ADHD is a common neurodevelopmental disorder with onset of symptoms typically in early childhood. First signs of the disorder, including language delay, motor delay and temperament characteristics, may be evident as early as infancy. The present review describes published evidence about early motor signs of either children with later symptoms of ADHD or a later diagnosis of the disorder. Nine published cohort studies were included after a systematic search of related terms in PubMed and PsycInfo databases. Study eligibility criteria included: (1) report on early motor function or any motor-related signs; (2) the presence of a participants' assessment by/at 12 months of age; (3) report of a later presence of ADHD symptoms. The limited number of reports included suggests an association between mild early neurological markers and later developmental coordination disorder and motor overflow movements. Unfortunately, due to their small sample sizes and focus on group reports rather than individuals, they have limited power to find strong associations. Early motor indicators of ADHD, if present, appear to be non-specific, and therefore not yet useful in clinical screening. Spontaneous motility seems to be a promising measure for early ADHD detection, although further studies with large cohorts are recommended to determine its clinical role in children at risk for ADHD.

Woodfordia fructicosa is used traditionally for the treatment of inflammation associated with arthritis.

This study aimed to systematically assess the outcomes of intentional replantation (IR) of teeth and to determine the survival rate, success rate, and prognostic factors related to the treatment. A search was conducted for all relevant English language articles published from January 2000 to October 2017. The search terms included "intentional replantation" and "teeth" according to the inclusion criteria. The Methodological Index for Non-randomized Studies (MINORS) was used to assess the methodological quality of included studies. Twelve studies were identified as relevant for the systematic review. In total, 896 patients with 905 teeth were examined for intentional teeth replantation. The success rate was greater than 90% in four studies (33.33%) and between 70% and 80% in five studies. At short-term follow-up (<6 months), the survival rate was approximately 90% in four studies. At longer-term follow-up (>36 months), the survival rates of teeth were slightly reduced in four studies, and tended to be stable after 48 months. In conclusion, the long-term success and survival rate of IR are likely dependent upon short extraoral time, reduced pocket depth, type of tooth, type of root-end filling material, and the prevention of atraumatic tooth root damage.

This study aimed to explore the effects of astragaloside IV on metabolic syndrome induced by a high-fructose/high-fat diet in rats.

Porcine respiratory disease is one of the most important health problems which causes significant economic losses.

Higher scores on the personality trait of neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between neuroticism and health typically operationalize neuroticism by summing the items from a neuroticism scale. However, neuroticism is made up of multiple heterogeneous facets, each contributing to the effect of neuroticism as a whole. A recent study showed that a 12-item neuroticism scale described one broad trait of general neuroticism and two special factors, one characterizing the extent to which people worry and feel vulnerable, and the other characterizing the extent to which people are anxious and tense. This study also found that, although individuals who were higher on general neuroticism lived shorter lives, individuals whose neuroticism was characterized by worry and vulnerability lived longer lives. Here, we examine the genetic contributions to the two special factors of neuroticism-anxiety/tension and worry/vulnerability-and how they contrast with that of general neuroticism. First, we show that, whereas the polygenic load for neuroticism is associated with the genetic risk of coronary artery disease, lower intelligence, lower socioeconomic status (SES), and poorer self-rated health, the genetic variants associated with high levels of anxiety/tension, and high levels of worry/vulnerability are associated with genetic variants linked to higher SES, higher intelligence, better self-rated health, and longer life. Second, we identify genetic variants that are uniquely associated with these protective aspects of neuroticism. Finally, we show that different neurological pathways are linked to each of these neuroticism phenotypes.

In this study, we first identified male-specific SNP markers using restriction site-associated DNA sequencing, and further developed a PCR-based sex identification technique for Charybdis feriatus. A total of 296.96 million clean reads were obtained, with 114.95 and 182.01 million from females and males. After assembly and alignment, 10 SNP markers were identified being heterozygous in males but homozygous in females. Five markers were further confirmed to be male-specific in a large number of individuals. Moreover, two male-specific sense primers and a common antisense primer were designed, using which, a PCR-based genetic sex identification method was successfully developed and used to identify the sex of 103 individuals, with a result of 49 females and 54 males. The presence of male-specific SNP markers suggests an XX/XY sex determination system for C. feriatus. These findings should be helpful for better understanding sex determination mechanism, and drafting artificial breeding program in crustaceans.

An integrative approach is presented to identify grade-specific biomarkers for breast cancer. Grade-specific molecular interaction networks were constructed with differentially expressed genes (DEGs) of cancer grade 1, 2, and 3. We observed that the molecular network of grade3 is predominantly associated with cancer-specific processes. Among the top ten connected DEGs in the grade3, the increase in the expression of UBE2C and CCNB2 genes was statistically significant across different grades. Along with UBE2C and CCNB2 genes, the CDK1, KIF2C, NDC80, and CCNB2 genes are also profoundly expressed in different grades and reduce the patient's survival. Gene set enrichment analysis of these six genes reconfirms their role in metastatic phenotype. Moreover, the coexpression network shows a strong association of these six genes promotes cancer specific biological processes and possibly drives cancer from lower to a higher grade. Collectively the identified genes can act as potential biomarkers for breast cancer diagnosis and prognosis.

The B-cell lymphoma/leukemia 11A protein (encoded by BCL11A gene) is a key regulator of fetal-to-adult hemoglobin switching as seen in post-natal life. Although genetic polymorphisms like SNPs in BCL11A gene are expected to affect fetal hemoglobin (HbF) expression levels, yet their implications are poorly studied. This study utilizes a computational approach to identify the deleterious SNPs which may affect the structure and function of BCL11A protein. The study also generated a 3D structure of native and mutants. The analysis identified two SNPs in BCL11A as highly deleterious: N391K and C414S which are expected to affect structure and stability of the protein. According to conservation analysis, both residues N391 and C414 were identified as highly conserved. Additionally, post-translational modification sites were predicted at both sites. Ligand binding sites were also predicted in N391 and C414. Therefore, N391K and C414S in BCL11A can considered as important candidates to mediate HbF variation.

Increasing the potassium use efficiency (KUE) of crops is important for agricultural sustainability. However, a greater understanding of this complex trait is required to develop new, high-KUE cultivars. To this end, a genome-wide association study (GWAS) was applied to diverse rice (Oryza sativa L.) genotypes grown under potassium-stressed and -replete conditions. Using high-stringency criteria, the genetic architecture of KUE was uncovered, together with the breadth of physiological responses to low-potassium stress. Specifically, three quantitative trait loci (QTLs) were identified, which contained >90 candidate genes. Of these, the sodium transporter gene OsHKT2;1 emerged as a key factor that impacts on KUE based on (i) the correlation between shoot Na+ and KUE, and (ii) higher levels of HKT2;1 expression in high-KUE lines.

Aberrant glycosylation resulting from altered expression of sialyltransferases, such as ST3 β-galactoside α2-3-sialyltransferase 6, plays an important role in disease progression in multiple myeloma (MM). Hypersialylation can lead to increased immune evasion, drug resistance, tumor invasiveness, and disseminated disease. In this study, we explore the in vitro and in vivo effects of global sialyltransferase inhibition on myeloma cells using the pan-sialyltransferase inhibitor 3Fax-Neu5Ac delivered as a per-acetylated methyl ester pro-drug. Specifically, we show in vivo that 3Fax-Neu5Ac improves survival by enhancing bortezomib sensitivity in an aggressive mouse model of MM. However, 3Fax-Neu5Ac treatment of MM cells in vitro did not reverse bortezomib resistance conferred by bone marrow (BM) stromal cells. Instead, 3Fax-Neu5Ac significantly reduced interactions of myeloma cells with E-selectin, MADCAM1 and VCAM1, suggesting that reduced sialylation impairs extravasation and retention of myeloma cells in the BM. Finally, we showed that 3Fax-Neu5Ac alters the post-translational modification of the α4 integrin, which may explain the reduced affinity of α4β1/α4β7 integrins for their counter-receptors. We propose that inhibiting sialylation may represent a valuable strategy to restrict myeloma cells from entering the protective BM microenvironment, a niche in which they are normally protected from chemotherapeutic agents such as bortezomib. Thus, our work demonstrates that targeting sialylation to increase the ratio of circulating to BM-resident MM cells represents a new avenue that could increase the efficacy of other anti-myeloma therapies and holds great promise for future clinical applications.

Tendinopathy, which is characterized by the ectopic ossification of tendon, is a common disease occurring in certain population, such as athletes that suffer from repetitive tendon strains. However, the molecular mechanism underlying the pathogenesis of tendinopathy caused by the overuse of tendon is still lacking. Here, we found that the mechanosensitive miRNA, miR-337-3p, had lower expression under uniaxial cyclical mechanical loading in tendon-derived stem cells (TDSCs) and negatively controlled chondro-osteogenic differentiation of TDSCs. Importantly, downregulation of miR-337-3p expression was also observed in both rat and human calcified tendons, and overexpressing miR-337-3p in patellar tendons of rat tendinopathy model displayed a robust therapeutic efficiency. Mechanistically, we found that the proinflammatory cytokine interleukin-1β was the upstream factor of miR-337-3p that bridges the mechanical loading with its downregulation. Furthermore, the target genes of miR-337-3p, NADPH oxidase 4, and insulin receptor substrate 1, activated chondro-osteogenic differentiation of TDSCs through JNK and ERK signaling, respectively. Thus, these findings not only provide novel insight into the molecular mechanisms underlying ectopic ossification in tendinopathy but also highlight the significance of miR-337-3p as a putative therapeutic target for clinic treatment of tendinopathy.

Polycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative treatments. The signaling rewiring in PKD that drives cyst formation is highly complex and not fully understood. As a consequence, the effects of drugs are sometimes difficult to predict. We previously established a high throughput microscopy phenotypic screening method for quantitative assessment of renal cyst growth. Here, we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules, including approved drugs. We identified 81 active molecules that inhibit cyst growth. Multi-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological properties. Celastrol, a triterpenoid from Tripterygium Wilfordii, was identified as a potent inhibitor of cyst growth in vitro. In an in vivo iKspCre-Pkd1lox,lox mouse model for PKD, celastrol inhibited the growth of renal cysts and maintained kidney function.

H7N9 avian influenza virus (AIV) caused human infections in 2013 in China. Phylogenetic analyses indicate that H7N9 AIV is a novel reassortant strain with pandemic potential. We conducted a systemic review regarding virus-induced pathogenesis, vaccine development, and diagnosis of H7N9 AIV infection in humans. We followed PRISMA guidelines and searched PubMed, Web of Science, and Google Scholar to identify relevant articles published between January 2013 and December 2018. Pathogenesis data indicated that H7N9 AIV belongs to low pathogenic avian influenza, which is mostly asymptomatic in avian species; however, H7N9 induces high mortality in humans. Sporadic human infections have recently been reported, caused by highly pathogenic avian influenza viruses detected in poultry. H7N9 AIVs resistant to adamantine and oseltamivir cause severe human infection by rapidly inducing progressive acute community-acquired pneumonia, multiorgan dysfunction, and cytokine dysregulation; however, mechanisms via which the virus induces severe syndromes remain unclear. An H7N9 AIV vaccine is lacking; designs under evaluation include synthesized peptide, baculovirus-insect system, and virus-like particle vaccines. Molecular diagnosis of H7N9 AIVs is suggested over conventional assays, for biosafety reasons. Several advanced or modified diagnostic assays are under investigation and development. We summarized virus-induced pathogenesis, vaccine development, and current diagnostic assays in H7N9 AIVs.

Psychotic disorders can be exacerbated by the hormonal changes associated with childbirth, but the extent to which exacerbations occur with the menstrual cycle is unclear. We addressed this issue by conducting a systematic review. Embase, Medline, and PsychINFO databases were searched for studies that measured exacerbations of psychotic disorders in relation to the menstrual cycle. We extracted exacerbation measure, definition of menstrual cycle phase, and measurement of menstrual cycle phase. Standard incidence ratios were calculated for the perimenstrual phase based on the observed admissions during this phase divided by the expected number of admissions if the menstrual cycle had no effect. Random effects models were used to examine pooled rates of psychiatric admission in the perimenstrual phase. Nineteen studies, comprising 1193 participants were eligible for inclusion. Eleven studies examined psychiatric admission rates, 5 examined symptoms scores, 2 examined self-reported exacerbation, and 1 examined both admission rates and symptom scores. A random effects model demonstrated the rate of admissions during the perimenstrual phase was 1.48 times higher than expected (95% CI: 1.31-1.67), with no significant heterogeneity detected. Four of six symptom score studies reported perimenstrual worsening, but lack of consistency in timepoints precluded meta-analysis. Two studies examining self-reported menstrual exacerbations reported prevalences ranging from 20% to 32.4%. Psychiatric admission rates are significantly higher than expected during the perimenstrual phase. There is some evidence that a worsening of psychotic symptoms also occurs during this phase, but further research with more precise measurement of the menstrual cycle and symptomatology is required.

The structures of proteins are intimately related to their functions. Significant efforts have been dedicated to the structural investigation of proteins, mainly those of purified proteins in in vitro environments. Proteins function in living cells and thus protein structures must be regulated by interactions with various molecules, some of which participate in reaction networks, depending on the states, conditions, or actions of the cell. Therefore, it is very important to understand the structural behavior of proteins in living cells.

Shati/Nat8l is a novel N-acetyltransferase identified in the brain of mice treated with methamphetamine (METH). Shati/Nat8l mRNA is expressed in various brain areas, including the prefrontal cortex (PFC), where the expression level is higher than that in other brain regions. Shati/Nat8l overexpression in the nucleus accumbens (NAc) attenuates the pharmacological response to METH via mGluR3. Meanwhile, dopamine (DA) and glutamate dysregulations have been reported in the medial prefrontal cortex (mPFC) and NAc after METH self-administration and during reinstatement. However, the mechanism, the reward system, and function of Shati/Nat8l in the mPFC is unclear. Here, we injected an adeno-associated virus (AAV) vector containing Shati/Nat8l into the mPFC of mice, to overexpress Shati/Nat8l in the mPFC (mPFC-Shati/Nat8l). Interestingly, the METH-induced conditioned place preference (CPP) was attenuated in the mPFC-Shati/Nat8l mice, but locomotor activity was not. Additionally, immunohistochemical results from mice that were injected with AAV-GFP showed fluorescence in the mPFC and other brain regions, mainly the NAc, indicating an mPFC-NAc top-down connection. Finally, in vivo microdialysis experiments revealed that Shati/Nat8l overexpression in the mPFC reduced extracellular DA levels and suppressed the METH-induced DA increase in the NAc. Moreover, decreased extracellular glutamate levels were observed in the NAc. These results indicate that Shati/Nat8l overexpression in the mPFC attenuates METH-induced CPP by decreasing extracellular DA in the NAc. In contrast, Shati/Nat8l-mPFC overexpression did not alter METH-induced hyperlocomotion. This study demonstrates that Shati/Nat8l in the mPFC attenuates METH reward-seeking behaviour but not the psychomotor activity of METH.

The affiliative effect of oxytocin on behavior toward other individuals can be modulated by positive and negative aspects of those individuals. However, the context-dependent effect of oxytocin on helping behavior is still unclear. In this study, we examined the effect of oxytocin administration on helping behavior in rats. The rats learned to open a door to help a cagemate soaked with water. The rats were divided into Pair and Solo groups. The rats in the Pair group were housed with their cagemates and those in the Solo group were housed individually. The rats in both groups received oxytocin (1.0 mg/kg) or saline injections intraperitoneally for 5 consecutive days before starting the experimental sessions. In the rats injected with oxytocin, the Solo group showed helping behavior faster than those in the Pair group. The results suggest that the effects of oxytocin administration on helping behavior are dependent on the social context.

Increased de novo fatty acid (FA) synthesis and cholesterol biosynthesis have been independently described in many tumour types, including hepatocellular carcinoma (HCC).

Researchers agree that early marriage (EM) and adolescent pregnancy (AP) can form severe risks for women's somatic, mental, and reproductive health, as well as on educational and social status. Yet, less is known about factors that may moderate or mediate these associations. This study examined, first, retrospectively the impacts of EM and AP on self-reported mental and somatic health among multicultural group of women living in Eastern Anatolia, Turkey. Second task was to analyze whether and how the partner violence would mediate and/or moderate between EM and AP and mental health problems. The participants were 1569 women (16-72 years of age), who reported their age of being married, first pregnancy, and demographic characteristics. They described their mental health status through General Health Questionnaire (GHQ-28: depressive, anxiety, social dysfunction, and somatization symptoms) and symptoms of posttraumatic stress disorder (PTSD; DSM-5). Women's reports of somatic illnesses were classified according to WHO-ICD-10. The revised conflict tactics scale, short form was used as a proxy to partner violence. Women who gave birth at 13-19 years of age reported more anxiety and somatization symptoms than later delivered, and those married younger than 25 showed a higher level of depressive symptoms than later married. Both AP and EM formed a heightened risk for somatic illnesses. The partner violence functioned as a moderator; AP was associated with especially high levels of depressive and anxiety symptoms among women exposed to sexual coercion in their marriage. Non-significant mediation analysis indicates that partner violence did not explain the severe impacts of the AP and EM on women's mental health. Yet, the AP and EM were associated with heightened level of partner violence. Adolescent pregnancy forms a comprehensive mental health risk, and both AP and EM were risks for somatic illnesses, such as cardiovascular problems. The mental health risk of AP further intensified if women experienced sexual coercion in their partnership. Our fundamental work is to abolish these patriarchal phenomena.