Establishment and characterization of a novel multidrug-resistant pancreatic ductal adenocarcinoma cell line, PDAC-X1.

Drug resistance remains a significant challenge in the treatment of pancreatic cancer. The development of drug-resistant cell lines is crucial to understanding the underlying mechanisms of resistance and developing novel drugs to improve clinical outcomes. Here, a novel pancreatic cancer cell line, PDAC-X1, derived from Chinese patients has been established. PDAC-X1 was characterized by the immune phenotype, biology, genetics, molecular characteristics, and tumorigenicity. In vitro analysis revealed that PDAC-X1 cells exhibited epithelial morphology and cell markers (CK7 and CK19), expressed cancer-associated markers (E-cadherin, Vimentin, Ki-67, CEA, CA19-9), and produced pancreatic cancer-like organs in suspension culture. In vivo analysis showed that PDAC-X1 cells maintained tumorigenicity with a 100% tumor formation rate. This cell line exhibited a complex karyotype, dominated by subtriploid karyotypes. In addition, PDAC-X1 cells exhibited intrinsic multidrug resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil, and oxaliplatin. In conclusion, the PDAC-X1 cell line has been established and characterized, representing a useful and valuable preclinical model to study the underlying mechanisms of drug resistance and develop novel drug therapeutics to improve patient outcomes.

Expression and clinical diagnostic value of CCHE1 in breast cancer.

OBJECTIVE: Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer. METHODS: CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan-Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay. RESULTS: CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966-1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice. CONCLUSION: Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease.

Diversity of Wolbachia infection and its influence on mitochondrial DNA variation in the diamondback moth, Plutella xylostella.

Plutella xylostella is a pest that severely damages cruciferous vegetables worldwide and has been shown to be infected with the maternally inherited bacteria Wolbachia, with the main infected strain was plutWB1. In this study, we performed a large-scale global sampling of P. xylostella and amplified 3 mtDNA genes of P. xylostella and 6 Wolbachia genes to analyze the infection status, diversity of Wolbachia in P. xylostella, and its effect on mtDNA variation in P. xylostella. This study provides a conservative estimate of Wolbachia infection rates in P. xylostella, which was found to be 7% (104/1440). The ST 108 (plutWB1) was shared among butterfly species and the moth species P. xylostella, revealing that Wolbachia strain plutWB1 acquisition in P. xylostella may be through horizontal transmission. The Parafit analyses indicated a significant association between Wolbachia and Wolbachia-infected P. xylostella individuals, and individuals infected with plutWB1 tended to cluster in the basal positions of the phylogenetic tree based on the mtDNA data. Additionally, Wolbachia infections were associated with increased mtDNA polymorphism in the infected P. xylostella population. These data suggest that Wolbachia endosymbionts may have a potential effect on mtDNA variation of P. xylostella.

Dataglove for Sign Language Recognition of People with Hearing and Speech Impairment via Wearable Inertial Sensors.

Finding ways to enable seamless communication between deaf and able-bodied individuals has been a challenging and pressing issue. This paper proposes a solution to this problem by designing a low-cost data glove that utilizes multiple inertial sensors with the purpose of achieving efficient and accurate sign language recognition. In this study, four machine learning models-decision tree (DT), support vector machine (SVM), K-nearest neighbor method (KNN), and random forest (RF)-were employed to recognize 20 different types of dynamic sign language data used by deaf individuals. Additionally, a proposed attention-based mechanism of long and short-term memory neural networks (Attention-BiLSTM) was utilized in the process. Furthermore, this study verifies the impact of the number and position of data glove nodes on the accuracy of recognizing complex dynamic sign language. Finally, the proposed method is compared with existing state-of-the-art algorithms using nine public datasets. The results indicate that both the Attention-BiLSTM and RF algorithms have the highest performance in recognizing the twenty dynamic sign language gestures, with an accuracy of 98.85% and 97.58%, respectively. This provides evidence for the feasibility of our proposed data glove and recognition methods. This study may serve as a valuable reference for the development of wearable sign language recognition devices and promote easier communication between deaf and able-bodied individuals.

Can China's carbon intensity constraint policies improve carbon emission performance? Evidence from regional carbon emissions.

Carbon Intensity Constraint Policies (CICPs) are vital for addressing climate change challenges and advancing sustainable development. Since 2010, China has rolled out three five-year CICPs. However, there is limited understanding of their impact on carbon emission performance (CEP). Addressing this, this study pioneers the exploration of the CICP's impact on China's CEP. Drawing from government intervention and green paradox theories, this study highlights a concerning scenario: local governments achieve emission targets via excessive intervention. For deeper insights, this study melds the overall technology frontier concept with a non-radial, non-angle directional distance function, introducing a novel efficiency model rooted in the Data Envelopment Analysis (DEA) method. This offers a CEP measure across 30 Chinese provincial regions from 2002 to 2019. Using the quasi-difference-in-differences (quasi-DID) and moderated mediation models, this study ascertains the presence of the green paradox, uncovers its reasons, and suggests mitigation strategies. The results indicate that high government intervention diminishes CEP. This negative effect intensifies under greater regional fiscal pressure. Alarmingly, local authorities' eagerness to meet targets shows a counterproductive, inverted N-shaped trend regarding CICPs' time-based influence on regional CEP. Moreover, the impact varies based on regional economic development levels and stages. This study has ensured the robustness of the findings via parallel trend tests, parallel exclusion policies, a strengthened quasi-DID framework, and diverse control variable configurations. This study underscores the need for more balanced government intervention. It offers valuable policy insights, guiding China's upcoming CICP phase to realize the ambition of peaking carbon by 2030 and achieving carbon neutrality by 2060.

The impact of the embryo banking on the cumulative live birth rate in women with poor ovarian response according to the Bologna criteria.

Purpose: To evaluate the impact of embryo banking on the cumulative live birth rate (CLBR) and the time to live birth (TTLB) in poor ovarian responders (POR) according to the Bologna criteria. Methods: A total of 276 infertile women undergoing IVF with POR were included in this retrospective study. They were divided into two groups with (n = 121) or without (n = 155) embryo banking at the discretion of the attending physicians. A total of 656 and 405 stimulation cycles were started in the two groups respectively during the 24 month follow-up. Results: The biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth rate per transfer were comparable between two groups (p > 0.05). The CLBR was significantly lower in the banking group than in the non-banking group (31.4% (38/121) and 43.2% (67/151), p < 0.05). TTLB was significantly longer in the banking group (20.5 months vs. 16.0 months, p < 0.001). In the Kaplan-Meier analysis, the cumulative incidence of live birth was significantly lower in the banking group compared with the non-banking group (Log rank test, chi-square = 21.958, p < 0.001). Conclusions: Embryo banking in women undergoing IVF with POR based on the Bologna criteria reduces CLBR and lengthens TTLB when compared with no embryo banking.

Maize SRO1e represses anthocyanin synthesis through regulating the MBW complex in response to abiotic stress.

Plants experiencing abiotic stress react by generating reactive oxygen species (ROS), compounds that, if allowed to accumulate to excess, repress plant growth and development. Anthocyanins induced by abiotic stress are strong antioxidants that neutralize ROS, whereas their over-accumulation retards plant growth. Although the mechanism of anthocyanin synthesis has been revealed, how plants balance anthocyanin synthesis under abiotic stress to maintain ROS homeostasis is unknown. Here, ROS-related proteins, SIMILAR TO RCD-ONEs (SROs), were analysed in Zea mays (maize), and all six SRO1 genes were inducible by a variety of abiotic stress agents. The constitutive expression of one of these genes, ZmSRO1e, in maize as well as in Arabidopsis thaliana increased the sensitivity of the plant to abiotic stress, but repressed anthocyanin biosynthesis and ROS scavenging activity. Loss-of-function mutation of ZmSRO1e enhanced ROS tolerance and anthocyanin accumulation. We showed that ZmSRO1e competed with ZmR1 (a core basic helix-loop-helix subunit of the MYB-bHLH-WD40 transcriptional activation complex) for binding with ZmPL1 (a core MYB subunit of the complex). Thus, during the constitutive expression of ZmSRO1e, the formation of the complex was compromised, leading to the repression of genes, such as ZmA4 (encoding dihydroflavonol reductase), associated with anthocyanin synthesis. Overall, the results have revealed a mechanism that allows the products of maize SRO1e to participate in the abiotic stress response.

The bidirectional association of C-peptide with cardiovascular risk in nondiabetic adults and patients with newly diagnosed type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. METHODS: A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. RESULTS: Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM. CONCLUSIONS: The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.

Establishment and characterization of a new intrahepatic cholangiocarcinoma cell line derived from a Chinese patient.

Patients with intrahepatic cholangiocarcinoma (ICC) require chemotherapy due to late detection, rapid disease progression, and low surgical resection rate. Tumor cell lines are extremely important in cancer research for drug discovery and development. Here, we established and characterized a new intrahepatic cholangiocarcinoma cell line, ICC-X1. STR testing confirmed the absence of cross-contamination and high similarity to the original tissue. ICC-X1 exhibited typical epithelial morphology and formed tumor spheres in the suspension culture. The population doubling time was approximately 48 h. The cell line had a complex hypotriploid karyotype. The cell line exhibited a strong migration ability in vitro and cell inoculation into BALB/c nude mice led to the formation of xenografts. Additionally, ICC-X1 cells were sensitive to gemcitabine and paclitaxel but resistant to 5-fluorouracil and oxaliplatin. RNA sequencing revealed that the upregulated cancer-related genes were mainly enriched in several signaling pathways, including the TNF signaling pathway, NOD-like receptor signaling pathway, and NF-κB signaling pathway. The downregulated cancer-related genes were mainly enriched in the Rap1 signaling pathway and Hippo signaling pathway among other pathways. In conclusion, we have created a new ICC cell line derived from Chinese patients. This cell line can be used as a preclinical model to study ICC, specifically tumor metastasis and drug resistance mechanisms.

A randomized double blind comparison of atosiban in patients with recurrent implantation failure undergoing IVF treatment.

BACKGROUND: Patients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF. METHODS: A prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban (n = 97) and the placebo (n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration. RESULTS: There was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844-1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E2) on the day of hCG above the median level. And, there was no correlation between the serum E2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth. CONCLUSIONS: These results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients. TRIAL REGISTRATION: The study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722.

Development of an Automatic Column Chromatography Separation Device for Metal Isotope Analysis Based on Droplet Counting.

A novel, simple, cost-effective, reliable, and practical automatic column chromatography separation device capable of simultaneously purifying samples for radiogenic and non-traditional stable isotope analysis has been developed. The device avoids the use of any pump and features eluent driving by the siphon effect (gravity) and quantitative control by infrared droplet counting. Several factors affecting the control of droplets were investigated, including types and concentrations of eluents and the height of the liquid level. Results showed that accurate dripping of the eluent could be readily achieved by controlling the number of droplets under selected conditions. The separation performance of the device was first demonstrated by the elution of Sr and Cd in synthetic matrix solutions. The recoveries of Sr and Cd samples were better than 87.6 and 95.0%, respectively, and the whole procedure blank was about 0.3 ng for Sr and 0.1 ng for Cd. Finally, the reliability of the device was further validated by the purification of Sr and Cd from different geological reference materials (NIST 2711a, Nod-A-1, BCR-2, and BHVO-2). The determined Cd and Sr isotope values agree well with their reference values within the uncertainty range. All these results clearly demonstrate the reliability and practicability of the proposed device, which provides a promising method for the automated purification of isotope samples.

Deficiency of miR-15a/16 upregulates NKG2D in CD8+ T cells to exacerbate dextran sulfate sodium-induced colitis.

The miR-15a/16 gene cluster is located in human chromosome 13 (13q14.3) and mouse chromosome 14 (14qC3). These genes are involved in cancer development and immune regulation. Our group has previously verified the binding of the 3'-untranslated region of NKG2D gene by miR-16 through dual-luciferase reporter assay. Herein, we found that miR-16 overexpression inhibited the NKG2D expression of CD8+ T cells, and that CD8+ NKG2D+ T cell frequency increased in miR-15/16-/- mice. CD8+ NKG2D+ T cells derived of miR-15/16-/- mice displayed activatory phenotype with enhanced IFN-γ production and cytotoxicity. The transfection of lentivirus containing antago-miR-16 sequences enhanced the NKG2D expression level of CD8+ T cells. However, no significant differences in CD8+ NKG2D+ T cell frequencies existed between wild-type and miR-15/16-transgenic mice because NKG2D was not expressed on the rest CD8+ T cells. When CD8+ T cells of miR-15/16-transgenic mice were treated with IL-2 in vitro, the magnitude of NKG2D expression and activation of CD8+ T cells was lower than that of wild-type mice. miR-15/16-/- mice showed that the exacerbation of colitis induced by dextran sulfate sodium (DSS) with more CD8+ T cells accumulated in inflamed colons, whereas miR-15/16-transgenic mice ameliorated DSS-induced colitis with less infiltration of CD8+ T cells. When NKG2D+ cells were depleted with NKG2D antibody in miR-15/16-/- mice, the aggravated colitis disappeared. All these results demonstrated that NKG2D could be upregulated by decreased miR-16 in CD8+ T cells to mediate inflammation. Thus, gene therapy based on the overexpression of miR-16 in CD8+ T cells can be used for patients with inflammatory diseases.

Calibration of T2 oximetry MRI for subjects with sickle cell disease.

PURPOSE: Cerebral T2 oximetry is a non-invasive imaging method to measure blood T2 and cerebral venous oxygenation. Measured T2 values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T2 oximetry calibration relationships in clinically meaningful ways. Previous in vitro works by two independent groups established potentially competing calibration models. METHODS: This study analyzed pooled datasets from these two studies to establish a unified and more robust sickle-specific calibration to serve as a reference standard in the field. RESULTS: Even though the combined calibration did not demonstrate statistical superiority compared to previous models, the calibration was unbiased compared to blood-gas co-oximetry and yielded limits of agreement of (-10.1%, 11.6%) in non-transfused subjects with sickle cell disease. In transfused patients, this study proposed a simple correction method based on individual hemoglobin S percentage that demonstrated reduced bias in saturation measurement compared to previous uncorrected sickle calibrations. CONCLUSION: The combined calibration is based on a larger range of hematocrit, providing greater confidence in the hematocrit-dependent model parameters, and yielded unbiased estimates to blood-gas co-oximetry measurements from both sites. Additionally, this work also demonstrated the need to correct for transfusion in T2 oximetry measurements for hyper-transfused sickle cell disease patients and proposes a correction method based on patient-specific hemoglobin S concentration.

Splicing exponential point spread function design for localization of nanoparticles.

We propose a point spread function for three-dimensional localization of nanoparticles. The axial detection range of the point spread function can be simply changed by adjusting the design parameters. In addition, the spatial extent of the point spread function can also be changed by adjusting the design parameters, which is an advantage other point spread functions do not have. We used our point spread functions and the existing point spread functions for dense multi-particle imaging, which proved the advantage that the point spread function with a smaller spatial extent we designed can effectively reduce the overlap between the point spread functions. The three-dimensional process of the fluorescent microsphere penetrating HT-22 cell membrane was successfully recorded, which verified the effectiveness of this method.

Particles 3D tracking with large axial depth by using the 2π-DH-PSF.

We propose a 2π-double-helix point spread function (2π-DH-PSF) using the Fresnel zone approach that can rotate 2π rad. When 16 Fresnel zones are used, the particles can be tracked in the axial range of 10 µm in a 100× microscopy imaging system (NA=1.4, λ=514nm). We measured the diffusion coefficient of nanospheres in different concentrations of glycerol with the 2π-DH-PSF, and the error between the measured results and theoretical value was within 10%, indicating the superior performance of 2π-DH-PSF in 3D localization imaging of nanoparticles. When combined with the defocus phase, the rotation angle can reach 4π rad, four times that of the conventional DH-PSF.

LncRNA SNHG16 contributes to tumor progression via the miR-302b-3p/SLC2A4 axis in pancreatic adenocarcinoma.

BACKGROUND: It has been reported that the lncRNA SNHG16 has significantly increased expression in pancreatic adenocarcinoma (PC). However, the functions and mechanisms of SNHG16 are not clear. The aim of this study was to explore the effects of SNHG16 on PC. METHODS: qRT-PCR analysis was applied to detect the expression levels of SNHG16, miR-302b-3p and SLC2A4 in PC tissues and cells. CCK8 and EdU assays were used to evaluate the proliferation of PC cells. Transwell assays were used to assess PC cell migration and invasion. Apoptosis was evaluated by flow cytometry, and the expression of apoptosis-related proteins (including Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9) was tested by western blotting. The interactions between miR-302b-3p and SNHG16 or miR-302b-3p and the 3'UTR of SLC2A4 mRNA were clarified by a dual luciferase reporter assay and RNA immunoprecipitation. RESULTS: SNHG16 expression was significantly elevated in PC tissues and cell lines and was associated with poor prognosis of PC patients. Knockdown of SNHG16 reduced PC cell proliferation, migration and invasion. SNHG16 acted as a sponge to regulate miR-302b-3p expression in PC cells. In addition, miR-302b-3p targeted SLC2A4 directly. CONCLUSIONS: SNHG16 promoted the progression of PC via the miR-302b-3p/SLC2A4 axis and was expected to be a potential target for the early diagnosis and treatment of PC.

Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias.

Anemia is the most common blood disorder in the world. In patients with chronic anemia, such as sickle cell disease or major thalassemia, cerebral blood flow increases to compensate for decreased oxygen content. However, the effects of chronic anemia on oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) are less well understood. In this study, we examined 47 sickle-cell anemia subjects (age 21.7 ± 7.1, female 45%), 27 non-sickle anemic subjects (age 25.0 ± 10.4, female 52%) and 44 healthy controls (age 26.4 ± 10.6, female 71%) using MRI metrics of brain oxygenation and flow. Phase contrast MRI was used to measure resting cerebral blood flow, while T2 -relaxation-under-spin-tagging (TRUST) MRI with disease appropriate calibrations were used to measure OEF and CMRO2 . We observed that patients with sickle cell disease and other chronic anemias have decreased OEF and CMRO2 (respectively 27.4 ± 4.1% and 3.39 ± 0.71 ml O2 /100 g/min in sickle cell disease, 30.8 ± 5.2% and 3.53 ± 0.64 ml O2 /100 g/min in other anemias) compared to controls (36.7 ± 6.0% and 4.00 ± 0.65 ml O2 /100 g/min). Impaired CMRO2 was proportional to the degree of anemia severity. We further demonstrate striking concordance of the present work with pooled historical data from patients having broad etiologies for their anemia. The reduced cerebral oxygen extraction and metabolism are consistent with emerging data demonstrating increased non-nutritive flow, or physiological shunting, in sickle cell disease patients.

Rauwolfia vomitoria Extract Represses Colorectal Cancer Cell Autophagy and Promotes Apoptosis.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent digestive tract tumors in the world with an increasing incidence. Currently, surgical resection and chemotherapy are the main therapeutic options; however, their effects are limited by various adverse reactions. Rauwolfia vomitoria extract (Rau) has been shown to repress the progression of multiple human cancers; however, whether Rau plays a role in CRC remains undetermined. METHODS: Influences of Rau treatment on HCT-116 and LoVo cells were estimated via MTT and colony formation experiments. Flow cytometry analysis was adopted to evaluate the apoptosis rate of HCT-116 and LoVo cells. Apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and autophagy-related proteins (LC3 and P62) were assessed by Western blotting. Effects of Rau on autophagy of HCT-116 and LoVo cell were evaluated through GFP-LC3 analysis. In vivo xenograft tumor assay was conducted to further examine the role of Rau in CRC tumor growth. RESULTS: Rau remarkably repressed HCT-116 and LoVo cell viability and promoted HCT-116 and LoVo cell apoptosis in vitro in a dose-dependent manner. Rau increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 in HCT-116 and LoVo cells. Moreover, Rau was demonstrated to decrease the LC3||/LC3| ratio and increase the level of P62 in HCT-116 and LoVo cells. In addition, we found that Rau repressed xenograft tumor growth and also repressed autophagy in vivo. CONCLUSION: Our findings revealed that Rau repressed CRC cell viability and autophagy in vitro and in vivo, suggesting that Rau might be a potent therapeutic agent of CRC.

A metabolomics study: Reveals the protective effect and mechanism of Terminalia chebula Retz on the cardiotoxicity induced by radix Aconiti kusnezoffii Reichb.

To reveal the protective effect of Terminalia chebula Retz (TCR) on cardiotoxicity induced by radix of Aconitum kusnezoffii Reichb (AKR). Control, AKR, AKR-TCR 1:3, AKR-TCR 1:1, AKR-TCR 3:1 and TCR-prepared AKR groups were set up. After treatment, the heart tissues were observed by H&E staining and transmission electron microscope. Serum myoglobin (MB) and troponin (cTn) were detected by ELISA. UPLC-Q Exactive/MS analysis was performed to detect the metabolic difference among the groups. ELISA results showed that the MB and cTn values of AKR group were significantly higher than Control group (P<0.05), while those of the other groups were lower than AKR group. TCR-prepared AKR group had similar MB and cTn contents to the Control group. Histopathological examination also indicated better detoxifying effects in the TCR-prepared AKR and AKR-TCR 1:1 group. The serum metabolomics analysis showed obvious distinction between the AKR and Control groups, while AKR-TCR combination reversed the metabolomics changes induced by AKR. Through multivariate statistical analysis, 9 metabolic markers related to energy, nucleic acid and amino acid metabolism were identified. Conclusively, AKR-induced cardiotoxicity may be related to energy, nucleic acid and amino acid metabolism, and TCR can reduce the cardiotoxicity by regulating the relative metabolism pathways.

Time skew enabled vestigial sideband modulation for dispersion-tolerant direct-detection transmission.

Fiber dispersion and square-law detection-induced power fading is a fundamental obstacle in intensity modulation with direct detection links. In this Letter, we propose a hardware-efficient vestigial sideband (VSB) transmitter to suppress such an impairment. By introducing an appropriate time skew between the differential arms of the Mach-Zehnder modulator, a VSB signal can be generated based on a single digital-to-analog convertor without optical filtering. At the receiver, a Volterra equalizer is utilized to mitigate the inter-symbol interference. In the proof-of-concept experiment, 32 Gbaud 4/6/8-ary pulse amplitude modulation signals can be successfully transmitted over an 80 km standard single-mode fiber with bit-error rates below the KP4, 7% hard-decision and 20% soft-decision forward error correction thresholds, respectively. The proposed scheme provides a promising and low-cost solution for high-speed metro and data center interconnect applications.