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1.
Proc Natl Acad Sci U S A ; 121(15): e2322127121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38568978

RESUMO

Soil moisture (SM) is essential for sustaining services from Earth's critical zone, a thin-living skin spanning from the canopy to groundwater. In the Anthropocene epoch, intensive afforestation has remarkably contributed to global greening and certain service improvements, often at the cost of reduced SM. However, attributing the response of SM in deep soil to such human activities is a great challenge because of the scarcity of long-term observations. Here, we present a 37 y (1985 to 2021) analysis of SM dynamics at two scales across China's monsoon loess critical zone. Site-scale data indicate that land-use conversion from arable cropland to forest/grassland caused an 18% increase in SM deficit over 0 to 18 m depth (P < 0.01). Importantly, this SM deficit intensified over time, despite limited climate change influence. Across the Loess Plateau, SM storage in 0 to 10 m layer exhibited a significant decreasing trend from 1985 to 2021, with a turning point in 1999 when starting afforestation. Compared with SM storage before 1999, the relative contributions of climate change and afforestation to SM decline after 1999 were -8% and 108%, respectively. This emphasizes the pronounced impacts of intensifying land-use conversions as the principal catalyst of SM decline. Such a decline shifts 18% of total area into an at-risk status, mainly in the semiarid region, thereby threatening SM security. To mitigate this risk, future land management policies should acknowledge the crucial role of intensifying land-use conversions and their interplay with climate change. This is imperative to ensure SM security and sustain critical zone services.

2.
EMBO Rep ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390258

RESUMO

Zinc transporter 1 (ZnT1), the principal carrier of cytosolic zinc to the extracellular milieu, is important for cellular zinc homeostasis and resistance to zinc toxicity. Despite recent advancements in the structural characterization of various zinc transporters, the mechanism by which ZnTs-mediated Zn2+ translocation is coupled with H+ or Ca2+ remains unclear. To visualize the transport dynamics, we determined the cryo-electron microscopy (cryo-EM) structures of human ZnT1 at different functional states. ZnT1 dimerizes via extensive interactions between the cytosolic (CTD), the transmembrane (TMD), and the unique cysteine-rich extracellular (ECD) domains. At pH 7.5, both protomers adopt an outward-facing (OF) conformation, with Zn2+ ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn2+ exhibits various conformations [OF/OF, OF/IF (inward-facing), and IF/IF]. These conformational snapshots, together with biochemical investigation and molecular dynamic simulations, shed light on the mechanism underlying the proton-dependence of ZnT1 transport.

3.
Am J Respir Cell Mol Biol ; 71(4): 442-452, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38864759

RESUMO

Lamellar bodies (LBs) are tissue-specific lysosome-related organelles in type II alveolar cells that are the main site for the synthesis, storage, and secretion of pulmonary surfactants. Defects in pulmonary surfactants lead to a variety of respiratory and immune-related disorders. LB biogenesis is closely related to their function, but the underlying regulatory mechanism is largely unclear. Here, we found that deficiency of HPS6, a subunit of BLOC-2 (biogenesis of lysosome-related organelles complex-2), led to a reduction of the steady-state concentration of vacuolar-type H+-ATPase and an increase in the luminal pH of LBs. Furthermore, we observed increased LB size, accumulated surfactant proteins, and altered lipid profiling of lung tissue and BAL fluid due to HPS6 deficiency. These findings suggest that HPS6 regulates the distribution of vacuolar-type H+-ATPase on LBs to maintain its luminal acidity and LB homeostasis. This may provide new insights into the LB pathology.


Assuntos
Células Epiteliais Alveolares , ATPases Vacuolares Próton-Translocadoras , ATPases Vacuolares Próton-Translocadoras/metabolismo , ATPases Vacuolares Próton-Translocadoras/genética , Animais , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Camundongos , Concentração de Íons de Hidrogênio , Lisossomos/metabolismo , Camundongos Endogâmicos C57BL , Organelas/metabolismo , Camundongos Knockout
4.
BMC Plant Biol ; 24(1): 615, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937722

RESUMO

Amorphophallus is a perennial monocotyledonous herbaceous plant native to the southwestern region of China, widely used in various fields such as food processing, biomedicine and chemical agriculture. However, Amorphophallus is a typical thermolabile plant, and the continuous high temperature in summer have seriously affected the growth, development and economic yield of Amorphophallus in recent years. Calmodulin (CaM), a Ca2+ sensor ubiquitous in eukaryotes, is the most important multifunctional receptor protein in plant cells, which affects plant stress resistance by participating in the activities of a variety of signaling molecules. In this study, the key gene AaCaM3 for the Ca2+-CaM regulatory pathway was obtained from A. albus, the sequence analysis confirmed that it is a typical calmodulin. The qRT-PCR results demonstrated that with the passage of heat treatment time, the expression of AaCaM3 was significantly upregulated in A. albus leaves. Subcellular localization analysis revealed that AaCaM3 localized on the cytoplasm and nucleus. Meanwhile, heterologous transformation experiments have shown that AaCaM3 can significantly improve the heat tolerance of Arabidopsis under heat stress. The promoter region of AaCaM3 was sequenced 1,338 bp by FPNI-PCR and GUS staining assay showed that the promoter of AaCaM3 was a high-temperature inducible promoter. Yeast one-hybrid analysis and Luciferase activity reporting system analysis showed that the AaCaM3 promoter may interact with AaHSFA1, AaHSFA2c, AaHSP70, AaDREB2a and AaDREB2b. In conclusion, this study provides new ideas for further improving the signal transduction network of high-temperature stress in Amorphophallus.


Assuntos
Arabidopsis , Calmodulina , Proteínas de Plantas , Calmodulina/metabolismo , Calmodulina/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico/genética , Temperatura Alta , Fabaceae/genética , Fabaceae/fisiologia , Fabaceae/metabolismo , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética , Regiões Promotoras Genéticas
5.
Bioorg Chem ; 143: 107051, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141329

RESUMO

Hypochlorous acid (HOCl) is a common reactive oxygen species (ROS) associated with the development of liver, tumor, inflammatory, and other diseases. In this work, the turn-on fluorescent probe named (WZ-HOCl) with a naphthalimide structure was designed and synthesized to detect endogenous HOCl in disease models. WZ-HOCl can achieve a fast response to HOCl with good linearity in the range of 0-45 µM (LOD = 147 nM). The application of WZ-HOCl in bioimaging was investigated by constructing a series of cellular disease models, and the results showed that WZ-HOCl could sensitively detect endogenous HOCl in inflammatory and liver disease models. It can also be used to differentiate between hepatocytes and hepatoma cells. WZ-HOCl will provide new methods and ideas for fluorescent probes in detecting drug-induced liver injury, alcoholic and non-alcoholic steatohepatitis, and some inflammation-related diseases.


Assuntos
Corantes Fluorescentes , Hepatopatias , Humanos , Corantes Fluorescentes/química , Ácido Hipocloroso/química , Linhagem Celular , Hepatopatias/diagnóstico por imagem
6.
J Cosmet Laser Ther ; 26(1-4): 86-88, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38914106

RESUMO

Contemporary approaches for facial rejuvenation encompass the utilization of both ablative and nonablative laser techniques. Extensive research has elucidated the adverse consequences associated with ablative laser treatment, such as the emergence of infectious, follicular, scarring, and pigmentary alterations. Nonablative fractional lasers exhibit commendable cosmetic outcomes, characterized by a diminished incidence of complications owing to their photomechanical mechanisms, in contrast to ablative laser modalities. Nonetheless, it is imperative to acknowledge that untoward effects may still manifest. In this report, we present two cases of herpes simplex virus (HSV) reactivation subsequent to nonablative fractional resurfacing. Timely identification and the appropriate administration of antiviral agents are important, which serve as imperative measures to mitigate the long-term consequences that may arise in the event of complications.


Assuntos
Envelhecimento da Pele , Humanos , Feminino , Envelhecimento da Pele/efeitos da radiação , Pessoa de Meia-Idade , Terapia com Luz de Baixa Intensidade/métodos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Herpes Simples/etiologia , Ativação Viral/efeitos da radiação , Simplexvirus , Antivirais/uso terapêutico , Rejuvenescimento , Técnicas Cosméticas/efeitos adversos , Técnicas Cosméticas/instrumentação , Face , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos
7.
J Esthet Restor Dent ; 36(9): 1236-1248, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38563216

RESUMO

OBJECTIVE: Occlusal reconstruction is a critical intervention for patients with dental hard tissue defects, temporomandibular joint (TMJ) disorders, and jaw position abnormalities. Clinical efficiency and outcomes of these procedures have improved with advances in digital technologies. This case report aims to illustrate a comprehensive digital workflow for occlusal reconstruction in a patient with congenital dentition defects, emphasizing the application of digital technologies to enhance treatment outcomes. CLINICAL CONSIDERATIONS: A 28-year-old woman with previously installed porcelain-fused-to-metal bridge restorations presented with a fractured prosthesis and TMJ symptoms. A multidisciplinary approach was adopted involving the use of digital facebow, intraoral scanners, digital smile design, and CAD/CAM technologies. The process included the extraction of defective restorations, temporary restorations to refine jaw position, and final permanent restorations. The digital workflow facilitated precise diagnostics and treatment, culminating in the successful installation of permanent restorations. Regular follow-ups at one- and three-months post-treatment confirmed stable occlusal function and high patient satisfaction. CONCLUSIONS: This case report showcases the potential of multiple digital technologies to streamline complex dental treatments and achieve high-quality results. CLINICAL SIGNIFICANCE: The integration of digital technologies in occlusal reconstruction treatments offers significant benefits in terms of precision, patient comfort, and esthetic outcomes.


Assuntos
Fluxo de Trabalho , Humanos , Feminino , Adulto , Desenho Assistido por Computador
8.
Molecules ; 29(17)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39274934

RESUMO

Sucrose phosphorylase (SPase), a member of the glycoside hydrolase GH13 family, possesses the ability to catalyze the hydrolysis of sucrose to generate α-glucose-1-phosphate and can also glycosylate diverse substrates, showcasing a wide substrate specificity. This enzyme has found extensive utility in the fields of food, medicine, and cosmetics, and has garnered significant attention as a focal point of research in transglycosylation enzymes. Nevertheless, SPase encounters numerous obstacles in industrial settings, including low enzyme yield, inadequate thermal stability, mixed regioselectivity, and limited transglycosylation activity. In-depth exploration of efficient expression strategies and molecular modifications based on the crystal structure and functional information of SPase is now a critical research priority. This paper systematically reviews the source microorganisms, crystal structure, and catalytic mechanism of SPase, summarizes diverse heterologous expression systems based on expression hosts and vectors, and examines the application and molecular modification progress of SPase in synthesizing typical glycosylated products. Additionally, it anticipates the broad application prospects of SPase in industrial production and related research fields, laying the groundwork for its engineering modification and industrial application.


Assuntos
Glucosiltransferases , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Glucosiltransferases/química , Glucosiltransferases/biossíntese , Glicosilação , Especificidade por Substrato , Expressão Gênica
9.
J Cell Mol Med ; 27(7): 920-926, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36871273

RESUMO

Obesity is widely recognized as a major global health problem caused by a chronic energy imbalance resulting from a combination of excess caloric intake and insufficient energy expenditure. Excessive energy intake and physical inactivity are traditional risk factors for obesity. Obesity is a risk factor for many diseases, including hypertension, diabetes and tumours. Recent studies have found a strong link between ferroptosis and obesity. Ferroptosis is an iron-dependent regulated cell death caused by iron overload and reactive oxygen species-dependent excessive accumulation of lipid peroxidation. Ferroptosis is involved in many biological processes, such as amino acid metabolism, iron metabolism and lipid metabolism. Some potential strategies to reduce the adverse effects of ferroptosis on obesity are suggested and future research priorities are highlighted.


Assuntos
Ferroptose , Sobrecarga de Ferro , Humanos , Ferro/metabolismo , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio/metabolismo , Obesidade
10.
Anal Biochem ; 666: 115072, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36738873

RESUMO

AIM: To develop a highly sensitive time-resolved fluorescence immunoassay (TRFIA) for the detection of serum matrix metalloproteinase-3 (MMP-3) and to assess MMP-3's clinical value in patients with colorectal cancer (CRC).st. METHODS: MMP-3 levels were established using the double antibody sandwich technique. The MMP-3 TRFIA technique was developed and optimized, and its linearity, sensitivity, accuracy, specificity, and recovery were assessed. Then, serum concentrations in healthy individuals and patients with CRC were determined by MMP-3 TRFIA. RESULTS: The linear range of MMP-3 TRFIA was 0.73-500 ng/mL. MMP-3 TRFIA had an intra-batch precision range of 2.16%-7.10% percent and an inter-batch precision range of 3.99%-11.21%. MMP-3, tumor-associated trypsinogen 2, and AFP had no cross reaction.The recovery is between 90% and 110%, and had no serum interference. Patients with CRC had serum MMP-3 levels (73.95 ± 78.43 ng/mL) that were considerably higher than those of healthy individuals (21.45 ± 11.12 ng/mL), and those with metastasis had serum MMP-3 levels (95.89 ± 76.21 ng/mL) that were considerably higher than those of patients without metastasis (52.74 ± 47.25 ng/mL). CONCLUSIONS: A highly sensitive MMP-3 TRFIA assay was successfully developed, and serum MMP-3 may be associated with CRC invasion and metastasis. Therefore, MMP-3 can be used in the auxiliary diagnosis of CRC.


Assuntos
Fluorimunoensaio , Metaloproteinase 3 da Matriz , Humanos , Fluorimunoensaio/métodos , Soro , Anticorpos
11.
Pharmacol Res ; 193: 106795, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37211241

RESUMO

Ageing is a universal and unavoidable phenomenon that significantly increases the risk of developing chronic kidney disease (CKD). It has been reported that ageing is associated with functional disruption and structural damage to the kidneys. Extracellular vesicles (EVs), which are nanoscale membranous vesicles containing lipids, proteins, and nucleic acids, are secreted by cells into the extracellular spaces. They have diverse functions such as repairing and regenerating different forms of ageing-related CKD and playing a crucial role in intercellular communication. This paper reviews the etiology of ageing in CKD, with particular attention paid to the roles of EVs as carriers of ageing signals and anti-ageing therapeutic strategies in CKD. In this regard, the double-edged role of EVs in ageing-related CKD is examined, along with the potential for their application in clinical settings.


Assuntos
Vesículas Extracelulares , Insuficiência Renal Crônica , Humanos , Vesículas Extracelulares/metabolismo , Rim , Insuficiência Renal Crônica/metabolismo , Proteínas/metabolismo , Envelhecimento
12.
J Fluoresc ; 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37782447

RESUMO

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using the well-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

13.
Int Urogynecol J ; 34(1): 115-124, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35831453

RESUMO

INTRODUCTION AND HYPOTHESIS: There were few data about the long-term outcomes of bio-compatible patches for pelvic organ prolapse (POP). The efficacy of poly (L-lactide-co-caprolactone) blended with fibrinogen [P(LLA-CL)/Fg] bio-patches were investigated for anterior vaginal wall prolapse treatment in a 6-year follow-up. METHODS: The P(LLA-CL)/Fg bio-patch was fabricated through electrospinning. Nineteen patients with symptomatic anterior prolapse (Pelvic Organ Prolapse Quantification [POP-Q] stage ≥ 2) were treated with anterior pelvic reconstruction surgery using a P(LLA-CL)/Fg bio-patch and were followed up at 1, 2, 3, 6 months, and 6 years. The primary outcome was objective anatomical cure (anterior POP-Q stage ≤ 1). Secondary outcomes included complications, MRI evaluation, and scores of the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and the Pelvic Floor Distress Inventory-20 (PFDI-20). RESULTS: The micro-morphology of the bio-patch resembled the extracellular matrix, which was suitable for the growth of fibroblasts. Sixteen (84.2%) patients were finally assessed, with a mean follow-up of 6.08 ± 0.18 years. The cure rate without anterior prolapse recurrence was 93.8% at 6 years. Compared with baseline, the POP-Q measurements of Aa, Ba, and C points and scores of PFIQ-7 and PFDI-20 manifested significant differences at all times (all p < 0.05). One (5.26%) case of bio-patch-related infection, 1 (5.26%) case of urinary retention, and no exposures and erosion occurred. MRI evaluation showed that the bio-patch gradually degraded to fragments at 1 month and was completely absorbed at 3 months. CONCLUSIONS: Among long-term follow-ups, anterior pelvic reconstruction surgery with a P(LLA-CL)/Fg bio-patch demonstrated significant improvements in anatomical correction of anterior pelvic prolapse and pelvic function without severe morbidity.


Assuntos
Prolapso de Órgão Pélvico , Prolapso Uterino , Feminino , Humanos , Resultado do Tratamento , Seguimentos , Vagina/cirurgia , Telas Cirúrgicas , Prolapso de Órgão Pélvico/cirurgia , Inquéritos e Questionários , Qualidade de Vida
14.
Int Urogynecol J ; 34(5): 1091-1101, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36208338

RESUMO

INTRODUCTION AND HYPOTHESIS: The study is aimed at bioinformatically deciphering immune cell infiltration, signature genes, and their correlations in POP. METHODS: Three microarray datasets were included. Matrixes representing the uterosacral ligament were merged as a test matrix and the others representing vaginal tissues were merged as a validation matrix. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was performed to evaluate immune cell infiltration. Correlations among differential immune cells were revealed by Spearman's rank correlation. Differentially expressed genes (DEGs) were screened by both "Batch correction" and "RobustRankAggreg" methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted for functional analysis. Hub genes were identified through cytoHubba of Cytoscape, and further validated by a validation matrix and clinical samples as signature genes. Correlations of differential immune cells with signature genes were analyzed by Spearman's rank correlation. RESULTS: Five differential immune cells (macrophages, monocytes, regulatory T cell [Treg], type 1 T cell [Th1], and natural killer T cells [NKT]) were identified and eight pairs of immune cells had significant correlations. Screened 230 DEGs were extracellular matrix (ECM) and immune related. Eleven hub genes were initially identified and five of them (LOX, IL-6, SDC1, ICAM1, and CD38) were validated as signature genes. Significant correlations of differential immune cells with signature genes were shown in twelve pairs, especially Th1-IL6, NKT-IL6, Th1-ICAM1, macrophage-IL6, and macrophage-LOX pairs. CONCLUSIONS: Pelvic organ prolapse could be considered immune related. Significantly infiltrated immune cells may contribute to the development of POP through close involvement with ECM- and immune-related signature genes.


Assuntos
Interleucina-6 , Prolapso de Órgão Pélvico , Feminino , Humanos , Prolapso de Órgão Pélvico/genética , Matriz Extracelular , Fáscia , Macrófagos
15.
BMC Ophthalmol ; 23(1): 4, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597100

RESUMO

BACKGROUND: An increasing prevalence of mental disorders (MDs) has been reported among children and adolescents. However, only few studies have conducted ocular examinations, including those on refractive status, in these groups of patients. Thus, the purpose of this study was to evaluate the refractive status and ocular findings in children and adolescents with MDs compared with matched controls with similar socioeconomic backgrounds. METHODS: A total of 178 participants with MDs and 200 controls were recruited between April 2021 and May 2022. All the children and adolescents underwent cycloplegic or noncycloplegic autorefraction and retinoscopy, slit-lamp biomicroscopy, and dilated fundus examinations. Ocular alignment was assessed using Hirschberg, Krimsky, or prism cover tests. The prevalence of refractive errors and ocular findings was the main outcome. RESULTS: Twenty-seven percent of patients with MDs and 8% of controls had ocular findings, the most common of which were conjunctivitis, keratitis, and trichiasis. For refractive status, 70% (124/178) of patients with MDs had myopia ≤-1.00 DS, and 2% (4/178) had hyperopia ≥+2.00 DS. In the control group, 70% (140/200) of patients had myopia ≤-1.00 DS, and 1% (2/200) had hyperopia ≥+2.00 DS. No differences were observed between the MD and control groups. However, the patients in the MD group (14.25±2.69 years) were significantly more susceptible to strabismus (P<0.05) and amblyopia (P<0.01) than those in the control group (13.65±3.04 years). There was a substantial difference between the two groups in the time spent on screen-based devices (P<0.001). Furthermore, mental retardation (OR=3.286, P<0.01), emotional disorders (OR=2.003, P<0.01), and adjustment disorders (OR=2.629, P<0.01) were associated with an increased risk of amblyopia. Depression (OR =1.362, P<0.01) and emotional disorders (OR=2.205, P<0.01) were associated with a higher prevalence of strabismus. CONCLUSION: Ophthalmological examinations should be performed in children and adolescents with MDs because MDs are associated with a high prevalence of refractive errors and ocular diseases. Detection and intervention of ocular and refractive findings in children and adolescents with MDs are necessary and effective in alleviating the economic burden in healthcare and improving individuals' quality of life.


Assuntos
Ambliopia , Hiperopia , Deficiência Intelectual , Miopia , Erros de Refração , Estrabismo , Humanos , Criança , Adolescente , Ambliopia/diagnóstico , Estudos Retrospectivos , Hiperopia/complicações , Acuidade Visual , Qualidade de Vida , Erros de Refração/diagnóstico , Refração Ocular , Estrabismo/diagnóstico , Miopia/epidemiologia , Deficiência Intelectual/complicações , Prevalência
16.
Proc Natl Acad Sci U S A ; 117(35): 21391-21402, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32817423

RESUMO

Syntaxin17, a key autophagosomal N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, can associate with ATG8 family proteins SNAP29 and VAMP8 to facilitate the membrane fusion process between the double-membraned autophagosome and single-membraned lysosome in mammalian macroautophagy. However, the inherent properties of Syntaxin17 and the mechanistic basis underlying the interactions of Syntaxin17 with its binding proteins remain largely unknown. Here, using biochemical, NMR, and structural approaches, we systemically characterized Syntaxin17 as well as its interactions with ATG8 family proteins, SNAP29 and VAMP8. We discovered that Syntaxin17 alone adopts an autoinhibited conformation mediated by a direct interaction between its Habc domain and the Qa-SNARE motif. In addition, we revealed that the Qa-SNARE region of Syntaxin17 contains one LC3-interacting region (LIR) motif, which preferentially binds to GABARAP subfamily members. Importantly, the GABARAP binding of Syntaxin17 can release its autoinhibited state. The determined crystal structure of the Syntaxin17 LIR-GABARAP complex not only provides mechanistic insights into the interaction between Syntaxin17 and GABARAP but also reveals an unconventional LIR motif with a C-terminally extended 310 helix for selectively binding to ATG8 family proteins. Finally, we also elucidated structural arrangements of the autophagic Syntaxin17-SNAP29-VAMP8 SNARE core complex, and uncovered its conserved biochemical and structural characteristics common to all other SNAREs. In all, our findings reveal three distinct states of Syntaxin17, and provide mechanistic insights into the Syntaxin17-mediated autophagosome-lysosome fusion process.


Assuntos
Autofagossomos/fisiologia , Lisossomos/fisiologia , Proteínas Qa-SNARE/metabolismo , Proteínas Qb-SNARE/metabolismo , Proteínas Qc-SNARE/metabolismo , Proteínas R-SNARE/metabolismo , Motivos de Aminoácidos , Proteínas Reguladoras de Apoptose/metabolismo , Família da Proteína 8 Relacionada à Autofagia/metabolismo , Escherichia coli , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo
17.
Environ Sci Technol ; 56(22): 15220-15237, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36330774

RESUMO

In view of the high risks brought about by organic micropollutants (OMPs), nanofiltration (NF) processes have been playing a vital role in advanced water and wastewater treatment, owing to the high membrane performance in rejection of OMPs, permeation of water, and passage of mineral salts. Though numerous studies have been devoted to evaluating and technically enhancing membrane performance in removing various OMPs, the trade-off effect between water permeance and water/OMP selectivity for state-of-the-art membranes remains far from being understood. Knowledge of this effect is significant for comparing and guiding membrane development works toward cost-efficient OMP removal. In this work, we comprehensively assessed the performance of 88 NF membranes, commercialized or newly developed, based on their water permeance and OMP rejection data published in the literature. The effectiveness and underlying mechanisms of various modification methods in tailoring properties and in turn performance of the mainstream polyamide (PA) thin-film composite (TFC) membranes were quantitatively analyzed. The trade-off effect was demonstrated by the abundant data from both experimental measurements and machine learning-based prediction. On this basis, the advancement of novel membranes was benchmarked by the performance upper-bound revealed by commercial membranes and lab-made PA membranes. We also assessed the potentials of current NF membranes in selectively separating OMPs from inorganic salts and identified the future research perspectives to achieve further enhancement in OMP removal and salt/OMP selectivity of NF membranes.


Assuntos
Membranas Artificiais , Purificação da Água , Estudos Prospectivos , Sais , Purificação da Água/métodos , Nylons , Água
18.
Trends Food Sci Technol ; 122: 211-222, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35250172

RESUMO

BACKGROUND: In the context of the current pandemic caused by the novel coronavirus, molecular detection is not limited to the clinical laboratory, but also faces the challenge of the complex and variable real-time detection fields. A series of novel coronavirus events were detected in the process of food cold chain packaging and transportation, making the application of molecular diagnosis in food processing, packaging, transportation, and other links urgent. There is an urgent need for a rapid detection technology that can adapt to the diversity and complexity of food safety. SCOPE AND APPROACH: This review introduces a new molecular diagnostic technology-biosensor analysis technology based on CRISPR-Cas12a. Systematic clarification of its development process and detection principles. It summarizes and systematically organizes its applications in viruses, food-borne pathogenic bacteria, small molecule detection, etc. In the past four years, which provides a brand-new and comprehensive solution for food detection. Finally, this article puts forward the challenges and the prospects for food safety. KEY FINDINGS AND CONCLUSIONS: The novel coronavirus hazards infiltrated every step of the food industry, from processing to packaging to transportation. The biosensor analytical technology based on CRISPR-Cas12a has great potential in the qualitative and quantitative analysis of infectious pathogens. CRISPR-Cas12a can effectively identify the presence of the specific nucleic acid targets and the small changes in sequences, which is particularly important for nucleic acid identification and pathogen detection. In addition, the CRISPR-Cas12a method can be adjusted and reconfigured within days to detect other viruses, providing equipment for nucleic acid diagnostics in the field of food safety. The future work will focus on the development of portable microfluidic devices for multiple detection. Shao et al. employed physical separation methods to separate Cas proteins in different microfluidic channels to achieve multiple detection, and each channel simultaneously detected different targets by adding crRNA with different spacer sequences. Although CRISPR-Cas12a technology has outstanding advantages in detection, there are several technical barriers in the transformation from emerging technologies to practical applications. The newly developed CRISPR-Cas12a-based applications and methods promote the development of numerous diagnostic and detection solutions, and have great potential in medical diagnosis, environmental monitoring, and especially food detection.

19.
Sensors (Basel) ; 22(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36015908

RESUMO

In order to reduce the influence of redundant features on the performance of the model in the process of accelerometer behavior recognition, and to improve the recognition accuracy of the model, this paper proposes an improved Whale Optimization algorithm with mixed strategy (IWOA) combined with the extreme gradient boosting algorithm (XGBoost) as a preferred method for chicken behavior identification features. A nine-axis inertial sensor was used to obtain the chicken behavior data. After noise reduction, the sliding window was used to extract 44 dimensional features in the time domain and frequency domain. To improve the search ability of the Whale Optimization algorithm for optimal solutions, the introduction of the good point set improves population diversity and expands the search range; the introduction of adaptive weight balances the search ability of the optimal solution in the early and late stages; the introduction of dimension-by-dimension lens imaging learning based on the adaptive weight factor perturbs the optimal solution and enhances the ability to jump out of the local optimal solution. This method's effectiveness was verified by recognizing cage breeders' feeding and drinking behaviors. The results show that the number of feature dimensions is reduced by 72.73%. At the same time, the behavior recognition accuracy is increased by 2.41% compared with the original behavior feature dataset, which is 95.58%. Compared with other dimensionality reduction methods, the IWOA-XGBoost model proposed in this paper has the highest recognition accuracy. The dimension reduction results have a certain degree of universality for different classification algorithms. This provides a method for behavior recognition based on acceleration sensor data.


Assuntos
Algoritmos , Galinhas , Animais
20.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555401

RESUMO

Excess fat deposition in broilers leads to great economic losses and is harmful to consumers' health. Chronic stress in the life cycle of chickens could be an important trigger. However, the underlying mechanisms are still unclear. In this study, 30-day-old chickens were subcutaneously injected with 2 mg/kg corticosterone (CORT) twice a day for 14 days to simulate long-term stress. It was shown that chronic CORT exposure significantly increased plasma triglyceride concentrations and enlarged the adipocyte sizes in chickens. Meanwhile, chronic CORT administration significantly enlarged the adipocyte sizes, increased the protein contents of FASN and decreased HSL, ATGL, Beclin1 and PPARA protein levels. Moreover, global m6A methylations were significantly reduced and accompanied by downregulated METTL3 and YTHDF2 protein expression by CORT treatment. Interestingly, the significant differences of site-specific m6A demethylation were observed in exon7 of PPARA mRNA. Additionally, a mutation of the m6A site in the PPARA gene fused GFP and revealed that demethylated RRACH in PPARA CDS impaired protein translation in vitro. In conclusion, these results indicated that m6A-mediated PPARA translational suppression contributes to CORT-induced visceral fat deposition in chickens, which may provide a new target for the treatment of Cushing's syndrome.


Assuntos
Galinhas , Corticosterona , Animais , Galinhas/genética , Gordura Intra-Abdominal/metabolismo , Triglicerídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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