Novel Social Stimulation Ameliorates Memory Deficit in Alzheimer's Disease Model through Activating α-Secretase.

As the most common form of dementia in the world, Alzheimer's disease (AD) is a progressive neurological disorder marked by cognitive and behavioral impairment. According to previous researches, abundant social connections shield against dementia. However, it is still unclear how exactly social interactions benefit cognitive abilities in people with AD and how this process is used to increase their general cognitive performance. In this study, we found that single novel social (SNS) stimulation promoted c-Fos expression and increased the protein levels of mature ADAM10/17 and sAPPα in the ventral hippocampus (vHPC) of wild-type (WT) mice, which are hippocampal dorsal CA2 (dCA2) neuron activity and vHPC NMDAR dependent. Additionally, we discovered that SNS caused similar changes in an AD model, FAD4T mice, and these alterations could be reversed by α-secretase inhibitor. Furthermore, we also found that multiple novel social (MNS) stimulation improved synaptic plasticity and memory impairments in both male and female FAD4T mice, accompanied by α-secretase activation and Aß reduction. These findings provide insight into the process underpinning how social interaction helps AD patients who are experiencing cognitive decline, and we also imply that novel social interaction and activation of the α-secretase may be preventative and therapeutic in the early stages of AD.

Phenazine biosynthesis protein MoPhzF regulates appressorium formation and host infection through canonical metabolic and noncanonical signaling function in Magnaporthe oryzae.

Microbe-produced secondary metabolite phenazine-1-carboxylic acid (PCA) facilitates pathogen virulence and defense mechanisms against competitors. Magnaporthe oryzae, a causal agent of the devastating rice blast disease, needs to compete with other phyllosphere microbes and overcome host immunity for successful colonization and infection. However, whether M. oryzae produces PCA or it has any other functions remains unknown. Here, we found that the MoPHZF gene encodes the phenazine biosynthesis protein MoPhzF, synthesizes PCA in M. oryzae, and regulates appressorium formation and host virulence. MoPhzF is likely acquired through an ancient horizontal gene transfer event and has a canonical function in PCA synthesis. In addition, we found that PCA has a role in suppressing the accumulation of host-derived reactive oxygen species (ROS) during infection. Further examination indicated that MoPhzF recruits both the endoplasmic reticulum membrane protein MoEmc2 and the regulator of G-protein signaling MoRgs1 to the plasma membrane (PM) for MoRgs1 phosphorylation, which is a critical regulatory mechanism in appressorium formation and pathogenicity. Collectively, our studies unveiled a canonical function of MoPhzF in PCA synthesis and a noncanonical signaling function in promoting appressorium formation and host infection.

Enhancing LiDAR performance using threshold photon-number-resolving detection.

Single-photon light detection and ranging (LiDAR) is widely used to reconstruct 3D scenes. Nevertheless, depth and reflectivity maps obtained by single-photon detection usually suffer from noise problems. Threshold LiDAR techniques using photon-number-resolving detectors were proposed to suppress noise by filtering low photon numbers, but these techniques renounce multiple levels of information and could not be compatible when it comes to high-noise low-signal regime. In this manuscript, we propose a detection scheme which combines the noise suppression of threshold detection with the signal amplification of photon-number-resolving detectors to further enhance LiDAR performance. The enhancement attained is compared to single-photon and threshold detection schemes under a wide range of signal and noise conditions, in terms of signal-to-noise-ratio (SNR), detection rate and false alarm rate, which are key metrics for LiDAR. Extensive simulations and real-world experiments show that the proposed scheme can reconstruct better depth and reflectivity maps. These results enable the development of high-efficient and low-noise LiDAR systems.

Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

Association between the triglyceride-glucose index and carotid artery plaque burden in patients with primary hypertension: A cross-sectional study.

BACKGROUND: Studies have shown an association between the triglyceride-glucose (TyG) index and carotid artery plaque (CAP). However, the relationship between the TyG index and plaque burden in individuals with primary hypertension remains uncertain. Our study specifically aimed to explore this relationship among primary hypertension patients. METHODS: This study involved 5,153 hospitalized patients diagnosed with primary hypertension who were undergoing treatment at the Affiliated Hospital of Jiangxi University of Chinese Medicine. We utilized multivariate logistic regression, penalized spline regression, and generalized additive models to assess the association between the TyG index and CAP burden. RESULTS: There were 2,400 patients with primary hypertension in all. The multivariate study, which took into account all covariables, showed a positive correlation between the TyG index and CAP (OR: 1.25, 95% CI: 1.04-1.5). When the TyG index was evaluated as quartiles, the risk of CAP in the Q3 and Q4 levels of the TyG index were 1.4 (95% CI: 1.03-1.91) and 1.54 (95% CI: 1.11-2.14) times greater than in the Q1 level after adjusting for all covariables (P for trend < .05). Regardless of whether the TyG index was used as a continuous variable or a categorical variable, it has no significant association with the risk of single plaque after adjusting for all confounders (p ≥ .05). The TyG index was found to be substantially correlated with the presence of multiple plaques when analyzed as a continuous variable (OR: 1.32, 95% CI: 1.09-1.59, p = .004). When the TyG index was evaluated as quartiles, the adjusted OR in Q3 and Q4 were 1.49 (95% CI: 1.06-2.1) and 1.67 (95% CI: 1.16-2.41), respectively, with Q1 as reference (P for trend = .005). The relationship between the TyG index and the presence of multiple plaques is also consistent in all subgroups. CONCLUSION: The TyG index is positively associated with the presence of multiple plaques in patients with primary hypertension, whereas no association is found between the TyG index and the presence of a single carotid plaque.

A Series of Lanthanide Coordination Polymers as Luminescent Sensors for Selective Detection of Inorganic Ions and Nitrobenzene.

Seven new lanthanide coordination polymers, namely [Ln(cpt)3H2O)]n(Ln = La (1), Pr (2), Sm (3), Eu (4), Gd (5), Dy (6), and Er (7)), which were synthesized under hydrothermal conditions using 4'-(4-(4-carboxyphenyloxy)phenyl)-4,2':6',4'-tripyridine (Hcpt) as the ligand. The crystal structures of these seven complexes were determined using single-crystal X-ray diffraction, and they were found to be isostructural, crystallizing in the triclinic P1- space group. The Ln(III) ions were nine-coordinated with tricapped trigonal prism coordination geometry. The Ln(III) cations were coordinated by carboxylic and pyridine groups from (cpt)- ligands, forming one-dimensional ring-chain structures. Furthermore, the luminescent properties of complexes 1-7 were investigated using fluorescent spectra in the solid state. The fluorescence sensing experiments demonstrated that complex 4 exhibits high selectivity and sensitivity for detecting Co2+, Cu2+ ions, and nitrobenzene. Moreover, complex 3 shows good capability for detecting Cu2+ ions and nitrobenzene. Additionally, the sensing mechanism was also thoroughly examined through theoretical calculations.

Mesenchymal stem cells reversibly de-differentiate myofibroblasts to fibroblast-like cells by inhibiting the TGF-ß-SMAD2/3 pathway.

BACKGROUND: Myofibroblasts (MFB), one of the major effectors of pathologic fibrosis, mainly derived from the activation of fibroblast to myofibroblast transition (FMT). Although MFBs were historically considered terminally differentiated cells, their potential for de-differentiation was recently recognized and implied with therapeutic value in treating fibrotic diseases, for instance, idiopathic pulmonary fibrosis (IPF) and post allogeneic hematopoietic stem cell transplantation bronchiolitis obliterans (BO). During the past decade, several methods were reported to block or reverse MFB differentiation, among which mesenchymal stem cells (MSC) have demonstrated potential but undetermined therapeutic values. However, the MSC-mediated regulation of FMT and underlying mechanisms remained largely undefined. METHOD: By identifying TGF-ß1 hypertension as the pivotal landmark during the pro-fibrotic FMT, TGF-ß1-induced MFB and MSC co-culture models were established and utilized to investigate regulations by MSC on FMT in vitro. Methods including RNA sequencing (RNA-seq), Western blot, qPCR and flow cytometry were used. RESULT: Our data revealed that TGF-ß1 readily induced invasive signatures identified in fibrotic tissues and initiated MFB differentiation in normal FB. MSC reversibly de-differentiated MFB into a group of FB-like cells by selectively inhibiting the TGF-ß-SMAD2/3 signaling. Importantly, these proliferation-boosted FB-like cells remained sensitive to TGF-ß1 and could be re-induced into MFB. CONCLUSION: Our findings highlighted the reversibility of MSC-mediated de-differentiation of MFB through TGF-ß-SMAD2/3 signaling, which may explain MSC's inconsistent clinical efficacies in treating BO and other fibrotic diseases. These de-differentiated FB-like cells are still sensitive to TGF-ß1 and may further deteriorate MFB phenotypes unless the pro-fibrotic microenvironment is corrected.

Morbidity, Mortality, and Pathologic Outcomes of Transanal Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer Short-term Outcomes From a Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection. BACKGROUND: Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME. METHODS: A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention-to-treat principle; this analysis was preplanned. RESULTS: Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention-to-treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, -1.3%; 95% confidence interval (CI), -4.2% to 1.7%; P =0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, -2.8% to 5.2%; P =0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, -1.9% to 2.2%; P >0.99). CONCLUSIONS: Experienced surgeons can safely perform taTME in selected patients with rectal cancer.

A comparative evaluation of child health care in China using multicriteria decision analysis methods.

Child health is an important public health issue in China and the Chinese government always attached great importance to child health care. With the implementation of a series of medical and health reforms in China in recent decades, the status of child health improved year by year. Objectives This study aims to comprehensively evaluate if the measures implemented in the medical and health reforms effectively promoted the development of Chinese child health care in recent years and provide theoretical support for future decision-making on the policies of child health care in China. Methods A total of six indicators were selected from the China Health Statistics Yearbook. Based on the multi-criteria decision analysis (MCDA) algorithm, three different evaluation methods were applied in the study, which are the weighted technique for order preference by similarity to an ideal solution (TOPSIS) method, the weighted rank-sum ratio (RSR) method, and the fuzzy comprehensive evaluation (FCE). Each indicator's weight was calculated by the entropy weight methods objectively. The sensitivity analysis was conducted to validate the stability and accuracy of the rank results. Results The results indicated that the rank values of each year's child health care calculated by the different evaluation methods were not exactly the same, but the overall trend is consistent which is that child health care in China improved year by year from 2000 to 2020. The top 5 were ranked from 2016-2020 and the bottom 5 were ranked from 2000-2004. Conclusions The results indicated that the policies and measures implemented in the medical and health reforms, as well as improved sanitation conditions, availability of healthy food and water, etc., have jointly promoted the development of child health care in China in the past 20 years, providing a scientific theoretical basis for future policy-making to promote child health care.

Combined Metabolite Analysis and Network Pharmacology to Elucidate the Mechanisms of Therapeutic Effect of Melastoma dodecandrum Ellagitannins on Abnormal Uterine Bleeding.

The abnormal uterine bleeding (AUB) is complex and usually leads to severe anemia. Melastomadodecandrum (MD) is clinically used for the treatment of metrorrhagia bleeding. The MD ellagitannins (MD-ETs) had been evidenced being effective at hemorrhage, and exerts biological activities upon their metabolites including ellagic acid and urolithins. In this study, the blood-permeated metabolites from theMD-ETs were analyzed using LC-MS approach, and 19 metabolites including ellagic acid and urolithin A derivatives were identified. Furthermore, a network pharmacology analysis including the target prediction analysis, AUB target analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to reveal the relationships between "metabolites-targets-pathways", which was further verified by molecular docking analysis. The results showed that methyl ellagic acid, urolithin A and isourolithin A produced from MD-ETs can be absorbed into the blood, and might act on the core targets of VEGFA, SRC, MTOR, EGFR and CCND1. And the hemostatic effects were exerted through PI3K-Akt, endocrine resistance and Rap 1 signaling pathways. These results implied the potential effective constituents and action mechanism of MD-ETs in the therapy of AUB, which will promote the application of MD-ETs as natural agent for the treatment of gynecological bleeding diseases.

Regulations for the Manufacture and Control of Live Poliovirus Vaccine: International Experience and China's Path.

The eradication of poliomyelitis is a landmark achievement in the history of public health, providing strong protection for children's health. The introduction of the Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine is a prerequisite and safeguard for the large-scale production and use of domestically produced live poliovirus vaccines, serving as an indispensable component of vaccine safety. This article, based on archival documents, letters, collections of essays, and oral interviews, examines the historical experience of the development of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine. It contends that the emphasis on localization and the active engagement in international cooperation are critical factors in the swift introduction of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine.

Detecting acute bilirubin encephalopathy in neonates based on multimodal MRI with deep learning.

BACKGROUND: Differentiating acute bilirubin encephalopathy (ABE) from non-ABE in neonates with hyperbilirubinemia (HB) from routine magnetic resonance imaging (MRI) is extremely challenging since both conditions demonstrate similar T1 hyperintensities. To this end, we investigated whether the integration of multimodal MRI from routine clinical scans with deep-learning approaches could improve diagnostic performance. METHODS: A total of 75 neonates with ABE and 75 neonates with HB (non-ABE) were included in the study. Each patient had three types of multimodal images taken, i.e., a T1-weighted image (T1WI), a T2-weighted image (T2WI), and an apparent diffusion coefficient (ADC) map. The three types of MRI contrasts and their combination were fed into two deep convolutional neural networks (CNNs), i.e., ResNet18 and DenseNet201. The performance of CNNs was compared with a traditional statistical method named logistic regression. RESULTS: We demonstrated that diagnostic methods with the multimodal data were better than any of the single-modal data. Both CNN models outperformed the logistic regression method. The best performance was achieved by DenseNet201 with the combination of three modalities of T1WI, T2WI, and ADC, with an accuracy of 0.929 ± 0.042 and an area under the curve (AUC) of 0.991 ± 0.007. CONCLUSIONS: Our study demonstrated that CNN models with multimodal MRI significantly improve the accuracy of diagnosing ABE. IMPACT: We proposed an efficient strategy of detecting ABE in neonates based on multimodal MRI with deep learning, which achieved an accuracy of 0.929 ± 0.042 and an AUC of 0.991 ± 0.007. We demonstrated the advantage of integrating multimodal MRI in detecting ABE in neonates with HB, using deep-learning models. Our strategy of diagnosing ABE using deep-learning techniques with multimodal MRI from routine clinical scans is potentially applicable to clinical practice.

Racial disparities in the association between resilience and ART adherence among people living with HIV: the mediating role of depression.

Research examining the mediating role of depressive symptoms in the association between resilience and antiretroviral therapy (ART) adherence is lacking. Therefore, this study aims to examine the mediating role of depression between resilience and ART adherence, as well as to explore whether this relationship varies across racial background. A total of 327 people living with HIV and on ART in South Carolina were surveyed about their ART adherence and mental health, including resilience and depressive symptoms. Path analyses were conducted to determine the direct and indirect effects between resilience, depressive symptoms, and ART adherence. After adjusting for age, gender, income, education, employment and time since diagnosis, among Black individuals, resilience was negatively associated with depressive symptoms (ß = --0.248, p < 0.001); depressive symptoms were negatively associated with ART adherence (ß = -0.166, p = 0.020); however, resilience was not significantly associated with ART adherence. Among White individuals, there was no statistically significant association. The indirect effect between resilience and ART adherence through depressive symptoms was statistically significant (ß = 0.041, p = 0.040) for Black individuals, while not statistically significant for White individuals (ß = 0.024, p = 0.578). Interventions aimed at improving ART adherence, which attenuate depressive symptoms through accentuating resilience may be especially beneficial for Black populations living with HIV.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high-grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study.

OBJECTIVE: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. DESIGN: Retrospective cohort study. SETTING: Two tertiary referral university hospitals. POPULATION: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020. METHODS: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. MAIN OUTCOME MEASURES: CRS 3, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups. CONCLUSIONS: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Hepatic NCoR1 deletion exacerbates alcohol-induced liver injury in mice by promoting CCL2-mediated monocyte-derived macrophage infiltration.

Nuclear receptor corepressor 1 (NCoR1) is a corepressor of the epigenetic regulation of gene transcription that has important functions in metabolism and inflammation, but little is known about its role in alcohol-associated liver disease (ALD). In this study, we developed mice with hepatocyte-specific NCoR1 knockout (NCoR1Hep-/-) using the albumin-Cre/LoxP system and investigated the role of NCoR1 in the pathogenesis of ALD and the underlying mechanisms. The traditional alcohol feeding model and NIAAA model of ALD were both established in wild-type and NCoR1Hep-/- mice. We showed that after ALD was established, NCoR1Hep-/- mice had worse liver injury but less steatosis than wild-type mice. We demonstrated that hepatocyte-specific loss of NCoR1 attenuated liver steatosis by promoting fatty acid oxidation by upregulating BMAL1 (a circadian clock component that has been reported to promote peroxisome proliferator activated receptor alpha (PPARα)-mediated fatty ß-oxidation by upregulating de novo lipid synthesis). On the other hand, hepatocyte-specific loss of NCoR1 exacerbated alcohol-induced liver inflammation and oxidative stress by recruiting monocyte-derived macrophages via C-C motif chemokine ligand 2 (CCL2). In the mouse hepatocyte line AML12, NCoR1 knockdown significantly increased ethanol-induced CCL2 release. These results suggest that hepatocyte NCoR1 plays distinct roles in controlling liver inflammation and steatosis, which provides new insights into the development of treatments for steatohepatitis induced by chronic alcohol consumption.

Automatic Classification of Hepatic Cystic Echinococcosis Using Ultrasound Images and Deep Learning.

BACKGROUND: Hepatic cystic echinococcosis is the main form of hepatic echinococcosis, which is a life-threatening liver disease caused by parasites that requires a precise diagnosis and proper treatment. OBJECTIVE: This study focuses on the automatic classification system of five different subtypes of hepatic cystic echinococcosis based on ultrasound images and deep learning algorithms. METHODS: Three popular deep convolutional neural networks (VGG19, Inception-v3, and ResNet18) with and without pretrained weights were selected to test their performance on the classification task, and the experiments were followed by a 5-fold cross-validation process. RESULTS: A total of 1820 abdominal ultrasound images covering five subtypes of hepatic cystic echinococcosis from 967 patients were used in the study. The classification accuracy for the models with pretrained weights (fine-tuning) ranged from 88.2 to 90.6%. The best accuracy of 90.6% was obtained by VGG19. For comparison, the models without pretrained weights (from scratch) achieved a lower accuracy, ranging from 69.4 to 75.1%. CONCLUSION: Deep convolutional neural networks with pretrained weights are capable of recognizing different subtypes of hepatic cystic echinococcosis from ultrasound images, which are expected to be applied in the computer-aided diagnosis systems in future work.

N-Octyl Caffeamide, a Caffeic Acid Amide Derivative, Prevents Progression of Diabetes and Hepatic Steatosis in High-Fat Diet Induced Obese Mice.

The underlying pathological mechanisms of diabetes are complicated and varied in diabetic patients, which may lead to the current medications often failing to maintain glycemic control in the long term. Thus, the discovery of diverse new compounds for developing medicines to treat diabetes and its complications are urgently needed. Polyphenols are metabolites of plants and have been employed in the prevention and treatment of a variety of diseases. Caffeic acid phenethyl ester (CAPE) is a category of compounds structurally similar to polyphenols. In this study, we aimed to investigate the antidiabetic activity and potential molecular mechanisms of a novel synthetic CAPE derivative N-octyl caffeamide (36M) using high-fat (HF) diet induced obese mouse models. Our results demonstrate that 36M prevented the progression of diabetes in the HF diet fed obese mice via increasing phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibiting expression of protein tyrosine phosphatase 1B (PTP1B). We also found that 36M could prevent hepatic lipid storage in the HF diet fed mice via inhibition of fatty acid synthase and lipid droplet proteins, including perilipins and Fsp27. In conclusion, 36M is a potential candidate compound that can be developed as AMPK inhibitor and PTP1B inhibitor for treating diabetes and hepatic steatosis.

Integrated analysis of mRNA-seq and miRNA-seq reveals the advantage of polyploid Solidago canadensis in sexual reproduction.

BACKGROUND: The invasion of Solidago canadensis probably related to polyploidy, which may promotes its potential of sexual reproductive. S. canadensis as an invasive species which rapidly widespread through yield huge numbers of seed, but the mechanism remains unknown. To better understand the advantages of sexual reproduction in hexaploid S. canadensis, transcriptome and small RNA sequencing of diploid and hexaploid cytotypes in flower bud and fruit development stages were performed in this study. RESULTS: The transcriptome analysis showed that in the flower bud stage, 29 DEGs were MADS-box related genes with 14 up-regulated and 15 down-regulated in hexaploid S. canadensis; 12 SPL genes were detected differentially expressed with 5 up-regulated and 7 down-regulated. In the fruit development stage, 26 MADS-box related genes with 20 up-regulated and 6 down-regulated in hexaploid S. canadensis; 5 SPL genes were all up-regulated; 28 seed storage protein related genes with 18 were up-regulated and 10 down-regulated. The weighted gene co-expression network analysis (WGCNA) identified 19 modules which consisted of co-expressed DEGs with functions such as sexual reproduction, secondary metabolism and transcription factors. Furthermore, we discovered 326 miRNAs with 67 known miRNAs and 259 novel miRNAs. Some of miRNAs, such as miR156, miR156a and miR156f, which target the sexual reproduction related genes. CONCLUSION: Our study provides a global view of the advantages of sexual reproduction in hexaploid S. canadensis based on the molecular mechanisms, which may promote hexaploid S. canadensis owing higher yield and fruit quality in the process of sexual reproduction and higher germination rate of seeds, and finally conductive to diffusion, faster propagation process and enhanced invasiveness.

Circ_CLIP2 promotes glioma progression through targeting the miR-195-5p/HMGB3 axis.

BACKGROUND: Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma. METHODS: The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and ß-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3. RESULTS: The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/ß-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/ß-catenin signaling, which were reversed by silencing of HMGB3. CONCLUSION: Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/ß-catenin signaling. This study may provide potential therapeutic targets against glioma.

Optical fiber time transmission technology based on a double-fiber round-trip method.

In this paper, an optical fiber time transmission technology based on a double-fiber round-trip method is provided. In the system, the one-way transmission delay from the master station to the slave station can be calculated directly through the measurement of three time interval counters and their ratio relationship. The method eliminates the influence of fiber length expansion and round-trip transmission delay fluctuation, which is caused by ambient temperature change. The master and slave stations are connected by 100 km and 80 km optical fibers, respectively, and the temperature of the optical fiber link varies from -20∘C to 40°C. Compared with the single-fiber round-trip method, the time interval error of a double-fiber round-trip method is reduced from 1.4 ns to 80 ps when the wavelength is 1310-1550 nm, and from 320 to 80 ps when the wavelength is 1490-1550 nm.