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1.
Neurosci Bull ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166647

RESUMO

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABAB receptors (GABABRs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABABRs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABABRs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABABR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABABRs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABABRs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32151557

RESUMO

BACKGROUND: To systematically evaluate the effect of bone morphogenetic protein-2 (BMP-2) and iliac cancellous bone graft (ICBG) on alveolar cleft bone grafting (ACBG) in cleft lip and palate. METHOD: Online databases were searched for case-control studies related to the application of BMP-2 and ICBG in ACBG. RESULT: Meta-analysis showed no significant statistical difference in the filling rate (OR = 4.1, 95% CI (0.06, 2.63)), the volume of bone graft area (OR=-0.42, 95% CI (-1.44, 0.60)), the height of bone graft area (OR = -21.38, 95% CI (-23.00, -19.76)), the density of bone graft area (OR = 0.43, 95% CI (-0.79, 1.64)), the failure rate of bone graft (OR = 0.02, 95% CI (-0.03, 0.06)), infection after operation, and the rate (OR = 0.20, 95% CI (0.05, 0.73)) and the incidence of postoperative oronasal fistula (OR = 4.1, 95% CI (0.06, 2.63)) between BMP-2 and ICBG in ACBG. However, there were obvious statistical differences in operative time (OR = -3.64, 95% CI (-7.35, 0.06)) and the length of hospital stay (OR = -1.97, 95% CI (-2.41, -1.53)). CONCLUSION: The meta-analysis shows that there is no significant difference between BMP-2 and ICBG in filling rate, volume, density, failure rate, and the occurrence of oronasal fistula after ACBG. There were significant differences between BMP-2 and ICBG in the operation time and hospitalization time of ACBG. Compared with ICBG bone graft, BMP-2 has more advantages in ACBG such as remaining area height, postoperative infection rate, operative time, and length of hospital stay.

3.
Hepatology ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32154934

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase SIRT1 is discovered in HCC, while its presence is positively correlated with malignancy and metastasis. N6 -methyladenosine (m6 A) is the most prominent modification but the exact mechanisms on how SIRT1 regulates m6 A modification to induce hepatocarcinogenesis remain unclear. APPROACH & RESULTS: Here we demonstrate that SIRT1 exerts oncogenic role by downregulating fat mass and obesity-associated protein (FTO), which is an m6 A demethylase. A crucial component of small ubiquitin-related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1 and it is indispensable for FTO SUMOylation at Lysine (K)-216 site that promotes FTO degradation. Moreover, Guanine nucleotide-binding protein G (o) subunit alpha (GNAO1) is firstly identified as m6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m6 A+ GNAO1 and downregulates its mRNA expression. CONCLUSIONS: We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m6 A+ of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a novel target of SIRT1 for therapeutic agents to treat HCC.

4.
Org Lett ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125860

RESUMO

A visible light photoredox-promoted and nitrogen radical catalyzed [3 + 2] cyclization of vinylcyclopropanes and N-tosyl vinylaziridines with alkenes is developed. Key to the success of this process is the use of the readily tunable hydrazone as a nitrogen radical catalyst. Preliminary mechanism studies suggest that the photogenerated nitrogen radical undergoes reversible radical addition to the vinylcyclopropanes and N-tosyl vinylaziridines to enable their ring-opening C-C and C-N bond cleavage and ensuing cyclization with alkenes.

5.
Chem Commun (Camb) ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129425

RESUMO

A [4+2] cycloaddition of photogenerated aza-ortho-quinone methides with formaldimines is described for the synthesis of perfluoroalkylated tetrahydroquinazolines. Key to this process is the photocatalytic radical-mediated generation of aza-o-QMs from 2-vinylanilines and perfluoroalkyl radical precursors as well as the in situ release of formaldimines from 1,3,5-triazinanes.

6.
Orthop Surg ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157830

RESUMO

BACKGROUND: Femoral avulsion fracture of the posterior cruciate ligament (PCL) in association with meniscus tear is extremely rare in children, and similar cases are not available in the existing literature. CASE PRESENTATION: In this paper, we present a case of a 9-year-old boy treated by an arthroscopic repair technique using two transfemoral tunnels sparing the epiphyseal plate for 8-shaped suture fixation of femoral avulsion fracture of the PCL and using the Fastfix repair system for a meniscus tear. At 3-month postoperative, the boy showed satisfactory recovery with a full range of motion of the right knee and normal muscular strength, and no complications were observed after operation. The patient had been followed up for 24 months and his final assessment demonstrated stable painless knee with excellent functional outcome. In view of this, we suggest that the "figure-of-eight" suture technique using two transfemoral tunnels sparing the epiphyseal plate can be considered a new choice for the treatment of the PCL femoral attachment avulsion, especially in skeletally immature patients. In addition, six similar cases were found in a comprehensive literature review targeting femoral avulsion fracture of the PCL. According to the relevant findings and cases studies, we proposed a new classification named "Xiangya" which might facilitate future clinical decision making.

7.
Org Lett ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32157891

RESUMO

A visible-light-driven, copper-catalyzed C(sp3)-O coupling of benzylic radicals with phenols is described for the first time. This operationally simple and robust process features mild conditions, broad scope, and high functional-group tolerance, enabling the construction of a diverse range of cyanoalkylated aryl ethers (33 examples). Key to this protocol is the dual role of copper salt that acts not only as a photosensitizer but also as a cross-coupling catalyst.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32115795

RESUMO

The prevalence of depressive symptoms in older Chinese adults has increased recently. Intergenerational relationships play an important role in the mental health conditions of older adults, especially in Chinese culture. Therefore, this study aims to unravel the complex connection between intergenerational relationships and depression, and to explore the potential mediating roles of loneliness and nighttime insomnia symptoms within that connection. A cross-sectional household survey was conducted in China with 2038 participants aged 65 years or above. Variables were measured using the Center for Epidemiologic Studies Short Depression Scale, the Intergenerational Relationship Quality Scale for Aging Chinese Parents (IRQS-AP), three nighttime insomnia symptoms extracted from the Insomnia Severity Index and the De Jong Gierveld Six-Item Loneliness Scale. The IRQS-AP includes four subdimensions: consensual-normative solidarity, structural-associational solidarity, affectual closeness and intergenerational conflicts. Path analyses were performed in Mplus to investigate regression coefficients and mediating effects. Results showed that three general intergenerational relationships (consensual-normative solidarity, affectual closeness and intergenerational conflicts) were significantly correlated with all mental health outcomes, including their symptoms of loneliness, insomnia and depression. A serial mediation model suggested that loneliness mediated the connection between those constructs of intergenerational relationships and depression, with an independent path to insomnia symptoms via loneliness. The proposed mediators fully mediated the effects of affectual closeness on depression. Nighttime insomnia symptoms alone mediated only the relationship between intergenerational conflicts and depression independently from paths involving depression. Removal of sleep item from CES-D did not affect the results of paths. Our findings highlight the importance of intergenerational relationships for mental health, especially for the mediating effects of loneliness and nighttime insomnia symptoms on the relationship between intergenerational relationships and depression. Effective mental health services for older adults can address their feelings of loneliness and sleep problems, especially for those who have a poor relationship with their adult children.

9.
Plant Cell Environ ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170871

RESUMO

When attacked by herbivores, plants emit volatiles to attract parasitoids and predators of herbivores. However, our understanding of the effect of plant volatiles on the subsequent behaviour of conspecific parasitoids when herbivores on plants are parasitized is limited. In this study, rice plants were infested with gravid females of the brown planthopper (BPH) Nilaparvata lugens for 24 hr followed by another 24 hr in which the BPH eggs on plants were permitted to be parasitized by their egg parasitoid, Anagrus nilaparvatae; volatiles from rice plants that underwent such treatment were less attractive to subsequent conspecific parasitoids compared to the volatiles from plants infested with gravid BPH females alone. Chemical analysis revealed that levels of JA and JA-Ile as well as of four volatile compounds-linalool, MeSA, α-zingiberene and an unknown compound-from plants infested with BPH and parasitized by wasps were significantly higher than levels of these compounds from BPH-infested plants. Laboratory and field bioassays revealed that one of the four increased chemicals-α-zingiberene-reduced the plant's attractiveness to the parasitoid. These results suggest that host plants can fine-tune their volatiles to help egg parasitoids distinguish host habitats with parasitized hosts from those without.

10.
Chem Soc Rev ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32195482

RESUMO

Due to their inherent ring strain, three-membered carbocyclic- and heterocyclic ring structures are versatile synthetic building blocks. Traditional ring-opening methods of these molecules require the use of thermolysis, acid catalysts or transition-metals via ionic reaction pathways. Recently, visible light-induced photoredox catalysis has emerged as a powerful platform for initiating new chemical transformations. In this tutorial review, the synthetic and mechanistic aspects of visible light-promoted ring-opening functionalization of three-membered carbo- and heterocycles are highlighted. By using these strategies, a variety of ring-opening functionalization products, including biologically important carbo- and heterocycles, can be efficiently accessed in a high chemo- and regioselective manner.

11.
Biochem Pharmacol ; : 113932, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32222456

RESUMO

Histone post-translational modifications (PTMs) have been shown to be highly associated with inflammation response, suggesting a therapeutic significance of pharmacologically editing histone PTMs. Currently reported anti-inflammation small-molecules mainly target histone PTMs writers or erasers for methylation, phosphorylation, and acetylation. Although histone chaperones also appear to be involved in inflammation signaling cascades, whether small-molecules could target histone chaperones to show anti-inflammation effects has still been rarely discovered. In this study, natural product artone was found to show obvious inhibitory effects on microglia-mediated neuroinflammation by directly targeting ASF1a, which is a histone-remodeling chaperone. Mechanism study revealed that artone modulated histone H3 PTMs profile by down-regulating acetylation and trimethylation modification levels at sites K4, K9, K18 and K27. Artone-dependent regulations on PTMs further caused an effective inhibition on transcription factor NF-κB assembling to promoters of pro-inflammatory cytokine genes including Tnf-α, Il-6 and Rgs3, indicating a distinctive anti-neuroinflammation mechanism. Collectively, we reported artone as the first small-molecule targeting histone-remodeling chaperone ASF1a for anti-neuroinflammation. Moreover, these findings broaden our knowledge of histone chaperone as a druggable target protein for neuroinflammation inhibition, and open a new avenue to novel therapy strategy for inflammation-associated neurological disorders.

12.
Comp Immunol Microbiol Infect Dis ; 70: 101452, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32120143

RESUMO

Canine babesiosis is an important global tick-borne infectious disease of domestic dogs and wild canids. B. gibsoni and B. vogeli are the most widespread species mainly endemic in dog population in southern and eastern regions of China. In this study, 272 blood samples were collected from pet dogs in five districts of Shenzhen, China. Babesia DNA was detected in 30 samples with an overall prevalence of 11.0 % in pet dogs in Shenzhen. The difference in the positive rate between female and male pet dogs, among different breed, and among the five sampling sites was not significant, while the age and health status of pet dogs significantly influence the positive rate of Babesia spp. infection. Sequencing results showed the presence of only B. vogeli in all of the samples tested. Sequence comparison and phylogenetic analysis revealed that all 30 strains of Babesia identified in this study shared the highest identity with B. vogeli. In sum, all results of this study showed a considerable high infection rate of Babesia spp. in pet dogs, and B. vogeli was the only Babesia species infecting pet dogs in Shenzhen city. Such information is necessary to help to elucidate the epidemiology of canine babesiosis in Shenzhen, and it is necessary to actively monitor this disease in pet dogs.

13.
Sci Rep ; 10(1): 5384, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214175

RESUMO

Over the past two decades, many studies have shown that the yam storage protein dioscorin, which is abundant in the wastewater of starch processing, exhibits many biological activities both in vitro and in vivo. In the present study, the acid-precipitation method was optimized using Box-Behnken design (BBD) combined with response surface methodology (RSM) for the recovery of yam soluble protein (YSP) from wastewater. The experimental yield of YSP reached 57.7%. According to relative quantitative proteomics (LC-MS/MS), the crude YSP was mainly composed of 15 dioscorin isoforms, which was further verified by anion-exchange and size-exclusion chromatography. YSP was found to be rich in glutamic acid and aspartic acid, and the eight essential acids made up approximately 33.7% of the YSP. Moreover, the YSP demonstrated antioxidant activity, including scavenging DPPH, hydroxyl and superoxide anion radicals, and the possible structure-activity relationships were discussed. These results indicated that YSP produced by acid precipitation may be used as a protein source with antioxidant properties.

14.
Schizophr Bull ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32185388

RESUMO

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier-NCT03774927.

15.
Chem Res Toxicol ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32162908

RESUMO

Columbin, a furanoid compound, is the major bioactive ingredient of Tinospora sagittata (Oliv.) Gagnep, a traditional Chinese medicine that has been reported to cause liver injury in the clinic. The aim of this study was to investigate the hepatotoxicity caused by columbin and its underlying mechanism. Our results indicated that columbin could result in a dose-dependent increase of mice serum alanine aminotransferase and aspartate aminotransferase after oral treatment with columbin, as well as local spotty necrosis in the liver of mice treated with columbin. No hepatotoxicity was observed in mouse treated with the same dose of tetrahydrocolumbin. Pretreatment with ketoconazole preserved the mice from columbin-induced hepatotoxicity. Further studies suggested that bioactivation of the furan ring played an indispensable role in columbin-caused hepatotoxicity. In vitro and in vivo metabolism studies demonstrated that columbin could be metabolized into the cis-butene-1,4-dial intermediate, which readily reacted with glutathione and N-acetyllysine to form stable adducts. Ketoconazole displayed strong inhibitory effect on the generation of M4 and M5 both in vitro and in vivo. Further recombinant human CYP450 screening demonstrated that CYP3A4 was the major enzyme responsible for columbin bioactivation. The present study demonstrated that columbin was hepatotoxic and CYP3A4-mediated bioactivation of the furan ring would serve as an underlying mechanism for columbin-induced hepatotoxicity.

16.
Org Lett ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186888

RESUMO

A visible-light-driven photoredox-catalyzed multicomponent reaction of 2-vinylanilines, sulfonyl chlorides, and sulfur ylides is described. This protocol features redox-neutral mild conditions, a broad substrate scope, and good functional group tolerance, providing access to various sulfonated 2,3-disubstituted indolines. The product can be transformed to a diverse range of functionalized indoles by a selective aromatization/nucleophilic substitution process. Mechanistic investigations suggest that both sulfonyl chlorides and sulfur ylides serve as radical sources, and the reaction proceeds through a sequential radical addition/addition/thermal SN2-substitution process.

17.
Mol Ther ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32209435

RESUMO

Recently, cytoophidium, a nonmembrane-bound intracellular polymeric structure, has been shown to exist in various organisms, including tumor tissues, but its function and mechanism have not yet been examined. Examination of cytoophidia-assembled gene inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase (CTPS) mRNA levels showed that only IMPDH1 levels were significantly higher in the clear cell renal cell carcinoma (ccRCC). IMPDH1 was positively correlated with the metastasis-related gene Y-box binding protein 1 (YB-1) and served as an independent prognostic factor in ccRCC. Kaplan-Meier analysis indicated that patients with tumors that expressed high IMPDH1 levels had a shorter overall survival (OS) and disease-free survival (DFS). Furthermore, detection of cytoophidia by immunofluorescence staining in ccRCC tissues showed that IMPDH1-assembled cytoophidia are positively associated with tumor metastasis. Mechanistically, IMPDH1 and YB-1 formed an autoregulatory positive feedback loop: IMPDH1 maintained YB-1 protein stabilization; YB-1 induced IMPDH1 expression by binding to the IMPDH1 promoter motif. Functionally, IMPDH1-assembled cytoophidia physically interacted with YB-1 and translocated YB-1 into the cell nucleus, thus correlating with ccRCC metastasis. Our findings provide the first solid theoretical rationale for targeting the IMPDH1/YB-1 axis to improve metastatic renal cancer treatment.

18.
ChemSusChem ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32112521

RESUMO

The photocatalytic reduction nitrogen (N2) to ammonia (NH3) has been considered as a promising strategy to alleviate human need and environmental pollution, for which developing photocatalyst is the effective method to complete the transformation of this process. We firstly design a series of highly efficient and stable polyoxometalates (POMs)-based zeolitic imidazolate framework-67 (ZIF-67) photocatalysts for N2 reduction. ZIF-67 can effectively fix N2 due to its porosity. Noted that the integration of POMs cluster contribute enormously advantages in terms of broadening absorption spectrum to improve the sunlight utilization, enhancing the stability of the materials, effectively inhibiting the recombination of photo-generated electron-hole pairs and reducing the charge transfer impedance. POMs can absorb light to convert into reduced POMs, which have stronger reducing ability to provide ample electrons to reduce N2. The reduced POMs can recover to the oxidation state by contacting with oxidant, which forms a self-recoverable and recyclable photocatalytic fixing N2 system. The photocatalytic activity enhances with the increasing number of substituted metals V in the POMs. Satisfactorily, ZIF-67@K11[PMo4V8O40] (PMo4V8) displays the most significant photocatalytic N2 activity with the NH3 yield of 149.0 µmol L-1 h-1 improving by 83.5% (ZIF-67) and 78.9% (PMo4V8). The introduction of POMs provides new insights in design high-performance photocatalyst nanomaterials to reduce N2.

19.
Environ Int ; 137: 105555, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32059142

RESUMO

The detrimental effects of perfluoroalkyl substances (PFASs) on several physiological systems have been reported, but the association of PFASs with eye, one of the most sensitive and exposed organ, has never been explored. To investigate the association between eye diseases including visual impairment (VI) and PFASs isomers, a cross-sectional stratified study was conducted in 1202 Chinese population, aged 22-96 years, from Shenyang, China. A standard protocol including Snellen vision chart, slit-lamp microscopy and direct ophthalmoscopy was used to examine eye diseases/conditions relating to anterior and posterior segment of eyes. In addition, we measured the blood concentrations of 19 linear and branched PFASs at one-time point. Results indicated that blood levels of PFASs were significantly higher in eye disease group than normal group. PFASs exposure were positively associated with both combined eye diseases and individual eye diseases. Among other PFASs, linear perfluorooctane sulfonate (n-PFOS; odds ratio [OR] = 3.37, 95% confidence interval [CI]: 2.50, 4.56), branched perfluorooctane sulfonate (Br-PFOS; OR = 2.25, 95% CI: 1.72, 2.93) and linear perfluorooctanoic acid (n-PFOA; OR = 1.79, 95% CI: 1.36, 2.37) significantly increases the odds of VI. Vitreous disorder was adversely associated with long-chain PFASs exposure. For example, perfluorotridecanoic acid (PFTrDA; OR = 1.86, 95% CI: 1.51, 2.29) and perfluorodecanoic acid (PFDA; OR = 1.79, 95% CI: 1.36, 2.36) showed the most significant association. In conclusion, this study suggests higher serum PFASs levels were associated with increase odds of VI and vitreous disorder in Chinese adults.

20.
Org Lett ; 22(5): 1976-1979, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32052978

RESUMO

A combined approach toward syntheses of epoxyguaiane sesquiterpenes is presented. By use of a fungus sesquiterpene cyclase, guaian-6,10(14)-diene was produced through metabolic engineering of the isoprenoid pathway in E. coli. (-)-Englerin A, (-)-oxyphyllol, (+)-orientatol E, and (+)-orientalol F have been synthesized in two to six steps. This strategy provided rapid access to the epoxyguaiane core structure and would facilitate syntheses of (-)-englerin A and its analogues for evaluation of their therapeutic potentials in drug discovery.

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