoptosis of 4T1 cells and upregulate the expression of inflammatory factors at the tumor site. In brief, DTX@H-bMSCs enhanced the chemotherapeutic effect in breast cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive and deadly form of prostate cancer. As a bone-predominant metastatic disease, liquid biopsy-based biomarkers have advantages in monitoring cancer dynamics. Previous studies have demonstrated the associations between circulating tumor cells (CTCs) and mCRPC outcomes, but little is known about the prognostic value of CTC-clusters. In this study, we investigated the associations of CTCs and CTC-clusters with mCRPC prognosis, individually and jointly, using longitudinal samples. We confirmed the associations of CTC counts with mCRPC outcomes in both baseline and longitudinal analyses. Our results also showed that the presence of CTC-clusters alone had prognostic value and that CTC-clusters may further improve CTC-based prognostic stratification in mCRPC. Our findings suggest the potential of combing CTC and CTC-clusters as non-invasive means to monitor progression and predict survival in mCRPC and build a premise for in-depth genomic and molecular analyses of CTCs and CTC-clusters. Liquid biopsy-based biomarkers have advantages in monitoring the dynamics of metastatic castration-resistant prostate cancer (mCRPC), a bone-predominant metastatic disease. Previous studies have demonstrated associations between circulating tumor cells (CTCs) and clinical outcomes of mCRPC patients, but little is known about the prognostic value of CTC-clusters. In 227 longitudinally collected blood samples from 64 mCRPC patients, CTCs and CTC-clusters were enumerated using the CellSearch platform. The associations of CTC and CTC-cluster counts with progression-free survival (PFS) and overall survival (OS), individually and jointly, were evaluated by Cox models. CTCs and CTC-clusters were detected in 24 (37.5%) and 8 (12.5%) of 64 baseline samples, and in 119 (52.4%) and 27 (11.9%) of 227 longitudinal samples, respectively. CTC counts were associated with both PFS and OS, but CTC-clusters were only independently associated with an increased risk of death. Among patients with unfavorable CTCs (≥5), the presence of CTC-clusters signified a worse survival (log-rank p = 0.0185). mCRPC patients with both unfavorable CTCs and CTC-clusters had the highest risk for death (adjusted hazard ratio 19.84, p = 0.0072), as compared to those with <5 CTCs. Analyses using longitudinal data yielded similar results. In conclusion, CTC-clusters provided additional prognostic information for further stratifying death risk among patients with unfavorable CTCs. [ABSTRACT FROM AUTHOR]

Background: Leukocyte telomere length (LTL) has been associated with the risks of several cancers in observational studies. Mendelian randomization (MR) studies, using genetic variants as instrumental variables, have also shown associations of genetically predicted LTL with cancer risks. In this study, we performed the first MR analysis on soft tissue sarcoma (STS) to investigate the causal relationship between LTL and the risk of STS. Methods: Genotypes from eleven LTL-associated single nucleotide polymorphisms (SNPs) in 821 STS cases and 851 cancer-free controls were aggregated into a weighted genetic risk score (GRS) to predict LTL. Multivariate logistic regression was used to assess the association of STS risk with individual SNPs and aggregated GRS. Results: Four SNPs displayed evidence for an individual association between long LTL-conferring allele and increased STS risk: rs7675998 (odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.02–1.43), rs9420907 (OR = 1.31, 95% CI = 1.08–1.59), rs8105767 (OR = 1.18, 95% CI = 1.02–1.37), and rs412658 (OR = 1.18, 95% CI = 1.02–1.36). Moreover, longer genetically predicted LTL, calculated as GRS, was strongly associated with an increased risk of STS (OR = 1.44, 95% CI = 1.18–1.75, p < 0.001), and there was a significant dose-response association (p for trend <0.001 in tertile and quartile analyses). The association of longer LTL with higher STS risk was more evident in women than in men. In stratified analyses by major STS subtypes, longer LTL was significantly associated with higher risks of leiomyosarcoma and gastrointestinal stromal tumors. Conclusions: Longer LTL is associated with increased risks of STS. [ABSTRACT FROM AUTHOR]

Metros are usually built and added on the basis of a completed bus network in Chinese cities. After the metro construction, it is faced with the problem of how to adjust and optimize the original bus lines based on the new metro system. This research mainly proposes a bus line optimization method based on bus and metro integration. In the consideration of the geographical space, the cooperation and competition relationship between bus and metro lines is qualitatively introduced according to the geographical location and service range of metro (800 m radius) and bus (500 m radius) stations. The competition and cooperation indexes are applied to define the co-opetition relationship between bus and metro lines. The bus line optimization model is constructed based on the co-opetition coefficient and Changsha Metro Line Number 2 is chosen as a case study to verify the optimization model. The results show that the positive competition, efficient cooperation, and travel efficiency between metro and bus has been significantly enhanced after optimization. Moreover, this paper provides a reasonable reference for public transport network planning and resource allocation. [ABSTRACT FROM AUTHOR]

The surface and volume discharge enhancement phenomena and streamer propagation direction control in catalytic pores are significant for the plasma catalytic degradation of pollutants. In this work, we use a two-dimensional particle-in-cell with Monte Carlo collisions model to explore the effect of lateral voltage on streamer enhancement and streamer propagation control for different driving voltages in pores of various shapes, sizes, and numbers. The driving voltage is applied to the top of the device, while the lateral voltages are applied at the left and right sides of the device. The surface and volume discharge enhancement phenomena become more significant and streamer propagation is more restricted within a narrow channel as the lateral voltage (with the same values on the left and right sides) increases from −5 kV to −30 kV for a fixed driving voltage of −20 kV. In this case, both the volume and surface discharges are intensive, leading to highly concentrated plasma species in a narrow channel. Moreover, the streamer propagates in a straight direction, from top to the bottom plate, with the lateral voltage added on both sides. The streamer propagation, however, deviates from the center and is directed to the right side when the lateral voltage is applied to the left. Our calculations also indicate that increasing the number or size of the pores enhances both the volume and surface discharges. [ABSTRACT FROM AUTHOR]

The mechanisms of traffic congestion generation are more than complicated, due to complex geometric road designs and complicated driving behavior at urban expressways in China. We employ a cell transmission model (CTM) to simulate the traffic flow spatiotemporal evolution process along the expressway, and reveal the characteristics of traffic congestion occurrence and propagation. Here, we apply the variable-length-cell CTM to adapt the complicated road geometry and configuration, and propose the merge section CTM considering drivers' mandatory lane-changing and other unreasonable behavior at the on-ramp merge section, and propose the diverge section CTM considering queue length end extending the expressway mainline to generate a dynamic bottleneck at the diverge section. In the new improved CTM model, we introduce merge ratio and diverge ratio to describe the effect of driver behavior at the merge and diverge section. We conduct simulations on the real urban expressway in China, with results showing that the merge section and diverge section are the original location of expressway traffic congestion generation, and on/off-ramp traffic flow has a great effect on the expressway mainline operation. When on-ramp traffic volume increases by 40%, the merge section delay increases by 35%, and when off-ramp capacity increases by 100 veh/hr, the diverge section delay decreases about by 10%, which proves the strong interaction between expressway and adjacent road networks. Our results provide the underlying insights of traffic congestion mechanism in urban expressway in China, which can be used to better understand and manage this issue. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. In the present study, male Institute of Cancer Research (ICR) mice aged 6 weeks were subjected to a single APAP (500 mg/kg) intraperitoneal injection after 7 days of fucoidan (100 or 200 mg/kg/day) or bicyclol intragastric administration. The mice continued to be administered fucoidan or bicyclol once per day, and were sacrificed at an indicated time. The indexes evaluated included liver pathological changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in the liver, and related proteins levels (CYP2E1, pJNK and Bax). Furthermore, human hepatocyte HL-7702 cell line was used to elucidate the potential molecular mechanism of fucoidan. The mitochondrial membrane potential (MMP) and nuclear factor-erythroid 2-related factor (Nrf2) translocation in HL-7702 cells were determined. The results showed that fucoidan pretreatment reduced the levels of ALT, AST, ROS, and MDA, while it enhanced the levels of GSH, SOD, and CAT activities. Additionally, oxidative stress-induced phosphorylated c-Jun N-terminal protein kinase (JNK) and decreased MMP were attenuated by fucoidan. Although the nuclear Nrf2 was induced after APAP incubation, fucoidan further enhanced Nrf2 in cell nuclei and total expression of Nrf2. These results indicated that fucoidan ameliorated APAP hepatotoxicity, and the mechanism might be related to Nrf2-mediated oxidative stress. [ABSTRACT FROM AUTHOR]

A high concentration of Zearalenone (ZEA) will perturb the differentiation of germ cells, and induce a death of germ cells, but the toxic mechanism and molecular mechanism remain unclear. The Sertoli cells (SCs) play an irreplaceable role in spermatogenesis. In order to explore the potential mechanism of ZEA male reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins and autophagy-related pathway the PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of autophagy and PI3K/AKT/m TOR signaling pathway on the SCs cell-cycle arrest induced by ZEA treated with the autophagy promoter RAPA, autophagy inhibitor CQ, and the PI3K inhibitor LY294002, respectively. The data revealed that ZEA could inhibit the proliferation of SCs by arresting the cell cycle in the G2/M phase and trigger the autophagy via inhibiting the PI3K/Akt/m TOR signaling pathway. Promoting or inhibiting the level of autophagy could either augment or reverse the arrest of cell cycle. And it was regulated by PI3K/Akt/m TOR signaling pathway. Taken together, this study provides evidence that autophagy and PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell-cycle arrest due to ZEA in vitro. To some extent, ZEA-induced autophagy plays a protective role in this process. [ABSTRACT FROM AUTHOR]

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for each clock. We discovered that higher HannumAge and HorvathAge GRS were significantly associated with increased bladder cancer risk (OR = 1.69 per SD increase, 95% CI, 1.44-1.98, p = 1.56 × 10 -10 and OR = 1.09 per SD increase, 95% CI, 1.00-1.19, p = 0.04, respectively). Employing a summary statistics-based Mendelian randomization (MR) method, inverse-variance weighting (IVW), we found consistent risk estimates for bladder cancer with both HannumAge and HorvathAge. Sensitivity analyses using weighted median analysis and MR-Egger regression further supported the validity of the IVW method. However, GrimAge and PhenoAge were not associated with bladder cancer risk. In conclusion, our data provide the first evidence that accelerated biological aging is associated with elevated bladder cancer risk.

Liver disease has become a major global health and economic burden due to its broad spectrum of diseases, multiple causes and difficult treatment. Most liver diseases progress to end-stage liver disease, which has a large amount of matrix deposition that makes it difficult for the liver and hepatocytes to regenerate. Liver transplantation is the only treatment for end-stage liver disease, but the shortage of suitable organs, expensive treatment costs and surgical complications greatly reduce patient survival rates. Therefore, there is an urgent need for an effective treatment modality. Cell-free therapy has become a research hotspot in the field of regenerative medicine. Mesenchymal stem cell (MSC)-derived exosomes have regulatory properties and transport functional "cargo" through physiological barriers to target cells to exert communication and regulatory activities. These exosomes also have little tumorigenic risk. MSC-derived exosomes promote hepatocyte proliferation and repair damaged liver tissue by participating in intercellular communication and regulating signal transduction, which supports their promise as a new strategy for the treatment of liver diseases. This paper reviews the physiological functions of exosomes and highlights the physiological changes and alterations in signaling pathways related to MSC-derived exosomes for the treatment of liver diseases in some relevant clinical studies. We also summarize the advantages of exosomes as drug delivery vehicles and discuss the challenges of exosome treatment of liver diseases in the future.

A high concentration of Zearalenone (ZEA) will perturb the differentiation of germ cells, and induce a death of germ cells, but the toxic mechanism and molecular mechanism remain unclear. The Sertoli cells (SCs) play an irreplaceable role in spermatogenesis. In order to explore the potential mechanism of ZEA male reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins and autophagy-related pathway the PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of autophagy and PI3K/AKT/m TOR signaling pathway on the SCs cell-cycle arrest induced by ZEA treated with the autophagy promoter RAPA, autophagy inhibitor CQ, and the PI3K inhibitor LY294002, respectively. The data revealed that ZEA could inhibit the proliferation of SCs by arresting the cell cycle in the G2/M phase and trigger the autophagy via inhibiting the PI3K/Akt/m TOR signaling pathway. Promoting or inhibiting the level of autophagy could either augment or reverse the arrest of cell cycle. And it was regulated by PI3K/Akt/m TOR signaling pathway. Taken together, this study provides evidence that autophagy and PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell-cycle arrest due to ZEA in vitro. To some extent, ZEA-induced autophagy plays a protective role in this process.

The goal of this research was to evaluate the anti-hepatitis B virus (HBV) activities of three compounds extracted and purified from Herpetospermum seeds (HS) on HepG2.2.15 cells. Herpetin (HPT), herpetone (HPO), and herpetfluorenone (HPF) were isolated from HS and identified using HR-ESI-MS and NMR. Different concentrations of the drugs were added to the HepG2.2.15 cells. Cell toxicity was observed with an MTT assay, cell culture supernatants were collected, and HBsAg and HBeAg were detected by ELISA. The content of HBV DNA was determined via quantitative polymerase chain reaction (PCR) with fluorescent probes. The 50% toxicity concentration (TC 50 ) of HPF was 531.48 μg/mL, suggesting that this species is less toxic than HPT and HPO. HPT and HPF showed more potent antiviral activities than HPO. The 50% inhibition concentration (IC 50 ) values of HPF on HBsAg and HBeAg were 176.99 and 134.53 μg/mL, respectively, and the corresponding therapeutic index (TI) values were 2.66 and 3.49, respectively. HPT and HPF were shown to significantly reduce the level of HBV DNA in the HepG2.2.15 culture medium compared to the negative control. This initial investigation of the anti-HBV constituents of HS yielded three compounds that revealed a synergistic effect of multiple components in the ethnopharmacological use of HS.

Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.

To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG) and its metabolite ginsenoside M1 (G-M1) on carbon tetrachloride (CCl(4))-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST) and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl(4)-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress.