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1.
Rev Sci Instrum ; 95(10)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39417665

RESUMO

A high pressure jump through a rapid compression within milliseconds (ms) provides an important approach for searching novel matters and investigating their physical and chemical properties. Herein, we report a unique rapid-compression large volume press with a high pressure jump above 10 GPa within 20 ms by introducing a Walker-type module and hydraulic accumulators. The sample pressure can be rapidly increased from 1-5 GPa to 12-16 GPa by different modest compression rates varying from 10-2 to 633.5 GPa/s. The rapid pressure jump on the specimen has been successfully verified through the observed rapid phase transition of ZnTe from semiconductor to metal transitions, as evidenced by the variation in its electrical conductivity. The highest pressure jump of 10.2 GPa within a rise time of 16.1 ms is achieved, which is significantly higher than previous results (5.8 GPa within 20 ms) using a Bridgman-type anvils in such an apparatus. We found that rapid compression significantly enhances the phase transformation of C70 fullerene from a disordered graphite to an amorphous phase compared to static high-pressure experiments. The high pressure jump technique developed in this study will thus have great applications in materials science, physics, chemistry, and earth science.

2.
Eur J Med Chem ; 280: 116907, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39368264

RESUMO

Ischemic stroke (IS) is characterized by intricate pathophysiological mechanisms, where single-target treatments have often proven insufficient. Thus, multi-target therapeutic approaches are essential for effective IS management. In this study, we employed a molecular hybridization strategy, merging the structures of the iNOS inhibitor 1400W and the multi-target neuroprotective agent NBP, to develop a series of novel iNOS inhibitors BN-1 ∼ BN-4 with neuroprotective properties. Among these, BN-4 exhibited the most potent cell protective activity in OGD/R-induced SH-SY5Y and BV-2 cells. BN-4 not only reduced ROS levels induced by OGD/R in SH-SY5Y cells but also mitigated necrosis and apoptosis. By binding to iNOS in a manner similar to 1400W, BN-4 significantly inhibited iNOS activity. Furthermore, BN-4 demonstrated high stability, excellent blood-brain barrier permeability, and more than 100-fold increase in aqueous solubility compared to NBP. Additionally, BN-4 notably decreased infarct size and showed neuroprotective effects in tMCAO rats. These findings indicate that BN-4 holds promise as a novel candidate for treatment IS, offering enhanced therapeutic efficacy due to its superior pharmacokinetic and pharmacodynamic properties.

3.
Front Plant Sci ; 15: 1441649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39372859

RESUMO

The combination of biochar and nitrogen (N) fertilization in agricultural salt-affected soils is an effective strategy for amending the soil and promoting production. To investigate the effect of nitrogen reduction combined with biochar application on a soda saline soil and soybean growth in black soil areas, a pot experiment was set up with two biochar application levels, 0 (B0) and 4.5 t/hm2 (B1); two biochar application depths, 0-20 cm (H1) and 0-40 cm (H2); and two nitrogen application levels, conventional nitrogen application (N0) and nitrogen reduction of 15% (N1). The results showed that the application of biochar improved the saline soil status and significantly increased soybean yield under lower nitrogen application. Moreover, increasing the depth of biochar application enhanced the effectiveness of biochar in reducing saline soil barriers to crop growth, which promoted soybean growth. Increasing the depth of biochar application increased the K+ and Ca2+ contents, soil nitrogen content, N fertilizer agronomic efficiency, leaf total nitrogen, N use efficiency, AN, Tr, gs, SPAD, leaf water potential, water content and soybean yield and its components. However, the Na+ content, SAR, ESP, Na+/K+, Ci and water use efficiency decreased with increasing biochar depth. Among the treatments with low nitrogen input and biochar, B1H1N1 resulted in the greatest soil improvement in the 0-20 cm soil layer compared with B0N0; for example, K+ content increased by 61.87%, Na+ content decreased by 44.80%, SAR decreased by 46.68%, and nitrate nitrogen increased by 26.61%. However, in the 20-40 cm soil layer, B1H2N1 had the greatest effect on improving the soil physicochemical properties, K+ content increased by 62.54%, Na+ content decreased by 29.76%, SAR decreased by 32.85%, and nitrate nitrogen content increased by 30.77%. In addition, compared with B0N0, total leaf nitrogen increased in B1H2N1 by 25.07%, N use efficiency increased by 6.7%, N fertilizer agronomic efficiency increased by 32.79%, partial factor productivity of nitrogen increased by 28.37%, gs increased by 22.10%, leaf water potential increased by 27.33% and water content increased by 6.44%. In conclusion, B1H2N1 had the greatest effect on improving the condition of saline soil; it not only effectively regulated the distribution of salt in soda saline soil and provided a low-salt environment for crop growth but also activated deep soil resources. Therefore, among all treatments investigated in this study, B1H2N1 was considered most suitable for improving the condition of soda saline soil in black soil areas and enhancing the growth of soybean plants.

4.
BMC Public Health ; 24(1): 2713, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367381

RESUMO

OBJECTIVE: Constructing a demand-oriented Internet + community home care service indicator system, starting from the actual needs of the elderly, and quantifying the demand into specific service contents that can be provided, so as to realize the effective supply of services. It aims to provide a theoretical basis for the government to formulate relevant aging policies and provide a reference basis for promoting the innovation and development of the Internet + elderly care model. METHODS: Based on existence needs, relationship needs and growth needs abbreviated as "Existence, Relatedness, Growth (ERG)" demand theory, through the discussion in the group meeting, form the expert consultation questionnaire of the demand-oriented Internet + community home care service indicator system, select experts in related fields to conduct two rounds of Delphi expert consultation, summarize the experts' opinions to determine the indicator system items, and use the Analytic Hierarchy Process (AHP) method to construct the judgment matrix to derive the weighting coefficients of the indicators, and establish the ultimate demand-oriented Internet + community home care service indicator system. RESULTS: The effective recovery rates for the two rounds of expert consoulation questionnaires were 100%, with expert authority coefficients of 0.852 and 0.868, respectively. The Kendall coefficients for the second round of expert views varied from 0.226 to 0.431, with coefficients of variation for all indexes less than 0.25.The finalized demand-oriented Internet + community home care service indicator system includes 3 first-level indicators, 10 s-level indicators, and 46 third-level indicators. The consistency ratios of indicator judgment matrices at all levels are less than 0.10, suggesting that the hierarchical analysis findings are consistent, implying that the weight coefficient distribution is appropriate. CONCLUSION: The demand-oriented Internet + community home care service Indicator System, which was created through expert consultation and AHP method, has reasonable content and is more dependable as an evaluation tool for reliably assessing demand for elderly servic.


Assuntos
Técnica Delphi , Serviços de Assistência Domiciliar , Internet , Humanos , Idoso , Inquéritos e Questionários , Necessidades e Demandas de Serviços de Saúde , Serviços de Saúde para Idosos/normas
5.
Discov Oncol ; 15(1): 518, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358650

RESUMO

PURPOSE: This study aimed to explore the prognostic factors and survival patterns based on the histological type for the perimenopausal endometrial carcinoma (PIPEC) patients treated with hysterectomy. METHODS: The PIPEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Methods of random survival forest (RSF) and Cox regression were used to identify the possible prognostic factors of PIPEC patients. Then overall survival (OS) and cancer-specific survival (CSS) of PIPEC data were analyzed by histological types with regional lymph nodes status and SEER-stage to investigate the survival patterns of the PIPEC patients. RESULTS: A total of 14,178 PIPEC patients were included in the study. We found tumor size, grade, histology, SEER-stage, AJCC-stage, AJCC-T stage, metastasis to distant organs and regional lymph nodes status had a significant survival outcome for PIPEC both for OS and CSS (all p < 0.05). Regardless of regional lymph nodes status and SEER-stage for OS and CSS, the low-grade endometrioid carcinoma had the best prognosis outcome, followed by the mix cell adenocarcinoma and high-grade endometrioid carcinoma, while the carcinosarcoma and undifferentiated carcinoma had relatively poor prognosis outcome. And the survival patterns of different histological types of PIPEC were diverse and changed along with the time. CONCLUSION: We identified the possible prognostic factors of PIPEC patients treated with hysterectomy. And survival analysis based on the regional lymph nodes status and SEER-stage revealed the different histological types of PIPEC had diverse survival patterns, which will be helpful for guiding clinical practice.

6.
PeerJ ; 12: e18275, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39421414

RESUMO

In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie bandavirus (DBV), was first discovered in Henan, China. It is a tick-borne zoonotic virus with a fatality rate ranging from 6% to 30%. Currently, we lack safe and effective vaccines or antiviral drugs to treat SFTSV infection. Therefore, the development of a specific, sensitive, and cost-effective detection method is crucial. Using inactivated SFTSV and recombinant SFTSV nucleocapsid protein (SFTSV-NP), we repeatedly immunized mice with different adjuvants and obtained two monoclonal antibodies against SFTSV-NP, which were used to develop a colloidal gold immunochromatographic assay (ICA) rapid test kit for SFTSV. Compared with nucleic acid testing (gold standard), the ICA test strips are 97.67% accurate in testing clinical serum samples (36 cases of clinical serum samples and seven cases of whole blood samples). The test kit was 100% accurate in detecting different SFTSV strains. No false-positive results were generated when detecting other arboviruses. Therefore, our developed SFTSV test kit conveniently, rapidly, and effectively detects SFTSV.


Assuntos
Coloide de Ouro , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Coloide de Ouro/química , Phlebovirus/imunologia , Animais , Camundongos , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Humanos , Cromatografia de Afinidade/métodos , Sensibilidade e Especificidade , Proteínas do Nucleocapsídeo/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia
7.
Food Chem ; 464(Pt 1): 141562, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39396475

RESUMO

This study explored the impact of sun drying (SD), freeze drying (FD), oven drying (OD), and microwave drying (MD) on the morphology, rehydration properties, metabolomic profile, and taste formation of Porphyra yezoensis. FD elicited a brighter colour, smooth surface, porous microstructure, and strong rehydration properties in P. yezoensis, while dramatically maintaining the umami, sweetness, and saltiness. OD and MD decreased structural openness owing to tissue collapse and affected water absorption. Metabolomic analysis revealed 1030 metabolites, among which taste-related compounds, especially free amino acids, nucleotides, organic acids, and their derivatives, were the main biomarkers for distinguishing the different drying methods. Their related metabolic pathways, such as taurine and hypotaurine metabolism; purine metabolism; glyoxylate and dicarboxylate metabolism; and citrate cycle, were the most active. A metabolic pathway network of the main taste compounds was built to provide novel insights into the mechanisms underlying the taste profile changes associated with different drying methods.

8.
Genome Biol ; 25(1): 273, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39407252

RESUMO

Methylation quantitative trait loci (meQTLs) quantify the effects of genetic variants on DNA methylation levels. However, most published studies utilize bulk methylation datasets composed of different cell types and limit our understanding of cell-type-specific methylation regulation. We propose a hierarchical Bayesian interaction (HBI) model to infer cell-type-specific meQTLs, which integrates a large-scale bulk methylation data and a small-scale cell-type-specific methylation data. Through simulations, we show that HBI enhances the estimation of cell-type-specific meQTLs. In real data analyses, we demonstrate that HBI can further improve the functional annotation of genetic variants and identify biologically relevant cell types for complex traits.


Assuntos
Teorema de Bayes , Metilação de DNA , Locos de Características Quantitativas , Humanos , Análise de Sequência de DNA/métodos , Modelos Genéticos
9.
Front Pharmacol ; 15: 1466424, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39444611

RESUMO

One of the most prevalent pathological types of Primary Liver Cancer (PLC) is the Hepatocellular Carcinoma (HCC) poses a global health issue. The high recurrence and metastasis rate of HCC, coupled with a low 5-year survival rate, result in a bleak prognosis. Exosomes, small extracellular vesicles released by various cells, contain diverse non-coding RNA molecules, including circular RNAs (circRNAs), which play a significant role in intercellular communication and can impact HCC progression. Studies have revealed the potential clinical applications of exosomal circRNAs as biomarkers and therapeutic targets for HCC. These circRNAs can be transferred via exosomes to nearby non-cancerous cells, thereby regulating HCC progression and influencing malignant phenotypes, such as cell proliferation, invasion, metastasis, and drug resistance. This review provides a comprehensive overview of the identified exosomal circRNAs, highlighting their potential as non-invasive biomarkers for HCC, and suggesting new perspectives for HCC diagnosis and treatment. The circRNA from exosomal organelles promotes metastasis and immune scape because of their unique chirality which is different from the Biomolecular Homochirality.

10.
Sci China Life Sci ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39428429

RESUMO

Autosomal recessive spinocerebellar ataxias (SCARs) are one of the most common neurodegenerative diseases characterized by progressive ataxia. Although SCARs are known to be caused by mutations in multiple genes, there are still many cases that go undiagnosed or are misdiagnosed. In this study, we presented a SCAR patient, and identified a probable novel pathogenic mutation (c.1A>G, p.M1V) in the AFG3L2 start codon. The proband's genotype included heterozygous mutations of the compound AFG3L2 (p.[M1V]; [R632X] (c.[1A>G]; [1894.C>T])), which were inherited from the father (c.1A>G, p.M1V) and mother (c.1894C>T, p.R632X). Functional studies performed on hiPSCs (human induced pluripotent stem cells) generated from the patients and HEK293T cells showed that the mutations impair mitochondrial function and the unbalanced expression of AFG3L2 mRNA and protein levels. Furthermore, this novel mutation resulted in the degradation of the protein and the reduction of the stability of the AFG3L2 protein, and MCU (mitochondrial calcium uniporter) complex mediated Ca2+ overload.

11.
J Ophthalmic Inflamm Infect ; 14(1): 55, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39446221

RESUMO

PURPOSE: To evaluate the safety and efficacy of intravitreal dexamethasone implantation during phacoemulsification and intraocular lens implantation in pediatric uveitis. METHODS: A retrospective analysis was conducted on pediatric uveitis patients undergoing phacoemulsification and intraocular lens implantation with intravitreal dexamethasone implantation. Patients with a minimum follow-up of 6 months were included. Primary outcome measures included ocular inflammation, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and worsening of uveitis. RESULTS: 36 eyes of 28 patients were ultimately included in this study. The mean preoperative BCVA was 1.00 (0.40-1.50) LogMAR. BCVA significantly improved to 0.40 (0.20-0.54) LogMAR at 1 month postoperatively (P = 0.006), further improving to 0.30 (0.20-0.40) LogMAR at 3 months postoperatively (P = 0.001). BCVA remained stable at 0.30 (0.20-0.70) LogMAR at 6 months postoperatively (P = 0.005). Mean IOP showed no statistically significant difference during the follow-up period of three to six months after surgery. Eight children experienced recurrence of ocular inflammation during the 6-month follow-up period. No cases of worsening macular edema, glaucoma, or elevated IOP were observed in any patient. CONCLUSION: Intravitreal dexamethasone implantation during phacoemulsification and intraocular lens implantation is a safe and effective method for preventing and treating postoperative inflammation in children with uveitis.

12.
Heliyon ; 10(18): e37463, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39309892

RESUMO

Tribbles pseudokinase 3 (TRIB3) expression significantly increases during terminal erythropoiesis in vivo. However, we found that TRIB3 expression remained relatively low during human embryonic stem cell (hESC) erythropoiesis, particularly in the late stage, where it is typically active. TRIB3 was expressed in megakaryocyte-erythrocyte progenitor cells and its low expression was necessary for megakaryocyte differentiation. Thus, we proposed that the high expression during late stage of erythropoiesis could be the clue for promotion of maturation of hESC-derived erythroid cells. To our knowledge, the role of TRIB3 in the late stage of erythropoiesis remains ambiguous. To address this, we generated inducible TRIB3 overexpression hESCs, named TRIB3tet-on OE H9, based on a Tet-On system. Then, we analyzed hemoglobin expression, condensed chromosomes, organelle clearance, and enucleation with or without doxycycline treatment. TRIB3tet-on OE H9 cells generated erythrocytes with a high proportion of orthochromatic erythroblast in flow cytometry, enhanced hemoglobin and related protein expression in Western blot, decreased nuclear area size, promoted enucleation rate, decreased lysosome and mitochondria number, more colocalization of LC3 with LAMP1 (lysosome marker) and TOM20 (mitochondria marker) and up-regulated mitophagy-related protein expression after treatment with 2 µg/mL doxycycline. Our results showed that TRIB3 overexpression during terminal erythropoiesis may promote the maturation of erythroid cells. Therefore, our study delineates the role of TRIB3 in terminal erythropoiesis, and reveals TRIB3 as a key regulator of UPS and downstream mitophagy by ensuring appropriate mitochondrial clearance during the compaction of chromatin.

13.
Kidney Blood Press Res ; : 1-16, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312892

RESUMO

BACKGROUND: Platelets play parts in infection and immune processes. However, the association between platelet count and the risk of peritoneal dialysis-associated peritonitis is unclear. METHODS: This was a retrospective, observational, single-center cohort study. A Cox regression analysis was used to evaluate the independent association of platelet count with the occurrence of first PD-associated peritonitis. Models were adjusted for gender, age, BMI, cardiovascular disease, diabetes mellitus, white blood cell count, neutrophil-lymphocyte ratio, hemoglobin level, albumin level, potassium level, and anti-platelet medication usage. RESULTS: A total of 2374 patients were enrolled in this study (59% men; mean age 47.40 ± 12.12). The average platelet count was 229.30±82.12 x 109/L. 467 (20%) patients suffered from PD-associated peritonitis at least once. In the multivariable model, the adjusted hazard ratios (HRs) for quartiles 2, 3 and 4 versus quartile 1 were 1.428 (95% CI 1.060-1.924, P=0.019), 1.663 (95% CI 1.240-2.229, P<0.001) and 1.843 (95% CI 1.363-2.492, P<0.001) with baseline data. A nonlinear relationship between platelet count and first PD-associated peritonitis was observed. Further, the association between platelet and first PD-associated peritonitis was significant in the patients with hypokalemia (P for interaction=0.040). CONCLUSION: In PD patients, elevated platelet counts were significantly associated with an increased risk of the first onset of PD-associated peritonitis.

14.
Gastroenterol Res Pract ; 2024: 9097892, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220730

RESUMO

Purpose of the study: We aim to examine the association between liver function-related indicators and gallstone disease (GSD) risk. Study design: The subjects who participated in the China Multicenter Physical Examination Cohort (CMPEC) were enrolled. Relative odds ratios (ORs) with 95% CIs and standardized mean differences (SMDs) were applied to investigate the effect of liver function-related indicators and GSD risk. Moreover, a systematic review and meta-analysis were conducted until July 2021. Additionally, the results in the CMPEC and the systematic review and meta-analysis were combined by meta-analysis. Finally, the results were validated by a cohort study of the UK Biobank (UKB). Results and conclusions: Totally, 369,931 subjects in CMPEC were included in the study. A total of 28 publications were incorporated into the systematic review and meta-analysis. The pooled analysis suggested that aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), and low albumin (ALB) were positively associated with the risk of GSD. Meanwhile, GSD present to have higher AST, ALT, gamma-glutamyl transferase (GGT), total bilirubin (TBil), globulin (G), and ALP levels and relatively lower TP and ALB levels than the healthy participants. These results were consistent when stratified by the study design, geographic background, and study quality. Only the association between ALP and GSD risk was validated in the UKB cohort. This study suggests liver function indicators were associated with GSD risk. The results may provide the basis for exploring the etiology of GSD and may help clinicians identify high-risk subjects. Trial Registration: PROSPERO (CRD42020179076).

15.
Opt Lett ; 49(18): 5067-5070, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39270229

RESUMO

The fabrication of anti-reflection (AR) subwavelength structures (SWSs) of lithium niobate (LN) is a challenging but rewarding task in mid-infrared LN laser systems. However, there are still some issues with the high-quality processing and fabrication of bifacial AR SWSs. Herein, a novel, to the best of our knowledge, approach to the fabrication of SWSs was proposed, which includes femtosecond laser ablation followed by wet etching and thermal annealing. The fabricated structures exhibit high surface quality (Ra = 0.08 nm) and uniformity. According to the experimental and simulated results, the transmittance of the mid-infrared AR SWSs with a period of 1.8 µm could be improved from 78% to 87% in the 3.6-5 µm band. Furthermore, the double-sided construction enabled a transmittance of up to 90%. The results have great potential in the promotion of the development of mid-infrared laser systems and LN-based photonics.

16.
Medicine (Baltimore) ; 103(37): e39681, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39287303

RESUMO

BACKGROUND: Post-stroke depression (PSD) is a prevalent complication of stroke that adversely affects patient outcomes. The etiology of PSD is complex, and no universally effective treatment exists. Acupuncture, with its historical use, combined with music therapy, presents a novel approach for PSD treatment. This study aims to systematically evaluate the clinical efficacy of combining acupuncture with music therapy for PSD through a meta-analysis. METHODS: We systematically searched both Chinese and English literature in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and the Chinese Science and Technology Periodical Database (VIP Database) for randomized controlled trials evaluating acupuncture combined with music therapy for PSD. Two independent evaluators conducted quality assessments and data extraction. Statistical analyses were performed using RevMan 5.4 and Stata 18.0 software. RESULTS: This article contains 11 studies, involving a total of 698 patients. The results of the meta-analysis showed that, compared with the control group, the test group showed significant improvement on multiple outcome measures: HAMD score [mean difference (MD) = -3.18, 95% confidence interval (CI) (-3.61, -2.76), P < .00001], Self-Rating Depression Scale score [MD = -5.12, 95% CI (-6.61, -3.63), P < .00001], Pittsburgh sleep quality index score [MD = -2.40, 95% CI (-2.96, -1.84), P < .00001], BI score [MD = 14.16, 95% CI (4.37, 23.94), P = .005] were all significantly lower, significantly higher effectiveness [risk ratio = 1.21, 95% CI (1.11, 1.33), P < .0001]. These differences were also statistically significant. CONCLUSION: The use of acupuncture combined with music therapy is effective in reducing depression in PSD patients.


Assuntos
Terapia por Acupuntura , Depressão , Musicoterapia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Terapia por Acupuntura/métodos , Terapia Combinada/métodos , Depressão/diagnóstico , Depressão/etiologia , Depressão/terapia , Musicoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Resultado do Tratamento , Reabilitação do Acidente Vascular Cerebral/métodos
17.
Stem Cell Res Ther ; 15(1): 310, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294765

RESUMO

BACKGROUND: Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), can undergo erythroid differentiation, offering a potentially invaluable resource for generating large quantities of erythroid cells. However, the majority of erythrocytes derived from hPSCs fail to enucleate compared with those derived from cord blood progenitors, with an unknown molecular basis for this difference. The expression of vimentin (VIM) is retained in erythroid cells differentiated from hPSCs but is absent in mature erythrocytes. Further exploration is required to ascertain whether VIM plays a critical role in enucleation and to elucidate the underlying mechanisms. METHODS: In this study, we established a hESC line with reversible vimentin degradation (dTAG-VIM-H9) using the proteolysis-targeting chimera (PROTAC) platform. Various time-course studies, including erythropoiesis from CD34+ human umbilical cord blood and three-dimensional (3D) organoid culture from hESCs, morphological analysis, quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry, karyotyping, cytospin, Benzidine-Giemsa staining, immunofluorescence assay, and high-speed cell imaging analysis, were conducted to examine and compare the characteristics of hESCs and those with vimentin degradation, as well as their differentiated erythroid cells. RESULTS: Vimentin expression diminished during normal erythropoiesis in CD34+ cord blood cells, whereas it persisted in erythroid cells differentiated from hESC. Depletion of vimentin using the degradation tag (dTAG) system promotes erythroid enucleation in dTAG-VIM-H9 cells. Nuclear polarization of erythroblasts is elevated by elimination of vimentin. CONCLUSIONS: VIM disappear during the normal maturation of erythroid cells, whereas they are retained in erythroid cells differentiated from hPSCs. We found that retention of vimentin during erythropoiesis impairs erythroid enucleation from hPSCs. Using the PROTAC platform, we validated that vimentin degradation by dTAG accelerates the enucleation rate in dTAG-VIM-H9 cells by enhancing nuclear polarization.


Assuntos
Diferenciação Celular , Células Eritroides , Células-Tronco Pluripotentes , Vimentina , Humanos , Linhagem Celular , Células Eritroides/citologia , Células Eritroides/metabolismo , Eritropoese , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Proteólise , Vimentina/metabolismo , Vimentina/genética
18.
J Hazard Mater ; 479: 135654, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39217941

RESUMO

The resource of trace lead (Pb2+) from wastewater bearing intricate components is imperative for sustainable progression of the lead-acid battery industry. Herein, we fabricated a tannic acid-based covalent polymeric hydrogel (TA@PMAM) with antimicrobial properties and stability via facile Michael addition reaction. The incorporation of tannic acid (TA) through robust covalent bond leads to a stable porous 3D covalent polymer network with almost no loss of mechanical properties even after 20 compression cycles. Batch adsorption experiments of TA@PMAM revealed an extraordinary adsorption capacity of Pb2+(Qe =196.6 mg/g), achieving 87.2 % of Pb2+ adsorption within the first 5 min owing to porous structure, numerous adsorption sites and good hydrophilicity. Moreover, TA@PMAM demonstrated a strong affinity for Pb2+ in the presence of the interfere metal ions (Cu2+, Co2+, Mn2+etc.) due to the carbonyl and phenolic hydroxyl that can specifically pair with Pb2+. Stable adsorption properties of TA@PMAM were confirmed in fixed bed column adsorption experiment using lead-acid batteries wastewater, retaining 79.56 % of initial adsorption capacity even after 10 times' reuse. Besides, TA@PMAM possesses a broad spectrum of antimicrobial properties. This study sheds novel light on the design and fabrication of adsorbent, which holds great potential for commercialization in recovering lead from battery industrial wastewater.

19.
Elife ; 122024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269442

RESUMO

Van Gogh-like 2 (Vangl2), a core planar cell polarity component, plays an important role in polarized cellular and tissue morphology induction, growth development, and cancer. However, its role in regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated in patients with sepsis and identify Vangl2 as a negative regulator of The nuclear factor-kappaB (NF-κB) signaling by regulating the protein stability and activation of the core transcription component p65. Mice with myeloid-specific deletion of Vangl2 (Vangl2ΔM) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2-deficient myeloid cells exhibit enhanced phosphorylation and expression of p65, therefore, promoting the secretion of proinflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 to catalyze K63-linked ubiquitination on p65, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate Vangl2 as a suppressor of NF-κB-mediated inflammation and provide insights into the crosstalk between autophagy and inflammatory diseases.


Assuntos
Autofagia , Sepse , Transdução de Sinais , Fator de Transcrição RelA , Animais , Camundongos , Humanos , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Sepse/metabolismo , NF-kappa B/metabolismo , Lipopolissacarídeos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Camundongos Endogâmicos C57BL , Ubiquitinação , Proteínas do Tecido Nervoso , Proteínas Adaptadoras de Transdução de Sinal , Proteínas com Domínio LIM
20.
Sci Total Environ ; 953: 176035, 2024 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-39236832

RESUMO

Microplastics (MPs) pollution and its ecological risks have attracted increasing global attention. The Bohai Rim region (BRR), as the economic and population center of the entire northern China, still lacks a precise assessment of MPs pollution. Although current attention on MPs pollution mainly focuses on large rivers, small and medium-sized rivers are more numerous and more closely connected to human activities. In this study, measurement data of MPs from 11 estuaries in the BRR was collected to understand MPs distribution and ecological risk. The results indicate that the overall MPs pollution in these estuaries is still at a low level, with an average abundance of 1254.3 particles m-3. While the pollution load index (1.85) is relatively low, the potential ecological risk of PVC in some area (S8, EPVC = 1433.78, III) warrants further attention. Then we integrated data from 22 relevant rivers (covering all size rivers) in this region from the literature to fit a MPs flux model and assessed the MPs outflow from the four provinces and cities in the region. A strong correlation is achieved between modeled estimates and field measurements (r2 = 0.74), which can well estimate the river MPs outflows in northern China such as the Nanfei River. The MPs outflow from the four provinces (cities) is calculated to be 123.235 (range 44.415-242.314) T year-1, of which Shandong accounted for >80 % (104.066 T year-1). The small and medium-sized rivers accounted for 47 % (58.08 T year-1), whose contribution to MPs outflows should not be underestimated. This study can help us to accurately assess MPs pollution in different coastal areas in northern China, benefiting the formulation of precise control measures and policies for marine MPs pollution.

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