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1.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(4): 412-421, 2024 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-38632059

RESUMO

Objective: To compare the effectiveness of three surgical methods in the treatment of Pauwels type Ⅲ femoral neck fracture in young and middle-aged patients, in order to provide reference for clinical selection of appropriate surgical methods. Methods: The clinical data of 103 patients with Pauwels type Ⅲ femoral neck fracture who met the selection criteria between June 2018 and December 2021 were retrospectively analyzed. The fractures were fixed with hollow screws in an inverted triangular shape (37 cases, hollow screw group), hollow screws in an inverted triangular shape combined with eccentric shaft screw (34 cases, eccentric shaft screw group), and hollow screws in an inverted triangular shape combined with medial support plate (32 cases, support plate group). There was no significant difference in age, gender, cause of injury, body mass index, time from injury to operation, side of the fracture, and Garden classification, whether they were in traction preoperatively, and other baseline data between groups ( P>0.05). The operation time, intraoperative blood loss, the number of fluoroscopy, the length of hospital stay, early postoperative complication and postoperative weight-bearing time of the three groups were recorded. Harris score was used to evaluate joint function at 6 and 12 months after operation, and the difference between the two time points (change value) was calculated for comparison between groups. X-ray films were reviewed to evaluate the quality of fracture reduction (Garden index) and healing, as well as the occurrence of internal fixation failure and femoral head necrosis. Results: The patients of the three groups were successfully completed. Compared with the hollow screw group and the eccentric shaft screw group, the operation time and intraoperative blood loss of the support plate group significantly increased, the number of fluoroscopy reduced, and the quality of fracture reduction was better, the differences were significant ( P<0.05). The operation time, intraoperative blood loss, and the number of fluoroscopy of the hollow screw group were less than those of the eccentric shaft screw group, the differences were significant ( P<0.05). There was no significant difference in the length of hospital stay between groups ( P>0.05). All patients in the three groups were followed up 21-52 months, with an average follow-up time of 36.0 months, and there was no significant difference between groups ( P>0.05). The incisions of all patients healed by first intention. Imaging reexamination showed that there was no significant difference in the incidence of fracture nonunion between groups ( P>0.05). The fracture healing, partial weight-bearing, and full weight-bearing were significantly earlier in the eccentric shaft screw group and the support plate group than in the hollow screw group ( P<0.05). There was no significant difference in change value of Harris score, the incidence of postoperative deep venous thrombosis and femoral head necrosis between groups ( P>0.05); however, the incidence of internal fixation failure in the support plate group and the eccentric shaft screw group was significantly lower than that in the hollow screw group ( P<0.05). The incidence of postoperative lateral thigh irritation in the support plate group was significantly lower than that in the hollow screw group ( P<0.05); there was no significant difference between the eccentric shaft screw group and the other two groups ( P>0.05). The overall incidences of postoperative complications in the eccentric shaft screw group and the support plate group were significantly lower than that in the hollow screw group ( P<0.05). Conclusion: For young and middle-aged patients with Pauwels type Ⅲ femoral neck fracture, compared with simple hollow screw fixation in an inverted triangular shape, combined with medial support plate or eccentric shaft screw internal fixation can shorten the fracture healing time, reduce the incidences of postoperative complication, more conducive to early functional exercise of the affected limb; at the same time, the operation time and blood loss of combined eccentric shaft screw internal fixation are less than those of combined medial support plate internal fixation, so the hollow screw in an inverted triangular shape combined with eccentric shaft screw fixation may be a better choice.


Assuntos
Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , Pessoa de Meia-Idade , Humanos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Resultado do Tratamento , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/métodos , Complicações Pós-Operatórias
2.
Plant Cell ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657116

RESUMO

Plants continuously remodel and degrade their organelles due to damage from their metabolic activities and environmental stressors, as well as an integral part of their cell differentiation programs. Whereas certain organelles use local hydrolytic enzymes for limited remodeling, most of pathways that control the partial or complete dismantling of organelles rely on vacuolar degradation. Specifically, selective autophagic pathways play a crucial role in recognizing and sorting plant organelle cargo for vacuolar clearance, especially under cellular stress conditions induced by factors like heat, drought, and damaging light. In these short reviews, we discuss the mechanisms that control the vacuolar degradation of chloroplasts, mitochondria, endoplasmic reticulum, Golgi, and peroxisomes, with an emphasis on autophagy, recently discovered selective autophagy receptors for plant organelles, and crosstalk with other catabolic pathways.

3.
Small ; : e2311930, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433391

RESUMO

Human health and the environment face significant challenges of air pollution, which is predominantly caused by PM2.5 or PM10 particles. Existing control methods often require elevated energy consumption or bulky high-voltage electrical equipment. To overcome these limitations, a self-powered, convenient, and compact direct current high-voltage triboelectric nanogenerator based on triboelectrification and electrostatic breakdown effects is proposed. By optimizing the structure-design of the direct current triboelectric nanogenerator and corresponding output voltage, it can easily achieve an output voltage of over 3 kV with a high charge density of 320 µC m-2 . A power management circuit is designed to overcome the influence of third domain self-breakdown, optimize 92.5% amplitude of voltage shake, and raise 5% charge utilization ratio. With a device size as tiny as 2.25 cm3 , it can continuously drive carbon nanowires to generate negative ions that settle dust within 300 s. This compact, simple, efficient, and safe high-voltage direct current triboelectric nanogenerator represents a promising sustainable solution. It offers efficient dust mitigation, fostering cleaner environments, and enhancing overall health.

4.
J Physiol ; 602(6): 1175-1197, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38431908

RESUMO

Non-invasive transcranial direct-current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se-dependent signalling in rat cerebral ischaemia-reperfusion (I/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct-current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen-glucose deprivation reoxygenation (OGD/R) but had no effect on SEPP1 level in OGD/R-insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD/R-insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality-control signalling, vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4), in OGD/R-insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS- and BtDCS-induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1/VAMP2/STX4 signalling in ischaemic neurons after rat cerebral I/R injury. KEY POINTS: Cathodal bilateral transcranial direct-current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra. Se plays a crucial role in cerebral ischaemia injury. Direct-current stimulation reduces mitochondria injury and blocks the reduction of vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4) in oxygen-glucose deprivation reoxygenation-insulted neurons following coculturing with astrocytes. Cathodal BtDCS regulates Se/VAMP2/STX4 signalling to confer neuroprotection after ischaemia.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Selênio , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Ratos , Animais , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Neuroproteção/fisiologia , Proteína 2 Associada à Membrana da Vesícula , Selenoproteína P , Oxigênio/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Glucose/metabolismo , Proteínas Qa-SNARE
5.
Cancer Res ; 84(8): 1237-1251, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38241700

RESUMO

Epigenetic alterations at cis-regulatory elements (CRE) fine-tune transcriptional output. Epigenetic readers interact with CREs and can cooperate with other chromatin regulators to drive oncogene transcription. Here, we found that the YEATS domain-containing histone acetylation reader ENL (eleven-nineteen leukemia) acts as a key regulator of super-enhancers (SE), which are highly active distal CREs, across cancer types. ENL occupied the majority of SEs with substantially higher preference over typical enhancers, and the enrichment of ENL at SEs depended on its ability to bind acetylated histones. Rapid depletion of ENL by auxin-inducible degron tagging severely repressed the transcription of SE-controlled oncogenes, such as MYC, by inducing the decommissioning of their SEs, and restoring ENL protein expression largely reversed these effects. Additionally, ENL was indispensable for the rapid activation of SE-regulated immediate early genes in response to growth factor stimulation. Furthermore, ENL interacted with the histone chaperone FACT complex and was required for the deposition of FACT over CREs, which mediates nucleosome reorganization required for transcription initiation and elongation. Proper control of transcription by ENL and ENL-associated FACT was regulated by the histone reader BRD4. ENL was overexpressed in colorectal cancer and functionally contributed to colorectal cancer growth and metastasis. ENL degradation or inhibition synergized with BET inhibitors that target BRD4 in restraining colorectal cancer progression. These findings establish the essential role of epigenetic reader ENL in governing SE-driven oncogenic transcription and uncover the potential of ENL intervention to increase sensitivity to BET inhibition. SIGNIFICANCE: ENL plays a key role in decoding epigenetic marks at highly active oncogenic super-enhancers and can be targeted in combination with BET inhibition as a promising synergistic strategy for optimizing cancer treatment.


Assuntos
Neoplasias Colorretais , Histonas , Humanos , Histonas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Nucleares/metabolismo , Epigênese Genética , Neoplasias Colorretais/genética , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
6.
Antonie Van Leeuwenhoek ; 117(1): 8, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38170331

RESUMO

During our studies on the microorganism diversity from air of manufacturing shop in a pharmaceutical factory in Shandong province, China, a Gram-stain-positive, aerobic, cocci-shaped bacterium, designated LY-0111T, was isolated from a settling dish. Strain LY-0111T grew at temperature of 10-42 °C (optimum 35 °C), pH of 5.0-10.0 (optimum pH 7.0) and NaCl concentration of 1-12% (optimum 0.5-3%, w/v). Based on the 16S rRNA gene sequence analysis, the strain shared the highest sequence similarities to Nesterenkonia halophila YIM 70179T (96.2%), and was placed within the radiation of Nesterenkonia species in the phylogenetic trees. The genome of the isolate was sequenced, which comprised 2,931,270 bp with G + C content of 66.5%. A supermatrix tree based on the gene set bac120 indicated that LY-0111T was close related to Nesterenkonia xinjiangensis YIM 70097T (16S rRNA gene sequence similarity 95.3%). Chemotaxonomic analysis indicated that the main respiratory quinones were MK-7, MK-8, and MK-9, the predominant cellular fatty acids were anteiso-C15:0 and iso-C15:0, and the major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. According to the phenotypic, chemotaxonomic and phylogenetic features, strain LY-0111T is considered to represent a novel species, for which the name Nesterenkonia aerolata sp. nov. is proposed. The type strain is LY-0111T (= JCM 36375T = GDMCC 1.3945T). In addition, Nesterenkonia jeotgali was proposed as a later synonym of Nesterenkonia sandarakina, according to the ANI (96.8%) and dDDH (72.9%) analysis between them.


Assuntos
Ácidos Graxos , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Hibridização de Ácido Nucleico , Ácidos Graxos/análise , Preparações Farmacêuticas , China , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Fosfolipídeos/análise
7.
Neuroepidemiology ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38295785

RESUMO

OBJECTIVE: To study the primary risk factors for the long-term trends of mortality rates in ischemic stroke (IS) in China. METHODS: Using the Global Burden of Disease Study 2019 (GBD 2019) database, research was conducted on the 11 primary risk factors for the mortality rates of IS in China from 1990 to 2019. This study employed Joinpoint regression software and the Age-Period-Cohort (APC) method to evaluate the trends of mortality rates divided by age, period, and cohort over time. RESULTS: From 1990 to 2019, the age-standardized mortality rate (ASMR) caused by a diet high in red meat and high body-mass index (BMI) in China showed an upward trend. ASMR increased first and then decreased due to smoking, diet high in sodium, particulate matter pollution, high fasting plasma glucose, and high systolic blood pressure. Low-density lipoprotein cholesterol (LDL-C), kidney dysfunction, low temperature, and lead exposure remained relatively stable during this period. In the 35-45 age group, the mortality rate of IS due to high LDL-C was up to about 60%, and smoking affected men more than women. Overall, high LDL-C, high systolic blood pressure, and particulate matter pollution were the most common risk factors in patients with IS. The risk of death rose with age. The period and cohort relative risks showed that metabolic risk factors had the greatest impact on the mortality of IS. CONCLUSION: Metabolic risk factors have become the primary risk factors for the ASMR of IS in China. Relevant authorities should pay attention to their long-term effects on IS. Effective public health policies and interventions should be implemented to reduce the burden of IS.

8.
Materials (Basel) ; 16(24)2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38138726

RESUMO

In this study, all-inorganic perovskite quantum dots (QDs) for pure blue emission are explored for full-color displays. We prepared CsPbBr3 and Cs3NdCl6 QDs via hot injection methods and mixed in various ratios at room temperature for color blending. Nd-doped CsPb(Cl/Br)3 QDs showed a blueshift in emission, and the photoluminescence quantum yields (PLQY, ΦPL) were lower in the 460-470 nm range due to surface halogen and Cs vacancies. To address this, we introduced a silane molecule, APTMS, via a ligand exchange process, effectively repairing these vacancies and enhancing Nd doping into the lattice. This modification promotes the PLQY to 94% at 466 nm. Furthermore, combining these QDs with [1]Benzothieno[3,2-b][1]benzothiophene (BTBT), a conjugated small-molecule semiconductor, in a composite film reduced PLQY loss caused by FRET in solid-state QD films. This approach achieved a wide color gamut of 124% National Television System Committee (NTSC), using a UV LED backlight and RGB perovskite QDs in a BTBT-based organic matrix as the color conversion layer. Significantly, the photostability of this composite was enhanced when used as a color conversion layer (CCL) under blue-LED excitation.

9.
Healthcare (Basel) ; 11(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37998456

RESUMO

The use of Diagnosis-Related Groups (DRG) is a prevalent payment system employed to control hospitalization costs and improve medical efficiency. China has developed an indigenized DRG payment system including Single Disease Payment (SDP), DRGs, and Big Data Diagnosis-Intervention Packet (DIP). In this study, we took cholecystitis as an example, drawing on both primary and secondary data to verify the effectiveness of China's indigenized DRG system and to introduce the evolution of DRGs in China. Primary data were gathered from Qilu Hospital in 2019-2021. Secondary data were collected from published literature from 2004-2016. Only studies with both pre-SDP/DRG and post-SDP/DRG groups were included. Among the studies included, 92.9% (13/14) reported a significant reduction in hospitalization costs after the implementation of SDP while other studies identified length of stay (LOS) and age as the most significant influential factors in SDP. Furthermore, we elaborated the efficiency of DRGs using data from 2738 inpatients in Qilu hospital. Moreover, 60% (6/10) of the studies from the databases also showed the efficiency of DRGs in different regions. SDP is efficient in saving hospitalization costs, but its implementation is limited. DRGs have a broader scope of application, but their effectiveness remains to be validated. DIP is a brand new concept in China, and more data are needed to assess its efficiency.

10.
Nat Commun ; 14(1): 6998, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919274

RESUMO

Itinerant kagome lattice magnets exhibit many novel correlated and topological quantum electronic states with broken time-reversal symmetry. Superconductivity, however, has not been observed in this class of materials, presenting a roadblock in a promising path toward topological superconductivity. Here, we report that novel superconductivity can emerge at the interface of kagome Chern magnet TbMn6Sn6 and metal heterostructures when elemental metallic thin films are deposited on either the top (001) surface or the side surfaces. Superconductivity is also successfully induced and systematically studied by using various types of metallic tips on different TbMn6Sn6 surfaces in point-contact measurements. The anisotropy of the superconducting upper critical field suggests that the emergent superconductivity is quasi-two-dimensional. Remarkably, the interface superconductor couples to the magnetic order of the kagome metal and exhibits a hysteretic magnetoresistance in the superconducting states. Taking into account the spin-orbit coupling, the observed interface superconductivity can be a surprising and more realistic realization of the p-wave topological superconductors theoretically proposed for two-dimensional semiconductors proximity-coupled to s-wave superconductors and insulating ferromagnets. Our findings of robust superconductivity in topological-Chern-magnet/metal heterostructures offer a new direction for investigating spin-triplet pairing and topological superconductivity.

11.
BMC Gastroenterol ; 23(1): 368, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904100

RESUMO

BACKGROUND: Ulcerative colitis (UC) represents a clinically challenging condition characterized by persistent damage to the colonic epithelial mucosa as the principal pathological feature. Polyvinyl alcohol (PVA) solution, primarily composed of glue, is a biodegradable polymer material that has found utility in the medical field. This research endeavors to investigate the therapeutic potential of PVA water solution in ameliorating UC in mice. METHODS: UC was induced in 48 C57BL/6 mice by administering 2.5% DSS in their diet for 6 days. Mice were treated with different concentrations of PVA (0.1 mg/ml PVA, 0.3 mg/ml PVA, 1 mg/ml PVA, 3 mg/ml PVA, 10 mg/ml PVA) enemas (n = 6). Disease Activity Index (DAI) and histologic score were evaluated for inflammation degree. Furthermore, mouse colon organoids were cultured, which were used to assess the effects of PVA on expansion in vitro. RESULTS: PVA aqueous solutions (1 mg/ml and 3 mg/ml) were able to alleviate the DAI in mice. By DAY 6, there was a significant 3/5-fold decrease in DAI within the 1 mg/ml PVA group (p = 0.02). Histopathology scores demonstrated improvements, while the levels of inflammatory factors in the intestinal mucosal tissue were reduced. Additionally, it was confirmed that PVA could promote the expansion of colonic organoids in vitro. CONCLUSIONS: In summary, our investigation has yielded findings indicating that PVA holds the potential to ameliorate symptoms associated with colitis in murine subjects afflicted by DSS-induced colitis, primarily through its facilitation of intestinal stem cell expansion. This study might provide a new candidate for the clinical treatment of ulcerative colitis.


Assuntos
Colite Ulcerativa , Colite , Humanos , Camundongos , Animais , Colite Ulcerativa/tratamento farmacológico , Álcool de Polivinil/efeitos adversos , Camundongos Endogâmicos C57BL , Colite/terapia , Colite/tratamento farmacológico , Colo/patologia , Enema , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças
12.
Int J Qual Health Care ; 35(4)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37757476

RESUMO

Ischemic stroke is featured with high incidence, mortality, and disability. The aim of this study is to use Global Burden of Disease database to describe and compare the burden of ischemic stroke in mainland China and Taiwan province and to further predict the expected changes in the next 11 years using statistical modeling methods. Information on ischemic stroke incidence and mortality in China (mainland and Taiwan province) during 1990-2019 was obtained from the Global Burden of Disease database to analyze the effects of region, gender, and age on the incidence and mortality of ischemic stroke in China. The autoregressive integrated moving average model was used to predict the age-standardized incidence rate and age-standardized mortality rate of ischemic stroke in males and females in mainland China and Taiwan province in the next 11 years. The period from 1990 to 2019 witnessed an overall upward trend in the number of incidence and deaths in mainland China and Taiwan province. In 2019, there were nearly 2.87 million ischemic incidence cases with stroke in mainland China, with more female patients than male in the age group of over 60 years. Among the nearly 1.03 million deaths, the death toll of men under the age of 85 years was higher than that of women, while in Taiwan province, the number of incidence was 28 771, with more female patients of all ages than male. Among the 6788 deaths, the death toll of men under the age of 80 years was higher than that of women. In 2019, the age group with the highest number of patients in the two regions was 65-69 years, while the highest number of deaths was found in people aged 85 years and above. As our autoregressive integrated moving average model predicted, the age-standardized incidence rate value of ischemic stroke is expected to be 163.23/100 000 persons in mainland China by 2030, which would continue to increase, while the age-standardized mortality rate value of ischemic stroke is expected to be 16.41/100 000 persons in Taiwan province by 2030, which showed a decreasing trend. Disease burden of ischemic stroke is still increasing in mainland China and Taiwan province, and health resources should be deployed to implement effective prevention and control strategies, taking into account region, gender, and age.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , China/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Incidência
13.
Int J Mol Sci ; 24(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37569400

RESUMO

Utilizing large-scale epigenomics data, deep learning tools can predict the regulatory activity of genomic sequences, annotate non-coding genetic variants, and uncover mechanisms behind complex traits. However, these tools primarily rely on human or mouse data for training, limiting their performance when applied to other species. Furthermore, the limited exploration of many species, particularly in the case of livestock, has led to a scarcity of comprehensive and high-quality epigenetic data, posing challenges in developing reliable deep learning models for decoding their non-coding genomes. The cross-species prediction of the regulatory genome can be achieved by leveraging publicly available data from extensively studied organisms and making use of the conserved DNA binding preferences of transcription factors within the same tissue. In this study, we introduced DeepSATA, a novel deep learning-based sequence analyzer that incorporates the transcription factor binding affinity for the cross-species prediction of chromatin accessibility. By applying DeepSATA to analyze the genomes of pigs, chickens, cattle, humans, and mice, we demonstrated its ability to improve the prediction accuracy of chromatin accessibility and achieve reliable cross-species predictions in animals. Additionally, we showcased its effectiveness in analyzing pig genetic variants associated with economic traits and in increasing the accuracy of genomic predictions. Overall, our study presents a valuable tool to explore the epigenomic landscape of various species and pinpoint regulatory deoxyribonucleic acid (DNA) variants associated with complex traits.


Assuntos
Aprendizado Profundo , Animais , Humanos , Bovinos , Suínos , Camundongos , Galinhas/genética , Cromatina/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , DNA
14.
J Exp Clin Cancer Res ; 42(1): 198, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37550764

RESUMO

BACKGROUND: Aberrant somatic genomic alteration including copy number amplification is a hallmark of cancer genomes. We previously profiled genomic landscapes of prostate cancer (PCa), yet the underlying causal genes with prognostic potential has not been defined. It remains unclear how a somatic genomic event cooperates with inherited germline variants contribute to cancer predisposition and progression. METHODS: We applied integrated genomic and clinical data, experimental models and bioinformatic analysis to identify GATA2 as a highly prevalent metastasis-associated genomic amplification in PCa. Biological roles of GATA2 in PCa metastasis was determined in vitro and in vivo. Global chromatin co-occupancy and co-regulation of GATA2 and SMAD4 was investigated by coimmunoprecipitation, ChIP-seq and RNA-seq assays. Tumor cellular assays, qRT-PCR, western blot, ChIP, luciferase assays and CRISPR-Cas9 editing methods were performed to mechanistically understand the cooperation of GATA2 with SMAD4 in promoting TGFß1 and AR signaling and mediating inherited PCa risk and progression. RESULTS: In this study, by integrated genomics and experimental analysis, we identified GATA2 as a prevalent metastasis-associated genomic amplification to transcriptionally augment its own expression in PCa. Functional experiments demonstrated that GATA2 physically interacted and cooperated with SMAD4 for genome-wide chromatin co-occupancy and co-regulation of PCa genes and metastasis pathways like TGFß signaling. Mechanistically, GATA2 was cooperative with SMAD4 to enhance TGFß and AR signaling pathways, and activated the expression of TGFß1 via directly binding to a distal enhancer of TGFß1. Strinkingly, GATA2 and SMAD4 globally mediated inherited PCa risk and formed a transcriptional complex with HOXB13 at the PCa risk-associated rs339331/6q22 enhancer, leading to increased expression of the PCa susceptibility gene RFX6. CONCLUSIONS: Our study prioritizes causal genomic amplification genes with prognostic values in PCa and reveals the pivotal roles of GATA2 in transcriptionally activating the expression of its own and TGFß1, thereby co-opting to TGFß1/SMAD4 signaling and RFX6 at 6q22 to modulate PCa predisposition and progression.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Próstata/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Cromatina , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteína Smad4/genética , Proteína Smad4/metabolismo , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismo
15.
FASEB Bioadv ; 5(7): 277-286, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37415929

RESUMO

Ischemic insult stimulates proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) after stroke. However, only a fraction of NSC-derived neuroblasts from SVZ migrate toward poststroke brain region. We have previously reported that direct-current stimulation guides NSC migration toward the cathode in vitro. Accordingly, we set up a new method of transcranial direct-current stimulation (tDCS), in which the cathodal electrode is placed on the ischemic hemisphere and anodal electrode on the contralateral hemisphere of rats subjected to ischemia-reperfusion injury. We show that the application of this bilateral tDCS (BtDCS) promotes the migration of NSC-derived neuroblasts from SVZ toward the cathode direction into poststroke striatum. Reversing the position of the electrodes blocks the effect of BtDCS on the migration of neuroblasts from SVZ. BtDCS protects against neuronal death and improves the functional recovery of stroke animals. Thus, the migration of NSC-derived neuroblasts from SVZ toward poststroke brain region contributes to the effect of BtDCS against ischemia-induced neuronal death, supporting a potential development of noninvasive BtDCS as an endogenous neurogenesis-based stroke therapy.

16.
Healthcare (Basel) ; 11(9)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37174747

RESUMO

BACKGROUND: Wound treatment in emergency care requires the rapid assessment of wound size by medical staff. Limited medical resources and the empirical assessment of wounds can delay the treatment of patients, and manual contact measurement methods are often inaccurate and susceptible to wound infection. This study aimed to prepare an Automatic Wound Segmentation Assessment (AWSA) framework for real-time wound segmentation and automatic wound region estimation. METHODS: This method comprised a short-term dense concatenate classification network (STDC-Net) as the backbone, realizing a segmentation accuracy-prediction speed trade-off. A coordinated attention mechanism was introduced to further improve the network segmentation performance. A functional relationship model between prior graphics pixels and shooting heights was constructed to achieve wound area measurement. Finally, extensive experiments on two types of wound datasets were conducted. RESULTS: The experimental results showed that real-time AWSA outperformed state-of-the-art methods such as mAP, mIoU, recall, and dice score. The AUC value, which reflected the comprehensive segmentation ability, also reached the highest level of about 99.5%. The FPS values of our proposed segmentation method in the two datasets were 100.08 and 102.11, respectively, which were about 42% higher than those of the second-ranked method, reflecting better real-time performance. Moreover, real-time AWSA could automatically estimate the wound area in square centimeters with a relative error of only about 3.1%. CONCLUSION: The real-time AWSA method used the STDC-Net classification network as its backbone and improved the network processing speed while accurately segmenting the wound, realizing a segmentation accuracy-prediction speed trade-off.

17.
Nat Plants ; 9(5): 749-765, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37081290

RESUMO

Above-optimal growth temperatures, usually referred to as heat stress (HS), pose a challenge to organisms' survival as they interfere with essential physiological functions and disrupt cellular organization. Previous studies have elucidated the complex transcriptional regulatory networks involved in plant HS responses, but the mechanisms of organellar remodelling and homeostasis during plant HS adaptations remain elusive. Here we report a non-canonical function of ATG8 in regulating the restoration of plant Golgi damaged by HS. Short-term acute HS causes vacuolation of the Golgi apparatus and translocation of ATG8 to the dilated Golgi membrane. The inactivation of the ATG conjugation system, but not of the upstream autophagic initiators, abolishes the targeting of ATG8 to the swollen Golgi, causing a delay in Golgi recovery after HS. Using TurboID-based proximity labelling, we identified CLATHRIN LIGHT CHAIN 2 (CLC2) as an interacting partner of ATG8 via the AIM-LDS interface. CLC2 is recruited to the cisternal membrane by ATG8 to facilitate Golgi reassembly. Collectively, our study reveals a hitherto unanticipated process of Golgi stack recovery from HS in plant cells and uncovers a previously unknown mechanism of organelle resilience involving ATG8.


Assuntos
Complexo de Golgi , Plantas , Autofagia/fisiologia , Organelas , Resposta ao Choque Térmico
18.
Appl Biol Chem ; 66(1): 7, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36742290

RESUMO

The ability of natural plants to treat chronic diseases is closely related to their antioxidant function. Lactic acid bacteria (LAB) fermentation is an effective way to improve the nutritional value, biological activity and flavor of food. This study investigated the pH, titratable acidity, total polysaccharide, total flavone, total saponin, total polyphenol, and antioxidant activity of the FH06 beverage before and after probiotic fermentation. Results: After fermentation, FH06 had lower contents of total polysaccharides, total flavonoids, total saponins and total polyphenols but higher titratable acidity. The antioxidant activity was tested by total antioxidant capacity (FRAP method) and DPPH· scavenging ability. The FRAP value significantly increased after fermentation (P < 0.05), and the maximum increase was observed for Lactobacillus fermentum grx08 at 25.87%. For DPPH· scavenging ability, the value of all fermentations decreased, and L. fermentum grx08 had the smallest reduction at 2.21% (P < 0.05). The results of GC-MS and sensory analysis showed that fermentation eliminated bad flavors, such as grass, cassia and bitterness, and highlighted the fruit aroma and soft sour taste. Conclusion: The FRAP value and sensory flavor of FH06 fermentation by L. fermentum grx08 were significantly improved, indicating its great potential as a functional food with both strong antioxidant activity and good flavor. Supplementary Information: The online version contains supplementary material available at 10.1186/s13765-022-00762-2.

20.
Adv Mater ; 35(3): e2205927, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36385535

RESUMO

Kagome magnets provide a fascinating platform for a plethora of topological quantum phenomena, in which the delicate interplay between frustrated crystal structure, magnetization, and spin-orbit coupling (SOC) can engender highly tunable topological states. Here, utilizing angle-resolved photoemission spectroscopy, the Weyl lines are directly visualized with strong out-of-plane dispersion in the A-A stacked kagome magnet GdMn6 Sn6 . Remarkably, the Weyl lines exhibit a strong magnetization-direction-tunable SOC gap and binding energy tunability after substituting Gd with Tb and Li, respectively. These results not only illustrate the magnetization direction and valence counting as efficient tuning knobs for realizing and controlling distinct 3D topological phases, but also demonstrate AMn6 Sn6 (A = rare earth, or Li, Mg, or Ca) as a versatile material family for exploring diverse emergent topological quantum responses.

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