Targeting In Vivo Metabolic Vulnerabilities of Th2 and Th17 Cells Reduces Airway Inflammation.

T effector cells promote inflammation in asthmatic patients, and both Th2 and Th17 CD4 T cells have been implicated in severe forms of the disease. The metabolic phenotypes and dependencies of these cells, however, remain poorly understood in the regulation of airway inflammation. In this study, we show the bronchoalveolar lavage fluid of asthmatic patients had markers of elevated glucose and glutamine metabolism. Further, peripheral blood T cells of asthmatics had broadly elevated expression of metabolic proteins when analyzed by mass cytometry compared with healthy controls. Therefore, we hypothesized that glucose and glutamine metabolism promote allergic airway inflammation. We tested this hypothesis in two murine models of airway inflammation. T cells from lungs of mice sensitized with Alternaria alternata extract displayed genetic signatures for elevated oxidative and glucose metabolism by single-cell RNA sequencing. This result was most pronounced when protein levels were measured in IL-17-producing cells and was recapitulated when airway inflammation was induced with house dust mite plus LPS, a model that led to abundant IL-4- and IL-17-producing T cells. Importantly, inhibitors of the glucose transporter 1 or glutaminase in vivo attenuated house dust mite + LPS eosinophilia, T cell cytokine production, and airway hyperresponsiveness as well as augmented the immunosuppressive properties of dexamethasone. These data show that T cells induce markers to support metabolism in vivo in airway inflammation and that this correlates with inflammatory cytokine production. Targeting metabolic pathways may provide a new direction to protect from disease and enhance the effectiveness of steroid therapy.

Intermittent versus continuous control of tracheal cuff pressure in patients undergoing mechanical ventilation: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To evaluate the effects and safety of intermittent versus continuous control of cuff pressure in patients with mechanical ventilation. BACKGROUND: Tracheal cuff pressure management is vital to the prognosis of patients with mechanical ventilation. DESIGN: A meta-analysis. METHODS: This meta-analysis was conducted and reported according to the PRISMA checklist. We searched Pubmed, Embase, The Cochrane Library, BMJ Best Practice, Web of Science, ProQuest Dissertations, as well as the Chinese Biomedical Literature Database, Wanfang, and China national knowledge infrastructure databases up to 5 August 2022 for randomised controlled trials (RCTs) on the intermittent versus continuous control of cuff pressure. Review Manager 5.3 software was used for relevant data analysis. RESULTS: A total of 18 RCTs involving 1998 patients with mechanical ventilation were included. The synthesised outcomes indicated that continuous control of cuff pressure is beneficial to reduce the incidence of ventilator-associated pneumonia (VAP) [RR = 0.41, 95%CI (0.35, 0.49)], aspiration [RR = 0.36, 95%CI (0.21, 0.63)], duration of mechanical ventilation [MD = -3.23, 95%CI (-4.66, -1.79)], length of ICU stay [MD = -4.12, 95%CI (-5.40, -2.83)], and increase the volume of subglottic drainage [MD = 18.54, 95%CI (16.50, 20.58)]. There was no significant difference in the mortality between two groups [RR = 1.01, 95%CI (0.84, 1.21)]. Egger regression analyses showed that there were no obvious publication biases in the synthesised results (all p > .05). CONCLUSIONS: Existing evidence shows that compared with intermittent monitoring of cuff pressure, continuous monitoring of cuff pressure can reduce the occurrence of aspiration and VAP, shorten the patient's duration of mechanical ventilation and length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Continuous monitoring of cuff pressure is more beneficial and should be promoted in clinical nursing care of patients undergoing mechanical ventilation.

Resveratrol inhibits neural apoptosis and regulates RAX/P-PKR expression in retina of diabetic rats.

PURPOSE: This study was to investigate the effect of resveratrol (RSV) administration on diabetes-induced neural apoptosis and on RNA-dependent-protein-kinase (PKR)-associated protein X (RAX), PKR and phosphorylated PKR (P-PKR) expression and distribution in retina of diabetic rats. METHODS: Retina was obtained from normal and diabetic Sprague-Dawley rats with or without RSV (5 and 10 mg/kg/d) treatment at 30-, 32-, 34- and 36-weeks. Apoptosis of retinal neural cells and distribution of RAX/P-PKR was assessed by TUNEL and immunofluorescence methods. Expression of RAX, PKR and P-PKR was evaluated by qRT-PCR and western-blotting methods. RESULTS: Our study showed that the TUNEL-positive cells were mainly localized in ganglion cells layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL) of the diabetic rat's retina at 30-, 32-, 34- and 36-weeks. RSV administration effectively suppressed the neural apoptosis in GCL, INL and ONL. Almost no TUNEL-positive cells were observed in retina of normal control and RSV-treated normal control rats. Our study also showed that the expression level of RAX, P-PKR in diabetic rats retina at 30-, 32-, 34-, and 36-weeks was elevated. With supplementation of 5 and 10 mg/kg/d RSV, the expression level of RAX and P-PKR was decreased (P < 0.05). The expression level of RAX and P-PKR in the retina of normal control rats was not altered by RSV. The expression level of PKR was not altered by streptozotocin injection and RSV treatment. CONCLUSIONS: Our results suggested that RSV attenuates retinal neural apoptosis in diabetic rats retina may be via regulation RAX/P-PKR expression.

The protective role of serum uric acid against premature membrane rupture in gestational diabetes: a cross-sectional study.

BACKGROUND: Uric acid has strong antioxidant activity, whereas its oxidative damage is closely related to many diseases. We assessed the association between serum uric acid (SUA) levels and premature rupture of membranes (PROM) in pregnant women with gestational diabetes (GDM) in China. METHODS: In this cross-sectional study, a total of 456 pregnant women were enrolled. Anthropometric parameters for pregnant women were collected within 12 weeks of gestation. Weight gain during pregnancy was obtained from the patients' records. GDM was diagnosed according to 75-g oral glucose tolerance tests at the 24-28th week of gestation, and SUA was determined simultaneously. PROM was identified as the natural rupture of foetal membranes before the first stage of labour. Logistic models were fitted to identify the presence of PROM using clinical characteristics with (Model 2) or without serum uric acid (Model 1). RESULTS: There were differences in BMI, haemoglobin A1c, fasting blood glucose, 1-h postprandial glucose (PG), 2-h PG, insulin levels, triglycerides,weight gain during pregnancy, the rate of macrosomia, fetus birth weight and PROM between women with and without GDM (all P < 0.05). Furthermore, GDM women with PROM had lower levels of SUA compared to those without PROM (P = 0.030). The odds ratio of PROM decreased with increasing SUA levels. The area under the receiver operating characteristic curves for PROM based on Model 2 was larger than that in Model 1 (0.86 versus 0.71, P < 0.05). CONCLUSION: Relatively elevated SUA levels at the 24-28th weeks of gestation were associated with a lower risk of PROM in women with GDM. Therefore, SUA may be a protective factor for PROM in GDM patients. The optimal concentration of uric acid in different diseases and different populations needs to be further studied.

Detection of epidermal growth factor receptor mutations in non-small cell lung cancer by immunohistochemistry. / å ç–«ç»„ç»‡åŒ–å­¦æ³•æ£€æµ‹éžå°ç»†èƒžè‚ºç™Œè¡¨çš®ç”Ÿé•¿å› å­å—ä½“çªå˜.

OBJECTIVES: To evaluate the sensitivity and specificity of immunohistochemistry (IHC) for detecting common epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and to estimate the cost-effectiveness of IHC testing. METHODS: A total of 208 NSCLC patients were included in the trial, and the EGFR mutation status in the patients were detected by PCR and IHC. Two mutation-specific antibodies against the most common exon 19 deletion (clone SP111) and exon 21 L858R mutation (clone SP125) were tested by using automated immunostainer. A cost-effectiveness analysis model was built for the analysis of optimal detection scheme. RESULTS: With a cutoff value of IHC 1+, the overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 81.7% (95% CI 72.4% to 89.0%) and 94.7% (95% CI 92.6% to 99.5%), respectively. EGFR 19del mutation was detected by SP111 antibody with a sensitivity of 65.9% (95% CI 49.4% to 79.9%) and specificity of 98.8% (95% CI 95.7% to 99.9%). EGFR L858R mutation was detected by SP125 antibody with a sensitivity of 94.2% (95% CI 84.1% to 98.8%) and specificity of 99.4% (95% CI 96.5% to 100%). The IHC and PCR cost ratio needed to be 1-to-3 or more in our patients to economically justify before the use of IHC. CONCLUSIONS: The study confirms an excellent specificity with fairly good sensitivity of IHC and mutation-specific antibodies for common EGFR mutations. It is cost-effective to use IHC method to detect EGFR mutation first when the IHC and PCR cost ratio is 1-to-3 or more in Chinese populations.

[Phenotype and Genotype Analysis in Two Pedigrees with Hereditary Coagulation Factor â ª Deficiency].

OBJECTIVE: To analyze the phenotype and genotype in two pedigrees with hereditary coagulation factor Ⅺ (FⅪ) deficiency, and investigate the molecular mechanisms of FⅪ deficiency. METHODS: Two patients with hereditary coagulation FⅪ deficiency were admitted to Chaozhou Central Hospital in Nov 2014 and Jan 2018. The prothrombin time (PT), activated partial thromboplastin time (APTT), FⅪ activity (FⅪ∶C) and FⅪ antigen (FⅪ∶Ag) were tested for phenotypic diagnosis. All the exons and exon-intron boundaries of FⅪ gene of proband were analyzed by PCR and sequencing. The family members were tested for the mutant site of proband. Then the mRNA of FⅪ in the proband was analyzed with RT-PCR. RESULTS: The proband-1 was a 7-year-old boy, PT was 10.7 s and APTT was 97.4 s (reference range: 9-12.8 s; 24-40 s), FⅪ∶C (0.6%) and FⅪ∶Ag<1% (reference range: 65%-150%; 72.1%-122.3%). The proband-2 was a 30-year-old female, and showed the PT (11.7 s), APTT (71.3 s), FⅪ∶C (0.7%) and FⅪ∶Ag<1%. FⅧ∶C, FⅨ∶C and FⅫ∶C of two proband were within the normal range. DNA sequencing showed that the proband-1 had a combined mutation of c.326-1G>A and c.1107C>A (p.Tyr351X) in exon 10. His grandmother, mother and brother had a heterozygous splicing mutation of c.326-1G>A, his grandmother and father had a homozygous mutation of c.1107C>A. FXI mRNA was undetected in the proband-1. The proband-2 had a homozygous mutation of c.841C>T (p.Gln263X) in exon 8, and this mutation was also found in her father, mother, daughter and son. CONCLUSION: The c.326-1G>A, c.1107C>A(p.Tyr351X) and c.841C>T (p.Gln263X) might be the molecular pathogenesis for two probands with hereditary coagulation factor Ⅺ deficiency.

MicroRNA-217 relieved neuropathic pain through targeting toll-like receptor 5 expression.

Neuropathic pain is the most common chronic pain that is caused by nerve injury or disease that influences the nervous system. Increasing evidence suggested that microRNAs (miRNAs) play a crucial role in neuropathic pain and neuroinflammation development. However, the functional role of miR-217 in the development of neuropathic pain remains unknown. In this study, we used rats to establish a neuropathic pain model and showed that the miR-217 expression level was upregulated in the spinal dorsal horn of bilateral sciatic nerve chronic constriction injury (bCCI). However, the expression of miR-217 was not changed in the anterior cingulated cortex (ACC), hippocampus, and dorsal root ganglion (DRG) of bCCI rats. Ectopic expression of miR-217 attenuated neuropathic pain and suppressed neuroinflammation expression in vivo. We identified toll-like receptor 5 (TLR5) as a direct target gene of miR-217 in the PC12 cell. In addition, we demonstrated that the expression level of TLR5 was upregulated in bCCI rats. Moreover, restoration of TLR5 rescued the inhibitory roles induced by miR-217 overexpression on neuropathic pain and neuroinflammation development. These data suggested that miR-217 played a pivotal role in the development of neuropathic pain partly through regulating TLR5 expression.

Poly(A) polymerase I participates in the indole regulatory pathway of Pantoea agglomerans YS19.

Pantoea agglomerans YS19 is a preponderant endophytic bacterium isolated from rice. It is characterized by the formation of symplasmata, a type of multicellular aggregate structure, contributing to a strong stress resistance and specific adaptation of YS19 in endophyte-host associations. Indole is an important signal molecule in intra- or interspecies relationships, regulating a variety of bacterial behaviours such as cell aggregation and stress resistance; however, the regulatory mechanism remains an ongoing area of investigation. This study selected YS19 as a model strain to construct a mutant library, utilizing the mTn5 transposon mutagenesis method, thus obtaining a positive mutant with an indole-inhibited mutation gene. Via thermal asymmetric interlaced PCR, the mutational site was identified as the gene of pcnB, which encodes the poly(A) polymerase I to catalyse the polyadenylation of RNAs. The full length of the pcnB sequence was 1332 bp, and phylogenetic analysis revealed that pcnB is extremely conserved among strains of P. agglomerans. The expression of the gene was significantly inhibited (by 36.6 % as detected via quantitative PCR) by indole (0.5 mM). Many physiological behaviours of YS19 were affected by this mutation: the cell decay rate in the post-stationary growth phase was promoted, symplasmata formation and motility were inhibited in the late stationary growth phase and the colonization ability and growth-promoting effect of YS19 on the host plant were also inhibited. This study discusses the indole regulatory pathways from the point of RNA post-transcriptional modification, thus enriching our knowledge of polyadenylation and expanding current research ideas of indole regulation.

Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina.

This study investigated the effects of resveratrol (RSV) on retinal functions, glutamate transporters (GLAST) and glutamine synthetase (GS) expression in diabetic rats retina, and on glutamate uptake, GS activity, GLAST and GS expression in high glucose-cultured Müller cells. The electroretinogram was used to evaluate retinal functions. Müller cells cultures were prepared from 5- to 7-day-old Sprague-Dawley rats. The expression of GLAST and GS was examined by qRT-PCR, ELISA and western-blotting. Glutamate uptake was measured as (3)H-glutamate contents of the lysates. GS activity was assessed by a spectrophotometric assay. 1- to 7-month RSV administrations (5 and 10 mg/kg/day) significantly alleviated hyperglycemia and weight loss in diabetic rats. RSV administrations also significantly attenuated diabetes-induced decreases in amplitude of a-wave in rod response, decreases in amplitude of a-, and b-wave in cone and rod response and decreases in amplitude of OP2 in oscillatory potentials. 1- to 7-month RSV treatments also significantly inhibited diabetes-induced delay in OP2 implicit times in scotopic 3.0 OPS test. The down-regulated mRNA and protein expression of GLAST and GS in diabetic rats retina was prevented by RSV administrations. In high glucose-treated cultures, Müller cells' glutamate uptake, GS activity, GLAST and GS expression were decreased significantly compared with normal control cultures. RSV (10, 20, and 30 mmol/l) significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST and GS expression (at least P < 0.05). These beneficial results suggest that RSV may be considered as a therapeutic option to prevent from diabetic retinopathy.

[Expressions of epithelial cell adhesion molecule, vimentin and N-cadherin in molecular subtypes of breast cancer and the correlation among them].

OBJECTIVE: To examine the expressions of epithelial cell adhesion molecule (EpCAM), vimentin and N-cadherin in breast cancer and its molecular subtypes, and to explore the correlation among them.
 Methods: The expressions of EpCAM, vimentin and N-cadherin were detected by immunohistochemistry in 835 patients with breast cancer, and their correlations with clinical pathological features and prognosis were analyzed.
 Results: The expression rates of EpCAM, vimentin and N-cadherin in the patients were 53.4%, 11.4% and 9.7% respectively, which were increased with the increase in tumor size, histological grade, lymph node size, tumor node stage of metastases classification, estrogen receptor and progesterone receptor levels (all P<0.05). The positive expression rates for EpCAM protein in luminal A, luminal B (HER2-), luminal B (HER2+), HER2 overexpression and triple-negative subtypes were 19.2%, 73.0%, 48.9%, 72.2%, and 62.1% respectively; for vimentin were 3.9%, 11.4%, 14.1%, 11.1%, and 20.5% respectively; for N-cadherin were 7.0%, 5.7%, 12.0%, 12.2% and 17.4% respectively, with statistical difference (all P<0.05). EpCAM expression was positively correlated with vimentin and N-cadherin in patients with breast cancer and triple-negative breast cancer.
 Conclusion: EpCAM is overexpressed in triple-negative subtype of breast cancer and it is associated with epithelial-mesenchymal transition markers, which might be related to breast cancer progression and metastasis.

Individualized supplementation of folic acid according to polymorphisms of methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR) reduced pregnant complications.

OBJECTIVE: This study aimed to detect the genotype distributions and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms of pregnant women in Jiaodong region in China, and to investigate whether folic acid supplementation affect the pregnancy complications. SETTING: A total of 7,812 pregnant women from the Jiaodong region in Shandong province in China. METHODS: By using Taqman-MGB, 2,928 pregnant women (case group) were tested for the genotype distributions and allele frequencies of MTHFR C677T, A1298C and MTRR A66G polymorphisms. Folic acid metabolism ability was ranked at four levels and then pregnant women in different rank group were supplemented with different doses of folic acid. Their pregnancy complications were followed up and compared with 4,884 pregnant women without folic acid supplementation (control group) in the same hospital. RESULTS: The allele frequencies of MTHFR C677T were 49.1 and 50.9%; those of MTHFR A1298C were 80.2 and 19.8%, and those of MTRR A66G were 74.1 and 25.9%. After supplemented with folic acid, the complication rates in different age groups were significantly reduced, especially for gestational diabetes mellitus and hypertension. CONCLUSION: Periconceptional folic acid supplementation and healthcare following gene polymorphism testing may be a powerful measure to decrease congenital malformations.

[Expression of PTEN, p53 and EGFR in the molecular subtypes of breast carcinoma and the correlation among them].

OBJECTIVE: To study the expression of PTEN, p53 and epidermal growth factor receptor (EGFR) in the molecular subtypes of breast carcinoma and to evaluate the correlations with triple-negative breast cancer.
 METHODS: Immunohistochemical MaxVision(TM) method was used to detect the expression of PTEN, p53, EGFR, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in 291 cases of infiltrating ductal carcinoma of breast. 
 RESULTS: The positive expression of PTEN, p53 and EGFR protein in breast carcinoma was 57.0%, 57.0% and 38.5%, respectively, which were significantly different from those in benign breast diseases (P<0.05). The expression of PTEN or EGFR in breast cancer was correlated with tumor size, histological grade, lymph node metastasis, TNM stage, ER and HER2 status (P<0.05); the expression of p53 was correlated with tumor size, histological grade and ER status (P<0.05). The difference of positive expression rates of PTEN, p53 and EGFR protein among different subtypes including luminal A, luminal B (HER2-), luminal B (HER2+), HER2 over-expression and triple-negative was statistically significant (P<0.05). There were close correlations among PTEN, p53 and EGFR in the triple-negative subtype (P<0.05).
 CONCLUSION: Low expression of PTEN and high expression of EGFR and p53 are observed in triple-negative breast cancer, which may synergistically contribute to the pathogenesis of triple-negative breast cancer.

Subcritical water extraction of antioxidant phenolic compounds from XiLan olive fruit dreg.

Olive fruit dreg (OFD), waste from olive softdrink processing, has caused disposal problems. Nevertheless, OFD is a good source of functional ingredients, such as phenolic compounds. This study investigated the extraction conditions of phenolic compounds from OFD by using subcritical water (SCW) extraction method, antioxidant activity of SCW extracts, and components of phenolic compounds by LC-MS. SCW extraction experiments were performed in a batch stainless steel reactor at temperatures ranging from 100 to 180 °C at residence time of 5 to 60 min, and at solid-to-liquid ratio of 1:20 to 1:60. Higher recoveries of phenolic compounds [37.52 ± 0.87 mg gallic acid equivalents (GAE)/g, dry weight (DW)] were obtained at 160 °C, solid-to-liquid ratio of 1:50, and extract time of 30 min than at 2 h extraction with methanol (1.21 ± 0.16 mg GAE/g DW), ethanol (0.24 ± 0.07 mg GAE/g DW), and acetone (0.34 ± 0.01 mg GAE/g DW). The antioxidant activities of the SCW extracts were significantly stronger than those in methanol extracts at the same concentration of total phenolic contents. LC-MS analysis results indicated that SCW extracts contained higher amounts of phenolic compounds, such as chlorogenic acid, homovanillic acid, gallic acid, hydroxytyrosol, quercetin, and syringic acid. SCW at 160 °C, 30 min, and solid-to-liquid ratio of 1:50 may be a good substitute of organic solvents, such as methanol, ethanol, and acetone to recover phenolic compounds from OFD.

Taurine prevents high glucose-induced angiopoietin-2/tie-2 system alterations and apoptosis in retinal microvascular pericytes.

Previously, we confirmed that taurine prevented diabetes-induced apoptosis in retinal glial cells via its anti-oxidation and anti-glutamate excitotoxicity mechanisms. The aim of this study is to investigate the effects of taurine on angiopoietin-2 (Ang-2)/Tie-2 system expressions and apoptosis in high glucose-treated retinal microvascular pericytes (RMPs). Also, the possible mechanism involved in the inhibition of taurine on RMPs apoptosis is investigated. The expressions of Ang-2, Tie-2 were detected by qRT-PCR and ELISA. The level of phosphorylated Tie-2 (P-Tie-2) was examined by ELISA. Hoechst 33342 and Annexin V/PI staining were used to detect RMPs apoptosis. The activity of caspase-3 was detected by assay kit. In 25 mM high glucose group, the expression of Ang-2 was increased significantly, taurine down-regulated Ang-2 in a dose (0.1, 1, and 10 mM)-dependent manner (P < 0.05). The Tie-2 expression and P-Tie-2 level were decreased in high glucose group (P < 0.05). Interestingly, taurine at 1 and 10 mM showed significant increase in Tie-2 expression and P-Tie-2 level (P < 0.05). The number of apoptotic RMPs and the activity of caspase-3 increased in the presence of high glucose (P < 0.05). Treatment with taurine at 1 mM decreased the number of apoptotic RMPs and the activity of caspase-3 (P < 0.05). Blocking antibody and small interfering RNA (siRNA) treatment showed that taurine required Tie-2 to perform its anti-apoptotic effect. Taken together, our data suggest that high glucose-induced Ang-2/Tie-2 system expressions alteration can be reversed by taurine, and that taurine can inhibit high glucose-induced RMPs apoptosis via Tie-2.

Bronchopulmonary infection of Lophomonas blattarum: a case and literature review.

Human infections with Lophomonas blattarum are rare. However, the majority of the infections occurred in China, 94.4% (136 cases) of all cases in the world. This infection is difficult to differentiate from other pulmonary infections with similar symptoms. Here we reported a case of L. blattarum infection confirmed by bronchoalveolar lavage fluid smear on the microscopic observations. The patient was a 21-year-old female college student. The previous case which occurred in Chongqing was 20 years ago. We briefly reviewed on this infection reported in the world during the recent 20 years. The epidemiological characteristics, possible diagnostic basis, and treatment of this disease is discussed in order to provide a better understanding of recognition, diagnosis, and treatment of L. blattarum infection.

A review: Interactions between protein from blue foods and functional components in delivery systems: Function exertion and transmembrane transport by in vitro digestion/cells model.

Functional compounds (FCs) had some functions, which are affected easily by digestion and transmembrane transport leading to low absorption rates, such as lutein, quercetin, xylo-oligosaccharide. Protein from blue foods is a potential bioactive compound, which had higher bioavailability, especially for bioactive peptides (BBPs). The BBPs has great limitations, especially the variability under pepsin digestion. However, the limitation of single FCs and BBPs in bioavailability might can be complemented by mixture of different bioactive compounds. Therefore, this review provides an in-depth study on the function and mechanism of different FCs/BBPs and their mixtures. Specifically, digestion effect of mixtures on function and transmembrane transport mechanisms of different bioactive compounds were exhibited to elaborate interactions between BBPs and FCs in delivery systems (function and bioavailability). Combination of FCs/BBPs could enhance bioactive compounds function by mutual complement of function mechanisms, as well as improving the function after digestion by regulating digestion process. Moreover, transmembrane absorption and transport of FCs/BBPs also could be facilitated by mixtures due to complement of transmembrane mechanism (endocytosis, protein channels, cell bypass way). This manuscript lays a foundation for the development of active ingredient bioavailability in functional food processing.

Multi-technology integrated network pharmacology-based study on phytochemicals, active metabolites, and molecular mechanism of Psoraleae Fructus to promote melanogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Compendium of Materia Medica (Shizhen Li, Ming dynasty) and Welfare Pharmacy (Song dynasty), Psoraleae Fructus (PF), a traditional Chinese medicine (TCM) has a bitter taste and warm nature, which has the effect of treating spleen and kidney deficiency and skin disease. Although PF has been widely used since ancient times and has shown satisfactory efficacy in treating vitiligo, the active substances and the mechanism of PF in promoting melanogenesis remain unclear. AIM OF THE STUDY: To explore the active substances and action mechanisms of PF in promoting melanogenesis. MATERIALS AND METHODS: Firstly, UPLC-UV-Q-TOF/MS was used to characterize the components in PF extract and identify the absorption components and metabolites of PF after oral administration at usual doses in rats. Secondly, the active substances and related targets and pathways were predicted by network pharmacology and molecular docking. Finally, pharmacodynamic and molecular biology experiments were used to verify the prediction results. RESULTS: The experimental results showed that 15 compounds were identified in PF extract, and 44 compounds, consisting of 8 prototype components and 36 metabolites (including isomers) were identified in rats' plasma. Promising action targets (MAPK1, MAPK8, MAPK14) and signaling pathways (MAPK signaling pathway) were screened and refined to elucidate the mechanism of PF against vitiligo based on network pharmacology. Bergaptol and xanthotol (the main metabolites of PF), psoralen (prototype drug), and PF extract significantly increased melanin production in zebrafish embryos. Furthermore, bergaptol could promote the pigmentation of zebrafish embryos more than psoralen and PF extract. Bergaptol significantly increased the protein expression levels of p-P38 and decreased ERK phosphorylation in B16F10 cells, which was also supported by the corresponding inhibitor/activator combination study. Moreover, bergaptol increased the mRNA expression levels of the downstream microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells. Our data elucidate that bergaptol may promote melanogenesis by regulating the p-P38 and p-ERK signaling pathway. CONCLUSIONS: This study will lay a foundation for discovering potential new drugs for treating vitiligo and provide feasible ideas for exploring the mechanism of traditional Chinese medicine.

Pioglitazone ameliorates endothelial dysfunction in those with impaired glucose regulation among the first-degree relatives of type 2 diabetes mellitus patients.

OBJECTIVE: To study the effects of pioglitazone on endothelial dysfunction of subjects with impaired glucose regulation (IGR) among the first-degree relatives of patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: The first-degree relatives of T2DM patients were screened with oral glucose test and IGR was diagnosed. IGR subjects whose blood glucose was still above the level after 1-month exercise were randomized to receive pioglitazone (15 mg/day) or vehicle for 12 weeks. Endothelial function was assessed as endothelium-dependent and -independent vasodilation. Blood nitric oxide (NO), blood pressure, body mass index, insulin and serum lipids were also measured. Area under the curve of glucose (AUC(glu)) and insulin (AUC(INS)), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of ß-cell function (HOMA-ß) and early insulin secretion index (ΔI(30)/ΔG(30)) were calculated. RESULTS: After pioglitazone treatment, fasting plasma, 2-hour plasma glucose, triglyceride (TG), fasting insulin, AUC(glu), HOMA-ß and HOMA-IR, 2-hour insulin, AUC(INS) and ΔI(30)/ΔG(30) decreased. Endothelium-dependent vasodilation and NO were significantly improved in the treatment group. Furthermore, the changes of endothelium-dependent vasodilation were negatively correlated with changes in AUC(INS) but positively with NO and HOMA-ß. Stepwise multivariate regression analysis showed that changes in NO and HOMA-ß were both independent parameters for improvement of endothelial dysfunction. CONCLUSION: Pioglitazone decreased blood glucose and TG, increased insulin sensitivity, and ameliorated endothelial dysfunction of IGR subjects among the first-degree relatives of T2DM patients. Increased NO production may be associated with the improvement of endothelial dysfunction.

C60-CN: A bifunctional interface modification material for perovskite solar cells.

Titanium dioxide (TiO2) is regularly used as an electron transport material in n-i-p perovskite solar cells (PSCs). However, massive defects exist on the TiO2 surface, which will lead to serious hysteresis and interface charge recombination of the device, thus affecting the device's efficiency. In this study, a cyano fullerene pyrrolidine derivative (C60-CN) was synthesized and applied to PSCs for the first time to modify the TiO2 electron transport layer. Systematic studies have shown that the addition of the C60-CN modification layer on the TiO2 surface will enlargement the perovskite grain size, improve the perovskite film quality, enhance electron transport, and reduce charge recombination. The C60-CN layer can significantly reduce the density of trap states in the perovskite solar cells. As a result, the PSCs based on C60-CN/TiO2 obtained a power conversion efficiency (PCE) of 18.60%, suppressing the hysteresis and improving the stability, whereas the PCE of the control device using the original TiO2 ETL was lower, 17.19%.

Influence of Mode of Delivery on Children's Attention Deficit Hyperactivity Disorder and Childhood Intelligence.

OBJECTIVE: To investigate whether differences exist in attention deficit hyperactivity disorder (ADHD) and intelligence between children born by cesarean delivery and those born by vaginal delivery. METHODS: This retrospective study included singleton children that were born between January 2013 and December 2014. The Chinese version of the Conners' Parent Rating Scale-Revised (CPRS-48) was required on the probability of psychological and behavioral problems. The China-Wechsler Intelligence Scale for Children (C-WIRS) was used for evaluation of crystallized intelligence and Raven's Standard Progressive Matrices for evaluation of fluid intelligence. RESULTS: A total of 10,568 valid questionnaires were obtained. CPRS-48 ADHD index and detection rate were higher in cesarean delivery group than those in vaginal delivery group. Cesarean delivery groups had a lower performance intelligence quotient score according to C-WISC. CONCLUSION: Children born by cesarean delivery were more likely to have a risk of ADHD and a lower performance intelligence quotient compared with those born by vaginal delivery.