Engineering Tough Supramolecular Hydrogels with Structured Micropillars for Tunable Wetting and Adhesion Properties.

Soft-lithography is widely used to fabricate microstructured surfaces on plastics and elastomers for designable physical properties such as wetting and adhesions. However, it remains a big challenge to construct high-aspect-ratio microstructures on the surface of hydrogels due to the difficulty in demolding from the gel with low strength and stiffness. Demonstrated here is the engineering of tough hydrogels by soft-lithography to form well-defined micropillars. The mechanical properties of poly(acrylamide-co-methacrylic acid) hydrogels with dense hydrogen-bond associations severely depend on temperature, with Young's modulus increasing from 8.1 MPa at 15 °C to 821.8 MPa at -30 °C, enabling easy demolding at low temperatures. Arrays of micropillars are maintained on the surface of the gel, and can be used at room temperature when the gel restores soft and stretchable. The hydrogel also exhibits good shape-memory property, favoring tailoring the morphology with a switchable tilt angle of micropillars. Consequently, the hydrogel shows tunable wetting and adhesion properties, as manifested by varying contact angles and adhesion strengths. These surface properties can also be tuned by geometry and arrangement of micropillars. This facile strategy by harnessing tunable viscoelasticity of supramolecular hydrogels should be applicable to other soft materials, and broaden their applications in biomedical and engineering fields.

Persistence of vitamin D deficiency among Italian patients with acute myocardial infarction.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic. METHODS AND RESULTS: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality. CONCLUSION: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality.

solid volume ratio in predicting pathological features of cT1 lung adenocarcinoma.

BACKGROUND: More effective methods are urgently needed for predicting the pathological grade and lymph node metastasis of cT1-stage lung adenocarcinoma. METHODS: We analyzed the relationships between CT quantitative parameters (including three-dimensional parameters) and pathological grade and lymph node metastasis in cT1-stage lung adenocarcinoma patients of our center between January 2015 and December 2023. RESULTS: A total of 343 patients were included, of which there were 233 males and 110 females, aged 61.8 ± 9.4 (30-82) years. The area under the receiver operating characteristic (ROC) curve for predicting the pathological grade of lung adenocarcinoma using the consolidation tumor ratio (CTR) and the solid volume ratio (SVR) were 0.761 and 0.777, respectively. The areas under the ROC curves (AUCs) for predicting lymph node metastasis were 0.804 and 0.873, respectively. Multivariate logistic regression analysis suggested that the SVR is an independent predictor of highly malignant lung adenocarcinoma pathology, while the SVR and pathological grade are independent predictors of lymph node metastasis. The sensitivity of predicting the pathological grading of lung adenocarcinoma based on SVR>5% is 97.2%, with a negative predictive value of 96%. The sensitivity of predicting lymph node metastasis based on SVR>47.1% is 97.3%, and the negative predictive value is 99.5%. CONCLUSIONS: The SVR has greater diagnostic value than the CTR in the preoperative prediction of pathologic grade and lymph node metastasis in stage cT1-stage lung adenocarcinoma patients, and the SVR may replace the diameter and CTR as better criteria for guiding surgical implementation.

[Effect of Staphylococcal Nuclease and Tudor Domain Containing 1/SLC7A11 on the Occurrence and Development of Osteosarcoma by Inhibiting Ferroptosis].

Objective To investigate the effect of staphylococcal nuclease and tudor domain containing 1(SND1) on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating ferroptosis in osteosarcoma cells via SLC7A11. Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small interfering RNA was employed to knock down the expression of SND1(si-SND1) in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11. Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Ferrostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resulted in down-regulated SLC7A11 expression(all P<0.001) and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020). Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferroptosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Follicle-stimulating hormone is negatively associated with nonalcoholic fatty liver disease in a Chinese elderly population: a retrospective observational study.

BACKGROUND: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. METHODS: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). RESULTS: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60-70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892-0.984 (P = 0.009), 0.971-0.993 (P = 0.002), 0.967-0.999 (P = 0.033), and 0.958-0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938-1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. CONCLUSIONS: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly.

Migrated Hem-o-Lok clips in the neobladder with giant stone formation: a case report.

INTRODUCTION: Neobladder urolithiasis is a rare but important delaying complication of orthotopic urinary diversion. We report a case of Hem-o-Lok (HOLC) migration into the neobladder with giant stone formation after orthotopic neobladder cystectomy. CASE REPORT: We report a case of a 57-year-old man with frequent urination and occasional discharge of stones 3 years after a laparoscopic orthotopic neobladder cystectomy. Computed tomography revealed a large round 3.5 cm calculus. An endoscopic neocystolitholapaxy was performed, and a Hem-o-Lok was found in the center of the stone. CONCLUSION: We described the case presentation, treatment and analysis of etiology of stone formation to avoid such complication.

Dose dependent effect of nitrogen on the phyto extractability of Cd in metal contaminated soil using Wedelia trilobata.

Cadmium (Cd) is one of the toxic heavy metal that negatively affect plant growth and compromise food safety for human consumption. Nitrogen (N) is an essential macronutrient for plant growth and development. It may enhance Cd tolerance of invasive plant species by maintaining biochemical and physiological characteristics during phytoextraction of Cd. A comparative study was conducted to evaluate the phenotypical and physiological responses of invasive W. trilobata and native W. chinensis under low Cd (10 µM) and high Cd (80 µM) stress, along with different N levels (i.e., normal 91.05 mg kg-1 and low 0.9105 mg kg-1). Under low-N and Cd stress, the growth of leaves, stem and roots in W. trilobata was significantly increased by 35-23%, 25-28%, and 35-35%, respectively, compared to W. chinensis. Wedelia trilobata exhibited heightened antioxidant activities of catalase and peroxidase were significantly increased under Cd stress to alleviate oxidative stress. Similarly, flavonoid content was significantly increased by 40-50% in W. trilobata to promote Cd tolerance via activation of the secondary metabolites. An adverse effect of Cd in the leaves of W. chinensis was further verified by a novel hyperspectral imaging technology in the form of normalized differential vegetation index (NDVI) and photochemical reflectance index (PRI) compared to W. trilobata. Additionally, W. trilobata increased the Cd tolerance by regulating Cd accumulation in the shoots and roots, bolstering its potential for phytoextraction potential. This study demonstrated that W. trilobata positively responds to Cd with enhanced growth and antioxidant capabilities, providing a new platform for phytoremediation in agricultural lands to protect the environment from heavy metals pollution.

Healable, Recyclable, and Multifunctional Soft Electronics Based on Biopolymer Hydrogel and Patterned Liquid Metal.

Recent years have witnessed the rapid development of sustainable materials. Along this line, developing biodegradable or recyclable soft electronics is challenging yet important due to their versatile applications in biomedical devices, soft robots, and wearables. Although some degradable bulk hydrogels are directly used as the soft electronics, the sensing performances are usually limited due to the absence of distributed conducting circuits. Here, sustainable hydrogel-based soft electronics (HSE) are reported that integrate sensing elements and patterned liquid metal (LM) in the gelatin-alginate hybrid hydrogel. The biopolymer hydrogel is transparent, robust, resilient, and recyclable. The HSE is multifunctional; it can sense strain, temperature, heart rate (electrocardiogram), and pH. The strain sensing is sufficiently sensitive to detect a human pulse. In addition, the device serves as a model system for iontophoretic drug delivery by using patterned LM as the soft conductor and electrode. Noncontact detection of nearby objects is also achieved based on electrostatic-field-induced voltage. The LM and biopolymer hydrogel are healable, recyclable, and degradable, favoring sustainable applications and reconstruction of the device with new functions. Such HSE with multiple functions and favorable attributes should open opportunities in next-generation electronic skins and hydrogel machines.

A novel amino acid site of N protein could affect the PRRSV-2 replication by regulating the viral RNA transcription.

BACKGROUND: Finding the key amino acid sites that could affect viral biological properties or protein functions has always been a topic of substantial interest in virology. The nucleocapsid (N) protein is one of the principal proteins of the porcine reproductive and respiratory syndrome virus (PRRSV) and plays a vital role in the virus life cycle. The N protein has only 123 or 128 amino acids, some of key amino acid sites which could affect the protein functions or impair the viral biological characteristics have been identified. In this research, our objective was to find out whether there are other novel amino acid sites of the N protein can affect N protein functions or PRRSV-2 replication. RESULTS: In this study, we found mutated the serine78 and serine 99of the nucleocapsid (N) protein can reduce the N-induced expression of IL-10 mRNA; Then, by using reverse genetics system, we constructed and rescued the mutant viruses, namely, A78 and A99.The IFA result proved that the mutations did not affect the rescue of the PRRSV-2. However, the results of the multistep growth kinetics and qPCR assays indicated that, compared with the viral replication ability, the titres and gRNA levels of A78 were significantly decreased compared with the wild-type. Further study showed that a single amino acid change from serine to alanine at position 78 of the N protein could abrogates the level of viral genomic and subgenomic RNAs. It means the mutation could significant decrease the viral replication efficiency in vitro. CONCLUSIONS: Our results suggest that the serine78 of N protein is a key site which could affect the N protein function and PRRSV replication ability.

Network pharmacological investigation into the mechanism of Kaixinsan powder for the treatment of depression.

Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).

[Clinical Comparative Analysis of Early-Onset Preeclampsia Combined with HELLP Syndrome].

Objective: To explore the clinical characteristics of early-onset preeclampsia (PE) combined with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and to improve the capacity for early diagnosis and treatment. Methods: Pregnant women who received treatment at Women's Hospital, School of Medicine, Zhejiang University between March 2014 and October 2021 were retrospectively enrolled. There were two patient groups, the HELLP group consisting of 70 cases of early-onset PE combined with HELLP syndrome and the control group consisting of 140 cases of early-onset PE without HELLP syndrome. Patients in the two groups were matched by age. The general clinical data, characteristics of pathogenesis, and laboratory findings of the patients were collected and the perinatal outcomes of the two groups were compared and analyzed. Results: 1) There was no significant difference in gravidity, pre-delivery body mass index, years from the last delivery, and family history of diabetes mellitus and hypertension between the two groups. 2) The highest systolic blood pressure, highest diastolic blood pressure during the pregnancy, and the postpartum hospital length-of-stay ( P<0.001) in the HELLP group were higher than those in the control group. The gestational age at the time of the diagnosis of PE ( P=0.001) and the gestational age at delivery ( P<0.001) in the HELLP group were significantly earlier than those in the control group. The difference between the gestational age at the time of blood pressure elevation and that at the time of delivery ( P<0.001), and the gestational age difference between the diagnosis of early-onset PE and delivery ( P=0.027) were lower than those in the control group. The incidences of eclampsia in the HELLP group, pleural effusion, and ascites were higher than those of the control group. 3) Neonates in the HELLP group had a higher probability of being admitted to NICU and developing cyanotic/pale asphyxia ( P<0.001). 4) Before the termination of pregnancy, the HELLP group had higher levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, urea, random glucose, lactate dehydrogenase, activated partial thromboplastin time, and the last 24-hour urine protein quantification than those of the control group (all P<0.05), while the platelet (PLT) counts were significantly lower than those of the control group ( P<0.001). 5) There was a significant correlation between PLT counts in the second trimester and the onset of HELLP syndrome ( P=0.006), with the area under the ROC curve reaching 0.746 (95% CI: 0.596-0.897). Conclusion: In comparison with early-onset PE patients without HELLP syndrome, patients with early-onset PE combined with HELLP syndrome are diagnosed for PE at an earlier gestational age, have higher blood pressure, are more prone to serious pregnancy complications, and have longer postpartum hospital length-of-stay and worse neonatal outcomes. Close monitoring of PLT counts of early-onset PE patients in the second trimester may help predict subsequent HELLP syndrome.

DYRK1A regulates Hap1-Dcaf7/WDR68 binding with implication for delayed growth in Down syndrome.

Huntingtin-associated protein 1 (Hap1) is known to be critical for postnatal hypothalamic function and growth. Hap1 forms stigmoid bodies (SBs), unique neuronal cytoplasmic inclusions of unknown function that are enriched in hypothalamic neurons. Here we developed a simple strategy to isolate the SB-enriched fraction from mouse brain. By analyzing Hap1 immunoprecipitants from this fraction, we identified a Hap1-interacting SB component, DDB1 and CUL4 associated factor 7 (Dcaf7)/WD40 repeat 68 (WDR68), whose protein level and nuclear translocation are regulated by Hap1. Moreover, we found that Hap1 bound Dcaf7 competitively in cytoplasm with dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), a protein implicated in Down syndrome (DS). Depleting Hap1 promoted the DYRK1A-Dcaf7 interaction and increased the DYRK1A protein level. Transgenic DS mice overexpressing DYRK1A showed reduced Hap1-Dcaf7 association in the hypothalamus. Furthermore, the overexpression of DYRK1A in the hypothalamus led to delayed growth in postnatal mice, suggesting that DYRK1A regulates the Hap1-Dcaf7 interaction and postnatal growth and that targeting Hap1 or Dcaf7 could ameliorate growth retardation in DS.

[Mechanism and experimental verification of Sijunzi Decoction in treatment of ulcerative colitis based on network pharmacology].

To explore the mechanism of Sijunzi Decoction in the treatment of ulcerative colitis(UC) based on network pharmacology. The active components and corresponding targets of Sijunzi Decoction were extracted with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets were standardized with the help of Uniprot database. The related targets of UC were obtained through GeneCards database and Disgenet database, and the intersection targets of drugs and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein-protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology(GO) and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG) pathway were carried out on Bioconductor platform, and some of the targets were verified by animal experiments. Through database analysis, a total of 135 active components of Sijunzi Decoction, 114 predicted targets and 80 common targets with UC were obtained. The core target proteins included interleukin 6(IL-6), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR) and so on. GO functional enrichment analysis involved 102 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis showed that 120 items were involved in human cytomegalovirus infection, cancer, apoptosis, inflammation and other pathways. Mouse experiments showed that Sijunzi Decoction could down-regulate the expression of target proteins IL-6 and caspase-3 and inhibit intestinal epithelial cell apoptosis. The treatment of UC with Sijunzi Decoction is the result of the interaction among multi-components, multi-targets and multi-pathways. It is proved by experiments that Sijunzi Decoction may play an effective role by regulating the expression of IL-6 and caspase-3, and getting involved in apoptosis, inflammation and other pathways.

[Regulatory effect of Jiaotai Pills on central and peripheral neurotransmitters in rats with heart-kidney imbalance insomnia].

To explore the pathogenesis of heart and kidney imbalance insomnia and the regulatory effect of Jiaotai Pills, in order to study the changes of central and peripheral neurotransmitters in rat. Insomnia rats with heart and kidney imbalance were induced through intraperitoneal injection with p-chlorophenylalanine(PCPA, 400 mg·kg~(-1)·d~(-1)), and the model rats were intragastrically administrated with Jiaotai Pills(3.3 g·kg~(-1)·d~(-1)) for 7 days. Nine neurotransmitters were determined by UPLC-MS/MS and principal component analysis(PCA) method in serum, urine, brain, heart, liver, kidney and adrenal gland of rats. The results showed that the ratio of 5-HT and 5-HIAA in platelet of insomnia rats was significantly lower than that in the normal group, and Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, the changed neurotransmitters in blood of insomnia rats were 5-HIAA, E, NE, DA, Glu and ACH, and except ACH, the changes of 7 kinds of neurotransmitters in urine were more significant, Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, all of the 8 neurotransmitters in insomnia rats except HVA were changed. Jiaotai Pills could regulate the neurotransmitters in each tissue of insomnia rats, especially in brain, liver and adrenal gland. In conclusion, insomnia is caused by not only a change of neurotransmitters in brain, but also a series of changes in peripheral tissues. It indicates that insomnia is a systematic imbalance of neurotransmitters. Jiaotai Pills not only regulates the central nervous system, but also has a certain protective effect on other organs, reflecting the multi-target and systematic effect of Jiaotai Pills in the treatment of insomnia.

PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma cell line CNE-2 by inducing endoplasmic reticulum stress, downregulating STAT3 signaling, and modulating the MAPK pathway.

Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor substance. In this study, we investigated the effect of PP-22, a monomer purified from P. polyphylla var. yunnanensis, on the nasopharyngeal carcinoma cell line CNE-2 in vitro. The results showed that PP-22 could inhibit the proliferation of CNE-2 cells via the induction of apoptosis, with evidence of the characteristic morphological changes in the apoptosis in the nucleus and an increase in Annexin V-positive cells. In addition, we found that PP-22 could activate the p38 mitogen-activated protein kinase (MAPK) pathway and that this activation was reversed by SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast, PP-22 promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum stress pathway, in a caspase-dependent manner. A further study showed that PP-22 also induced apoptosis by downregulating the signal transducers and activators of transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by STAT3 small interfering RNA. In addition, PP-22 could promote autophagy by inhibiting the extracellular regulated protein kinases (ERK) pathway. And autophagy plays a protective role against apoptosis. Together, these data show that PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE-2 cell line.

Single-cell RNA sequencing reveals distinct gene expression patterns in glucose metabolism of human preimplantation embryos.

Precise regulation of glucose metabolism-related genes is essential for early embryonic development. Although previous research has yielded detailed information on the biochemical processes, little is yet known of the dynamic gene expression profiles in glucose metabolism of preimplantation embryos at a single-cell resolution. In the present study, we performed integrated analysis of single-cell RNA sequencing (scRNA-seq) data of human preimplantation embryos that had been cultured in sequential medium. Different cells in the same embryo have similar gene expression patterns in glucose metabolism. During the switch from the cleavage to morula stage, the expression of glycolysis-related genes, such as glucose transporter genes (solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) and solute carrier family 2 (facilitated glucose transporter), member 3 (SLC2A3) and genes encoding hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase, is increased. The genes involved in the pentose phosphate pathway are highly expressed at the cleavage stage, generating the reducing power to balance oxidative stress derived from biosynthesis. Expression of the genes involved in the biosynthesis of glycerophospholipids is increased after the morula stage. Nevertheless, the expression of tricarboxylic acid-related genes remains relatively unchanged during the preimplantation stages. In conclusion, we discovered that the gene expression profiles are dynamic according to glucose utilisation in the embryos at different stages, which contributes to our understanding of regulatory mechanisms of glucose metabolism-related genes in human preimplantation embryos.

A Robust PDR/UWB Integrated Indoor Localization Approach for Pedestrians in Harsh Environments.

Wireless sensor networks (WSNs) and the Internet of Things (IoT) have been widely used in industrial, construction, and other fields. In recent years, demands for pedestrian localization have been increasing rapidly. In most cases, these applications work in harsh indoor environments, which have posed many challenges in achieving high-precision localization. Ultra-wide band (UWB)-based localization systems and pedestrian dead reckoning (PDR) algorithms are popular. However, both have their own advantages and disadvantages, and both exhibit a poor performance in harsh environments. UWB-based localization algorithms can be seriously interfered by non-line-of-sight (NLoS) propagation, and PDR algorithms display a cumulative error. For ensuring the accuracy of indoor localization in harsh environments, a hybrid localization approach is proposed in this paper. Firstly, UWB signals cannot penetrate obstacles in most cases, and traditional algorithms for improving the accuracy by NLoS identification and mitigation cannot work in this situation. Therefore, in this study, we focus on integrating a PDR and UWB-based localization algorithm according to the UWB communication status. Secondly, we propose an adaptive PDR algorithm. UWB technology can provide high-precision location results in line-of-sight (LoS) propagation. Based on these, we can train the parameters of the PDR algorithm for every pedestrian, to improve the accuracy. Finally, we implement this hybrid localization approach in a hardware platform and experiment with it in an environment similar to industry or construction. The experimental results show a better accuracy than traditional UWB and PDR approaches in harsh environments.

[Research progress in molecular pharmacognosy of Pogostemon cablin].

Molecular pharmacognosy( MP) is a new interdisciplinary science,which integrates the pharmacognosy and molecular biology,and focuses on the crude drugs' classification and identification,cultivation and protection,and production of active ingredients at the molecular level. Pogostemon cablin is one of the ten major southern medicines in China,MP research on this famous herb has developed on the basis of traditional research methods,and achieved certain results. This article summarized the MP research achievements of P. cablin in recent years,the prospect of this field is also discussed to provide references for the protection,development and utilization of P. cablin resources.

[Simultaneous rapid detection of eight neurotransmitters in rat tissues,blood and urine samples by UPLC-MS/MS].

Ultra performance liquid chromatography-tandem mass spectrometry( UPLC-MS/MS) was used to establish the simultaneous determination method of eight neurotransmitters in brain,liver,kidney,adrenal gland,serum and urine,including serotonin,5-hydroxyindole acetic acid,epinephrine,norepinephrine,dopamine,glutamic acid,γ-aminobutyric acid,and acetylcholine,and then investigate the distribution characteristics of neurotransmitters in rat tissues,blood and urine. Waters ACQUITY UPLC BEH C_(18) column( 2. 1 mm×100 mm,1. 7 µm) was used,with 0. 3% formic acid solution-acetonitrile as the mobile phase for gradient elution.Multiple reaction monitoring( MRM) scanning method under positive mode by atmospheric pressure electrospray ion source( ESI) was also performed to establish the detection method of neurotransmitters for methodological research. The plasma,urine and tissues of normal rats were pre-treated including homogenization,centrifuging,and protein removal,then the 2 µL supernatant was injected for analysis. The results showed that eight kinds of neurotransmitters could be accurately determined within 7 min,with linear correlation coefficients all greater than 0. 99. This method showed high accuracy and good precision,with specificity,stability,extraction recovery and matrix effects all complying with the biological sample analysis requirements. The most abundant transmitters in the brain,liver,kidney,kidney gland,blood and urine were γ-aminobutyric acid,glutamic acid,glutamic acid,adrenaline,glutamic acid and dopamine.The method is sensitive,rapid,precise,accurate and specific,and can be used for simultaneous quantitative analysis of eight neurotransmitters in biological samples. The investigation of the distribution ratio of transmitters in rats is of important significance to disease prevention and treatment.