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1.
Biomed Pharmacother ; 151: 113091, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35576662

RESUMO

Diabetes mellitus comprises a group of heterogeneous disorders, which are usually subdivided into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Both genetic and environmental factors have been implicated in the onset of diabetes. Type 1 diabetes primarily involves autoimmune insulin deficiency. In comparison, type 2 diabetes is contributed by the pathological state of insulin deficiency and insulin resistance. In recent years, significant differences were found in the abundance of microflora, intestinal barrier, and intestinal metabolites in diabetic subjects when compared to normal subjects. To further understand the relationship between diabetes mellitus and intestinal flora, this paper summarizes the interaction mechanism between diabetes mellitus and intestinal flora. Furthermore, the natural compounds found to treat diabetes through intestinal flora were classified and summarized. This review is expected to provide a valuable resource for the development of new diabetic drugs and the applications of natural compounds.

2.
Sci Rep ; 12(1): 8071, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577924

RESUMO

The involvement of circRNAs in ß-thalassemia and their actions on fetal hemoglobin (HbF) is unclear. Here, the circRNAs in ß-thalassemia carriers with high HbF levels were comprehensively analyzed and compared with those of healthy individuals. Differential expression of 2183 circRNAs was observed and their correlations with hematological parameters were investigated. Down-regulated hsa-circRNA-100466 had a strong negative correlation with HbF and HbA2. Bioinformatics was employed to construct a hsa-circRNA-100466­associated competing endogenous RNA (ceRNA) network to identify hub genes and associated miRNAs. The hsa-circRNA-100466▁miR-19b-3p▁SOX6 pathway was identified using both present and previously published data. The ceRNA network was verified by qRT-PCR analysis of ß-thalassemia samples, RNA immunoprecipitation of K562 cell lysates, and dual-luciferase reporter analysis. qRT-PCR confirmed that hsa-circRNA-100466 and SOX6 were significantly down-regulated, while miR-19b-3p was up-regulated. Hsa-circRNA-100466, miR-19b-3p, and SOX6 were co-immunoprecipitated by anti-argonaute antibodies, indicating involvement with HbF induction. A further dual-luciferase reporter assay verified that miR-19b-3p interacted directly with hsa-circRNA-100466 and SOX6. Furthermore, spearman correlation coefficients revealed their significant correlations with HbF. In conclusion, a novel hsa-circRNA-100466▁miR-19b-3p▁SOX6 pathway was identified, providing insight into HbF induction and suggesting targets ß-thalassemia treatment.

3.
BMC Complement Med Ther ; 22(1): 133, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568844

RESUMO

BACKGROUND: The blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats. METHODS: BTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues. RESULTS: QJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB. CONCLUSION: These results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.

4.
Front Genet ; 13: 845967, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571067

RESUMO

Objective: Hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL) is a rare form of leukodystrophy presenting with varying clinical and imaging features. We report a case of HBSL to investigate the clinical and radiological characteristics of HBSL resulting from cytoplasmic aspartyl-tRNA synthetase gene (DARS) mutations. Subjects: We report a patient of HBSL with compound heterozygous mutations in DARS1. To study the potential genetic variations of the patient, targeted next-generation sequencing, whole-exome sequencing, and Sanger sequencing were used. We reviewed the clinical and radiological features of the patient. The literature was thoroughly evaluated. Results: The patient suffered from developmental regression associated with lower limbs spasticity, developmental delay, and paralysis of the lower limbs since childhood. Decreased T1 and increased T2 signals were observed on the bilateral basal, centrum ovale, frontal lobe, parietal lobe, and ganglia in cervical cord magnetic resonance imaging (MRI). The patient had two compound heterozygous mutations (NM_001349:c.1363T > C and NM_001349:c.821C > G) in the DARS1 gene. Conclusion: Two mutations in DARS1 were found to be associated with HBSL, one of them being reported for the first time. These findings can be valuable for diagnosing and providing genetic counseling to HBSL patients in the future.

5.
Small ; : e2201123, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35555970

RESUMO

Neural stem cells (NSCs) are used to treat various nervous system diseases because of their self-renewal ability and multidirectional differentiation potential. However, an insufficient ability to track their migration in vivo and poor control over their survival and differentiation efficiency are two major critical challenges for clinical application. Here, it is shown that when magnetic nanobubbles (MNBs), which are assembled from magnetic nanoparticles, are internalized by NSCs, intramembrane volumetric oscillation of the MNBs induces an increase in intracellular hydrostatic pressure and cytoskeleton force, resulting in the activation of the Piezo1-Ca2+ mechanosensory channel. This subsequently triggers the BMP2/Smad biochemical signaling pathway, leading to differentiation of NSCs into the neuronal phenotype. Signaling through the Piezo1-Ca2+ -BMP2/Smad pathway can be further accelerated by application of an external shear stress force using low-intensity pulsed ultrasound. More importantly, magnetic resonance imaging and ultrasound imaging surveillance of NSCs based on MNB labeling can be leveraged to provide NSC therapeutic outcomes. Both the in vitro and in vivo findings demonstrate that a bubble nanostructure-induced physical force can modulate and control the mechanical signaling pathway regulating stem cell development.

6.
Bioact Mater ; 18: 526-538, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35415298

RESUMO

Despite the progress made to improve therapeutic outcomes for acute myeloid leukemia (AML), many unmet clinical needs remain to be resolved. Unlike existing anti-AML strategies, here we developed a biomimetic nanocomposite to efficiently eliminate the leukemia cells in the bone marrow and prevent the homing of AML. To fulfill our design, the ultra-small nanozyme was conjugated onto the surface of an oxygen-carrying nanoparticle, which was further coated with bone marrow stromal cell membrane. After entering the blood, this biomimetic nanocomposite got actively internalized by the leukemia cells in the blood and released the loaded chemotherapeutics and nanozyme inside the leukemia cells to achieve a synergistic antitumor efficacy. Meanwhile, the adhesive properties of the stromal cell membrane enabled the nanocomposite to home to the bone marrow, where the nanocomposite effectively killed the retained leukemia cells. More importantly, the biomimetic cell membrane also acted as a CXCR4 antagonism to block the CXCR4/CXCL12-mediated homing of leukemia cells to the bone marrow and infiltration to other organs like the liver and spleen. In conclusion, this proof-of-concept study demonstrated that our designed platform effectively kills leukemia cells while preventing their infiltration, thus providing a promising prospect for resolving the clinical challenges in current AML treatment.

7.
Front Vet Sci ; 9: 868966, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464352

RESUMO

This study aimed to determine the population pharmacokinetics of danofloxacin in healthy Yellow River carp (Cyprinus carpio Haematopterus) after single oral administration at 10 mg/kg body weight (BW). A sparse sampling was applied in this study and plasma samples were randomly collected from the tail veins of six carp at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 and 144 h after administration. A maximum of four plasma samples was collected from each carp. Then the concentrations of danofloxacin in plasma samples were determined through an HPLC method. Danofloxacin could be quantified in plasma up to 144 h after administration. The corresponding population pharmacokinetic modeling was developed according to the non-linear mixed effect method, including covariate and covariance models to explain some variations from unknown sources and improve the prediction ability. On the premise of sparse sampling, the typical values of the population (fixed effect) and inter-individual variation (random effect) were described by the current population pharmacokinetic model. The estimated typical values and coefficient of variation between individuals (CV%) of absorption rate constant (tvKa), apparent distribution volume (tvV) and clearance (tvCL) were 2.48 h-1 and 0.203%, 47.8 L/kg and 8.40%, 0.694 L/h/kg and 4.35%, respectively. The current danofloxacin oral dosing (10 mg/kg BW) can provide suitable plasma concentrations to inhibit those pathogens with MIC values below 0.016 µg/ml based on the calculated PK/PD indices of AUC/MIC or Cmax/MIC. Further studies are still needed to determine the in vitro and in vivo antibacterial efficacy of danofloxacin against pathogens isolated from Yellow River carp and finally draw a reasonable dosing regimen.

8.
Neurosciences (Riyadh) ; 27(2): 111-115, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35477912

RESUMO

Kearns-Sayre Syndrome (KSS) is a subtype of chronic progressive external ophthalmoplegia (CPEO). In this case, A 21-year-old man diagnosed with KSS, and presented with chronic progressive blepharoptosis (ptosis) and external ophthalmoplegia, diffuse depigmentation of the retinal pigment epithelium, and cerebellar ataxia, with a cerebrospinal fluid protein of 254 mg/dL, was reported. Genetic screening revealed a novel mutated gene in SLC25A4 in the patient as well as in his mother: NM_001151:c.170G>C in exon 2. Its imaging finding is a characteristic progressive atrophy of the right cerebellar hemisphere. In conclusion, we found a case of KSS with a novel mutated gene in SLC25A4: NM_001151:c.170G>C in exon 2 as the pathogenic mechanism, and found that KSS can be caused only when the proportion of mutations in the SLC25A4 gene reach a certain degree, and the patient with KSS showed a unique cranial imaging feature of unilateral progressive cerebellar atrophy.


Assuntos
Síndrome de Kearns-Sayre , Oftalmoplegia Externa Progressiva Crônica , Translocador 1 do Nucleotídeo Adenina/genética , Adulto , Atrofia , Feminino , Humanos , Síndrome de Kearns-Sayre/diagnóstico por imagem , Síndrome de Kearns-Sayre/genética , Masculino , Mães , Mutação/genética , Oftalmoplegia Externa Progressiva Crônica/diagnóstico , Oftalmoplegia Externa Progressiva Crônica/genética , Adulto Jovem
9.
ACS Nano ; 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35377604

RESUMO

The clean production of hydrogen from water using sunlight has emerged as a sustainable alternative toward large-scale energy generation and storage. However, designing photoactive semiconductors that are suitable for both light harvesting and water splitting is a pivotal challenge. Atomically thin transition metal dichalcogenides (TMD) are considered as promising photocatalysts because of their wide range of available electronic properties and compositional variability. However, trade-offs between carrier transport efficiency, light absorption, and electrochemical reactivity have limited their prospects. We here combine two approaches that synergistically enhance the efficiency of photocarrier generation and electrocatalytic efficiency of two-dimensional (2D) TMDs. The arrangement of monolayer WS2 and MoS2 into a heterojunction and subsequent nanostructuring into a nanoscroll (NS) yields significant modifications of fundamental properties from its constituents. Spectroscopic characterization and ab initio simulation demonstrate the beneficial effects of straining and wall interactions on the band structure of such a heterojunction-NS that enhance the electrochemical reaction rate by an order of magnitude compared to planar heterojunctions. Phototrapping in this NS further increases the light-matter interaction and yields superior photocatalytic performance compared to previously reported 2D material catalysts and is comparable to noble-metal catalyst systems in the photoelectrochemical hydrogen evolution reaction (PEC-HER) process. Our approach highlights the potential of morphologically varied TMD-based catalysts for PEC-HER.

10.
Bioact Mater ; 16: 293-300, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35386321

RESUMO

Bacterial keratitis is the most common corneal infection which may lead to blindness, and seriously threatened the human visual health worldwide. Clinical treatment with antibiotic eye drops formulation usually falls in low bioavailability and poor therapeutic efficiency. Hydrogel has gained much attention as ophthalmic formulation recently due to the prolonged drug retention on ocular surface. In this study, we proposed a type of all-small-molecule supramolecular hydrogel assembled from guanosine-5'-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis. Guanosine-5'-monophosphate disodium salt assembled into guanosine-quartet nanofibers via hydrogen bonding and π-π stacking, and tobramycin with five primary amine groups further crosslinked the nanofibers bearing multiple phosphate moieties into gel networks via ionic interactions. The supramolecular gel showed shear thinning and thixotropic properties, good biocompatibility, and antibacterial activity. The gel treatment significantly ameliorated P. aeruginosa induced bacterial keratitis, and showed higher therapeutic efficacy compared to tobramycin eye drop. This study provides a facile and efficient antibiotic gel formulation for clinical treatment of bacterial keratitis.

11.
Math Biosci Eng ; 19(5): 4976-4990, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35430850

RESUMO

In a retrieval system for mathematical documents based on mathematical expressions, the input and matching of mathematical expressions are key steps that affect the system's usability, accessibility and efficiency because of their special attributes. Therefore, this paper mainly focuses on improving the input efficiency and matching accuracy of mathematical expressions. This paper proposes a method for retrieval and ranking of mathematical documents based on CA-YOLOv5 and HFS (hesitation fuzzy set) by utilizing the advantages of CA (coordinate attention) model and YOLOv5 in target detection and the superiority of HFS in multiattribute decision-making. By embedding the CA model into the YOLOv5 network, the mathematical expressions in layout images are extracted and recognized to form mathematical query expressions. These expressions are then analyzed to obtain similarity evaluation features and matched with the candidate mathematical expressions indexed with the same features in a library of mathematical documents by employing the HFS as the similarity evaluation measure. Experiments were performed based on the TFD-ICDAR2019v2 dataset and the NTCIR dataset. The F1-score of the mathematical expression detection result was 76.54%, the MAP (mean average precision) of the mathematical documents retrieval result was 71.73%, and the average nDCG of mathematical documents ranking was 80.89%.


Assuntos
Projetos de Pesquisa , Coleta de Dados
12.
Am J Chin Med ; 50(3): 749-772, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450513

RESUMO

The endothelium covers the internal lumen of the entire circulatory system and plays an important modulatory role in vascular homeostasis. Endothelium dysfunction, characterized by a vasoconstrictive, pro-inflammatory, and pro-coagulant state, usually manifests as a significant pathological process of vascular diseases, including hypertension, atherosclerosis (AS), stroke, diabetes mellitus, coronary artery disease, and cancer. Therefore, there is an urgent necessity to seek promising therapeutic drugs or remedies to ameliorate endothelial dysfunction-induced vascular ailments and complications. Recently, much attention has been attached to ginsenosides, the most significant active components of ginseng, which have always been referred to as "all-healing" and widely used for its extensively medicinal value. Surprisingly, ginsenosides have diverse biological activity which might be related to inflammation, apoptosis, oxidative stress, and angiogenesis. In this review, a brief introduction about endothelial dysfunction and ginsenosides was demonstrated, and the emphasis was put on summarizing multi-faceted pharmacological effects and underlying molecular mechanisms of ginsenosides on the endothelium, including vasorelaxation, anti-oxidation, anti-inflammation, and angio-modulation. Beyond that, nanotechnology to improve efficacy and the existing clinical trials of ginsenosides were concluded. Hopefully, our work will give suggestions for promoting clinical application of traditional Chinese medicine, e.g., hypertension, AS, diabetes, ischemic stroke, and cancer. This review provides a comprehensive base of knowledge for ginsenosides to prevention and treatment of vascular injury- related diseases with clinical significance.


Assuntos
Ginsenosídeos , Hipertensão , Neoplasias , Panax , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas
13.
Curr Med Sci ; 42(2): 417-425, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35366148

RESUMO

OBJECTIVE: Previous studies have shown that the autonomic nervous system (ANS), which can be affected by emotions, is important in the occurrence or progression of glaucoma. The autonomic innervation distributed in the anterior chamber (AC) structures might play an efferent role in the neural regulation of intraocular pressure (IOP). This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC. METHODS: A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein (PRV531) and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice, respectively. Fluorescent localization in the emotional brain and preganglionic nuclei was studied. Five and a half days after PRV531 injection into the right AC, fluorescent signals were observed in several emotional brain regions, including the amygdala, agranular insular cortex, lateral septal nuclei, periaqueductal gray, and hypothalamus. Autonomic preganglionic nuclei, including Edinger-Westphal nucleus, superior salivatory nucleus, and intermediolateral nucleus, were labeled using PRV531. RESULTS: The sensory trigeminal nuclei were not labeled using PRV531. The fluorescence signals in the nuclei mentioned above showed bilateral distribution, primarily on the ipsilateral side. Seven days after injecting FAST Dil into the AC, we observed no FAST Dil-labeled neurons in the central nervous system. CONCLUSION: Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC, which provides anatomical support for the emotional influence of IOP via the ANS.


Assuntos
Sistema Nervoso Autônomo , Herpesvirus Suídeo 1 , Animais , Câmara Anterior/inervação , Emoções , Hipotálamo , Camundongos
14.
J Healthc Eng ; 2022: 6955870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444780

RESUMO

Patients undergo surgery and anaesthesia on a daily basis across the United States and throughout the world. A major source of worry for these patients continues to be inadvertent hypothermia, once core temperature <36°C (96.8°F). Despite well-documented adverse physiological consequences, anaesthesia nurses continue to have a difficult task in keeping patient warmth pre-/peri-/post-surgical procedure. Thermostasis within postoperative patient necessitates the collaboration of many individuals. In order to provide safe and high-quality treatment, it is essential to use the most up-to-date data to guide therapeutic procedures targeted at achieving balance body temperature in surgical patients. Providing a review of the physiology of perioperative temperature variations and the comorbidities linked with accidental intraoperative hypothermia, this article will also provide preventive and treatment methods.


Assuntos
Hipotermia , Temperatura Corporal , Humanos , Hipotermia/complicações , Hipotermia/prevenção & controle , Temperatura
15.
ACS Med Chem Lett ; 13(4): 701-706, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35450372

RESUMO

ERK1/2 kinase is a key downstream node of the RAS-RAF-MEK-ERK signaling pathway. A highly potent and selective ERK1/2 inhibitor is a promising option for cancer treatment that will provide a potential solution for overcoming drug resistance. Herein we designed and synthesized a novel scaffold featuring a pyrrole-fused urea template. The lead compound, SHR2415, was shown to be a highly potent ERK1/2 inhibitor that exhibited high cell potency based on the Colo205 assay. In addition, SHR2415 displayed favorable PK profiles across species as well as robust in vivo efficacy in a mouse Colo205 xenograft model.

16.
Transl Vis Sci Technol ; 11(4): 20, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35446407

RESUMO

Purpose: To evaluate microvascular abnormalities in the macula and peripapillary area in diabetic patients without clinical signs of diabetic retinopathy (DR) and compare them with healthy control eyes, using optical coherence tomography angiography (OCTA). Methods: A prospective study was performed of 49 eyes from 49 diabetic patients without clinical signs of DR and a control group of 52 eyes from 52 healthy normal individuals. The 3 × 3 mm macular scans and 4.5 × 4.5 mm optic disc scans were obtained with the OCTA RTVue-XR Avanti system. Angiograms from the superficial capillary plexus, the deep capillary plexus of the macula scans, and radial peripapillary capillary plexus of the optic disc scans were analyzed with MATLAB. Multivariate binary logistic regression and the least absolute shrinkage and selection operator (LASSO) regression were used to select ideal parameters that distinguish diabetic eyes without DR from normal eyes. A receiver operating characteristic (ROC) curve was generated, and sensitivity and specificity were calculated. Results: Our final model identified FD-300 (foveal vessel density in a 300-µm-wide region around foveal avascular zone) as the only parameter selected by both the LASSO regression and the final multivariate logistic regression model that significantly differentiates diabetic eyes without clinical signs of DR from healthy normal eyes. The area under the ROC curve of FD-300 was 0.685, and sensitivity and specificity were 65.3% and 71.2%, respectively. Conclusions: Quantitative evaluation of retinal microvascular abnormalities using OCTA identified FD-300 as a useful biomarker versus the other macular and peripapillary OCTA metrics in the early detection of preclinical diabetic retinal abnormalities. Translational Relevance: OCTA may be useful in detecting early retinal microvascular abnormalities in diabetic patients before the clinical findings of DR become visible.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico por imagem , Angiofluoresceinografia/métodos , Humanos , Estudos Prospectivos , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos
17.
J Clin Med ; 11(7)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35407462

RESUMO

Although the pan-genotypic direct-acting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. We evaluated the real-world safety and efficacy of two pan-genotypic regimens (Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir) for HCV-infected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua Christian Care System that commenced treatment between August 2018 and December 2020. This retrospective study evaluated the efficacy and safety of pan-genotypic direct-acting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment. Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow-up during treatment and one more patient after treatment. A total of four patients died. However, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%). Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotype-undetermined HCV infection real-world settings.

18.
J Invest Dermatol ; 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35413293

RESUMO

Palmoplantar keratoderma-congenital alopecia syndrome type 2 (PPKCA2) is an autosomal recessive disorder with unknown genetic basis. Herein, we identified biallelic variants in the LSS gene in two unrelated PPKCA2 cases (c.3G>A, p.Met1? and c.1025T>G, p.Ile342Ser in patient 1; c.1522G>T, p.Gly508Trp and c.428+42T>A in patient 2) presenting with additional clinical features including early-onset cataracts, pseudoainhum and agenesis of corpus callosum. LSS encodes lanosterol synthase (LSS), which functions in the cholesterol biosynthesis pathway by converting (S)-2,3-oxidosqualene to lanosterol. The c.3G>A variant resulted in an alternative translation initiation at residue Met81, producing an N-terminal truncated protein (LSS-ΔN80), as demonstrated by immunoblotting. The c.428+42T>A variant introduced a potential splicing site, leading to a premature stop codon. Ex vivo studies revealed a downregulation of LSS in both patients. Remarkably decreased lanosterol levels were found in vitro in three LSS variants, LSS-ΔN80, p.Ile342Ser, and p.Gly508Trp, suggesting loss of enzymatic activity. Transmission electron microscopy and immunofluorescence demonstrated abnormal cornified envelope formation in the stratum corneum of the patients. Taken together, our findings indicate LSS as a causative gene for PPKCA2, which emphasizes the importance of cholesterol synthesis pathway in human skin cornification.

19.
RSC Adv ; 12(10): 5990-5996, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35424587

RESUMO

Two-dimensional molybdenum disulfide (MoS2) has attracted increasing attention due to its promise for next-generation electronics. To realize MoS2-based electronics, however, a synthesis method is required that produces a uniform single-layer material and that is compatible with existing semiconductor fabrication techniques. Here, we demonstrate that uniform films of single-layer MoS2 can be directly produced on Si/SiO2 at wafer-scale without the use of catalysts or promoters. Control of the precursor transport through oxygen dosing yielded complete coverage and increased connectivity between crystalline MoS2 domains. Spectroscopic characterization and carrier transport measurements furthermore revealed a reduced density of defects compared to conventional chemical vapor deposition growth that increased the quantum yield over ten-fold. To demonstrate the impact of enhanced scale and optoelectronic performance, centimeter-scale arrays of MoS2 photosensors were produced that demonstrate unprecedentedly high and uniform responsivity. Our approach improves the prospect of MoS2 for future applications.

20.
Sci Total Environ ; 834: 155320, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35447173

RESUMO

This study investigated the physical characteristics and removal efficiency of microplastics in wastewater from regions with different climatic conditions and economic development levels. Microplastics with different shapes and sizes were analyzed from the influent and effluent of 48 wastewater treatment plants in three regions of Shaanxi Province (China). Results indicated that the abundance of microplastics in the influent samples was higher in the region with less regional water resources. However, the per capita microplastics emissions was higher in the region with higher economic development level. There were less fibers and more foams and beads in the more developed region. The removal efficiency of microplastics was related to their shape and size. Particularly, the removal efficiency showed a significant negative correlation with the percentage of foams, while it had a significant positive relationship with the proportions of films and fibers. The highest removal efficiency was obtained when the size of microplastics was ranged from 0.5 to 1.0 mm. This study suggests, compared to improving the removal efficiency of microplastics, that reducing the input at source is a more scientific and promising method.

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