Metabolome and Transcriptome Analysis Revealed the Pivotal Role of Exogenous Melatonin in Enhancing Salt Tolerance in Vitis vinifera L.

Vitis vinifera L. possesses high economic value, but its growth and yield are seriously affected by salt stress. Though melatonin (MT) has been widely reported to enhance tolerance towards abiotic stresses in plants, the regulatory role melatonin plays in resisting salt tolerance in grapevines has scarcely been studied. Here, we observed the phenotypes under the treatment of different melatonin concentrations, and then transcriptome and metabolome analyses were performed. A total of 457 metabolites were detected in CK- and MT-treated cell cultures at 1 WAT (week after treatment) and 4 WATs. Exogenous melatonin treatment significantly increased the endogenous melatonin content while down-regulating the flavonoid content. To be specific, the melatonin content was obviously up-regulated, while the contents of more than a dozen flavonoids were down-regulated. Auxin response genes and melatonin synthesis-related genes were regulated by the exogenous melatonin treatment. WGCNA (weighted gene coexpression network analysis) identified key salt-responsive genes; they were directly or indirectly involved in melatonin synthesis and auxin response. The synergistic effect of salt and melatonin treatment was investigated by transcriptome analysis, providing additional evidence for the stress-alleviating properties of melatonin through auxin-related pathways. The present study explored the impact of exogenous melatonin on grapevines' ability to adapt to salt stress and provided novel insights into enhancing their tolerance to salt stress.

Short- and long-term outcomes of laparoscopic versus open gastrectomy after neoadjuvant chemotherapy: A case-control study using a propensity score matching method.

Background: Neoadjuvant chemotherapy (NACT) is increasingly becoming the recommended treatment for locally advanced gastric cancer (LAGC) with promising results. According to previous reports, few studies have evaluated the benefits of laparoscopic gastrectomy (LG) after NACT. Methods: 135 patients from our center who underwent gastrectomy with NACT were available, including 41 patients of LG and 94 OG between July 2018 and July 2022. To reduce selection bias, we used the nearest neighbor method and set caliper = 0.2 for 3:1 matching between LG and OG groups for propensity score matching method (PSM). After PSM, the matched 41 patients with LG and 80 patients with OG formed the cohort, respectively. Univariate and multivariate Cox analyses were performed on all variables to determine independent risk factors associated with survival. Results: LG had a longer operating time compared to OG [260.00 min (220.00 min, 300.00 min) vs. 200.00 min (160.00 min, 260 min), P < 0.001]. The estimated blood loss, metastatic lymph nodes (LN), total LN examined, postoperative hospital stays, blood transfusion (P>0.05) and the incidence of postoperative complications did not show statistical differences from the OG group (P = 0.084). The type of surgery (LG vs. OG) did not show a significant risk propensity in the univariate and multivariate Cox analysis (HR = 0.69, P = 0.36, 95 % CI: 0.31-1.53). Through the Kaplan-Meier curves, a certain trend showed that the LG group had a better long-term survival outcomes than the OG group, although there was no statistical difference between two groups (P>0.05). Conclusion: LG is a promising treatment option for LAGC patients receiving NACT and had an acceptable safety and efficacy compared to OG.

Multidimensional Analysis of a Cell-Free DNA Whole Methylome Sequencing Assay for Early Detection of Gastric Cancer: Protocol for an Observational Case-Control Study.

BACKGROUND: Commonly used noninvasive serological indicators serve as a step before endoscope diagnosis and help identify the high-risk gastric cancer (GC) population. However, they are associated with high false positives and high false negatives. Alternative noninvasive approaches, such as cancer-related features in cell-free DNA (cfDNA) fragments, have been gradually identified and play essential roles in early cancer detection. The integrated analysis of multiple cfDNA features has enhanced detection sensitivity compared to individual features. OBJECTIVE: This study aimed to develop and validate an assay based on assessing genomic-scale methylation and fragmentation profiles of plasma cfDNA for early cancer detection, thereby facilitating the early diagnosis of GC. The primary objective is to evaluate the overall specificity and sensitivity of the assay in predicting GC within the entire cohort, and subsequently within each clinical stage of GC. The secondary objective involved investigating the specificity and sensitivity of the assay in combination with possible serological indicators. METHODS: This is an observational case-control study. Blood samples will be prospectively collected before gastroscopy from 180 patients with GC and 180 nonmalignant control subjects (healthy or with benign gastric diseases). Cases and controls will be randomly divided into a training and a testing data set at a ratio of 2:1. Plasma cfDNA will be isolated and extracted, followed by bisulfite-free low-depth whole methylome sequencing. A multidimensional model named Thorough Epigenetic Marker Integration Solution (THEMIS) will be constructed in the training data set. The model includes features such as the methylated fragment ratio, chromosomal aneuploidy of featured fragments, fragment size index, and fragment end motif. The performance of the model in distinguishing between patients with cancer and noncancer controls will then be evaluated in the testing data set. Furthermore, GC-related biomarkers, such as pepsinogen, gastrin-17, and Helicobacter pylori, will be measured for each patient, and their predictive accuracy will be assessed both independently and in combination with the THEMIS model. RESULTS: Recruitment began in November 2022 and will be ended in April 2024. As of August 2022,250 patients have been enrolled. The final data analysis is anticipated to be completed by September 2024. CONCLUSIONS: This is the first registered case-control study designed to investigate a stacked ensemble model integrating several cfDNA features generated from a bisulfite-free whole methylome sequencing assay. These features include methylation patterns, fragmentation profiles, and chromosomal copy number changes, with the aim of identifying the GC population. This study will determine whether multidimensional analysis of cfDNA will prove to be an effective strategy for distinguishing patients with GC from nonmalignant individuals within the Chinese population. We anticipate the THEMIS model will complement the standard-of-care screening and aid in identifying high-risk patients for further diagnosis. TRIAL REGISTRATION: ClinicalTrial.gov NCT05668910; https://www.clinicaltrials.gov/study/NCT05668910. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48247.

Metabolomics and Transcriptomics Revealed a Comprehensive Understanding of the Biochemical and Genetic Mechanisms Underlying the Color Variations in Chrysanthemums.

Flower color is an important characteristic of ornamental plants and is determined by various chemical components, including anthocyanin. In the present study, combined metabolomics and transcriptomics analysis was used to explore color variations in the chrysanthemums of three cultivars, of which the color of JIN is yellow, FEN is pink, and ZSH is red. A total of 29 different metabolites, including nine anthocyanins, were identified in common in the three cultivars. Compared with the light-colored cultivars, all of the nine anthocyanin contents were found to be up-regulated in the dark-colored ones. The different contents of pelargonidin, cyanidin, and their derivates were found to be the main reason for color variations. Transcriptomic analysis showed that the color difference was closely related to anthocyanin biosynthesis. The expression level of anthocyanin structural genes, including DFR, ANS, 3GT, 3MaT1, and 3MaT2, was in accordance with the flower color depth. This finding suggests that anthocyanins may be a key factor in color variations among the studied cultivars. On this basis, two special metabolites were selected as biomarkers to assist in chrysanthemum breeding for color selection.

Astrocytic AT1R deficiency ameliorates Aß-induced cognitive deficits and synaptotoxicity through ß-arrestin2 signaling.

Alzheimer's disease (AD) seriously influences human health, and there is no effective treatment to prevent or cure AD. Recent studies have shown that angiotensin II type 1 receptor (AT1R) blockers significantly reduce the prevalence of AD, while the precise role and mechanism of AT1R in AD remain obscure. In this study, for the first time, we identified that astrocytic but not neuronal AT1R levels were significantly increased in AD model rats and found that astrocyte-specific knockout of AT1R significantly ameliorated amyloid ß (Aß)-induced cognitive deficits and synaptotoxicity. Pretreating astrocytes with an AT1R blocker also alleviated Aß-induced synaptotoxicity in the coculture system of hippocampal neurons and astrocytes. Moreover, AT1R could directly bind to Aß1-42 and activate the astrocytic ß-arrestin2 pathway in a biased manner, and biased inhibition of the astrocytic AT1R/ß-arrestin2 pathway relieved Aß-induced neurotoxicity. Furthermore, we demonstrated that astrocytic AT1R/ß-arrestin2 pathway-mediated synaptotoxicity was associated with the aggregation of autophagosomes, which triggered the disordered degradation of Aß. Our findings reveal a novel molecular mechanism of astrocytic AT1R in Aß-induced neurodegeneration and might contribute to establishing new targets for AD prevention and therapy.

Multidrug-resistant Klebsiella Pneumoniae Infection Led to Resection of the Graft in a Small Bowel Transplant Recipient: A Case Report and Review of the Literature.

BACKGROUND: Infection due to multidrug-resistant Klebsiella pneumoniae is a common cause of graft resection after small bowel transplantation. We report a failed case in which the intestinal graft was resected 18 days after the operation due to postoperative infection with multidrug-resistant K pneumoniae and a literature review of other common causes of small bowel transplantation failure have been reported. METHODS: A female, 29 years of age, underwent partial living small bowel transplantation for short bowel syndrome. After the operation, the patient was infected with multidrug-resistant K pneumoniae, even though various anti-infective regimens were employed. It further developed into sepsis and disseminated into intravascular coagulation, leading to exfoliation and necrosis of the intestinal mucosa. Finally, the intestinal graft had to be resected to save the patient's life. RESULTS: Multidrug-resistant K pneumoniae infection often affects the biological function of intestinal grafts and can even lead to necrosis. Other common causes of failure, including postoperative infection, rejection, post-transplantation lymphoproliferative disorder, graft-vs-host disease, surgical complications, and other related diseases, were also discussed throughout the literature review. CONCLUSIONS: Pathogenesis due to diverse and interrelated factors makes the survival of intestinal allografts a great challenge. Therefore, only by fully understanding and mastering the common causes of surgical failure can the success rate of small bowel transplantation be effectively improved.

Comparison of thoracoabdominal versus abdominal-transhiatal surgical approaches in Siewert type II adenocarcinoma at the esophagogastric junction: Protocol for a prospective multicenter randomized controlled trial.

Background: Siewert type II adenocarcinoma of the esophagogastric junction (Siewert II AEG) can be resected by the right thoracoabdominal surgical approach (RTA) or abdominal-transhiatal surgical approach (TH) under minimally invasive conditions. Although both surgical methods achieve complete tumor resection, there is a debate as to whether the former method is superior to or at least noninferior to the latter in terms of surgical safety. Currently, a small number of retrospective studies have compared the two surgical approaches, with inconclusive results. As such, a prospective multicenter randomized controlled trial is necessary to validate the value of RTA (Ivor-Lewis) compared to TH. Methods: The planned study is a prospective, multicenter, randomized clinical trial. Patients (n=212) with Siewert II AEG that could be resected by either of the above two surgical approaches will be included in this trial and randomized to the RTA group (n=106) or the TH group (n=106). The primary outcome will be 3-year disease-free survival (DFS). The secondary outcomes will include 5-year overall survival (OS), incidence of postoperative complications, postoperative mortality, local recurrence rate, number and location of removed lymph nodes, quality of life (QOL), surgical Apgar score, and duration of the operation. Follow-ups are scheduled every three months for the first 3 years after the surgery and every six months for the next 2 years. Discussion: Among Siewert II AEG patients with resectable tumors, this is the first prospective, randomized clinical trial comparing the surgical safety of minimally invasive RTA and TH. RTA is hypothesized to provide better digestive tract reconstruction and dissection of mediastinal lymph nodes while maintaining a high quality of life and good postoperative outcome. Moreover, this trial will provide a high level of evidence for the choice of surgical procedures for Siewert II AEG. Clinical trial registration: Chinese Ethics Committee of Registering Clinical Trials, identifier (ChiECRCT20210635); Clinical Trial.gov, identifier (NCT05356520).

Simple security proof of coherent-one-way quantum key distribution.

Coherent-one-way quantum key distribution (COW-QKD), which requires a simple experimental setup and has the ability to withstand photon-number-splitting attacks, has been not only experimentally implemented but also commercially applied. However, recent studies have shown that the current COW-QKD system is insecure and can only distribute secret keys safely within 20 km of the optical fiber length. In this study, we propose a practical implementation of COW-QKD by adding a two-pulse vacuum state as a new decoy sequence. This proposal maintains the original experimental setup as well as the simplicity of its implementation. Utilizing detailed observations on the monitoring line to provide an analytical upper bound on the phase error rate, we provide a high-performance COW-QKD asymptotically secure against coherent attacks. This ensures the availability of COW-QKD within 100 km and establishes theoretical foundations for further applications.

Study protocol for feasibility and safety of adopting early oral feeding in post total laparoscopic total gastrectomy (overlap esophagojejunostomy): A multicentre randomized controlled trial.

Background: Total laparoscopic total gastrectomy (TLTG) for gastric cancer, especially with overlap esophagojejunostomy, has been verified that it has advantages of minimally invasion, less intraoperative bleeding, and faster recovery. Meanwhile, early oral feeding (EOF) after the operation has been demonstrated to significantly promote early rehabilitation in patients, particularly with distal gastrectomy. However, due to the limited application of TLTG, there is few related research proving whether it is credible or safe to adopt EOF after TLTG (overlap esophagojejunostomy). So, it is urgent to start a prospective, multicenter, randomized clinical trials to supply high level evidence. Methods/design: This study is a prospective, multicenter, randomized controlled trial with 200 patients (100 in each group). These eligible participants are randomly allocated into two different groups, including EOF group and delay oral feeding (DOF) group after TLTG (overlap esophagojejunostomy). Anastomotic leakage will be carefully observed and recorded as the primary endpoints; the period of the first defecation and exhaust, postoperative length of stay and hospitalization expenses will be recorded as secondary endpoints to ascertain the feasibility and safety of adopting EOF after TLTG (overlap esophagojejunostomy). Discussion: Recently, the adoption of TLTG was limited due to its difficult anastomotic procedure, especially in vivo esophagojejunostomy. With the innovation and improvement of operating techniques, overlap esophagojejunostomy with linear staplers simplified the anastomotic steps and reduced operational difficulties after TLTG. Meanwhile, EOF had received increasing attention from surgical clinicians as a nutrition part of enhanced recovery after surgery (ERAS), which had shown better results in patients after distal gastrectomy. Considering the above factors, we implemented EOF protocol to evaluate the feasibility and safety of adopting EOF after TLTG (overlap esophagojejunostomy), which provided additional evidence for the development of clinical nutrition guidelines. Clinical trial registration: [www.chictr.org.cn], identifier [ChiECRCT20200440 and ChiCTR2000040692].

Prognostic model based on m6A-associated lncRNAs in esophageal cancer.

Background: This research aimed to build an m6A-associated lncRNA prognostic model of esophageal cancer that can be used to predict outcome in esophageal cancer patients. Methods: RNA sequencing transcriptome data and clinical information about patients with esophageal cancer were obtained according to TCGA. Twenty-four m6A-associated genes were selected based on previous studies. m6A-associated lncRNAs were determined through Pearson correlation analysis. Three m6A-associated lncRNA prognostic signatures were built through analysis of the training set using univariate, LASSO, and multivariate Cox regression. To validate the stabilization of the risk signature, Kaplan-Meier and ROC curve analyses were performed on the testing and complete sets. The prognoses of EC patients were predicted quantitatively by building a nomogram. GSEA was conducted to analyze the underlying signaling pathways and biological processes. To identify the underlying mechanisms through which the lncRNAs act, we constructed a PPI network and a ceRNA network and conducted GO and KEGG pathway analyses. EC samples were evaluated using the ESTIMATE algorithm to compute stromal, immune, and estimate scores. The ssGSEA algorithm was used to quantitatively infer immune cell infiltration and immune functions. The TIDE algorithm was performed to simulate immune evasion and predict the response to immunotherapy. Results: We identified and validated an m6A-associated lncRNA risk model in EC that could correctly and reliably predict the OS of EC patients. The ceRNA network, PPI network, and GO and KEGG pathway analyses confirmed and the underlying mechanisms and functions provided enlightenment regarding therapeutic strategies for EC. Immunotherapy responses were better in the low-risk subgroup, and PD-1 and CTLA4 checkpoint immunotherapy benefited the patients in the low-risk subgroup. Conclusions: We constructed a new m6A-related lncRNA prognostic risk model of EC, based on three m6A-related lncRNAs: LINC01612, AC025166.1 and AC016876.2, that can predict the prognoses of EC patients.

Knockdown of astrocytic Grin2a exacerbated sleep deprivation-induced cognitive impairments and elevation of amyloid-beta.

Sleep disorders are associated with cognitive impairments, greater amyloid-ß (Aß) burden and increased risk of developing Alzheimer's disease, while the underlying mechanism is unclear. N-methyl-d-aspartate receptors (NMDARs), as vital modulators of cognition, are sensitive to sleep disturbance. Sleep deprivation (SD) could induce the alterations of neuronal NMDAR subunits expression, however the alterations of astrocytic NMDARs in SD have not been reported. Our previous study has demonstrated knockdown of astrocytic Grin2a (gene encoding NMDAR subunit GluN2A) could aggravate Aß-induced cognitive impairments, but what role astrocytic GluN2A may play in SD is unknown. Here we focused on the changes and roles of hippocampal astrocytic GluN2A in SD. Our results showed SD increased the expression of astrocytic GluN2A. Specific knockdown of hippocampal astrocytic Grin2a aggravated SD-induced cognitive decline, elevated Aß, and attenuated the SD-induced increase in autophagy flux. Our finding, for the first time, revealed a novel neuroprotective role for astrocytic GluN2A in SD, which may be helpful for developing new preventive and therapeutic targets to sleep disorders.

Comparison of the Efficacy of D2 Gastrectomy Plus Liver Radiofrequency Combined With Chemotherapy Versus Chemotherapy Alone in the Treatment of Advanced Gastric Cancer With Unresectable Synchronous Liver Metastases: A Multicenter Randomized Controlled Trial Protocol.

Background: Whether patients with advanced gastric cancer with unresectable synchronous liver metastases require surgical treatment remains a controversial topic among surgeons. Recently, an open-label multicenter, international RCT study show that compared with chemotherapy alone, gastric resection combined with chemotherapy had no survival advantage for advanced gastric cancer with unresectable synchronous liver metastases. A limitation of this study was that gastrectomy for gastric cancers was restricted to D1 lymphadenectomy and no metastatic lesions were removed. Whether D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy could provide benefits to these patients is worthy of further confirmation by high-level evidence-based medicine. Methods/Design: This study will investigate the efficacy of D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy compared to chemotherapy alone in a prospective, multicenter, randomized controlled trial that will enroll 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. The patients will be randomly divided into two groups: the test group (D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy, n=100) and the control group (chemotherapy alone, n=100). The patients' general information, past medical history, laboratory tests, imaging results, surgery details, and chemotherapy details will be recorded and analysed. The overall survival (OS) will be recorded as primary endpoints. Progression-free survival (PFS) and the total incidence of complications will be recorded as secondary endpoints. Discussion: This study is to establish a multicentre randomized controlled trial to compare the efficacy of D2 gastrectomy plus liver radiofrequency combined with postoperative chemotherapy versus chemotherapy alone. Trial Registration: Chinese Clinical Trial Registry, Approved No. of ethics committee:ChiECRCT20200331. Registered on 15 November 2020. Registration number:ChiCTR2000039964. The study has received full ethical and institutional approval. Advantages and Limitations of this Study: This is the first clinical trial that will provide evidence on the efficacy of D2 gastrectomy plus liver radiofrequency combined with chemotherapy versus chemotherapy alone for the treatment of advanced gastric cancer with unresectable synchronous liver metastases. A prospective RCT with 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier ChiCTR2000039964.

Initial experience with triple port laparoscopic distal gastrectomy.

Objective: This study aimed to compare the feasibility and short-term clinical efficacy of triple-port laparoscopic distal gastrectomy (TPLDG) with five-port laparoscopic distal gastrectomy (FPLDG). Methods: From April 2020 to December 2021, this retrospective study included all consecutive patients (n = 21) who underwent TPLDG + D2 lymph node dissection, and randomly screened patients who underwent FPLDG + D2 lymph node dissection during this period (n = 30). Results: There were no significant differences in intraoperative (P > 0.05) and postoperative complication rate (P = 0.635) between the two groups. The changes in the first ambulation, flatus, water intake after surgery and postoperative hospitalization were also similar between the two groups (P > 0.05). However, time to abdominal drainage tube removal (1.62 ± 0.15 days vs. 2.00 ± 0.12 days, P = 0.046), NRS pain score on the first postoperative day (1.91 ± 0.15 days vs. 2.47 ± 0.12 days, P = 0.004) and hemameba level on the third postoperative day (7.89 ± 0.51 days vs. 10.52 ± 0.58 days, P = 0.002) were significantly lower in the TPLDG group compared to the FPLDG group. Conclusion: TPLDG is a safer, feasible, and short-term alternative to conventional LDG for distal gastric cancer.

Deformable Generator Networks: Unsupervised Disentanglement of Appearance and Geometry.

We present a deformable generator model to disentangle the appearance and geometric information for both image and video data in a purely unsupervised manner. The appearance generator network models the information related to appearance, including color, illumination, identity or category, while the geometric generator performs geometric warping, such as rotation and stretching, through generating deformation field which is used to warp the generated appearance to obtain the final image or video sequences. Two generators take independent latent vectors as input to disentangle the appearance and geometric information from image or video sequences. For video data, a nonlinear transition model is introduced to both the appearance and geometric generators to capture the dynamics over time. The proposed scheme is general and can be easily integrated into different generative models. An extensive set of qualitative and quantitative experiments shows that the appearance and geometric information can be well disentangled, and the learned geometric generator can be conveniently transferred to other image datasets that share similar structure regularity to facilitate knowledge transfer tasks.

Generative VoxelNet: Learning Energy-Based Models for 3D Shape Synthesis and Analysis.

3D data that contains rich geometry information of objects and scenes is valuable for understanding 3D physical world. With the recent emergence of large-scale 3D datasets, it becomes increasingly crucial to have a powerful 3D generative model for 3D shape synthesis and analysis. This paper proposes a deep 3D energy-based model to represent volumetric shapes. The maximum likelihood training of the model follows an "analysis by synthesis" scheme. The benefits of the proposed model are six-fold: first, unlike GANs and VAEs, the model training does not rely on any auxiliary models; second, the model can synthesize realistic 3D shapes by Markov chain Monte Carlo (MCMC); third, the conditional model can be applied to 3D object recovery and super resolution; fourth, the model can serve as a building block in a multi-grid modeling and sampling framework for high resolution 3D shape synthesis; fifth, the model can be used to train a 3D generator via MCMC teaching; sixth, the unsupervisedly trained model provides a powerful feature extractor for 3D data, which is useful for 3D object classification. Experiments demonstrate that the proposed model can generate high-quality 3D shape patterns and can be useful for a wide variety of 3D shape analysis.

Secure and practical multiparty quantum digital signatures.

Quantum digital signatures (QDSs) promise information-theoretic security against repudiation and forgery of messages. Compared with currently existing three-party QDS protocols, multiparty protocols have unique advantages in the practical case of more than two receivers when sending a mass message. However, complex security analysis, numerous quantum channels and low data utilization efficiency make it intractable to expand three-party to multiparty scenario. Here, based on six-state non-orthogonal encoding protocol, we propose an effective multiparty QDS framework to overcome these difficulties. The number of quantum channels in our protocol only linearly depends on the number of users. The post-matching method is introduced to enhance data utilization efficiency and make it linearly scale with the probability of detection events even for five-party scenario. Our work compensates for the absence of practical multiparty protocols, which paves the way for future QDS networks.

Suppression of TCAB1 expression induced cellular senescence by lessening proteasomal degradation of p21 in cancer cells.

BACKGROUND: TCAB1, a.k.a. WRAP53ß or WDR79, is an important molecule for the maintenance of Cajal bodies and critically involved in telomere elongation and DNA repair. Upregulation of TCAB1 were discovered in a variety types of cancers. However, the function of TCAB1 in tumor cell senescence remains absent. METHODS: The TCAB1 knockdown cell lines were constructed. The expression levels of TCAB1, p21, p16 and p53 were detected by qRT-PCR and western blotting. Staining of senescence-associated ß-galactosidase was used to detect senescent cells. The ubiquitination of the p21 was analysed by immunoprecipitation and in vivo ubiquitination assay. TCGA databases were employed to perform in silico analyses for the mRNA expression of TCAB1, p21, p16 and p53. RESULTS: Here, we discovered that knockdown of TCAB1 induced rapid progression of cellular senescence in A549, H1299 and HeLa cells. In exploiting the mechanism underlining the role of TCAB1 on senescence, we found a significant increase of p21 at the protein levels upon TCAB1 depletion, whereas the p21 mRNA expression was not altered. We verified that TCAB1 knockdown was able to shunt p21 from proteasomal degradation by regulating the ubiquitination of p21. In rescue assays, it was demonstrated that decreasing the expression of p21 or increasing the expression of TCAB1 were able to attenuate the cellular senescence process induced by TCAB1 silencing. CONCLUSIONS: This study revealed the importance of TCAB1 for its biological functions in the regulation of cell senescence. Our results will be helpful to understand the mechanisms of senescence in cancer cells, which could provide clues for designing novel strategies for developing effective treatment regimens.

S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation.

Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.

Classification of schizophrenia using general linear model and support vector machine via fNIRS.

Schizophrenia is a type of serious mental illness. In clinical practice, it is still a challenging problem to identify schizophrenia-related brain patterns due to the lack of objective physiological data support and a unified data analysis method, physicians can only use the subjective experience to distinguish schizophrenia patients and healthy people, which may easily lead to misdiagnosis. In this study, we designed an optimized data-preprocessing method accompanied with techniques of general linear model feature extraction, independent sample t-test feature selection and support vector machine to identify a set of robust fNIRS pattern features as a biomarker to discriminate schizophrenia patients and healthy people. Experimental results demonstrated that the proposed combination way of data preprocessing, feature extraction, feature selection and support vector machine classification can effectively identify schizophrenia patients and the healthy people with a leave-one-out-cross-validation classification accuracy of 89.5%.

Cooperative Training of Descriptor and Generator Networks.

This paper studies the cooperative training of two generative models for image modeling and synthesis. Both models are parametrized by convolutional neural networks (ConvNets). The first model is a deep energy-based model, whose energy function is defined by a bottom-up ConvNet, which maps the observed image to the energy. We call it the descriptor network. The second model is a generator network, which is a non-linear version of factor analysis. It is defined by a top-down ConvNet, which maps the latent factors to the observed image. The maximum likelihood learning algorithms of both models involve MCMC sampling such as Langevin dynamics. We observe that the two learning algorithms can be seamlessly interwoven into a cooperative learning algorithm that can train both models simultaneously. Specifically, within each iteration of the cooperative learning algorithm, the generator model generates initial synthesized examples to initialize a finite-step MCMC that samples and trains the energy-based descriptor model. After that, the generator model learns from how the MCMC changes its synthesized examples. That is, the descriptor model teaches the generator model by MCMC, so that the generator model accumulates the MCMC transitions and reproduces them by direct ancestral sampling. We call this scheme MCMC teaching. We show that the cooperative algorithm can learn highly realistic generative models.