Catalpol represses the migration, proliferation and epithelial mesenchymal transition of TGF β2 stimulated lens epithelial cells via TGF β/Smad and Notch1 signaling pathways

Purpose: To investigate the role of catalpol in posterior capsule opacification (PCO). Methods: Human lens epithelial cells (SRA01/04) were treated with TGF-β2 or co-treated with TGF-β2 and different concentrations of catalpol. Cell migration and viability were assessed via wound healing and CCK8, respectively. Epithelial- esenchymal transition and the underlying mechanism of action were evaluated using western blot. Results: Treatment with TGF-β2 significantly increased cell viability and promoted the migration of SRA01/04 (p < 0.001). However, catalpol significantly reduced cell viability and repressed the migration of TGF-β2-stimulated SRA01/04 (p < 0.001). Moreover, TGF-β2-stimulated increases in fibronectin, α-smooth muscle actin (α-SMA), snail and vimentin. Decreases of E-cadherin and connexin-43 in SRA01/04 were reversed by catalpol. Moreover, TGF-β2-stimulated the up-regulation of p-smad2/3, while SRA01/04 was down-regulated by catalpol, but attenuated TGF-β2-stimulated increases in Notch1 and Jagged1 in SRA01/04. Conclusion: Catalpol inhibits TGF-β2-stimulated migration, proliferation and epithelial- esenchymal transition of SRA01/04 through the inactivation of TGF-β/Smad and Notch1 signaling. Catalpol might be a novel preventive agent for PCO. However, the effect of catalpol on animal models of PCO should be investigated further

STUDY ON THE PERFORMANCE OF HIGH-MODULUS ASPHALT CONCRETE PAVEMENT IN EXTREME CURVES OR STEEP SLOPES OF TRUNK HIGHWAY

With the purpose of the project, we determined the performance of high modulus asphalt concrete (HMAC) pavement in sharp curves or steep slopes of the trunk highway. We selected bending of road surface, bending and stretching strain at the bottom of surface layer, vertical compressive strain at the bottom of surface layer as research parameter index. By using the three-dimensional model analysis function of the finite element software ANSYS, the mechanical models of asphalt pavement with three different structures under the action of steep slope and heavy traffic are established. Firstly, the conventional asphalt pavement consists of 4cmAC-13 bituminous pavement (the top layer) and 6cmAC-20 bituminous pavement (the bottom layer). Then, the HMAC pavement 1 consists of 4cmAC-13 bituminous pavement (the top layer) and 6cmAC-EME14 bituminous pavement (the bottom layer).The HMAC pavement 2 consists of 6cmAC-EME14 bituminous pavement (the top layer) and 4cmAC-13 bituminous pavement (the bottom layer). Then we tried it out that for the deflection value, the HMAC pavement 1 was 5.34 percentage point reduced than the conventional asphalt pavement. At the same time, the HMAC pavement 2 was 6.95 percentage point reduced than the conventional asphalt pavement. So, it can significantly reduce the bending strain at the bottom of the surface layer by using HMAC as asphalt pavement structure. For the resistance to shear strain and vertical compressive strain at the bottom of the surface layer, the HMAC pavement 1 is the best. Then the HMAC pavement 2 follows and then the conventional asphalt pavement. The results show that the HMAC can significantly improve the overall stiffness of the pavement and reduce the bending, shearing and vertical strain. Meanwhile, it can also reduce the occurrence of wheel rut, upheaval, fatigue crack and other common diseases

Hi Sheldon! Creating Deep Personalized Characters from TV Shows

Imagine an interesting multimodal interactive scenario that you can see, hear, and chat with an AI-generated digital character, who is capable of behaving like Sheldon from The Big Bang Theory, as a DEEP copy from appearance to personality. Towards this fantastic multimodal chatting scenario, we propose a novel task, named Deep Personalized Character Creation (DPCC): creating multimodal chat personalized characters from multimodal data such as TV shows. Specifically, given a single- or multi-modality input (text, audio, video), the goal of DPCC is to generate a multi-modality (text, audio, video) response, which should be well-matched the personality of a specific character such as Sheldon, and of high quality as well. To support this novel task, we further collect a character centric multimodal dialogue dataset, named Deep Personalized Character Dataset (DPCD), from TV shows. DPCD contains character-specific multimodal dialogue data of ~10k utterances and ~6 hours of audio/video per character, which is around 10 times larger compared to existing related datasets.On DPCD, we present a baseline method for the DPCC task and create 5 Deep personalized digital Characters (DeepCharacters) from Big Bang TV Shows. We conduct both subjective and objective experiments to evaluate the multimodal response from DeepCharacters in terms of characterization and quality. The results demonstrates that, on our collected DPCD dataset, the proposed baseline can create personalized digital characters for generating multimodal response.Our collected DPCD dataset, the code of data collection and our baseline will be published soon

Learning List-Level Domain-Invariant Representations for Ranking

Domain adaptation aims to transfer the knowledge learned on (data-rich) source domains to (low-resource) target domains, and a popular method is invariant representation learning, which matches and aligns the data distributions on the feature space. Although this method is studied extensively and applied on classification and regression problems, its adoption on ranking problems is sporadic, and the few existing implementations lack theoretical justifications. This paper revisits invariant representation learning for ranking. Upon reviewing prior work, we found that they implement what we call item-level alignment, which aligns the distributions of the items being ranked from all lists in aggregate but ignores their list structure. However, the list structure should be leveraged, because it is intrinsic to ranking problems where the data and the metrics are defined and computed on lists, not the items by themselves. To close this discrepancy, we propose list-level alignment -- learning domain-invariant representations at the higher level of lists. The benefits are twofold: it leads to the first domain adaptation generalization bound for ranking, in turn providing theoretical support for the proposed method, and it achieves better empirical transfer performance for unsupervised domain adaptation on ranking tasks, including passage reranking.Comment: NeurIPS 2023. Comparison to v1: revised presentation and proof of Corollary 4.

Blow to the northeast? Intraspecific differentiation of populus davidiana suggests a northeastward skew of a phylogeographic break boundary in East Asia

Aim There is increasing interest in the role that biological traits, and historical and biogeographic processes, play in the formation of phylogeographic patterns. An arid belt that once existed in northern China might have affected many plants, but this has yet to be tested in an arid-tolerant, wind-dispersed species. Here, we tested how intrinsic and extrinsic factors have affected the phylogeography of Populus davidiana. Location East Asia. Methods Genetic variation was surveyed across 40 populations (555 individuals) covering the Chinese range of P. davidiana, using 16 nuclear microsatellite loci (nSSRs) and four chloroplast fragments (cpDNA). Demographic and migration hypotheses were tested using coalescent-based approaches, and the present and past potential distributions were predicted using species distribution modelling. Results Molecular data divide P. davidiana into two lineages, north-eastern China (NECR) and central and northern China (CNCR); however, the dividing line is around 118ºE for nSSRs, but 122ºE for cpDNA. The range and habitat of the two lineages barely overlap at present, and their ecological separation may have initiated around the Pliocene-Quaternary boundary, when major intraspecific cpDNA clades diverged. NECR and CNCR experienced post-glacial north-eastward and northward range shifts respectively. Bi-directional historical gene flow was detected between NECR and CNCR for both bi-parentally inherited nSSRs and maternally inherited cpDNA. Demographic inferences suggest a severe bottleneck for CNCR and especially NECR, around the latest Pleistocene. Main conclusions The phylogeographic break within P. davidiana reflects the impacts of biogeographic history, climate and biological traits. Its plumed, wind-dispersed seeds might be especially significant because prevailing south-western spring winds may have moved the NECR-CNCR boundary further east than similar phylogenetic breaks in other species, and also moved the cpDNA boundary relative to that for nuclear markers. Biological traits, therefore, should also be considered when examining the genetic and ecological differentiation between closely related taxa

Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia

Background: Although tolvaptan treatment improves hyponatremia, only few studies have investigated whether tolvaptan actually benefits the survival of cirrhotic patients. This study evaluated the impact of tolvaptan on six-month survival of decompensated cirrhotic patients with and without hyponatremia. Methods: Two hundred forty-nine decompensated cirrhotic patients with or without hyponatremia were enrolled in a multicenter cohort study. Patients were divided into two groups according to receiving either tolvaptan or placebo treatment for 7-day. Subsequently, the patients were followed up for 6 months. Results: Two hundred thirty patients, including 98 with hyponatremia (tolvaptan vs. placebo: 69 vs. 29) finished the study. Tolvaptan did not alter serum sodium levels and survival outcome of decompensated cirrhotic patients without hyponatremia. However, tolvaptan treatment remarkably improved serum sodium levels and six-month survival in patients with hyponatremia. Following tolvaptan treatment, serum sodium levels were restored to normal in 63.8% of patients, whereas in patients receiving placebo, only 36.2% showed the same effect (P < 0.05). Compared to a six-month survival rate of 68.97% in patients receiving placebo, the survival rate in tolvapatan-treated patients was 89.94% (P < 0.05). Furthermore, six-month survival rate in the tolvaptan-treated hyponatremia patients with resolved serum sodium was 81.32%, whereas the survival in those with unresolved serum sodium was only 24% (P < 0.05). Conclusions: Tolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium. Trials registration: Clinical trial one: ClinicalTrials.gov ID: NCT00664014 , Registered on April 14, 2008. Clinical trial two: ClinicalTrials.gov ID: NCT01349335 , Registered on March 5, 2010. Clinical trial three: ClinicalTrials.gov ID: NCT01349348 , Registered on May 4, 2011

High sodium intake and fluid overhydration predict cardiac structural and functional impairments in chronic kidney disease

BackgroundHigh sodium intake and fluid overhydration are common factors of and strongly associated with adverse outcomes in chronic kidney disease (CKD) patients. Yet, their effects on cardiac dysfunction remain unclear.AimsThe study aimed to explore the impact of salt and volume overload on cardiac alterations in non-dialysis CKD.MethodsIn all, 409 patients with CKD stages 1–4 (G1–G4) were enrolled. Daily salt intake (DSI) was estimated by 24-h urinary sodium excretion. Volume status was evaluated by the ratio of extracellular water (ECW) to total body water (TBW) measured by body composition monitor. Recruited patients were categorized into four groups according to DSI (6 g/day) and median ECW/TBW (0.439). Echocardiographic and body composition parameters and clinical indicators were compared. Associations between echocardiographic findings and basic characteristics were performed by Spearman’s correlations. Univariate and multivariate binary logistic regression analysis were used to determine the associations between DSI and ECW/TBW in the study groups and the incidence of left ventricular hypertrophy (LVH) and elevated left ventricular filling pressure (ELVFP). In addition, the subgroup effects of DSI and ECW/TBW on cardiac abnormalities were estimated using Cox regression.ResultsOf the enrolled patients with CKD, the median urinary protein was 0.94 (0.28–3.14) g/d and estimated glomerular filtration rate (eGFR) was 92.05 (IQR: 64.52–110.99) mL/min/1.73 m2. The distributions of CKD stages G1–G4 in the four groups was significantly different (p = 0.020). Furthermore, compared to group 1 (low DSI and low ECW/TBW), group 4 (high DSI and high ECW/TBW) showed a 2.396-fold (95%CI: 1.171–4.902; p = 0.017) excess risk of LVH and/or ELVFP incidence after adjusting for important CKD and cardiovascular disease risk factors. Moreover, combined with eGFR, DSI and ECW/TBW could identify patients with higher cardiac dysfunction risk estimates with an AUC of 0.704 (sensitivity: 75.2%, specificity: 61.0%). The specificity increased to 85.7% in those with nephrotic proteinuria (AUC = 0.713). The magnitude of these associations was consistent across subgroups analyses.ConclusionThe combination of high DSI (>6 g/d) and high ECW/TBW (>0.439) independently predicted a greater risk of LVH or ELVFP incidence in non-dialysis CKD patients. Moreover, the inclusion of eGFR and proteinuria improved the risk stratification ability of DSI and ECW/TBW in cardiac impairments in CKD

Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice

Background: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus. Methodology Principal Findings: Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60 % lethality on days 8–10 postinoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. Conclusions/Significance: These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus

Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee

Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2df<5×10−8 in GWAIS, and OR = 0.41, P = 3×10−8 in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients