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1.
Transl Pediatr ; 11(4): 537-546, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35558967

RESUMO

Background: This study aimed to evaluate the effect of mineral trioxide aggregate (MTA) pulp capping for caries-exposed permanent teeth. However, the efficacy of MTA in the treatment of children's gums is still controversial, and different studies have shown different efficacy. Therefore, it is necessary to systematically review the efficacy and safety of MTA pulp incision in the treatment of pediatric caries using meta methods. Methods: We used meta-analysis to compare differences in the efficacy of MTA and calcium hydroxide (CH) for treating caries in permanent teeth. The mean treatment success rate of MTA for reversible and irreversible pulpitis groups was calculated, and the effect of apical opening condition and surgical type on success rate were investigated. Results: A total of 15 studies were included, and meta-analysis showed that there was a significant statistical difference between the MTA group and CH group in efficacy [odds ratio (OR) =1.87, 95% confidence interval (CI): 1.28, 2.73, P=0.001, I2=63%, Z=3.25], success rate (OR =3.20, 95% CI: 1.93, 5.30, P<0.00001, I2=0%, Z=4.52), influence of apical foramen condition on success rate (OR =1.77, 95% CI: 1.14, 2.73, P=0.01, I2=15%, Z=2.56), and surgical procedure on success rate (OR =2.64, 95% CI: 1.65, 4.23, P<0.0001, I2=45%, Z=4.05). Discussion: Our results showed that MTA pulpotomy was superior to CH. Nonclosure of apical openings and complete coronal pulpotomy may be more beneficial than partial pulpotomy.

2.
Crit Rev Food Sci Nutr ; : 1-20, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35531941

RESUMO

The human brain grows rapidly in early life which requires adequate nutrition. Human milk provides optimal nutrition for the developing brain, and breastfeeding significantly improves the cognition development of infants. These benefits have been largely attributed to human milk oligosaccharides (HMOS), associated with sialic acid (Sia). Subsequently, sialylated HMOS present a vital source of exogenous Sia to infants. Sialic acid is a key molecule essential for proper development of gangliosides, and therefore critical in brain development and function. Recent pre-clinical studies suggest dietary supplementation with Sia or sialylated oligosaccharides enhances intelligence and cognition performance in early and later life. Furthermore, emerging evidence suggests the involvement of Sia in brain homeostasis and disbalance correlates with common pathologies such as Alzheimer's disease (AD). Therefore, this review will discuss early brain health and development and the role of Sia in this process. Additionally, studies associating breastfeeding and specific HMOS to benefits in cognitive development are critically assessed. Furthermore, the review will assess studies implying the potential role of HMOS and microbiota in brain development via the gut-brain axis. Finally, the review will summarize recent advances regarding the role of Sia in neurodegenerative disease in later life and potential roles of dietary Sia sources.

3.
J Coll Physicians Surg Pak ; 32(5): 559-564, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35546687

RESUMO

OBJECTIVE: To assess the effects of trimetazidine (TMZ) added to conventional drug therapy on cardiac autonomic nervous CANS in patients with coronary heart disease (CHD) after the percutaneous coronary intervention (PCI). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY:  Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei, China, from May 2018 to September 2019. METHODOLOGY: The study included 50 patients with CHD after a successful PCI who received trimetazidine plus conventional therapy were included as cases (exposed group), and 50 matched patients were identified as controls (non-exposed group). Heart rate (HR) and heart rate variability (HRV) parameters including sympathetic activity (SDNN, LF), parasympathetic activity (RMSSD, pNN50, SDSD, HF), and sympathovagal balance (LF/HF ratio) were used to evaluate CANS function. RESULTS: There were no statistical differences in the HR and HRV parameters before and after PCI (p>0.05). In the non-exposed group, conventional therapy significantly improved the HRV parameters (all p<0.05), while not affecting HR (p>0.05). In the exposed group, all HRV parameters except HR were improved after 4 weeks of treatment. After 4 weeks of treatment, the exposed group had higher parasympathetic-nerve activity, lower sympathetic-nerve activity, and LF/HF ratio compared to the non-exposed group (all p<0.05). CONCLUSIONS: The application of TMZ based on conventional therapy effectively improved the CANS in CHD patients who underwent PCI. KEY WORDS: Coronary heart disease, Percutaneous coronary intervention, Trimetazidine, Cardiac autonomic nervous system, Heart rate variability.

4.
Front Pharmacol ; 13: 713848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571119

RESUMO

Acute pulmonary embolism (APE) is a disabling diseases with high incidence rate and mortality rate. Although with high specificity, D-Dimer lacks specificity to assess APE, hence additional diagnostic and prognostic biomarkers are necessary. APE is widely treated with serine protease urokinase or urokinase-type plasminogen activator (uPA), which act as a catalyst for conversion of plasminogen to plasmin to resolve blood clots. However, it is unknown the role of differential expression of microRNAs (miRNAs) in protective effect of uPA against APE. Hence, we performed miRNA profiling in a hypoxia/reoxygenation (H/R) model of bronchial epithelial BEAS-2B cells in vitro and a APE mice model in vivo. Our analysis revealed that miR-34a-5p, miR-324-5p, miR-331-3p are upregulated with H/R or APE induction, whereas miR-429, miR-491-5p, and miR-449a are downregulated. The differential expression of the miRNAs was attenuated to levels comparable to control by treatment with uPA both in vitro and in vivo. In situ target prediction and analysis of potential functions of the target genes showed that the enrichment of biological processes and pathways were related to cell growth, proliferation, and inflammation. Ectopic overexpression of miR-449a using a mimic completely attenuated the protective effect of uPA in the H/R model in vitro. These results provide a group of miRNAs that could be used as markers, and the modulation of these miRNAs might have potential therapeutic benefits in patients with APE, which need to be validated in additional studies in humans.

5.
Pain ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35559917

RESUMO

ABSTRACT: Recent studies have noted the role of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in developing neuropathic pain, but the underlying mechanisms are obscure. We found that PTEN was mainly expressed in astrocytes in the rat spinal cord and dramatically downregulated after chronic constriction injury (CCI). Intrathecal injection of a PTEN inhibitor induced pain-related behaviors in naïve rats. In contrast, administration of a PTEN protector effectively mitigated CCI-induced pain. Adeno-associated virus (AAV)-mediated overexpression of astrocytic PTEN in the spinal cord reduced glial activation and neuroinflammation and subsequently alleviated pain-related behaviors. Importantly, astrocyte-specific PTEN-knockout (Pten conditional knockout, Pten CKO) mice showed nociceptive sensitization and glial activation. Proteomic analysis revealed that PTEN overexpression upregulated at least 7 enzymes in the cholesterol biosynthesis pathway and the total cholesterol level in the spinal cord of CCI rats. Furthermore, PTEN directly interacted with enzymes, including 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), in the cholesterol biosynthesis pathway. Astrocytic HMGCR overexpression alleviated both CCI-induced pain and mechanical allodynia in Pten CKO mice. Finally, cholesterol replenishment attenuated CCI-induced pain and suppressed spinal glial activation. Taken together, these findings imply that spinal astrocytic PTEN plays a beneficial role in CCI-induced pain by regulating cholesterol biosynthesis, and increased level of PTEN may accelerate cholesterol biosynthesis and reduce glial activation, thereby alleviating neuropathic pain. Recovery of PTEN or cholesterol might be an effective therapeutic strategy for neuropathic pain.

6.
Front Cell Neurosci ; 16: 861425, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602555

RESUMO

Background: Cognitive impairment commonly occurs in aneurysmal subarachnoid hemorrhage (aSAH) survivors. Cerebrospinal fluid (CSF) biomarkers have been proven useful in several central neurological disorders. No such diagnostic biomarkers are available for predicting cognitive impairment after aSAH to date. Here, we aimed to identify novel CSF biomarkers for cognitive deficits after aSAH using an in-depth proteomic approach. Methods: We applied mass spectrometry with data independent acquisition (DIA) quantification to identify biomarker candidates in CSF samples from a well-characterized cohort comprising patients with impaired cognition (n = 9) and patients with intact cognition (n = 9). The potential biological processes and signaling pathways associated with differential proteins were analyzed using R software. The candidates were further validated in a larger independent cohort (n = 40) using ELISA. The diagnostic utility of these proteins was investigated by using receiver operating characteristic curve analysis. Results: In total, we identified 628 proteins. The discovery cohort revealed that 115 proteins were differentially expressed in cognitive impairment patients compared to patients with intact cognition (P < 0.05). Independent cohort replication confirmed NCAM2, NPTXR, NRXN2, RELN, and CNTN2 as sensitive and specific candidate biomarkers for disorders of cognition. Lower CSF levels of all biomarker candidates, except RELN, were associated with more pronounced cognitive decline. Conclusion: We identified and validated five CSF biomarkers for cognitive impairment in aSAH patients. These particular proteins have important predictive and discriminative potential for cognitive impairment in aSAH and could be potential targets for early disease intervention.

7.
Chemosphere ; 302: 134868, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35533937

RESUMO

In this study, nitrogen self-doping layered graphitic biochar (Na-BC900) was prepared by catalytic pyrolysis of lotus leaves at 900 °C, in the presence of NaCl catalyst, for peroxydisulfate (PDS) activation and sulfamethoxazole (SMX) degradation. NaCl as catalyst played a crucial part in the preparation of Na-BC900 and could be reused. The SMX degradation rate in Na-BC900/PDS system was 12 times higher than that in un-modified biochar (BC900)/PDS system. The excellent performance of Na-BC900 for PDS activation was attributed to its large specific surface areas (SSAs), the enhanced graphitization structure and the high graphitic N content. The quenching and electrochemical experiments, electron paramagnetic resonance (EPR) studies inferred that the radicals included SO4•-, •OH, O2•- and the non-radical processes were driven by 1O2 and biochar mediated electron migration. Both radical and non-radical mechanisms contributed to the removal of SMX. Additionally, this catalytic pyrolysis strategy was clarified to be scalable, which can be applied to produce multiple biomass-based biochar catalysts for restoration of polluted water bodies.

8.
Chemosphere ; 303(Pt 2): 134936, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35569633

RESUMO

Rich protein within excess sludge could be recovered to prepare high value-added products such as liquid fertilizer and foaming agents. Low-intensity ultrasonication was adopted to help extract sludge protein by improving enzyme activity. Alkaline protease was added to the sludge for ultrasonic irradiation, and the maximum enzyme activity at 3500 kJ/kg TS was approximately 21% higher than that without ultrasonication. The protein extraction effect, specific resistance of sludge (SRS) and economics of low-intensity ultrasound-assisted enzymatic hydrolysis (LUEH) were compared with those of single enzymatic hydrolysis (EH) and HUEH under optimal conditions. The protein extraction rates of HUEH and LUEH were both higher than that of EH. Although the protein extraction rate of LUEH was 13.6% lower than that of HUEH, the amino acid content was similar because the low-intensity ultrasonic radiation promoted the enzyme activity and thereby enhanced the protein hydrolysis capacity. After hydrolysis, the SRS of LUEH was lower than that of HUEH, indicating that LUEH possessed a better dewatering performance, which was beneficial to the subsequent separation of the protein solution. The amount consumed by LUEH was approximately 20% lower than that consumed by HUEH and 17.3% lower than that consumed by EH. In addition, the enzyme dosage was reduced by approximately 38.5% with LUEH. Therefore, the total cost of LUEH was less than that of EH and HUEH, indicating that LUEH is more economically feasible for the extraction of protein from excess sludge.

9.
Adv Sci (Weinh) ; : e2200307, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35435329

RESUMO

The excessive dependence on fossil fuels contributes to the majority of CO2 emissions, influencing on the climate change. One promising alternative to fossil fuels is green hydrogen, which can be produced through water electrolysis from renewable electricity. However, the variety and complexity of hydrogen evolution electrocatalysts currently studied increases the difficulty in the integration of catalytic theory, catalyst design and preparation, and characterization methods. Herein, this review first highlights design principles for hydrogen evolution reaction (HER) electrocatalysts, presenting the thermodynamics, kinetics, and related electronic and structural descriptors for HER. Second, the reasonable design, preparation, mechanistic understanding, and performance enhancement of electrocatalysts are deeply discussed based on intrinsic and extrinsic effects. Third, recent advancements in the electrocatalytic water splitting technology are further discussed briefly. Finally, the challenges and perspectives of the development of highly efficient hydrogen evolution electrocatalysts for water splitting are proposed.

10.
Sci Total Environ ; 831: 154924, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35364178

RESUMO

Rainwater harvesting (RWH) projects in a decentralized way are significant measures to deal with the water scarcity dilemma in rural areas of the karst mountains in Southwest China at present. Due to the differences in cistern construction features and geomorphological positions, the water sources of cisterns were characterized by marked spatial variability, and the recharge stability of cisterns was strongly influenced by precipitation seasonality. Nevertheless, in hydrological processes on karst hillsides, the identification of different runoff types of RWH has not been sufficiently studied. The stable isotopes of hydrogen and oxygen of eleven cisterns and epikarst springs in subtropic cockpit karst landforms were monitored from 2020 to 2021 to investigate the runoff characteristics in RWH. Evaporative fractionation in different hydrological cycles is the predominant factor regulating the stable isotopic signature of cistern water. The results indicated that the typical roles that occurred in the recharge process contributed differently to water harvesting, with surface runoff (SR) and subsurface runoff (SSR) contributing much more than rainwater (RW) and epikarst runoff (ER). Three mixing patterns were proposed by end-member analysis in which SR + SSR, ER, and RW were three end members with indicators of isotopic value and the total dissolved solids (TDS). The recharge of SR + SSR was the predominated source, which contributed to 64% of the total water resources collected through RWH in the rainy season. In addition, the influence of various runoffs on the recharge stability of the cistern can be reflected by the multiple statistical analysis of isotopic fluctuation. Poor recharge stability is caused by excessive SR + SSR, whereas a higher percentage of ER and RW leads to better recharge stability. The applied method of hydrological process analysis is significant to the cistern water resources management in rural areas of the karst mountains.

11.
Polymers (Basel) ; 14(7)2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35406339

RESUMO

Dielectric elastomers (DE) are ideal electro-active polymers with large voltage-induced deformation for the design and realization of soft machines. Among the diversity of configurations of DE-based soft machines, dielectric elastomer minimum energy structures (DEMES) are unique due to their ease of fabrication, readiness to extend into multiple segments, and versatility of design configurations. Despite many successful demonstrations of DEMES actuators, these DEMES devices are limited to immobile use. We report several possible implementations of soft mobile machines through the combination of DEMES design, finite element simulation, and experiment. Our designs mimic the biomimetic locomotion of inchworms and marry complex components such as ratchet wheels with soft DEMES actuators. We even elucidate that buckling of DE can be harnessed to achieve asymmetric feet, which is otherwise realized via more complicated means. The examples presented here enrich DE devices' design and provide valuable insights into the design and fabrication of soft machines that other soft-active materials enable. All the codes and files used in this paper can be downloaded from GitHub.

12.
Life Sci ; 300: 120578, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489565

RESUMO

BACKGROUND: Depression is the most known complication of type 2 diabetes mellitus (T2DM). Aerobic exercise improves glycemic control in T2DM, although the underlying mechanisms of comorbid depression-like behaviors in T2DM have not yet been fully elucidated. METHODS: 120 zebrafish were randomly assigned to four groups: Control, T2DM, T2DM + metformin, and T2DM + aerobic exercise. Then, all animals except the control group were fed with high glucose fairy shrimp (~40 g/kg/day) and exposed reserpine (40 µg/ml for 20 min) for 10 days. Here, behavioral tests were used for model verification. Following the verification, all groups were treated as before. Additionally, the T2DM + metformin group received metformin (~10.6 mg/kg/day) at the same time, while the T2DM + aerobic exercise group received aerobic exercise 30 min/day. Finally, blood glucose and behavioral tests, as well as protein and molecular levels were determined at Day 11 and 12. RESULTS: Aerobic exercise alleviated depressive-like behavior and enhanced the levels of antidepressant biomarkers (NE, 5-HIAA) in zebrafish after 10 consecutive days of exercise. Additionally, 10 consecutive days of aerobic exercise decreased the levels of inflammatory biomarkers (IFN-γ, IL-1, IL-4) and depressive biomarkers (cortisol). Meanwhile, it also aided in the reduction of CD11b, IL-6, IL-6R, and caspase-3 expression to combat the neuroinflammation induced by T2DM, mediated the BDNF-TrkB pathway, and increased Bcl-2/Bax levels. CONCLUSION: Given the remarkable similarity in neurochemistry between humans and zebrafish, this study supports the effectiveness of aerobic exercise as clinical guidance in preventing and treating T2DM complicated with depression.

13.
Mol Biol Evol ; 39(5)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35438770

RESUMO

Land plants first evolved from freshwater algae, and flowering plants returned to water as early as the Cretaceous and multiple times subsequently. Alismatales is the largest clade of aquatic angiosperms including all marine angiosperms, as well as terrestrial plants. We used Alismatales to explore plant adaptations to aquatic environments by analyzing a data set that included 95 samples (89 Alismatales species) covering four genomes and 91 transcriptomes (59 generated in this study). To provide a basis for investigating adaptations, we assessed phylogenetic conflict and whole-genome duplication (WGD) events in Alismatales. We recovered a relationship for the three main clades in Alismatales as (Tofieldiaceae, Araceae) + core Alismatids. We also found phylogenetic conflict among the three main clades that was best explained by incomplete lineage sorting and introgression. Overall, we identified 18 putative WGD events across Alismatales. One of them occurred at the most recent common ancestor of core Alismatids, and three occurred at seagrass lineages. We also found that lineage and life-form were both important for different evolutionary patterns for the genes related to freshwater and marine adaptation. For example, several light- or ethylene-related genes were lost in the seagrass Zosteraceae, but are present in other seagrasses and freshwater species. Stomata-related genes were lost in both submersed freshwater species and seagrasses. Nicotianamine synthase genes, which are important in iron intake, expanded in both submersed freshwater species and seagrasses. Our results advance the understanding of the adaptation to aquatic environments and WGDs using phylogenomics.


Assuntos
Alismatales , Magnoliopsida , Adaptação Fisiológica/genética , Alismatales/genética , Evolução Biológica , Magnoliopsida/genética , Filogenia , Plantas
14.
Front Nutr ; 9: 749948, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433788

RESUMO

Background: The decrease of bone mineral density (BMD) after the intake of Tenofovir disoproxil fumarate (TDF)-based drugs in people living with HIV/AIDS (PLWHA) and HIV-negative key populations under pre-exposure prophylaxis (PrEP) regimen raised concerns. Previous findings on the effects of vitamin D (VD) and calcium supplements and the recovery of BMD loss were inconclusive. The optimal doses of VD and calcium and its supplementary duration remained unknown. Therefore, we conducted a systematic review and meta-analysis to synthesize current evidence on VD and calcium supplements to inform clinical practice. Methods: We searched PubMed, Web of Science, Cochrane library, and EMBASE databases for all placebo-controlled trials and prospective cohort studies published before March 5, 2021 that investigated VD and calcium supplements in participants taking TDF-based drugs. The keywords calcium, vitamin D, Tenofovir, and BMD were used for the searches. The primary outcome was changes of spine and hip BMD. A subgroup analysis was performed to determine the factors that were related to the effects of VD supplements on BMD. Locally weighted regression (loess) was used to determine the relationships of VD supplements, supplementary duration, and changes of BMD. This study was registered at PROSPERO (No. 42021231000). Findings: Seven eligible studies including 703 participants were included in the analyses. The meta-analysis found that VD and calcium supplementation was related to a significant increase of BMD in the spine and hip [standardized mean difference (SMD) 0.43; 95% CI, 0.25 to 0.61, p = 0.009]. Moreover, positive dose-response relationships were demonstrated between doses of VD and calcium supplements, supplementary duration, and BMD recovery. Patients who took VD with the dose level of 4,000 IU/D obtained the highest BMD improvement (SMD 0.59, 95% CI, 0.43 to 0.74). No side effects were reported on VD and calcium supplementation. Interpretation: We found the VD and calcium supplementation was associated with increases of BMD in participants taking TDF-based drugs. An optimal supplementary dose of 4,000 IU/D for VD was suggested for clinicians. The findings could be used in clinical practice to improve the BMD outcomes in people who were taking TDF-based drugs.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

15.
RSC Adv ; 12(14): 8592-8599, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35424789

RESUMO

Biomass-derived porous carbons are regarded as the most preferential adsorbents for CO2 capture due to their well-developed textural properties, tunable porosity and low cost. Herein, novel porous carbons were facilely prepared by activation of palm sheath for the highly selective separation of CO2 from gas mixtures. The textural features of carbon materials were characterized by the analysis of surface morphology and N2 isotherms for textural characterization. The as-prepared carbon adsorbents possess an excellent CO2 adsorption capacity of 3.48 mmol g-1 (298 K) and 5.28 mmol g-1 (273 K) at 1 bar, and outstanding IAST selectivities of CO2/N2, CO2/CH4, and CH4/N2 up to 32.7, 7.1 and 4.6 at 298 K and 1 bar, respectively. Also, the adsorption evaluation criteria of the vacuum swing adsorption (VSA) process, the breakthrough experiments, and the cyclic experiments have comprehensively demonstrated the palm sheath derived porous carbons as efficient adsorbents for practical applications.

16.
J Phys Chem B ; 126(17): 3338-3346, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35446590

RESUMO

Photocages can provide spatial and temporal control to accurately release the various chemicals and bioactive groups when excited by light. Although the absorption spectra of most photocages are in the ultraviolet absorption region, only a few absorb in the visible or near-infrared region. Blebbistatin (Bleb) would release a hydroxyl radical under blue one-photon or two-photon near-infrared light (800 nm) irradiation. In this work, typical chlorine and bromine as leaving groups substituted hydroxyl compounds (Bleb-Cl, Bleb-Br) are synthesized to evaluate the photocage's capability of Bleb's platform. Driven by the excited-state charge transfer, Bleb-Cl and Bleb-Br show good photolysis quantum yield to uncage the halogen anion and the uncaging process would be accelerated in water solution. The photochemical reaction, final product's analysis, and femtosecond transient absorption studies on Bleb-Cl/Bleb-Br demonstrate that Bleb can act as a photocage platform to release the halogen ion via heterolytic reaction when irradiated by blue or near-infrared light. Therefore, Bleb can be a new generation of visible or near-infrared light-triggered photocage.


Assuntos
Vesícula , Halogênios , Halogênios/química , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Raios Infravermelhos , Fotólise
17.
BMC Neurol ; 22(1): 125, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365121

RESUMO

BACKGROUND: Previous studies have revealed that low frequency repeated transcranial magnetic stimulation (rTMS) on the contralesional primary motor cortex (cM1) is less effective in severe stroke patients with poor neural structural reserve than in patients with highly reserved descending motor pathway. This may be attributed to the fact that secondary motor cortex, especially contralesional dorsal premotor cortex (cPMd), might play an important compensatory role in the motor function recovery of severely affected upper extremity. The main purpose of this study is to compare the effectiveness of low frequency rTMS on cM1 and high frequency rTMS on cPMd in subcortical chronic stroke patients with severe hemiplegia. By longitudinal analysis of multimodal neuroimaging data, we hope to elucidate the possible mechanism of brain reorganization following different treatment regimens of rTMS therapy, and to determine the cut-off of stimulation strategy selection based on the degree of neural structural reserve. METHODS/DESIGN: The study will be a single-blinded randomized controlled trial involving a total of 60 subcortical chronic stroke patients with severe upper limb motor impairments. All patients will receive 3 weeks of conventional rehabilitation treatment, while they will be divided into three groups and receive different rTMS treatments: cM1 low frequency rTMS (n = 20), cPMd high frequency rTMS (n = 20), and sham stimulation group (n = 20). Clinical functional assessment, multimodal functional MRI (fMRI) scanning, and electrophysiological measurement will be performed before intervention, 3 weeks after intervention, and 4 weeks after the treatment, respectively. DISCUSSION: This will be the first study to compare the effects of low-frequency rTMS of cM1 and high-frequency rTMS of cPMd. The outcome of this study will provide a theoretical basis for clarifying the bimodal balance-recovery model of stroke, and provide a strategy for individualized rTMS treatment for stroke in future studies and clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027399. Registered on 12 Nov 2019, http://www.chictr.org.cn/showproj.aspx?proj=43686 .


Assuntos
Córtex Motor , Acidente Vascular Cerebral , Humanos , Córtex Motor/diagnóstico por imagem , Neuroimagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
18.
J Genet Genomics ; 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35259542

RESUMO

Facial and cranial variation represent a multidimensional set of highly correlated and heritable phenotypes. Little is known about the genetic basis explaining this correlation. We develop a software package ALoSFL for simultaneous localization of facial and cranial landmarks from head computed tomography (CT) images, apply it in the analysis of head CT images of 777 Han Chinese women, and obtain a set of phenotypes representing variation in face, skull and facial soft tissue thickness (FSTT). Association analysis of 301 single nucleotide polymorphisms (SNPs) from 191 distinct genomic loci previously associated with facial variation reveals an unexpected larger number of loci showing significant (P < 1e-3) association with cranial phenotypes than expected under the null (O/E = 3.39), suggesting facial and cranial phenotypes share a substantial proportion of genetic components. Adding FSTT to a SNP-only model shows a large impact in explaining facial variance. A gene ontology analysis reveals that bone morphogenesis and osteoblast differentiation likely underlie our cranial-significant findings. Overall, this study simultaneously investigates the genetic effects on both facial and cranial variation of the same sample, supporting that facial variation is a composite phenotype of cranial variation and FSTT.

19.
Nat Struct Mol Biol ; 29(3): 218-228, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35256802

RESUMO

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine.


Assuntos
Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases , Endocitose , Lipídeos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais
20.
Environ Pollut ; 303: 119167, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35307493

RESUMO

In the context of global spread of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2), there is a controversial issue on whether the use of facemasks is promising to control or mitigate the COVID-19 transmission. This study modeled the SARS-CoV-2 transmission process and analyzed the ability of surgical mask and N95 in reducing the infection risk with Sobol's analysis. Two documented outbreaks of COVID-19 with no involvers wearing face masks were reviewed in a restaurant in Guangzhou (China) and a choir rehearsal in Mount Vernon (USA), suggesting that the proposed model can be well validated when airborne transmission is assumed to dominate the virus transmission indoors. Subsequently, the uncertainty analysis of the protection efficiency of N95 and surgical mask were conducted with Monte Carlo simulations, with three main findings: (1) the uncertainty in infection risk is primarily apportioned by respiratory activities, virus dynamics, environment factors and individual exposures; (2) wearing masks can effectively reduce the SARS-CoV-2 infection risk to an acceptable level (< 10-3) by at least two orders of magnitude; (3) faceseal leakage can reduce protection efficiency by approximately 4% when the infector is speaking or coughing, and by approximately 28% when the infector is sneezing. This work indicates the effectiveness of non-pharmaceutical interventions during the pandemic, and implies the importance of the synergistic studies of medicine, environment, social policies and strategies, etc., on reducing hazards and risks of the pandemic.


Assuntos
COVID-19 , Máscaras , COVID-19/prevenção & controle , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Incerteza
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