Search

The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P =.001), 1.40 for Group III (P =.150), and 2.31 for Group IV (P <.001). Adiposity status in 2007 could predict hypertension (OR = 2.5, P <.001), as opposed to the initial adiposity status (P =.148). Subsequently adiposity status could have major effects on hypertension. Our society is very short of public health resources, particularly in developing countries, we should pay more attention to current adiposity status and encourage middle‐aged people to lose weight. [ABSTRACT FROM AUTHOR]

Objective: Irritability in children with autism spectrum disorder (ASD) is prominent and often leads to distress to both autistic children and their families. However, the nature of irritability in autism and the difference from nonautistic children have rarely been examined. This study aimed to investigate the clinical characteristics of irritability in autism, and to compare the symptom profiles with those of disruptive mood dysregulation disorder (DMDD) in nonautistic children. Methods: Fifty-six children aged 7–17 years (mean age 10.36 ± 3.05) were recruited into this study (21 with DMDD, 21 with high-functioning autism [hfASD], and 14 healthy volunteers [HV]). Their parents completed the Aberrant Behavior Checklist-Irritability (ABC-I) subscale and the Strengths and Difficulties Questionnaire (SDQ) parent report form. The ABC-I subscale was analyzed as a whole and broken into subsets (ABC-I-Irritability, ABC-I-Agitation, and ABC-I-Crying). The symptom profiles of irritability and the association with psychosocial difficulties were compared between groups. Results: The ABC-I-Irritability scores of children with hfASD closely matched to those of children with DMDD. In addition, both DMDD and hfASD groups could be differentiated from HV group in five of the six items except "depressed mood." However, in the ABC-I-Agitation scale, children with DMDD, but not hfASD, had higher scores in "Aggressive to other patients and staff" and "Stamps feet while banging objects or slamming doors" than HV. Regarding psychosocial outcomes, irritability in children with DMDD and hfASD were associated with emotional problems as measured by the SDQ. Moreover, irritability in DMDD was associated with conduct problems, and the hfASD group exhibited the similar trend. Conclusions: Symptom profiles of irritability and the associated emotional and conduct problems in children with hfASD were similar to those of DMDD in the nonautistic population. Future studies are warranted to explore the underlying neurophysiological mechanisms of irritability between autistic and nonautistic children for further insight into the nature of irritability in autism. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. Methods: In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism–Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. Results: Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (ra) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (ra = 0.31), functional diarrhea (ra = 0.27) as well as mixed gastrointestinal disorders (ra = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (ra = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (ra = 0.30, 0.17, and 0.17, respectively). Limitations: Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. Conclusions: Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity. [ABSTRACT FROM AUTHOR]

There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63–2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06–1.56), guanfacine (OR = 1.43, 95% CI = 1.12–1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09–1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended. [ABSTRACT FROM AUTHOR]

Public messages on the Internet political inquiry platform rely on manual classification, which has the problems of heavy workload, low efficiency, and high error rate. A Bi-directional long short-term memory (Bi-LSTM) network model based on attention mechanism was proposed in this paper to realize the automatic classification of public messages. Considering the network political inquiry data set provided by the BdRace platform as samples, the Bi-LSTM algorithm is used to strengthen the correlation between the messages before and after the training process, and the semantic attention to important text features is strengthened in combination with the characteristics of attention mechanism. Feature weights are integrated through the full connection layer to carry out classification calculations. The experimental results show that the F1 value of the message classification model proposed here reaches 0.886 and 0.862, respectively, in the data set of long text and short text. Compared with three algorithms of long short-term memory (LSTM), logistic regression, and naive Bayesian, the Bi-LSTM model can achieve better results in the automatic classification of public message subjects. [ABSTRACT FROM AUTHOR]

The etiological significance of neurological disorders in autism is debated, but it is clear that they complicate support provision and clinical management, and can have negative impact on outcomes. This systematic review and meta-analysis explored the full range of co-occurring neurological disorders in autism. We estimated the odds of having neurological complications compared to the general population and other neurodevelopmental conditions, as well as the overall prevalence of different neurological disorders. Seventy-nine articles were eligible for the systematic review, including 28 case-control studies, 43 prevalence studies, and 8 cohort studies. Findings were heterogeneous across studies. Overall, autistic individuals were significantly more likely than the general population to exhibit epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and congenital abnormalities of the nervous system, with prevalence estimates ranging from 1.1% (0%–3.3%; hydrocephalus) to 14.2% (11.3%–17.2%; epilepsy). Epilepsy was also more common in autism than in attention-deficit/hyperactivity disorder (odds ratio [95% confidence interval] = 4.06 [2.81–5.88]). Findings indicate that awareness of neurological disorders and neurological check-ups are indicated in autism to ensure adequate physical health care and support. Prospective studies of neurological disorders in children diagnosed with or at risk of autism might further enhance our understanding of causal pathways. Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism. [ABSTRACT FROM AUTHOR]

The article focuses on the association between caffeine consumption, ADHD, and pediatric headaches. Topics include increased caffeine consumption and its potential role in self-medication for ADHD symptoms, caffeine withdrawal headache in children and adolescents, and the mechanisms of caffeine-associated headaches, including adenosine receptor up-regulation and interference with the circadian system.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk for physical comorbidity. This study used a twin cohort to investigate the association between physical diseases and phenotypic variations of ADHD. A twin cohort enriched for ADHD and other neurodevelopmental conditions were analysed. The Attention Problems subscale of the Child Behavior Checklist/Adult Behavior Checklist (CBCL/ABCL-AP) was used to measure the participants' severity of ADHD symptoms. Physical health issues were obtained with a validated questionnaire and were tested in relation to ADHD symptom severity in a co-twin control model. Neurological problems were significantly associated with a diagnosis of ADHD. A conditional model for the analysis of within-twin pair effects revealed an inverse association between digestive problems and the severity of ADHD symptoms, after adjusting for co-existing autism spectrum disorder and ADHD medications. Our findings suggest that individuals with ADHD are susceptible to neurological problems, why a thorough neurological check-up is indicated in clinical practice for this population. In addition, health conditions of digestive system could be considered as a non-shared environmental factor for behavioral phenotypes in ADHD. It supports the possible role of gut-brain axis in the underpinnings of ADHD symptoms, at least for a subgroup of individuals with certain genetic predisposition. [ABSTRACT FROM AUTHOR]

This study used a twin cohort to investigate the association of autism spectrum disorder (ASD) and autistic traits with somatic health. A total of 344 twins (172 pairs; mean age 15.56 ± 5.62 years) enriched for ASD and other neurodevelopmental conditions were examined. Medical history and current physical problems were collected with a validated questionnaire to determine twin's somatic health. The Social Responsiveness Scale (SRS-2) was used to measure the participant's severity of autistic traits. Identified somatic health issues with significant within-twin pair differences were tested in relation to both ASD diagnosis and autistic traits in a co-twin control model. Twins with ASD exhibited more neurological and immunological health problems compared to those without ASD (p = 0.005 and p = 0.004, respectively). The intra-pair differences of neurological conditions and SRS-2 score were significantly correlated in monozygotic twins differing for autism traits (r = 0.40, p = 0.001), while the correlation was not found for immunological problems. In addition, a conditional model for analysis of within-twin pair effects revealed an association between neurological problems and clinical ASD diagnosis (Odds ratio per neurological problem 3.15, p = 0.02), as well as autistic traits (β = 10.44, p = 0.006), after adjusting for possible effects of co-existing attention deficit hyperactivity disorder and general intellectual abilities. Our findings suggest that neurological problems are associated with autism, and that non-shared environmental factors contribute to the overlap for both clinical ASD and autistic traits. Further population-based twin studies are warranted to validate our results and examine in detailed the shared genetic and environmental contributions of neurological problems and ASD. [ABSTRACT FROM AUTHOR]

Objectives: Irritability is among the most bothersome emotional symptoms in children. It often leads to mental health services referral, significant impairment, and distress to their families. Although there is increasing scientific evidence supporting the existence of extreme irritability in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) diagnosis of disruptive mood dysregulation disorder, few studies have investigated the measurement of irritability in children. This pilot study aimed to examine the psychometric properties of the Chinese version of the Affective Reactivity Index (ARI) and the Aberrant Behavior Checklist (ABC)-irritability subscale. In addition, we investigated adaptive difficulties among children with irritability.Methods: A total of 97 children and adolescents 6 to 17 years of age (M = 10.20, SD = 2.70) were recruited from the psychiatric outpatient department of a university hospital in Taipei. The participants completed the Chinese version of the ARI self-report form and the Social Adjustment Inventory for Children and Adolescents (SAICA). Their parents completed the ARI parent report form, the Chinese version of the ABC-irritability subscale, and the Child Behavior Checklist. Diagnostic interviews were administered based on diagnostic criteria of DSM-5 to confirm the participants' psychiatric diagnoses.Results: The Chinese ABC-irritability subscale and the parent and self-report scales of the Chinese ARI showed good test-retest reliability, internal consistency, and concurrent validity. Scores from the ABC-irritability subscale and two forms of the ARI were all significantly correlated with aggressive behaviors, anxious/depressed symptoms, and social problems. In addition, irritability among children was significantly associated with maladjustment in school, with peer problems, and with problems at home.Conclusions: Our findings suggest that irritability may be associated with impaired social adaptive functioning among children and adolescents. The Chinese version of the ARI and the ABC-irritability subscale are useful for measuring irritability in both clinical and research settings in the Chinese population. [ABSTRACT FROM AUTHOR]

Objectives: Disruptive mood dysregulation disorder (DMDD) is characterized by nonepisodic irritability and has a high rate of comorbidity with attention-deficit/hyperactivity disorder (ADHD). This is the first study to explore the effects of aripiprazole combined with methylphenidate on clinical symptoms and cognitive functions in patients with DMDD and ADHD.Methods: Patients with DMDD and ADHD (the DMDD-ADHD Group, n = 24; aged 7-17 years) completed a 6-week, open-label trial of aripiprazole and methylphenidate. The pre- and posttreatment outcome measures included the parent-rated Swanson, Nolan, and Pelham Scale-version IV, Child Behavior Checklist, and self-reported Beck Youth Inventories-II, as well as a neuropsychological battery composed of the Children's Color Trail Test and Conner's Continuous Performance Test. The comparison group consisting of patients with ADHD (the ADHD Group, n = 27) was recruited to investigate the differences in clinical and neuropsychological profiles between the two groups at baseline.Results: The DMDD-ADHD Group showed worse irritability, disruptive behaviors, anxious/depressed symptoms, and social problems relative to the ADHD Group at baseline assessments. The combination treatment significantly improved irritability, externalizing symptoms, depression, anxiety, attention, social problems, and reaction time variability. The effect sizes of reductions in parent-rated irritability, oppositional defiant symptoms, and inattention were comparable (Cohen's d = 1.26, 1.11, and 1.40, respectively).Conclusions: This pilot study showed the tolerability of the aripiprazole/methylphenidate combination by patients with DMDD and ADHD and its efficaciousness for treating clinical symptoms and for improving cognitive function. Further randomized, controlled, cross-over studies are needed. [ABSTRACT FROM AUTHOR]

The solubilities and diffusion coefficients of 1,1,1,3,3-pentafluoropropane (R245fa), 1,1,1,2,3,3,3-heptafluoropropane (R227ea) and 1,1,1,3,3,3-hexafluoropropane (R236fa) in 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([HMIM][Tf 2 N]) were determined experimentally along five isotherms (303.15, 313.15, 323.15, 333.15 and 343.15 K) with pressures from 0.01 to 0.50 MPa. The solubility measurements were carried out using the isochoric saturation method. A semi-infinite volume method was used to calculate diffusion coefficient via the time-dependent pressure-decay data. NRTL model was used to correlate the gas solubility data of R245fa, R227ea and R236fa in [HMIM][Tf 2 N] with the average absolute relative deviations less than 1.0%, while Wilke-Chang equation was used to correlate the diffusion coefficient data with the average absolute relative deviations less than 9.7%. [ABSTRACT FROM AUTHOR]

Nitrogen-doped carbon (NC) decorated Cu 2 NiSnS 4 (CNTS) microflower composites (NC@CNTS) were fabricated through a facile solvothermal and pyrrole polymerization with further annealing treatment. The NC@CNTS composites possessed a three-dimension (3D) microflower-like hierarchical structure. The unique microflower structure of NC@CNTS composites exhibited remarkable electrochemical performance as electrode materials for long life lithium ion batteries. The as-prepared composites had a stable and reversible capacity that reached 943 mA h g −1 after 160 cycles at a current rate of 0.1 A g −1 . It showed satisfactory cycle stability and rate capability even at 2 A g −1 , and specific capacity stabilized at 288 mA g −1 after 1000 cycles. The present facile and cost-effective strategy can be applied for the synthesis of other transition metal sulfide nanomaterials for energy storage and conversion applications. [ABSTRACT FROM AUTHOR]

Abstract In this paper, new data for the solubilities and diffusion coefficients of difluoromethane (R32), fluoroethane (R161) and 1,1-difluoroethane (R152a) in ionic liquid 1-hexyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate ([HMIM][FEP]) at temperatures ranging from 293 K to 343 K and at pressures up to 0.5 MPa were presented. The solubilities of R32, R161 and R152a in [HMIM][FEP] can be improved by decreasing the temperature and increasing the pressure. With the increasing temperature, the diffusion coefficients and Henry's law constants of the three hydrofluorocarbons increase. The solubilities and diffusion coefficients of R32, R152a, and R161 in [HMIM][FEP] were correlated well with the NRTL equation and the Wilke-Chang equation, respectively. Highlights • Solubilities and diffusion coefficients of R-32, R-161 and R-152a in [HMIM][FEP] were reported. • Effects of pressure, temperature and anion of ionic liquid on solubility and diffusion coefficient were studied. • Solubility and diffusion coefficient were successfully correlated with NRTL equation and Wilke-Chang equation. [ABSTRACT FROM AUTHOR]

Free-standing and binder-free electrodes of carbon cloth uniformly covered with Cu 2 NiSnS 4 nanospheres are synthesized via a facile surfactant-assisted hydrothermal method combined with post annealing treatment. The flexible composites are directly applied as electrodes for lithium ion batteries (LIBs) and sodium ion batteries (SIBs). The as-prepared electrodes display outstanding electrochemical performance. They deliver high reversible capacities of 1537 and 329 mAh g −1 after 150 cycles at a current density of 0.1 A g −1 for LIBs and SIBs, respectively. Even when the current density increases to 2 A g −1 , the specific capacity remains at 1200 mAh g −1 for LIBs. Benefiting from the intrinsic nature of materials, structure features, and good electrochemical performance, the as-prepared flexible electrode can be utilized for flexible energy storage devices. [ABSTRACT FROM AUTHOR]

In the present study, protein complexes emerged in high molecular weight (MW) region (95-170 kDa) were observed in fertilised chicken egg white after 7 days of incubation. Investigations were performed to reveal the possible proteins involved in these complexes. The emerged 10 protein bands from SDS-PAGE gel were confirmed to be ovalbumin through matrix-assisted laser desorption/ionisation time-of-flight tandem mass spectrometry (MALDI-TOF MS/MS) followed by Western blot analysis. To reveal the possible interactions among ovalbumin and other egg white proteins, LC connected to LTQ-Orbitrap mass spectrometer was used. Besides ovalbumin, 11 egg white proteins were identified including ovotransferrin, lysozyme, ovalbumin-related protein X, ovalbumin-related protein Y, hep21, alpha-enolase, ovoinhibitor, and a protein similar to ryanodine receptor 1. These results indicated widespread thermal-induced protein interactions among ovalbumin and other egg white proteins. [ABSTRACT FROM AUTHOR]

Adolescents with attention-deficit/hyperactivity disorder (ADHD) often exhibit functional impairment even those having less visible symptoms. Therefore, it is of great clinical importance to identify ADHD symptoms among adolescents in the community. Furthermore, little is known regarding the role of internalizing symptoms in their quality of life. Thus, this study aimed to screen ADHD in a sample of high school students using the Adult ADHD Self-report Scale (ASRS) and to investigate the impact of internalizing symptoms on their well-being. In the first year, adolescents aged 15-17 years old from a senior high school ( N = 1947) completed the Adult ADHD Self-rating Scale (ASRS), Wender Utah Rating Scale, Impulsiveness Scale, Beck's Depression Inventory and Beck's Anxiety Inventory. In the second year, the World Health Organization Quality of Life-BREF was applied for the measurement of their psychosocial outcomes. Results showed that adolescents with higher ASRS scores manifested more severe concurrent depressive and anxiety symptoms. ADHD symptoms among these adolescents were significantly associated with poorer quality of life 1 year later ( p < 0.001). And both depressive and anxiety symptoms were mediators in the relationship between ADHD symptoms and quality of life. The finding of this study supports that the concurrent internalizing symptoms may underlie the negative relations between ADHD symptoms and quality of life in adolescents in the community. The application of ASRS in adolescents may help clinicians in early intervention for their ADHD problems as well as emotional symptoms. [ABSTRACT FROM AUTHOR]

Radiotherapy is adopted to obliterate multiple malignant tumors clinically, which might also induce antitumor immune response. However, traditional radiotherapy is not enough to ablate tumors and activate long-term immunological response. Here, we developed a hybrid nanoplatform (MGTe) composed of GTe (glutathione (GSH) decorated Te nanoparticles) and fusing tumor cell membranes (TM) and bacterial outer membranes (BM). In this nanoplatform, GTe was designed for radiotherapy sensitization, concurrently the fusion of TM and BM was expected for amplifying antitumor immune. With a high-Z element, MGTe could enhance radiosensitivity by reactive oxygen species (ROS) production and cancer cell immunogenic death (ICD) under X-ray irradiation, which would also trigger antitumor immune. At meanwhile, TM and BM would further enlarge the immunological effects through antigen presenting cells (APCs) maturation and cytotoxic T lymphocytes (CTLs) stimulation. In this synergistic strategy, the combination of MGTe and X-ray showed significant tumor inhibition by radiation-driven immunotherapy, which will find great potential as an attractive clinical alternative to fight against tumor with reduced side effects. [ABSTRACT FROM AUTHOR]

Although cancer vaccines exhibit great advances in the field of immunotherapy, developing an efficient vaccine platform for personalized tumor immunotherapy is still a major challenge. Here we demonstrate that a bioactive vaccine platform (HMP@Ag) fabricated with hybrid M13 phage and personal tumor antigens can facilitate delivery of antigens into lymph nodes and activate antigen-presenting cells (APCs) through the Toll-like receptor 9 (TLR9) signaling pathway, which boosts both innate and adaptive immune response. As an adjuvant platform, hybrid M13 phages can deliver various tumor-specific antigens through simple adsorption to support the current development of personalized vaccines for cancers. Notably, the HMP@Ag vaccine not only prevented the tumors, but also delayed the tumor growth in established (subcutaneous and orthotopic) and metastatic tumor-bearing models while synergy with immune checkpoint blockade (ICB) therapy. Moreover, HMP@Ag triggered a robust neoantigen-based specific immune response in tumor-specific mutation models. In a clinically relevant surgery model, using autologous cell membrane from primary tumors-based HMP@Ag cooperation with ICB dramatically inhibited the post-operation recurrence, and elicited a long-term immune memory effect simultaneously. These findings imply that the M13 phage represents a powerful tool to develop a bio-activated hybrid platform for personalized therapy. [ABSTRACT FROM AUTHOR]

Background: Losartan and glimepiride are commonly used drugs to treat chronic diseases of hypertension and diabetes; they are both substrates of CYP2C9. The aim of the present study was to investigate the possible interaction of losartan and glimepiride both in vitro (rat liver microsomes) and in vivo (healthy Sprague-Dawley rats). Methods: In rat liver microsomes, 1-10 μmol/l losartan and glimepiride were coincubated, and the inhibitory effect was analyzed. In the subsequent pharmacokinetic study, 15 healthy Sprague-Dawley rats received administrations of 5 mg/kg losartan or 1 mg/kg glimepiride or a coadministration. Results: In the rat liver microsome system, glimepiride showed a slight inhibition of losartan at concentrations of 1-10 μmol/l, whereas losartan exhibited no inhibitory effect on glimepiride. In vivo, glimepiride did not modify the plasma concentration of losartan and its metabolite E-3174. The alteration of an increased AUC and Cmax was observed in the pharmacokinetic parameters of glimepiride and hydroxy glimepiride. Conclusions: Glimepiride did not affect losartan pharmacokinetics in rats, while losartan potently altered glimepiride metabolism; this result was inconsistent with the in vitro outcome. The mechanism requires further investigation. In clinical settings, attention should be paid to the interaction of these two drugs in the human body as well as the possible adverse reactions of glimepiride. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

1. CYP2C9 is an important member of the cytochrome P450 enzyme superfamily, with 57 CYP2C9 allelic variants being previously reported. Among these variants, we recently identified 21 novel alleles ( *36-*56) in the Han Chinese population. The aim of this study was to assess the catalytic activities of 36 CYP2C9 variants found in the Chinese population toward losartan in vitro. 2. Insect microsomes expressing the 36 CYP2C9 variants were incubated with 0.5-25 μM losartan for 30 min at 37 °C. Next, the products were extracted, and signal detection was performed using high-performance liquid chromatography. 3. Compared with wild-type CYP2C9.1, the intrinsic clearance ( Vmax /Km) values of all variants except for CYP2C9.56 were significantly altered. One variant exhibited markedly increased values (>250%), whereas 33 variants exhibited significantly decreased values (from 20 to 96%) due to increased Km and/or decreased Vmax values. 4. These findings suggest that more attention should be paid to subjects carrying these infrequent CYP2C9 alleles when administering losartan in the clinic. [ABSTRACT FROM AUTHOR]

Abstract: Aims of the study: Kanglaite (KLT) is a useful antitumor drug with proven effects when combined with chemotherapy, radiotherapy or surgery. We hypothesize that KLT has antitumor activity and immunomodulatory effects in Lewis lung carcinoma. Materials and methods: C57BL/6 mice with Lewis lung carcinoma were divided into four groups: the control group (C), cisplatin group (1mg/kg, DDP), low KLT group (6.25ml/kg body weight [L]), and high KLT group (12.5ml/kg body weight [H]). T cell proliferation was determined by the MTT assay. Nuclear factor-kappa B (NF-κB), inhibitor kappa B alpha (IκBα), IκB kinase (IKK) and epidermal growth factor receptor (EGFR) levels were measured by western blotting. An enzyme-linked immunosorbent assay was used to analyze the expression of interleukin-2 (IL-2). Results: Intraperitoneal KLT significantly inhibited the growth of Lewis lung carcinoma, and the spleen index was significantly higher in the L and H groups than in the C group. KLT stimulated T cell proliferation in a dose-dependent manner. Treatment with KLT at either 6.25 or 12.5ml/kg decreased the level of NF-κB in the nucleus in a dose-dependent manner, and KLT markedly decreased the expression of IκBα, IKK and EGFR in the cytoplasm of tumor cells and overall. IL-2 was significantly increased in the supernatant of splenocytes in the H group. Conclusions: These results demonstrate that KLT has pronounced antitumor and immunostimulatory activities in C57BL/6 mice with Lewis lung carcinoma. These may affect the regulation of NF-κB/IκB expression, in addition to cytokines such as IL-2 and EGFR. Further work needs to investigate the relevant signaling pathway effects, but our findings suggest that KLT may be a promising antitumor drug for clinical use. [Copyright &y& Elsevier]

Aims of the study: Sodium houttuyfonate (SH) is an addition compound of sodium bisulfite and houttuynin. Houttuynin is one of the main ingredients in the volatile oil of Houttuynia cordata Thunb, which has been widely used in traditional Chinese medicines. In this study, we investigated the effect of SH in membranous glomerulonephritis (MGN) induced by cationic Bovine Serum Albumin (C-BSA) in BALB/c mice. Materials and methods: Mice were divided into four groups, including normal vehicle-treated controls (N group), model (M group), low SH of 60mg/kg body weight (L group), or high SH of 120mg/kg body weight (H group). Urine protein quantification was detected by the urine protein strip test. Morphological assessment in kidneys was observed by light microscope and electron microscopy. The level of nuclear factor-kappaB (NF-κB) in the nuclear was evaluated by Western blot. Immunohistochemical was used to analyze the expression of MCP-1. Results: SH was shown to reverse C-BSA induced increases in urinary protein, and changes in morphology. Treatment with SH at 60–120mg/kg (L and H groups, respectively) dose-dependently decreased the level of nuclear NF-κB and MCP-1 expression compared to that of the M group. Conclusions: This study reveals that SH could treat C-BSA induced MGN in BALB/c mice by suppressing NF-κB activation and MCP-1 expression. Therefore, the most likely mechanism underlying the biological effects of SH is inhibition of an NF-κB mediated-cytokine pathway. [Copyright &y& Elsevier]

Abstract: Developing a photocatalyst system for the conversion of solar energy to electric energy or chemical energy is a topic of great interest with fundamental and practical importance. The semiconductor catalysts, such as InTaO4, have been extensively used for water splitting under visible light irradiation. However, it has not been used for photoreduction of carbon dioxide with water. InTaO4 was synthesized by solid-state reaction. NiO was added by incipient-wetness impregnation method as the cocatalysts. The catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet–visible spectroscopy (UV–Vis) and X-ray photoelectron spectroscopy (XPS). The photocatalytic reduction was carried out in a Pyrex reactor under visible light illumination using 500W halogen light as the light source. The band gap of InTaO4 was estimated, from UV–Vis spectrum, to be 2.6eV, showing that these catalysts have ability to reduce CO2 into methanol. The effects of the NiO cocatalyst and pretreatment process on the photocatalytic reduction of the catalyst to methanol were investigated. The methanol yield increased with the amount of NiO cocatalyst. The reduction–oxidation pretreatment had a positive effect on the catalyst. [Copyright &y& Elsevier]

Multitudinous industrial products in daily life put human health at risk of heavy metal exposure, and natural bacteria have displayed superior performance in bioadsorption and biodegradation of heavy metal. In this study, a bacteria‐based bioreactor is developed to precisely bioadsorb lead (Pb) ions, eliminate concomitant reactive oxygen species (ROS), and remit the injury of acute/chronic Pb poisoning. A nonpathogenic bacteria Escherichia coli MG1655 (Bac) is decorated with antioxidative cerium oxide nanoparticles (Ceria) on the surface through a bio‐orthogonal reaction, and the complex bioreactor could spontaneously aggregate in organs with high concentration of Pb. Furthermore, the excess Pb is bioadsorbed by bacteria and the concomitant ROS is eliminated by Ceria nanoparticles. In vitro and in vivo studies demonstrate that this integral biotic/abiotic hybrid bioreactor successfully realizes detoxication of Pb and reparation of injury, also accompanied with inappreciable side effects. [ABSTRACT FROM AUTHOR]

The article presents case study of a 73-year-old retired document delivery woman with failed trials of specific serotonergic and noradrenaline agents, antipsychotics and selective serotonin reuptake inhibitors for depression treatment. Topics discussed include beneficial effects of laughter for emotional health, laughter therapy club attended by the patient wherein she received a therapeutic program and increased sense of resilience, self-efficacy and optimism resulting from laughter.

Two copper(I)‐based frameworks of complexes {[Cu(L)2(ClO4)]⋅CH3CN}(2) and {[Cu(L)(ClO4)]⋅ 2CH3CN} (3) (L = 1,3,5‐tris(4‐pyridylethynyl) benzene) were produced by reacting [Cu(MeCN)4(ClO4)] with different amounts of a ligand (L) using a hydrothermal method at temperatures of up to 130°C. The nitrogen atoms in the pyridine moieties of the ligand coordinate to the Cu(I) ion. The charge on the Cu(I) ion can be stabilized by extending the degree of conjugation in the system and by taking advantage of its highly symmetrical structure. The large degree of conjugation also supports numerous π–π interactions in the framework. [ABSTRACT FROM AUTHOR]

Purpose: This study analyzed the interdisciplinary characteristics of Chinese research studies in library and information science (LIS) measured by knowledge elements extracted through the Lexicon-LSTM model. Design/methodology/approach: Eight research themes were selected for experiment, with a large-scale (N = 11,625) dataset of research papers from the China National Knowledge Infrastructure (CNKI) database constructed. And it is complemented with multiple corpora. Knowledge elements were extracted through a Lexicon-LSTM model. A subject knowledge graph is constructed to support the searching and classification of knowledge elements. An interdisciplinary-weighted average citation index space was constructed for measuring the interdisciplinary characteristics and contributions based on knowledge elements. Findings: The empirical research shows that the Lexicon-LSTM model has superiority in the accuracy of extracting knowledge elements. In the field of LIS, the interdisciplinary diversity indicator showed an upward trend from 2011 to 2021, while the disciplinary balance and difference indicators showed a downward trend. The knowledge elements of theory and methodology could be used to detect and measure the interdisciplinary characteristics and contributions. Originality/value: The extraction of knowledge elements facilitates the discovery of semantic information embedded in academic papers. The knowledge elements were proved feasible for measuring the interdisciplinary characteristics and exploring the changes in the time sequence, which helps for overview the state of the arts and future development trend of the interdisciplinary of research theme in LIS. [ABSTRACT FROM AUTHOR]

Objectives: The myeloid‐derived suppressor cells (MDSCs) frequently have a high expansion in cancer patients. This research explored whether administration of β‐glucan could increase anti‐tumor immunity in oral squamous cell carcinoma (OSCC) patients. Materials and Methods: This study evaluated the MDSC level of circulating blood as CD33+/CD11b+/HLA‐DR‐/low by flow cytometry in 30 healthy donors (HDs, group I), in 48 oral squamous cell carcinoma (OSCC) patients before and after 14‐day preoperative administration of β‐glucan (group II), and in 52 OSCC patients without taking β‐glucan (group III). Results: A significantly higher mean MDSC level was observed in 100 OSCC patients than in 30 HDs (p <.001). There was a significant reduction of the mean MDSC level in group II patients after taking β‐glucan (p <.001). Moreover, we discovered a significantly higher recurrence‐free survival (RFS) in group II than in group III patients (p =.026). Finally, the multivariate Cox regression further identified the MDSC level ≤1% and administration of β‐glucan as more favorable prognostic factors for OSCC patients. Conclusion: Preoperative administration of β‐glucan can augment anti‐tumor immunity and increase RFS rate via subversion of suppressive function of MDSC in OSCC patients. [ABSTRACT FROM AUTHOR]

We report the design, synthesis and evaluation of a class of phosphatidylserine-targeting zinc (II) dipicolylamine drug conjugates and show that conjugate 16b elicits immune cell infiltration and remodels the "cold" hepatic tumor microenvironment to the inflamed "hot" tumor. Structure-property relationship study via linker modifications and subsequent pharmacokinetics profiling were carried out to improve the solubility and stability of the conjugates in vivo. In a spontaneous hepatocellular carcinoma mouse model, we showed that conjugate 16b exhibited better antitumor efficacy than sorafenib. In particular, significant increase of CD8+ T cell infiltration and granzyme B level was observed, providing insights in sensitizing tumors from intrinsic immune suppressive microenvironment. Evaluation of tumor inflammation-related mRNA expression profile revealed that conjugate 16b, through inductions of key gene expressions including STAT1, CXCL9, CCL5, and PD-L1, rejuvenated tumor microenvironment with enhancement in T cell-, macrophage-, NK cell-, chemokines and cytokines'- functions. Our study establishes that an apoptosis-targeting theranostic enables enrichment of multifaceted immune cells into the tumor mass, which provides potential therapeutic strategies in the combination with immune checkpoint blockade treatment. [Display omitted] • Designing phosphatidylserine-targeting zinc (II) dipicolylamine drug conjugates. • Reducing hepatic tumor burden and increasing immune cells infiltration. • Remodeling of hepatic tumor microenvironment to inflamed "hot" tumor. [ABSTRACT FROM AUTHOR]

Taking inspiration from percutaneous ethanol injection (PEI) for tumor ablation, an acetaldehyde generator (SC@ZIF@ADH) is constructed for tumor treatment by modifying a metal–organic framework nanocarrier (ZIF), which is loaded with alcohol dehydrogenase (ADH), onto the surface of Saccharomyces cerevisiae (SC). Oral administration of SC@ZIF@ADH can target tumor via mannose‐mediated targeting to tumor associated macrophages (TAMs) and generate ethanol at the hypoxic tumor areas. Ethanol is subsequently catalyzed to toxic acetaldehyde by ADH, inducing tumor cells apoptosis and polarizing TAMs toward the anti‐tumor phenotype. In vivo animal results show that this acetaldehyde generator can cause a temulence‐like reaction in the tumor, significantly inhibiting tumor progression, and might provide an intelligent and nonsurgical substitute for PEI therapy. [ABSTRACT FROM AUTHOR]

Sleep disorders are known to increase the risk of hypertension, yet few studies have investigated the relation between sleep disorders and morning blood pressure (BP). This study aimed to determine, whether the morning BP is associated with sleep quality and sleep-disordered breathing. A total of 144 hypertensive patients were included in this cross-sectional study. Each subject underwent anthropometric measurements, biochemical testing, 24-h ambulatory BP monitoring, and polysomnography (PSG). Sleep quality and sleep-disordered breathing were determined by PSG parameters of sleep architecture and sleep respiratory. There were no significant differences between subjects with and without morning hypertension in the parameters of sleep architecture and sleep respiratory. In multiple regression analysis, morning BP was independently associated with night-time BP and morning BP surge, but not with the parameters of sleep architecture and sleep respiratory. Further analysis showed that both night-time BP and morning BP surge were independently associated with the sleep respiratory parameters. In conclusion, sleep-disordered breathing might indirectly affect the morning BP by elevated night-time BP, yet neither poor sleep quality nor sleep-disordered breathing was major determinants of elevated morning BP in hypertensive patients. [ABSTRACT FROM AUTHOR]

A reprogrammable transgenic mouse strain, called Col1a1 4F2A‐Oct4‐GFP, was bred for the present study. Because the somatic cells of this mouse strain contain only two copies of each Yamanaka factor, these animals are inefficient at producing induced pluripotent stem cells (iPSCs; approx. 0.005%) under traditional culture conditions. With an optimized culture condition, the iPSC production rate of mouse embryonic fibroblasts (MEFs) of Col1a1 4F2A‐Oct4‐GFP mice (MEFCol1a14F2A‐Oct4‐GFP) was increased to approximately 8%. Further, promotion of cell proliferation by serum supplementation did not enhance iPSC production. Inhibition of transforming growth factor β (TGF‐β) in the serum by SB431542 neither affected the growth rate of MEFCol1a14F2A‐Oct4‐GFP nor promoted iPSC production. However, the use of the gamma‐irradiated STO‐NEO‐LIF (γSNL) cells to serve as feeders for iPSC production resulted in a 5‐fold higher rate of iPSC production than the use of γMEFICR feeders. Interestingly, the use of SB431542 with the γMEFICR‐adopted system could eliminate this difference. RT‐PCR‐based comparative analysis further demonstrated that TGF‐β expression was 10‐fold higher in γMEFICR than in γSNL cells. Consistent with previous reports, mesenchymal to epithelial transition was found to participate in the initial steps of reprogramming in the specific context of MEFCol1a14F2A‐Oct4‐GFP. Moreover, we found that the initial seeding density is one of the pivotal factors for determining a high efficiency of iPSC generation. The iPSCs efficiently generated from our MEFCol1a14F2A‐Oct4‐GFP resembled mouse embryonic stem cells (mESCs) in aspects of teratoma formation and germline transmission. Depending on the culture conditions, our Col1a1 4F2A‐Oct4‐GFP mouse system can generate bona fide iPSCs with variable efficiencies, which can serve as a tool for interrogating the route taken by cells during somatic reprogramming. [ABSTRACT FROM AUTHOR]

High performance nitrogen-doped carbon (NC) materials decorated with MnO hybrid (MnO@NC) composites with a nanopeapod appearance were synthesized by with a simple hydrothermal method and insuit-polymeric route. As an anode material for lithium ion batteries (LIBs), the nanopeapod structure of MnO@NC composites with internal void spaces exhibits good rate capability, high conductivity and excellent cycling stability. After 200 cycles, the nanopeapod composites yield a specific capacity of 775.4 mAh g −1 at 100 mA g −1 and a high-rate capacity of 559.7 mAh g −1 at 1000 mA g −1 . The proposed synthesis of nanopeapod structure composites with an internal room is an efficient design with excellent electrode materials for rechargeable LIBs. [ABSTRACT FROM AUTHOR]

A semi-infinite volume technique was used to measure the diffusion coefficients of six hydrofluorocarbons in three room-temperature ionic liquids in the temperature range from 303.2 K to 343.2 K. The Henry’s constants were also determined at the same time. The hydrofluorocarbons are difluoromethane (R-32), pentafluoroethane (R-125), fluoroethane (R-161), 1,1,1-trifluoroethane (R-143a), 2,3,3,3-tetrafluoropropene (R-1234yf), and 1,1-difluoroethane (R-152a). The room-temperature ionic liquids are 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([HMIM][Tf 2 N]), 1-hexyl-3-methylimidazolium trifluoromethanesulfonate ([HMIM][TfO]), and 1-hexyl-3-methylimidazolium tetrafluoroborate ([HMIM][BF 4 ]). The diffusion coefficients and the Henry’s constants of hydrofluorocarbons in the three RTILs all increase with the increasing temperature, but the orders of them are different. In addition, the relationship between the diffusion coefficient and the Henry’s constant was investigated. Finally, the Wilke-Chang equation was successfully applied to correlate the diffusion coefficients of hydrofluorocarbons in room-temperature ionic liquids. [ABSTRACT FROM AUTHOR]

The association between central pulsatile hemodynamic load, arterial stiffness, and orthostatic hypotension (OH) is unclear. The authors recruited 1099 participants from the community. Questionnaire, physical examination, and laboratory tests were performed. To assess the correlation between central pulsatile hemodynamic load, arterial stiffness, and OH, multiple logistic regression analysis was performed, and the discriminatory power was assessed by the area under the receiver operating curve. The prevalence of OH in this population was 5.6%. After adjusting for potential confounders, brachial-ankle pulse wave velocity (BaPWV) was significantly and positively correlated with OH in both the hypertension and nonhypertension groups (all P<.05), while central systolic blood pressure (CSBP) was only significantly associated with OH in the hypertension subgroup. In addition, BaPWV seemed to have a better discriminatory power than CSBP in both subgroups. BaPWV appears to be a better indicator of OH than CSBP in routine clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: The reaction of 1,2,4-benzenetricarboxylic acid (H3btc), as a ligand, under pH-controlled hydrothermal conditions with nickel salts leads to the formation of a coordination polymer of {CsNi3(OH)(H2O)3[C6H3(CO2)3]2·3H2O} n (1). The subunit of compound 1 contains a hydroxide- and carboxylate-bridged trinickel clusters that are linked by an unsymmetrical organic carboxylate spacer to form a chiral three-dimensional anionic framework, in which cesium cations and guest water molecules are located in one-dimensional channels. The presence of a hydroxide ion serves both as a deprotonation agent and a cation source during the hydrothermal reaction, thus permitting the extent of deprotonation of the unsymmetrical ligand H3btc to be controlled, which is essential for the successful formation of compound 1. The magnetic properties of compound 1 were analyzed. Both dc and ac magnetic susceptibility as well as reduced magnetization measurements confirmed the spin-frustration nature of 1. [Copyright &y& Elsevier]

Abstract: Carbonic anhydrases (CAs) comprise a family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. CAs contribute to a myriad of physiological processes, including pH regulation, anion transport and water balance. To date, 16 known members of the mammalian alpha-CA family have been identified. Given that the catalytic family members share identical reaction chemistry, their physiologic roles are influenced greatly by their tissue and sub-cellular locations. CAVI is the lone secreted CA and exists in both saliva and the gastrointestinal mucosa. An alternative, stress-inducible isoform of CAVI (CAVI-b) has been shown to be expressed from a cryptic promoter that is activated by the CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP). The CAVI-b isoform is not secreted and is currently of unknown physiological function. Here we use neuronal models, including a model derived using Car6 and CHOP gene ablations, to delineate a role for CAVI-b in ischemic protection. Our results demonstrate that CAVI-b expression, which is increased through CHOP-signaling in response to unfolded protein stress, is also increased by oxygen–glucose deprivation (OGD). While enforced expression of CAVI-b is not sufficient to protect against ischemia, CHOP regulation of CAVI-b is necessary for adaptive changes mediated by BDNF that reduce subsequent ischemic damage. These results suggest that CAVI-b comprises a necessary component of a larger adaptive signaling pathway downstream of CHOP. [Copyright &y& Elsevier]

Independent component analysis (ICA) was integrated with near infrared (NIR) spectroscopy for rapid quantification of sugar content in wax jambu (Syzygium samarangense Merrill & Perry). The JADE algorithm (Joint Approximate Diagonalization of Eigenmatrices) and linear regression with spectral pretreatments were incorporated to analyze the NIR spectra of wax jambu against sucrose solutions. Unlike other multivariate approaches, ICA enabled comprehensive quantification of sugar content in wax jambu. In the present study, ICA was applied as the sole tool to build the NIR calibration model of internal quality of intact wax jambu without any other multivariate analysis methods. The best spectral calibration model of wax jambu (600 to 700 nm and 900 to 1,098 nm) yielded rc = 0.988, SEC = 0.243 °Brix, rv = 0.971, SEV = 0.381 °Brix, and RPD = 4.15 using the normalized first derivative spectra and 9 independent components (ICs). All ICA results were better than those of partial least squares regression (PLSR). Thus, ICA can quickly identify and effectively quantify the sugar contents in wax jambu with calibration models achieving high predictability. [ABSTRACT FROM AUTHOR]

Abstract: The role of hydrothermal vents as either a source or a sink for chromophoric and fluorescent dissolved organic matter (CDOM and FDOM) in the oceans is unknown, since DOM absorption and fluorescence have not been reported for submarine hydrothermal vents. Water samples were collected from two shallow submarine hydrothermal vents off NE Taiwan, the white vent and the yellow vent, during two cruises in August, 2010. Absorption and excitation-emission-matrix fluorescence spectroscopy were used to characterize the optical properties of DOM from such extremely special environments. The absorption coefficients at wavelength 300nm (a 300) were much higher at the white vent mouth and 1m below it (2.52±0.88m-1) than in the background (0.34±0.12m-1). This indicated that the white vent was a source of CDOM for seawater. Three fluorescent components were identified using parallel factor analysis: humic-like C1, tyrosine-like C3, and C2 as a combination of tryptophan-like and marine humic-like components. Both C1 and C3 (but not C2) had their highest fluorescence intensity at the white vent mouth and 1m below it, suggesting the role of the vent as a source for both humic-like and tyrosine-like DOM. Samples from the yellow vent mouth also had a higher a 300 than the ambient seawater in our first cruise, but had fluorescence intensities of C(1–3) similar to the ambient seawater. Overall, the low humification index (HIX: 1.40±0.30) and the high autochthonous index (BIX: 1.27±0.63) indicated that the DOM likely had low humic contents and was mainly autochthonous of biological or bacterial origin in the study area. A biplot of HIX and BIX showed that DOM from the hydrothermal vents had a characteristic similar to terrestrial cave and spring waters, but was distinct from isolated humics. [Copyright &y& Elsevier]

Abstract: Carbonic anhydrase VI (CA VI), encoded by type A transcripts of the gene Car6, is a secretory product of salivary glands and is found in the enamel pellicle. Because higher caries prevalence is associated with lower salivary concentrations of CA VI in humans, we tested whether CA VI protects enamel surfaces from caries induced by Streptococcus mutans, using Car6 −/− mice, in which salivary CA VI expression is absent. We detected aberrant Car6 type A transcripts in Car6 −/− mice, likely targets for nonsense-mediated mRNA decay. Expression of the intracellular stress-induced isoform of CA VI encoded by type B transcripts was restricted to parotid and submandibular glands of wild type mice. The salivary function of Car6 −/− mice was normal as assessed by the histology and protein/glycoprotein profiles of glands, salivary flow rates and protein/glycoprotein compositions of saliva. Surprisingly, total smooth surface caries and sulcal caries in Car6 −/− mice were more than 6-fold and 2-fold lower than in wild type mice after infection with S. mutans strain UA159. Recoveries of S. mutans and total microbiota from molars were also lower in Car6 −/− mice. To explore possible mechanisms for increased caries susceptibility, we found no differences in S. mutans adherence to salivary pellicles, in vitro. Interestingly, higher levels of Lactobacillus murinus and an unidentified Streptococcus species were cultivated from the oral microbiota of Car6 −/− mice. Collective results suggest salivary CA VI may promote caries by modulating the oral microbiota to favor S. mutans colonization and/or by the enzymatic production of acid within plaque. [Copyright &y& Elsevier]

[Display omitted] Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are currently used therapy for non-small cell lung cancer (NSCLC) patients; however, drug resistance during cancer treatment is a critical problem. Survivin is an anti-apoptosis protein, which promotes cell proliferation and tumor growth that highly expressed in various human cancers. Here, we show a novel synthetic compound derived from gefitinib, do-decyl-4-(4-(3-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propyl) piper-azin-1-yl)-4-oxobutanoate, which is named as SP101 that inhibits survivin expression and tumor growth in both the EGFR-wild type and -T790M of NSCLC. SP101 blocked EGFR kinase activity and induced apoptosis in the A549 (EGFR-wild type) and H1975 (EGFR-T790M) lung cancer cells. SP101 reduced survivin proteins and increased active caspase 3 for inducing apoptosis. Ectopic expression of survivin by a survivin-expressed vector attenuated the SP101-induced cell death in lung cancer cells. Moreover, SP101 inhibited the gefitinib-resistant tumor growth in the xenograft human H1975 lung tumors of nude mice. SP101 substantially reduced survivin proteins but conversely elicited active caspase 3 proteins in tumor tissues. Besides, SP101 exerted anticancer abilities in the gefitinib resistant cancer cells separated from pleural effusion of a clinical lung cancer patient. Consistently, SP101 decreased the survivin proteins and the patient-derived xenografted lung tumor growth in nude mice. Anti-tumor ability of SP101 was also confirmed in the murine lung cancer model harboring EGFR T790M-L858R. Together, SP101 is a new EGFR inhibitor with inhibiting survivin that can be developed for treating EGFR wild-type and EGFR-mutational gefitinib-resistance in human lung cancers. [ABSTRACT FROM AUTHOR]