A viral small interfering RNA-host plant mRNA pathway modulates virus-induced drought tolerance by enhancing autophagy.

Virus-induced drought tolerance presents a fascinating facet of biotic-abiotic interaction in plants, yet its molecular intricacies remain unclear. Our study shows that cowpea mild mottle virus (CPMMV) infection enhances drought tolerance in common bean (Phaseolus vulgaris) plants through a virus-derived small interfering RNA (vsiRNA)-activated autophagy pathway. Specifically, a 21-bp vsiRNA originating from the CPMMV Triple Gene Block1 (TGB1) gene targeted the 5' untranslated region (UTR) of the host Teosinte branched 1, Cycloidea, Proliferating Cell Factor (TCP) transcription factor gene PvTCP2, independent of the known role of TGB1 as an RNA silencing suppressor. This targeting attenuated the expression of PvTCP2, which encodes a transcriptional repressor, and in turn upregulated the core autophagy-related gene (ATG) PvATG8c, leading to activated autophagy activity surpassing the level induced by drought or CPMMV infection alone. The downstream EARLY RESPONSIVE TO DEHYDRATION (ERD) effector PvERD15 is a homologue of Arabidopsis thaliana AtERD15, which positively regulates stomatal aperture. PvERD15 was degraded in PvATG8c-mediated autophagy. Therefore, we establish a TGB1-PvTCP2-PvATG8c-PvERD15 module as a trans-kingdom fine-tuning mechanism that contributes to virus-induced drought tolerance in plant-drought-virus interactions.

High-resolution magnetic resonance vessel wall imaging provides new insights into Moyamoya disease.

Moyamoya disease (MMD) is a rare condition that affects the blood vessels of the central nervous system. This cerebrovascular disease is characterized by progressive narrowing and blockage of the internal carotid, middle cerebral, and anterior cerebral arteries, which results in the formation of a compensatory fragile vascular network. Currently, digital subtraction angiography (DSA) is considered the gold standard in diagnosing MMD. However, this diagnostic technique is invasive and may not be suitable for all patients. Hence, non-invasive imaging methods such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are often used. However, these methods may have less reliable diagnostic results. Therefore, High-Resolution Magnetic Resonance Vessel Wall Imaging (HR-VWI) has emerged as the most accurate method for observing and analyzing arterial wall structure. It enhances the resolution of arterial walls and enables quantitative and qualitative analysis of plaque, facilitating the identification of atherosclerotic lesions, vascular entrapment, myofibrillar dysplasia, moyamoya vasculopathy, and other related conditions. Consequently, HR-VWI provides a new and more reliable evaluation criterion for diagnosing vascular lesions in patients with Moyamoya disease.

Effect of nitrogen application levels on photosynthetic nitrogen distribution and use efficiency in soybean seedling leaves.

BACKGROUND: Nitrogen nutrition is strongly associated with crop growth and development. Nitrogen application level affects leaf size as well as nitrogen content and distribution, and thus affects photosynthetic nitrogen-use efficiency (PNUE) and yield. In this study, soybean varieties "Jinyuan 55" and "Keshan 1" were treated with nitrogen as urea at: N0, 0 kg hm-2; N0.5, 60 kg hm-2; N1, 120 kg hm-2; and N1.5, 180 kg hm-2. We compared the effect of nitrogen level on plant morphology, biomass, photosynthetic physiology, nitrogen distribution, PNUE, and other soybean seedling leaf characteristics. RESULTS: Maximum carboxylation and electron transfer, net photosynthetic rates, and PNUE of both soybean varieties showed initial significant increases with increasing nitrogen application rate and subsequent stabilization. PNUE, carboxylation system components, electron transport components, and non-photosynthetic system distribution ratios in the photosynthetic system increased and subsequently decreased with increased nitrogen application rate. The nitrogen ratio between carboxylation and electron transport systems was positively correlated with PNUE in both soybean varieties. The nitrogen ratio in light-harvesting and non-photosynthetic systems showed a linear negative correlation with PNUE. CONCLUSIONS: Overall, an appropriate nitrogen level maintained a high photosynthetic nitrogen ratio, whereas low- or high-nitrogen conditions increased or decreased the nitrogen ratio in non-photosynthetic and photosynthetic systems, respectively, thus decreasing the PNUE and photosynthetic capacity. Moreover, increased nitrogen application rate led to a decreased nitrogen ratio in the light-harvesting system and an increased nitrogen ratio of electron transport and carboxylation systems. Our results provide a theoretical basis for optimizing leaf nitrogen distribution, determining optimum nitrogen levels, and promoting soybean seedling growth.

Impacts of cigarette smoking on blood circulation: do we need a new approach to blood donor selection?

Smoking is a major public health problem and is considered the leading cause of preventable death worldwide. Gas-phase smoke carries bioactive substances and toxic compounds, affecting human health and reducing life spans. The negative effects of smoking on red blood cell (RBC) quality include destroying RBCs and increasing carboxy hemoglobin (COHb). Smoking increases the concentrations of heavy metals such as cadmium (Cd) and lead (Pb) in the blood. Moreover, tobacco smoking has been found to be associated with heightened platelet (PLT)-dependent thrombin level which will induce a prothrombotic state. Smoking may affect the blood circulation of donors, and subsequently the blood components, and ultimately the recipients of transfusion. Nevertheless, there are no restrictions on smoking for volunteer blood donor screenings currently. We reviewed the articles about the influence of smoking on smokers' blood circulation as well as the impact of donated blood products on transfusion when these smokers act as blood donors. We aim to attract blood collection centers' attention to strengthen the management of blood donors who smoke, avoiding their use in massive transfusion protocol and susceptible recipients, especially pediatric ones.

Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study.

Background: Observational studies have suggested the association between atopic dermatitis (AD) and the risks of autoimmune diseases. It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded. Objectives: Our study seeks to assess the possibility of AD as a cause of autoimmune diseases, and to estimate the magnitude of the causal effect. Methods: Two-sample mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary-level statistics. Specifically, bidirectional MR analyses were conducted to examine the direction of association of AD with autoimmune diseases; multivariable MR analyses (MVMR1) were used to test the independence of causal association of AD with autoimmune diseases after controlling other atopic disorders (asthma and allergic rhinitis), while MVMR2 analyses were conducted to account for potential confounding factors such as smoking, drinking, and obesity. Genetic instruments for AD (Ncases=22 474) were from the latest GWAS meta-analysis. The GWAS summary data for asthma and allergic rhinitis were obtained from UK Biobank. The GWAS summary data for smoking, alcohol consumption, obesity and autoimmune diseases (alopecia areata, vitiligo, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and type 1 diabetes) were selected from the largest GWASs available. Causal estimates were derived by the inverse-variance weighted method and verified through a series of sensitivity analyses. Results: Genetically predicted AD linked to higher risks of rheumatoid arthritis (OR, 1.28; P=0.0068) (ORMVMR1, 1.65; P=0.0020) (ORMVMR2, 1.36; P<0.001), type 1 diabetes (OR, 1.37; P=0.0084) (ORMVMR1, 1.42; P=0.0155) (ORMVMR2, 1.45; P=0.002), and alopecia areata (OR, 1.98; P=0.0059) (ORMVMR1, 2.55; P<0.001) (ORMVMR2, 1.99; P=0.003) in both univariable and multivariable MR. These causal relationships were supported by sensitivity analyses. No causal effect of AD was identified in relation to systemic lupus erythematosus, vitiligo, and ankylosing spondylitis. Concerning the reverse directions, no significant association was noted. Conclusion: The results of this MR study provide evidence to support the idea that AD causes a greater risk of rheumatoid arthritis, type 1 diabetes and alopecia areata. Further replication in larger samples is needed to validate our findings, and experimental studies are needed to explore the underlying mechanisms of these causal effects.

A low power respiratory sound diagnosis processing unit based on LSTM for wearable health monitoring.

Early prevention and detection of respiratory disease have attracted extensive attention due to the significant increase in people with respiratory issues. Restraining the spread and relieving the symptom of this disease is essential. However, the traditional auscultation technique demands a high-level medical skill, and computational respiratory sound analysis approaches have limits in constrained locations. A wearable auscultation device is required to real-time monitor respiratory system health and provides consumers with ease. In this work, we developed a Respiratory Sound Diagnosis Processor Unit (RSDPU) based on Long Short-Term Memory (LSTM). The experiments and analyses were conducted on feature extraction and abnormality diagnosis algorithm of respiratory sound, and Dynamic Normalization Mapping (DNM) was proposed to better utilize quantization bits and lessen overfitting. Furthermore, we developed the hardware implementation of RSDPU including a corrector to filter diagnosis noise. We presented the FPGA prototyping verification and layout of the RSDPU for power and area evaluation. Experimental results demonstrated that RSDPU achieved an abnormality diagnosis accuracy of 81.4 %, an area of 1.57 × 1.76 mm under the SMIC 130 nm process, and power consumption of 381.8 µW, which met the requirements of high accuracy, low power consumption, and small area.

Identification reproducible microbiota biomarkers for the diagnosis of cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence in China, which is mainly related to chronic hepatitis B (CHB) and liver cirrhosis (LC) caused by hepatitis B virus (HBV) infection. This study aimed to identify reproducible gut microbial biomarkers across Chinese population for LC and HCC diagnosis. In this study, a group of 21 CHB, 25 LC, 21 HCC and 15 healthy control (HC) were examined, and used as the training data. Four published faecal datasets from different regions of China were collected, totally including 121 CHB, 33 LC, 70 HCC and 96 HC. Beta diversity showed that the distribution of community structure in CHB, LC, HCC was significantly different from HC. Correspondingly, 14 and 10 reproducible differential genera across datasets were identified in LC and HCC, respectively, defined as LC-associated and HCC-associated genera. Two random forest (RF) models based on these reproducible genera distinguished LC or HCC from HC with an area under the curve (AUC) of 0.824 and 0.902 in the training dataset, respectively, and achieved cross-region validations. Moreover, AUCs were greatly improved when clinical factors were added. A reconstructed random forest model on eight genera with significant changes between HCC and non-HCC can accurately distinguished HCC from LC. Conclusively, two RF models based on 14 reproducible LC-associated and 10 reproducible HCC-associated genera were constructed for LC and HCC diagnosis, which is of great significance to assist clinical early diagnosis.

Association of atopic dermatitis with conjunctivitis and other ocular surface diseases: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Observational studies have suggested associations of atopic dermatitis (AD) with conjunctivitis and other ocular surface diseases (OSDs). It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded. OBJECTIVE: Our study aims to examine the causal association of AD with conjunctivitis and other OSDs. METHODS: A bidirectional two-sample Mendelian randomization (MR) study was performed with genome-wide association study (GWAS) summary-level statistics. Genetic instruments for AD from a GWAS meta-analysis study conducted by the EArly Genetics & Lifecourse Epidemiology eczema consortium were used to investigate AD's relationships to conjunctivitis and other OSDs among cases from the FinnGen consortium. Genetic correlations were calculated using linkage disequilibrium score regression. Causal estimates were derived by the inverse-variance weighted method and were verified through a series of sensitivity analyses. RESULTS: Genetically predicted AD linked to higher risk of conjunctivitis (OR, 1.48; 95% CI, 1.33-1.65; p = 8.65 × 10-13 ) and allergic conjunctivitis (OR, 1.53; 95%CI, 1.31-1.77; p = 3.77 × 10-8 ), as well as atopic conjunctivitis (OR, 1.76; 95%CI, 1.24-2.52; p = 1.76 × 10-3 ). Additionally, suggestive causal effects of AD on chronic conjunctivitis (OR, 1.76; 95%CI, 1.24-2.52; p = 5.78 × 10-3 ) and keratitis (OR, 1.14; 95%CI, 1.01-1.30; p = 3.58 × 10-2 ) were found. No significant causal effect of AD was identified in relation to keratitis, keratoconus and pterygium. Concerning the reverse directions, no significant associations were noted. CONCLUSIONS: Findings of this MR study support a causal effect between AD and conjunctivitis, but not vice versa. These findings have clinical implications for the management of AD and conjunctivitis.

Research progress of endogenous hematoma absorption after intracerebral hemorrhage.

Non-traumatic intraparenchymal brain hemorrhage is referred to as intracerebral hemorrhage (ICH). Although ICH is associated with a high rate of disability and case fatality, active intervention can significantly lower the rate of severe disability. Studies have shown that the speed of hematoma clearance after ICH determines the patient's prognosis. Following ICH, depending on the hematoma volume and mass effect, either surgical- or medication-only conservative treatment is chosen. The goal of promoting endogenous hematoma absorption is more relevant because surgery is only appropriate for a small percentage of patients, and open surgery can cause additional trauma to patients. The primary method of removing hematoma after ICH in the future will involve understanding how to produce and manage macrophage/microglial endogenous phagocytic hematomas. Therefore, it is necessary to elucidate the regulatory mechanisms and key targets for clinical purposes.

Postharvest treatments with MnCl2 and ZnCl2 reduce enzymatic browning and enhance antioxidant accumulation in soya bean sprout.

Soya bean sprout is a nutrient-abundant vegetable. However, enzymatic browning of soya bean sprouts during storage remains a challenge. In this study, the effects of treatment with MnCl2 or ZnCl2 on the browning index, antioxidant nutrient accumulation, total antioxidant capacity and enzyme activities of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were investigated in soya bean sprouts after storage at 4 °C and 90% relative humidity for 0, 7, 14 and 21 days. The results showed that postharvest treatment with 1, 2 and 10 mM MnCl2 or ZnCl2 profoundly retarded enzymatic browning in soya bean sprouts to different extents. Compared with the control, the 10 mM MnCl2 and ZnCl2 treatments drastically enhanced ascorbic acid, total thiol and phenolic content, and enhanced FRAP (ferric-reducing ability of plasma) antioxidant capacity in stored soya bean sprouts. Moreover, the MnCl2 and ZnCl2 treatments enhanced SOD, CAT and PAL but decreased PPO and POD activities compared with the control. In addition, the Mn and Zn content in soya bean sprouts significantly increased, by approximately two- to threefold, compared with the control. This study provides a new method for improving the nutrient quality of soya bean sprouts based on postharvest Mn or Zn supplementation.

Tumor Microenvironment-Based Stimuli-Responsive Nanoparticles for Controlled Release of Drugs in Cancer Therapy.

With the development of nanomedicine technology, stimuli-responsive nanocarriers play an increasingly important role in antitumor therapy. Compared with the normal physiological environment, the tumor microenvironment (TME) possesses several unique properties, including acidity, high glutathione (GSH) concentration, hypoxia, over-expressed enzymes and excessive reactive oxygen species (ROS), which are closely related to the occurrence and development of tumors. However, on the other hand, these properties could also be harnessed for smart drug delivery systems to release drugs specifically in tumor tissues. Stimuli-responsive nanoparticles (srNPs) can maintain stability at physiological conditions, while they could be triggered rapidly to release drugs by specific stimuli to prolong blood circulation and enhance cancer cellular uptake, thus achieving excellent therapeutic performance and improved biosafety. This review focuses on the design of srNPs based on several stimuli in the TME for the delivery of antitumor drugs. In addition, the challenges and prospects for the development of srNPs are discussed, which can possibly inspire researchers to develop srNPs for clinical applications in the future.

Ultrasoft Porous 3D Conductive Dry Electrodes for Electrophysiological Sensing and Myoelectric Control.

Biopotential electrodes have found broad applications in health monitoring, human-machine interactions, and rehabilitation. Here, we report the fabrication and applications of ultrasoft breathable dry electrodes that can address several challenges for their long-term wearable applications - skin compatibility, wearability, and long-term stability. The proposed electrodes rely on porous and conductive silver nanowire based nanocomposites as the robust mechanical and electrical interface. The highly conductive and conformable structure eliminates the necessity of conductive gel while establishing a sufficiently low electrode-skin impedance for high-fidelity electrophysiological sensing. The introduction of gas-permeable structures via a simple and scalable method based on sacrificial templates improves breathability and skin compatibility for applications requiring long-term skin contact. Such conformable and breathable dry electrodes allow for efficient and unobtrusive monitoring of heart, muscle, and brain activities. In addition, based on the muscle activities captured by the electrodes and a musculoskeletal model, electromyogram-based neural-machine interfaces were realized, illustrating the great potential for prosthesis control, neurorehabilitation, and virtual reality.

Epigenetic regulation of synaptic disorder in Alzheimer's disease.

Synapses are critical structures involved in neurotransmission and neuroplasticity. Their activity depends on their complete structure and function, which are the basis of learning, memory, and cognitive function. Alzheimer's disease (AD) is neuropathologically characterized by synaptic loss, synaptic disorder, and plasticity impairment. AD pathogenesis is characterized by complex interactions between genetic and environmental factors. Changes in various receptors on the postsynaptic membrane, synaptic components, and dendritic spines lead to synaptic disorder. Changes in epigenetic regulation, including DNA methylation, RNA interference, and histone modification, are closely related to AD. These can affect neuronal and synaptic functions by regulating the structure and expression of neuronal genes. Some drugs have ameliorated synaptic and neural dysfunction in AD models via epigenetic regulation. We reviewed the recent progress on pathological changes and epigenetic mechanisms of synaptic dysregulation in AD to provide a new perspective on this disease.

LncRNA NCK1-AS1 Aggravates Hepatocellular Carcinoma by the miR-22-3p/YARS Axis to Activate PI3K/AKT Signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is frequently diagnosed at late stages when curative treatments are no more appliable. Many studies have proved the active role of long non-coding RNAs (lncRNAs) in cancers' biology; here, the functional role of lncRNA NCK1-AS1 in HCC was identified. METHODS: Gene expression in tumor tissues of HCC was evaluated by examining online databases and 88 collected HCC samples from our hospital. The interactions of miR-22-3p with NCK1-AS1 and tyrosyl-tRNA synthetase (YARS) were tested by conducting bioinformatics analysis, luciferase report, and RNA pulldown experiments. CCK-8, colony formation, flow cytometry, wound healing, transwell experiments were used to dissect the role of the NCK1-AS1/miR-22-3p/YARS axis in HCC. RESULTS: NCK1-AS1 was overexpressed in HCC cells and tissues. Functional assays depicted that depletion of NCK1-AS1 hampered malignant character of HCC cells. NCK1-AS1 controlled the availability of miR-22-3p, resulting in YARS upregulation. YARS was found to have a clinical value for HCC diagnosis. Moreover, rescue experiments revealed that miR-22-3p inhibition or YARS overexpression partially blocked the function of NCK1-AS1 deficiency in HCC cells. As for the downstream signaling pathway, we discovered that NCK1-AS1 activated PI3K/AKT signaling by the miR-22-3p/YARS axis. CONCLUSION: The present study verified that NCK1-AS1 could promote HCC progression via the miR-22-3p/YARS axis to activate PI3K/AKT signaling.

[Mild and moderate postpartum depression treated with acupuncture of Tiaoren Tongdu: a real world study].

OBJECTIVE: To observe the clinical therapeutic effect on mild and moderate postpartum depression treated with acupuncture of Tiaoren Tongdu (regulating the conception vessel and unblocking the governor vessel) on the base of real world. METHODS: A total of 116 patients with mild and moderate postpartum depression were divided into an acupuncture group (103 cases) and a non-acupuncture group (13 cases) according to treatment regimen provided. In the acupuncture group, acupuncture of Tiaoren Tongdu was applied to Baihui (GV 20), Yintang (GV 29), Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Neiguan (PC 6), Shenmen (HT 7), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). Needles were retained for 30 min each time, the treatment was given once every other day, 3 times a week. In the non-acupuncture group, psychotherapy was provided, once daily. The duration of treatment in the two groups was 8 weeks. According to the treatment times of acupuncture, the acupuncture group was subdivided into an acupuncture A group (60 cases with total treatments ≥ 6 times) and an acupuncture B group (43 cases with total treatments<6 times). Using propensity score matching method, the patients of the acupuncture A and B groups were matched each other. Finally, 31 pairs of cases were matched successfully. Before treatment, at 1st, 2nd, 4th and 8th weeks of treatment, as well as at 3-month follow-up, the scores of Hamilton depression scale (HAMD) were compared in patients among the three groups. Using Logistic regression, the impact of acupuncture frequencies on the therapeutic effect was analyzed and the clinical therapeutic effect was assessed. RESULTS: The total effective rate of the acupuncture A group was 100.0% (31/31), better than 76.9% (10/13) in the non-acupuncture group and 58.1% in the acupuncture B group (18/31) (P<0.05). HAMD score at each time point after treatment was lower than that before treatment in the patients of each group (P<0.05). But HAMD score at each time point after treatment in either the acupuncture A group or the acupuncture B group was lower than that in the non-acupuncture group separately (P<0.05), HAMD scores in the acupuncture A group at the 4th and 8th weeks of treatment and at follow-up were lower than those in the acupuncture B group (P<0.05). Logistic regression analysis showed that the total times of acupuncture treatment and the persistent days of treatment had a certain relation to therapeutic effect (P<0.05). CONCLUSION: Acupuncture of Tiaoren Tongdu effectively improves in mild and moderate postpartum depression and its therapeutic effect is closely related to treatment course.

Nitric oxide-releasing micelles with intelligent targeting for enhanced anti-tumor effect of cisplatin in hypoxia.

BACKGROUND: Hypoxic tumor microenvironment (TME) promotes tumor metastasis and drug resistance, leading to low efficiency of cancer chemotherapy. The development of targeted agents or multi-target therapies regulating hypoxic microenvironment is an important approach to overcome drug resistance and metastasis. METHODS: In this study, chitosan oligosaccharide (COS)-coated and sialic acid (SA) receptor-targeted nano-micelles were prepared using film dispersion method to co-deliver cisplatin (CDDP) and nitric oxide (NO) (denoted as CTP/CDDP). In addition, we explored the mechanisms by which NO reversed CDDP resistance as well as enhanced anti-metastatic efficacy in hypoxic cancer cells. RESULTS: Because of the different affinities of COS and SA to phenylboronic acid (PBA) under different pH regimes, CTP/CDDP micelles with intelligent targeting property increased cellular uptake of CDDP and enhanced cytotoxicity to tumors, but reduced systemic toxicity to normal organs or tissues. In addition, CTP/CDDP showed stimulus-responsive release in TME. In terms of anti-tumor mechanism, CTP/CDDP reduced CDDP efflux and inhibited epithelial-mesenchymal transition (EMT) process of tumor by down-regulating hypoxia-inducible factor-1α (HIF-1α), glutathione (GSH), multidrug resistance-associated protein 2 (MRP2) and matrix metalloproteinase 9 (MMP9) expression, thus reversing drug resistance and metastasis of hypoxic tumor cells. CONCLUSIONS: The designed micelles significantly enhanced anti-tumor effects both in vitro and in vivo. These results suggested that CTP/CDDP represented a promising strategy to treat resistance and metastatic tumors.

Exploring the mechanism of aidi injection for lung cancer by network pharmacology approach and molecular docking validation.

BACKGROUND: Aidi injection (ADI) is an effective Traditional Chinese medicine preparation widely used for lung cancer. However, the pharmacological mechanisms of ADI on lung cancer remain to be elucidated. METHODS: A network pharmacology (NP)-based approach and the molecular docking validation were conducted to explore underlying mechanisms of ADI on lung cancer. The compounds and target genes were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (Batman-TCM) database. The STRING database was utilized for protein interaction network construction. The R package clusterProfiler was used for bioinformatics annotation of hub target genes. The gene expression analysis and survival analysis were performed based on The Cancer Genome Atlas (TCGA) database. The Autodock Vina was used for molecular docking validation. RESULTS: A total of five key compounds with 324 putative target genes were screened out, and 14 hub target genes were identified for treating lung cancer. Six hub genes could influence the survival of non-small cell lung cancer (NSCLC) patients. Of these hub genes, the expression pattern of EGFR, MYC, PIK3CA, and SMAD3 were significantly higher in the LUSC, while PIK3CA and RELA expressed lower in the LUAD group and LUSC group, respectively. These six hub genes had good docking affinity with the key compounds of ADI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that ADI may exert therapeutic effects on lung cancer by regulating critical pathways including the thyroid hormone signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: The present study explored the potential pharmacological mechanisms of ADI on lung cancer, promoting the clinical application of ADI in treating lung cancer, and providing references for advanced researches.

Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC50 values 0.85 µM and 0.59 µM for eeAChE and eqBuChE, respectively. Kinetic analysis and docking study indicated that compound 4j was a mixed-type inhibitor for both AChE and BuChE. Additionally, it exhibited good abilities to penetrate BBB, scavenge free radicals (4.6 trolox equivalent) and selectively chelate with Cu2+ and Al3+ at a 1:1.4 ligand/metal molar ratio. Importantly, after assessments of cytotoxic and acute toxicity, we found compound 4j could improve memory function of scopolamine-induced amnesia mice. Hence, the compound 4j can be considered as a promising lead compound for further investigation in the treatment of AD.

[Effects of oral administration of ceftriaxone in early life on glucolipid metabolism of high fat diet-induced mice].

OBJECTIVE: This study aimed to explore whether exposure to ceftriaxone during early life could influences glucose and lipid metabolism of high fat diet-induced mice. METHODS: Total 48 of female BALB/c aged 2 week old were randomly divided into control group(treated with saline), antibiotic group(treated with100 mg/kg ceftriaxone), high-fat diet group(treated with saline) and combined action group(treated with 100 mg/kg ceftriaxone)(n=12), respectively to stop gavage 2 weeks later. Then high-fat diet group and combined action group were fed with high-fat diet for 12 weeks. Fasting blood glucose(FBG) and oral glucose tolerance test were conducted in the last week. Serum total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), fasting insulin, leptin and TG, TC in liver were also measured. Furthermore, homeostasis model assessment of insulin resistance(HOMA-IR) was calculated from FBG and insulin. RESULTS: Compared with normal chow diet, high-fat diet impaired oral glucose tolerance and increased the levels of abdominal adipose tissue, FBG, HOMA-IR, lips in serum and liver and leptin(P<0. 05). The oral administration of ceftriaxone in early life impaired oral glucose tolerance and increased the levels of abdominal adipose tissue, FBG and TG in liver(P<0. 05). In addition, early ceftriaxone intervention could enhance the impaired glucose tolerance, the increasing FBG, insulin resistance and liver lipids associated with high-fat diet(P<0. 05). CONCLUSION: Early ceftriaxone intervention not only significantly increases the level of abdominal adipose tissue, FBG, insulin resistance and liver lipids, but also enhances glycolipid metabolic disorders induced by high-fat diet. These result suggest that the exposure to antibiotics in the early life might increase the sensitivity of host animal to high fat diet induced abnormal glycolipid metabolism late.

Gas-Permeable, Ultrathin, Stretchable Epidermal Electronics with Porous Electrodes.

We present gas-permeable, ultrathin, and stretchable electrodes enabled by self-assembled porous substrates and conductive nanostructures. An efficient and scalable breath figure method is employed to introduce the porous skeleton, and then silver nanowires (AgNWs) are dip-coated and heat-pressed to offer electric conductivity. The resulting film has a transmittance of 61%, sheet resistance of 7.3 Ω/sq, and water vapor permeability of 23 mg cm-2 h-1. With AgNWs embedded below the surface of the polymer, the electrode exhibits excellent stability in the presence of sweat and after long-term wear. We demonstrate the promising potential of the electrode for wearable electronics in two representative applications: skin-mountable biopotential sensing for healthcare and textile-integrated touch sensing for human-machine interfaces. The electrode can form conformal contact with human skin, leading to low skin-electrode impedance and high-quality biopotential signals. In addition, the textile electrode can be used in a self-capacitance wireless touch sensing system.