Search

Recent studies indicate existence of beige adipocytes in adults. Upon activation, beige adipocytes burn energy for thermogenesis and contribute to regulation of energy balance. In this study, we have analyzed whether Jinlida granules (JLD) could activate beige adipocytes. JLD suspended in 0.5% carboxymethyl cellulose (CMC) was gavage fed to db/db mice at a daily dose of 3.8 g/kg. After 10 weeks, body weight, biochemical, and histological analyses were performed. In situ hybridization, immunofluorescence, and western blotting were conducted to test beige adipocyte activation in mice. X9 cells were induced with induction medium and maintenance medium containing 400 μg/mL of JLD. After completion of induction, cells were analyzed by Nile red staining, time polymerase chain reaction (PCR), western blotting, and immunofluorescence to understand the effect of JLD on the activation of beige adipocytes. A molecular docking method was used to preliminarily identify compounds in JLD, which hold the potential activation effect on uncoupling protein 1 (UCP1). JLD treatment significantly improved obesity in db/db mice. Biochemical results showed that JLD reduced blood glucose (GLU), triglyceride (TG), and low-density lipoprotein cholesterol (LDL) levels as well as liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in mice. Hematoxylin and eosin staining (H&E) showed that JLD reduced hepatocyte ballooning changes in the liver. Immunofluorescence showed that JLD increased the expression of the thermogenic protein, UCP1, in the beige adipose tissue of mice. JLD also increased the expression of UCP1 and inhibited the expression of miR-27a in X9 cells. Molecular docking results showed that epmedin B, epmedin C, icariin, puerarin, and salvianolic acid B had potential activation effects on UCP1. The results suggest that JLD may activate beige adipocytes by inhibiting miR-27a expression, thereby promoting thermogenesis in beige adipocytes. This study provides a new pharmacological basis for the clinical use of JLD.

Rapid advances in the smartphone, wearable sensing, and wireless communication provide an unprecedented opportunity to develop mobile systems for smart health management. Mobile cardiac sensing collects health-related data from individuals and enables the extraction of information pertinent to cardiac conditions. However, wireless sensors in ambulatory care settings operate on batteries. All-time sensing and monitoring will result in fast depletion of the battery in the mobile system. There is an urgent need to develop optimal sensing schemes that will reduce energy consumption while satisfying the requirements in the detection of cardiac events. In this article, we develop a constrained Markov decision process (CMDP) framework to optimize mobile electrocardiography (ECG) sensing under the constraint of the energy budget. We first characterize the cardiac states from ECG signals using the heterogeneous recurrence analysis. Second, we model the stochastic dynamics in cardiac processes as a continuous-time Markov chain (CTMC). Third, we optimize the ECG sensing through a CMDP framework under the constraint of energy budget. Finally, we validate and evaluate the performance of our CMDP policy in both simulation and real-world case studies. Experimental results demonstrate that the proposed CMDP policy significantly outperforms the traditional uniform and mean-time-to-event (MTTE) policies. Specifically, the error of state estimation is reduced by 34.0% in the real-world case study for energy-constrained sensing of cardiac events.

Obtaining high-quality sperm is key to improving the success rate of assisted reproductive technology (ART). Although cytokines secreted by cumulus-oocyte complexes (COCs) bind to sperm surface receptors to improve sperm quality, the effects of adding mouse COCs to human tubal fluid (HTF) medium on sperm capacitation have not yet been explored. Eight-week-old ICR mouse COCs were added to HTF medium and crushed to obtain the post-modified HTF medium. Compared with using HTF medium, the fertilisation rate and number of sperm combined with the zona pellucida significantly increased after in vitro capacitation using the post-modified HTF medium (P 0.01). Proteomic and Western blotting analyses showed that the level of SERPINA5 in sperm increased significantly following in vitro capacitation with the post-modified HTF medium (P 0.05). Immunohistochemical staining analysis demonstrated that SERPINA5 protein was expressed in mouse cumulus cells. A SERPINA5 antibody was added in the post-modified HTF medium to block the effects of SERPINA5 after in vitro capacitation, which significantly decreased the fertilisation rate and the number of sperm combined with the zona pellucida (P 0.05). Recombinant mouse SERPINA5 protein (1 ~ 2 μg/ml) was added to HTF medium and the fertilisation rate and the number of sperm combined with the zona pellucida significantly increased (P 0.01). Moreover, recombinant human SERPINA5 protein (5 μg/ml) was added before human semen freezing. Compared with adding no SERPINA5 protein, the percentage of normal sperm morphology and the intact acrosome significantly increased (P 0.05). Our study provides a reference method for optimising sperm quality in the process of in vitro capacitation.

Sepsisis among the leading causes of morbidity and mortality in modern intensive care units. Accurate sepsis prediction is of critical importance to save lives and reduce medical costs. The rapid advancements in sensing and information technology facilitate the effective monitoring of patients' health conditions, generating a wealth of medical data, and provide an unprecedented opportunity for data-driven diagnosis of sepsis. However, real-world medical data are often complexly structured with a high level of uncertainty (e.g., missing values, imbalanced data). Realizing the full data potential depends on developing effective analytical models. In this paper, we propose a novel predictive framework with Multi-Branching Temporal Convolutional Network (MB-TCN) to model the complexly structured medical data for robust prediction of sepsis. The MB-TCN framework not only efficiently handles the missing value and imbalanced data issues but also effectively captures the temporal pattern and heterogeneous variable interactions. We evaluate the performance of the proposed MB-TCN in predicting sepsis using real-world medical data from PhysioNet/Computing in Cardiology Challenge 2019. Experimental results show that MB-TCN outperforms existing methods that are commonly used in current practice.

This study used aluminum powder as a raw material to fabricate a wick for loop heat pipes by the powder metallurgy method and took advantage of the excellent corrosion resistance, low density and low cost of aluminum. The average pore diameter, porosity and permeability of the aluminum wicks were 9 ?m, 47.65%, and 2.1 ? 10?13 m?2, respectively. Then, to verify the feasibility of the aluminum wick, it was installed into a loop heat pipe to test the heat transfer performance. The experimental results showed that the loop heat pipe could transport a heating load of 130 W with a thermal resistance of 0.04 K/W under horizontal condition. A steady-state loop heat pipe mathematical model was developed, and the numerical results were compared with the experimental data. The results show that the model data are consistent with the experimental data, which means that Al wicks are suitable for use in the case of a high heating load and light weight.

Here, we fabricated a home-made strain loading device and proposed a compressive strain measurement method, by which the strain-dependent optical absorption properties of MoS2 monolayers under compression has been studied.

A 3D structure-mediated growth method is developed to synthesize high quality zero dimensional Cs4SnX6 nanocrystals.

In this article, we design a family of scale-free networks and study its random target access time and weighted spanning trees through the eigenvalues of transition weight matrix. First, we build a type of fractal network with a weight factor r r and a parameter m m . Then, we obtain all the eigenvalues of its transition weight matrix by revealing the recursive relationship between eigenvalues in every two consecutive time steps and obtain the multiplicities corresponding to these eigenvalues. Furthermore, we provide a closed-form expression of the random target access time for the network studied. The obtained results show that the random target access is not affected by the weight; it is only affected by parameters m m and t t . Finally, we also enumerate the weighted spanning trees of the studied networks through the obtained eigenvalues.

Two pairs of rotation-restricted TADF compounds via through-space charge transfer are investigated. Sandwich molecules exhibit similar photophysical properties and better electroluminescent performance compared with the open sandwich counterparts.

In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

Up to today, there is no effective, specific and non-invasive evaluation method to assess the endometrial receptivity. This study aimed to establish a non-invasive and effective model with the clinical indicators to evaluate endometrial receptivity. Ultrasound elastography can reflect the overall state of the endometrium. Ultrasonic elastography images from 78 hormonally prepared frozen embryo transfer (FET) patients were assessed in this study. Meanwhile, the clinical indicators reflecting endometrium in the transplantation cycle were collected. The patients were received to transfer only one high-quality blastocyst. A novel code rule that can generate a large number of 0–1 symbols was designed to collect data on different factors. At the same time, a logistic regression model of the machine learning process with an automatic combination of factors was designed for analysis. The logistic regression model was based on age, body mass index, waist-hip ratio, endometrial thickness, perfusion index (PI), resistance index (RI), elastic grade, elastic ratio cutoff value, serum estradiol level and 9 other indicators. The accuracy rate of predicting pregnancy outcome of the logistic regression model was 76.92%. Elastic ultrasound can reflect the endometrial receptivity of patients in FET cycles. We established a prediction model including ultrasound elastography and the model precisely predicted the pregnancy outcome. The predictive accuracy of endometrial receptivity by the predictive model is significantly higher than that of the single clinical indicator. The prediction model by integrating the clinical indicators to evaluate endometrial receptivity may be a non-invasive and worthwhile method for evaluating endometrial receptivity.

Three carbazole derivatives, AcPTC, PxPTC and PtPTC, consisting of two 9,9-dimethyl-9,10-dihydroacridine, phenoxazine or phenothiazine donor groups and one diphenyltriazine acceptor group fixed at 1,8,9-positions of a single carbazole ring via phenylene, are designed and synthesized. X-ray diffraction analysis of AcPTC reveals that there exist multiple π-π interactions between the donor and acceptor groups to form a sandwich-like structural unit with edge-to-face interaction model. The compounds thus show obvious thermally activated delayed fluorescence with through-space charge transfer character and possess considerable photoluminescence quantum yields of up to 73% in doped films with sky-blue to yellow emissions. The solution-processed electroluminescent devices achieve the highest maximum external quantum efficiencies of 10.0%, 11% and 5.6% for AcPTC, PxPTC and PtPTC, respectively, with small efficiency roll-offs.

For random walks on a complex network, the configuration of a network that provides optimal or suboptimal navigation efficiency is meaningful research. It has been proven that a complete graph has the exact minimal mean hitting time, which grows linearly with the network order. In this paper, we present a class of sparse networks G(t) in view of a graphic operation, which have a similar dynamic process with the complete graph; however, their topological properties are different. We capture that G(t) has a remarkable scale-free nature that exists in most real networks and give the recursive relations of several related matrices for the studied network. According to the connections between random walks and electrical networks, three types of graph invariants are calculated, including regular Kirchhoff index, M-Kirchhoff index and A-Kirchhoff index. We derive the closed-form solutions for the mean hitting time of G(t), and our results show that the dominant scaling of which exhibits the same behavior as that of a complete graph. The result could be considered when designing networks with high navigation efficiency.

The discovery of reldesemtiv, a second-generation fast skeletal muscle troponin activator (FSTA) that increases force production at submaximal stimulation frequencies, is reported. Property-based optimization of high throughput screening hit 1 led to compounds with improved free exposure and in vivo muscle activation potency compared to the first-generation FSTA, tirasemtiv. Reldesemtiv demonstrated increased muscle force generation in a phase 1 clinical trial and is currently being evaluated in clinical trials for the treatment of amyotrophic lateral sclerosis.

GGC repeat expansions within NOTCH2NLC have been identified as the genetic cause of neuronal intranuclear inclusion disease (NIID). To understand the molecular pathogenesis of NIID, here, we established both a transgenic mouse model and a human neural progenitor cells (hNPCs) model. Expression of the NOTCH2NLC with expanded GGC repeats produced widespread intranuclear and perinuclear polyglycine (polyG), polyalanine (polyA), and polyarginine (polyR) inclusions, leading to behavioral deficits and severe neurodegeneration, which faithfully mimicked the clinical and pathological features associated with NIID. Furthermore, conserved alternative splicing events were identified between the NIID mouse and hNPC models, among which was the enrichment of the binding motifs of hnRNPM, an RNA binding protein known as alternative splicing regulator. Expanded NOTCH2NLC-polyG and NOTCH2NLC-polyA could interact with and sequester hnRNPM, while overexpression of hnRNPM could ameliorate the cellular toxicity. These results together suggested that dysfunction of hnRNPM could play an important role in the molecular pathogenesis of NIID.

Polycystic ovary syndrome (PCOS), characterized by the androgen excess and arrest of antral follicles, is a common endocrine disorder among women lacking specific diagnostic biomarkers and therapeutic targets. Herein, we studied the molecular mechanism of miR-96-5p in the process of PCOS and its potential applications in PCOS. Clinically, we found that miR-96-5p significantly decreased in serum, follicular fluid (FF) and primary human granulosa cells (hGCs) of PCOS patients (n=70) vs. non-PCOS women (n=60), as well as in the ovaries of 3-types of induced PCOS-like mice. Furthermore, we demonstrated that the elevated circulating miR-96-5p levels were significantly correlated with the PCOS disordered endocrine clinical features, and the area under the curve of receiver operating characteristic was 0.8344, with 75.71% specificity and 80% sensitivity. Mechanically, we identified miR-96-5p as an androgen-regulated miRNA that directly targets the forkhead transcription factor FOXO1. Inhibition of miR-96-5p decreased estrogen synthesis, while decreasing the cell proliferation index of KGN via regulating the expression of FOXO1 and its downstream genes. Inversely, inhibition of FOXO1 abrogated the effect of miR-96-5p on estrogen synthesis and proliferation index. Of note, ovarian intra-bursal injection of miR-96-5p agomir rescued the phenotypes of dehydroepiandrosterone-induced PCOS like mice. In conclusion, our results clarified a vital role of miR-96-5p in the pathogenesis of PCOS and might serve as a novel diagnostic biomarker and therapeutic target for PCOS.

The first total synthesis of daphgraciline has been achieved, which also represents the first example of the synthesis of

The wick is the most crucial element of loop heat pipes (LHPs). At present, wick materials are limited to copper, stainless steel, nickel, and so on. Little research has been carried out on new wick materials. This paper reports the fabrication of aluminum wicks and performance tests of LHPs using aluminum wicks. Experimental data show that this LHP is capable of transferring a heating load of 130 W, while the thermal resistance is only approximately 0.04 K/W. Then, the experimental data were compared with those for LHPs using a polytetrafluoroethylene (PTFE) wick. Based on the SIMPLE algorithm, a 2-D unsteady-state heat transfer model and a 2-D steady-state flow model of the wicks are established to analyze the effects of wick material, pore size and porosity on the performance of the evaporator. The experimental data for LHPs with PTFE wicks are from the literature. The simulation results show that a PTFE wick can effectively reduce heat leakage, while an aluminum wick has better temperature uniformity and a lower casing temperature. However, wicks with large porosities have lower flow resistance.

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489,and TMEM147-AS1,and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus (GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.

A series of new cyclic siloxane side-chain liquid crystal oligomers containing chiral (-)-menthyl monomer (M1) and achiral benzene methyl ester monomer (M2), denoted as O1–O4, were successfully syn...

Endometrial cancer (EC) is the most common gynecological malignancy worldwide. However, the molecular mechanisms underlying EC progression are still largely unknown, and chemotherapeutic options for EC patients are currently very limited. In this study, we found that histone methyltransferase EZH2 and DNA methyltransferase DNMT3B were upregulated in EC samples from patients, and promoted EC cell proliferation as evidenced by assays of cell viability, cell cycle, colony formation. Mechanistically, we found that EZH2 promoted EC cell proliferation by epigenetically repressing TCF3, a direct transcriptional activator of CCKN1A (p21WAF1/Cip1), in vitro and in vivo. In addition, we found that DNMT3B specifically methylated the TCF3 promoter, repressing TCF3 expression and accelerating EC cell proliferation independently of EZH2. Importantly, elevated expression of EZH2 or DNMT3B in EC patients inversely correlated with expression of TCF3 and p21, and was associated with shorter overall survival. We show that combined treatment with GSK126 and 5-Aza-2d treatment wit synergistically inhibited methyltransferase activity of EZH2 and DNMT3B, resulting in a profound block of EC cell proliferation as well as EC tumor progression in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. These findings reveal that TCF3 functions as a tumor suppressor epigenetically silenced by EZH2 and DNMT3B in EC, and support the notion that targeting the EZH2/DNMT3B/TCF3/p21 axis may be a novel and effective therapeutic strategy for treatment of EC.