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Background: The efficacy of bright light therapy (BLT) in ameliorating depression has been validated. The present study is to investigate the changes of depressive symptoms, cognitive function and cerebellar functional connectivity (FC) following BLT in individuals with subthreshold depression (StD). Method: Participants were randomly assigned to BLT group (N = 47) or placebo (N = 41) in this randomized controlled trial between March 2020 and June 2022. Depression severity and cognitive function were assessed, as well as resting-state functional MRI scan was conducted before and after 8-weeks treatment. Seed-based whole-brain static FC (sFC) and dynamic FC (dFC) analyses of the bilateral cerebellar subfields were conducted. Besides, a multivariate regression model examined whether baseline brain FC was associated with changes of depression severity and cognitive function during BLT treatment. Results: After 8-week BLT treatment, individuals with StD showed improved depressive symptoms and attention/vigilance cognitive function. BLT also increased sFC between the right cerebellar lobule IX and left temporal pole, and decreased sFC within the cerebellum, and dFC between the right cerebellar lobule IX and left medial prefrontal cortex. Moreover, the fusion of sFC and dFC at baseline could predict the improvement of attention/vigilance in response to BLT. Conclusions: The current study identified that BLT improved depressive symptoms and attention/vigilance, as well as changed cerebellum-DMN connectivity, especially in the cerebellar-frontotemporal and cerebellar internal FC. In addition, the fusion features of sFC and dFC at pre-treatment could serve as an imaging biomarker for the improvement of attention/vigilance cognitive function after BLT in StD.
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MicroRNAs (miRNAs) are bio-active elements cargoed by seminal plasma extracellular vesicles extracellular vesicles (SPEVs) which are crucial for sperm function and fertility modulation. This study aimed to isolate, characterize, and identify the miRNA expression profiles in the SPEVs from high (HSM) and low sperm motility (LSM) groups that could serve as fertility biomarkers and explain the underlying mechanisms. The isolated SPEVs were round spherical structures of approximately 50-200 nm in diameter expressing molecular markers. A total of 1006 and 1084 miRNAs were detected in HSM and LSM, respectively, with 34 being differentially expressed. Their targeted genes involved in SNARE interactions in vesicular transport, Metabolic pathways, and Apelin signaling pathway, etc. The joint analysis with mRNAs of sperm and sperm storage tubules cells highlighted the cellular communication mediated by SPEVs miRNAs, where they may rule fertility by affecting sperm maturation and amino acid metabolism. SPEVs as additives could improve fertility of fresh and frozen sperm, while the knockdown of one of the differentially expressed miRNAs, miR-24-3p, diminished this effect, indicating its crucial roles. This study expands our understanding of SPEVs miRNAs mediated sperm maturation and fertility modulation, and may help to develop new therapeutic strategies for infertility and sperm storage.
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BACKGROUND: Coronary perfusion pressure (CPP) indicates spontaneous return of circulation and is recommended for high-quality cardiopulmonary resuscitation (CPR). This study aimed to investigate a method for non-invasive estimation of CPP using electrocardiography (ECG) and photoplethysmography (PPG) during CPR. METHODS: Nine pigs were used in this study. ECG, PPG, invasive arterial blood pressure (ABP), and right atrial pressure (RAP) signals were simultaneously recorded. The CPPs were estimated using three datasets: (a) ECG, (b) PPG, and (c) ECG and PPG, and were compared with invasively measured CPPs. Four machine-learning algorithms, namely support vector regression, random forest (RF), K-nearest neighbor, and gradient-boosted regression tree, were used for estimation of CPP. RESULTS: The RF model with a combined ECG and PPG dataset achieved better estimation of CPP than the other algorithms. Specifically, the mean absolute error was 4.49 mmHg, the root mean square error was 6.15 mm Hg, and the adjusted R2 was 0.75. A strong correlation was found between the non-invasive estimation and invasive measurement of CPP (r = 0.88), which supported our hypothesis that machine-learning-based analysis of ECG and PPG parameters can provide a non-invasive estimation of CPP for CPR. CONCLUSIONS: This study proposes a novel estimation of CPP using ECG and PPG with machine-learning-based algorithms. Non-invasively estimated CPP showed a high correlation with invasively measured CPP and may serve as an easy-to-use physiological indicator for high-quality CPR treatment.
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Algoritmos , Reanimação Cardiopulmonar , Eletrocardiografia , Parada Cardíaca , Aprendizado de Máquina , Fotopletismografia , Animais , Fotopletismografia/métodos , Parada Cardíaca/fisiopatologia , Suínos , Reanimação Cardiopulmonar/métodos , Modelos Animais de Doenças , Circulação Coronária , Pressão SanguíneaRESUMO
(1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with r/r B-cell lymphoma received either CAR-T therapy alone or in combination with ASCT at our institution. We evaluated the incidence of CRS and CRES and utilized a logistic regression model to identify factors contributing to severe CRS (grade 3-4) and CRES (grade 3-4). (3) Results: The overall incidence of CRS and CRES was 78.9% and 8.2% in 147 patients receiving CAR-T alone, and 95.9% and 15.2% in 145 patients receiving CAR-T combined with ASCT, respectively. The incidence of overall CRS (p < 0.0001) and mild CRS (grade 1-2) (p = 0.021) was elevated in the ASCT combined with CAR-T group. No significant difference was observed in severe CRS and CRES between the groups. Among the 26 cases of lymphoma involving the central nervous system (CNS), 96.2% (25/26) developed CRS (15.4% grade 3-4), and 34.6% (9/26) manifested CRES (7.7% grade 3-4). Female patients had a lower incidence of severe CRS but a higher incidence of severe CRES. Lymphomas with CNS involvement demonstrated a higher risk of CRES compared to those without central involvement. (4) Conclusions: The combination of ASCT with CAR-T demonstrated a preferable option in r/r B-cell lymphoma without an increased incidence of severe CRS and CRES.
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Past research has revealed cognitive improvements resulting from engagement with both traditional action video games and newer action-like video games, such as action real-time strategy games (ARSG). However, the cortical dynamics elicited by different video gaming genres remain unclear. This study explored the temporal dynamics of cortical networks in response to different gaming genres. Functional magnetic resonance imaging (fMRI) data were obtained during eye-closed resting and passive viewing of gameplay videos of three genres: life simulation games (LSG), first-person shooter games (FPS), and ARSG. Data analysis used a seed-free Co-Activation Pattern (CAP) based on Regions of Interest (ROIs). When comparing the viewing of action-like video games (FPS and ARSG) to LSG viewing, significant dynamic distinctions were observed in both primary and higher-order networks. Within action-like video games, compared to FPS viewing, ARSG viewing elicited a more pronounced increase in the Fraction of Time and Counts of attentional control-related CAPs, along with an increased Transition Probability from sensorimotor-related CAPs to attentional control-related CAPs. Compared to ARSG viewing, FPS viewing elicited a significant increase in the Fraction of Time of sensorimotor-related CAPs, when gaming experience was considered as a covariate. Thus, different video gaming genres, including distinct action-like video gaming genres, elicited unique dynamic patterns in whole-brain CAPs, potentially influencing the development of various cognitive processes.
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Atenção , Encéfalo , Imageamento por Ressonância Magnética , Jogos de Vídeo , Humanos , Masculino , Adulto Jovem , Feminino , Adulto , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Atenção/fisiologia , Mapeamento Encefálico/métodosRESUMO
Insects harbor a remarkable diversity of gut microbiomes critical for host survival, health, and fitness, but the mechanism of this structured symbiotic community remains poorly known, especially for the insect group consisting of many closely related species that inhabit the Qinghai-Tibet Plateau. Here, we firstly analyzed population-level 16S rRNA microbial dataset, comprising 11 Parnassius species covering 5 subgenera, from 14 populations mostly sampled in mountainous regions across northwestern-to-southeastern China, and meanwhile clarified the relative importance of multiple factors on gut microbial community structure and evolution. Our findings indicated that both host genetics and larval host plant modulated gut microbial diversity and community structure. Moreover, the effect analysis of host genetics and larval diet on gut microbiomes showed that host genetics played a critical role in governing the gut microbial beta diversity and the symbiotic community structure, while larval host plant remarkably influenced the functional evolution of gut microbiomes. These findings of the intimate insect-microbe-plant interactions jointly provide some new insights into the correlation among the host genetic background, larval host plant, the structure and evolution of gut microbiome, as well as the mechanisms of high-altitude adaptation in closely related species of this alpine butterfly group.
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As the major DNA sensor that activates the STING-TBK1 signaling cascade, cGAS is mainly present in the cytosol. A number of recent reports have indicated that cGAS also plays critical roles in the nucleus. Our previous work demonstrated for the first time that cGAS is translocated to the nucleus upon the occurrence of DNA damage and inhibits homologous recombination (HR), one of the two major pathways of DNA double strand break (DSB) repair. However, whether nuclear cGAS regulates the other DSB repair pathway, nonhomologous end joining (NHEJ), which can be further divided into the less error-prone canonical NHEJ (c-NHEJ) and more mutagenic alternative NHEJ (alt-NHEJ) subpathways, has not been characterized. Here, we demonstrated that cGAS tipped the balance of the two NHEJ subpathways toward c-NHEJ. Mechanistically, the cGAS-Ku80 complex enhanced the interaction between DNA-PKcs and the deubiquitinase USP7 to improve DNA-PKcs protein stability, thereby promoting c-NHEJ. In contrast, the cGAS-Ku80 complex suppressed alt-NHEJ by directly binding to the promoter of Polθ to suppress its transcription. Together, these findings reveal a novel function of nuclear cGAS in regulating DSB repair, suggesting that the presence of cGAS in the nucleus is also important in the maintenance of genome integrity.
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Reparo do DNA por Junção de Extremidades , Autoantígeno Ku , Nucleotidiltransferases , Humanos , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Autoantígeno Ku/metabolismo , Autoantígeno Ku/genética , Quebras de DNA de Cadeia Dupla , Proteína Quinase Ativada por DNA/metabolismo , Células HEK293 , Animais , Células HeLa , CamundongosRESUMO
INTRODUCTION: Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options. METHODS: A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy. RESULTS: In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy. CONCLUSION: PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.
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Imunoterapia Adotiva , Receptor de Morte Celular Programada 1 , Receptores de Antígenos Quiméricos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Adulto Jovem , Linfoma de Células B/terapia , Linfoma de Células B/imunologia , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas , Resultado do TratamentoRESUMO
Chimeric antigen receptor (CAR) T cell therapy has made great progress in treating lymphoma, yet patient outcomes still vary greatly. The lymphoma microenvironment may be an important factor in the efficacy of CAR T therapy. In this study, we designed a highly multiplexed imaging mass cytometry (IMC) panel to simultaneously quantify 31 biomarkers from 13 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) who received CAR19/22 T cell therapy. A total of 20 sections were sampled before CAR T cell infusion or after infusion when relapse occurred. A total of 35 cell clusters were identified, annotated, and subsequently redefined into 10 metaclusters. The CD4+ T cell fraction was positively associated with remission duration. Significantly higher Ki67, CD57, and TIM3 levels and lower CD69 levels in T cells, especially the CD8+/CD4+ Tem and Te cell subsets, were seen in patients with poor outcomes. Cellular neighborhood containing more immune cells was associated with longer remission. Fibroblasts and vascular endothelial cells resided much closer to tumor cells in patients with poor response and short remission after CAR T therapy. Our work comprehensively and systematically dissects the relationship between cell composition, state, and spatial arrangement in the DLBCL microenvironment and the outcomes of CAR T cell therapy, which is beneficial to predict CAR T therapy efficacy.
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Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Análise de Célula Única , Microambiente Tumoral , Humanos , Imunoterapia Adotiva/métodos , Microambiente Tumoral/imunologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/imunologia , Análise de Célula Única/métodos , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Feminino , Masculino , Resultado do Tratamento , Pessoa de Meia-Idade , Adulto , Biomarcadores Tumorais , IdosoRESUMO
Transcriptome analysis, relying on the cutting-edge sequencing of cDNA libraries, has become increasingly prevalent within functional genome studies. However, the dependence on cDNA in most RNA sequencing technologies restricts their ability to detect RNA base modifications. To address this limitation, the latest Oxford Nanopore Direct RNA Sequencing (ONT DRS) technology was employed to investigate the transcriptome of maize seedling roots under salt stress. This approach aimed to unveil both the RNA transcriptional profiles and alterations in base modifications. The analysis of the differential expression revealed a total of 1398 genes and 2223 transcripts that exhibited significant variation within the maize root system following brief exposure to salt stress. Enrichment analyses, such as the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway assessments, highlighted the predominant involvement of these differentially expressed genes (DEGs) in regulating ion homeostasis, nitrogen metabolism, amino acid metabolism, and the phytohormone signaling pathways. The protein-protein interaction (PPI) analysis showed the participation of various proteins related to glycolytic metabolism, nitrogen metabolism, amino acid metabolism, abscisic acid signaling, and the jasmonate signaling pathways. It was through this intricate molecular network that these proteins collaborated to safeguard root cells against salt-induced damage. Moreover, under salt stress conditions, the occurrence of variable shear events (AS) in RNA modifications diminished, the average length of poly(A) tails underwent a slight decrease, and the number of genes at the majority of the variable polyadenylation (APA) sites decreased. Additionally, the levels of N5-methylcytosine (m5C) and N6-methyladenosine (m6A) showed a reduction. These results provide insights into the mechanisms of early salt tolerance in maize.
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Typhoons are recognized as one of the most destructive meteorological phenomena, exerting significant influences on marine ecosystems. Sea surface chlorophyll-a concentration (CHL)an essential indicator of phytoplankton biomass, can be utilized to characterize the disturbances of typhoons on the marine ecosystem. However, it is challenging to investigate this impact at a daily scale due to the missing CHL remote sensing data caused by cloud cover. Given that concurrent passing typhoons may interact with CHL, this study analyzes the effect of the simultaneous passage of binary typhoons Tembin and Bolaven on CHL by using daily CHL reconstruction data, and investigates the role of ocean environmental factors in driving the dynamics of CHL, including sea surface temperature (SST), mixed layer depth (MLD), and sea surface height anomaly (SSHA). The results show that typhoons Tembin and Bolaven increase CHL with the maximum increment of â¼3.2 mgâm-3 during 4-6 days after typhoons passage. The maximum change areas of CHL are distributed near the intersection of typhoon track of (32°N, 125.2°E), corresponding to the regions of greater variation in SST and MLD. During 15 days before and after typhoons (i.e., from 15 August to 15 September 2012), SST is negatively correlated with CHL (the correlation coefficient of -0.85) and MLD is positively correlated with CHL (the correlation coefficient of -0.80). SST immediately declines after typhoons with a maximum cooling of 7.8 deg. C, showing the decreased SST from â¼28 deg. C to â¼23 deg. C can promote phytoplankton growth. MLD deepens from 10 m to >25 m caused by typhoon-induced strong winds, allowing more nutrients to be transported from the subsurface layer to the euphotic layer for phytoplankton blooms. Furthermore, oceanic eddies captured by SSHA change from cyclonic to anticyclonic eddies accompanied by the beginning of CHL increases, and the largest CHL increases correspond to the distribution of pre-existing cyclonic eddies. It suggests that Tembin and Boravin promote phytoplankton growth to increase CHL by enhancing vertical mixing and upwelling to transport nutrients to the sea surface. These findings inspire us to rethink the daily effects of typhoons on CHL, with critical importance for predicting and managing the ecological consequences of typhoons in the ocean.
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Tempestades Ciclônicas , Ecossistema , Clorofila A , Clorofila , Oceanos e Mares , Fitoplâncton , Estações do AnoRESUMO
This report of cases aims to share our treatment experiences in 4 sinus graft infection cases after sinus floor elevation and simultaneous implant placement. The preoperative and postoperative intraoral and radiographic photographs were collected and used to assess the treatment outcomes. The sinus cavity status, bone augmentation results, and implant stability were used as measurements to determine the treatment effectiveness. Four patients received partial graft removal as their surgical treatment for sinus graft infection combined with antibiotic therapy, with or without immediate secondary grafting. After early intervention, antibiotic therapy, and partial debridement of the infected sinus grafts, radiographic and clinical outcomes indicate successful resolution of the graft infection and stable bone graft levels around the implants. The keys to the successful management of the sinus graft infection were: early detection of the infection; early intervention, including partial debridement of the infected graft particles; and antibiotic therapy.
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Antibacterianos , Transplante Ósseo , Desbridamento , Implantação Dentária Endóssea , Levantamento do Assoalho do Seio Maxilar , Humanos , Levantamento do Assoalho do Seio Maxilar/métodos , Masculino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Transplante Ósseo/métodos , Feminino , Resultado do Tratamento , Substitutos Ósseos/uso terapêutico , Seio Maxilar/cirurgia , Adulto , Infecção da Ferida Cirúrgica , Seguimentos , IdosoRESUMO
BACKGROUND: Distiller's grains (DGs), which are rich in natural ingredients such as prolamins, are often used as low-value feed or discarded directly, resulting in great environmental pollution and resource waste. Prolamins from DGs (PDGs) were found to be a potential material for the construction of biopolymer films due to their good film-forming properties. In this study, extrusion processing was conducted to modify the physicochemical and structural properties of PDGs to facilitate the construction of biopolymer films with superior characteristics. RESULTS: Results indicated that extrusion led to improved solubility (17.91% to 39.95%) and increased disulfide bonds (1.46 to 6.13 µmol g-1) in PDGs. The total and sulfur amino acid contents of extruded PDGs were increased by 13.26% and 38.83%, respectively. New aggregation patterns were formed after extrusion according to the results of scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. Extrusion resulted in reduced surface hydrophobicity of PDGs (10 972 to 3632), sufficient evidence for which could be also found from structure analyses of PDGs. Finally, PDGs extruded at 110 °C were found to facilitate the forming of biopolymer films with superior mechanical properties, water resistance and thermal stability. CONCLUSIONS: Physicochemical and structural properties of PDGs were effectively modified by extrusion processing, and extrusion modification of PDGs could be a great way to facilitate the construction of biopolymer films with superior characteristics. It could provide more possibilities to extend the applications of DGs to alleviate the problems of environmental pollution and resource waste. © 2024 Society of Chemical Industry.
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Prolaminas , Solubilidade , Biopolímeros/química , Prolaminas/química , Grão Comestível/química , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Resistência à TraçãoRESUMO
The aggregation of amyloid-ß (Aß) is one of the important pathological markers of Alzheimer's disease. Ruthenium(II) complexes have good stability, low cytotoxicity, a high fluorescence quantum yield, and a good Stokes shift as fluorescent probes. Based on this, we constructed a fluorescent probe for in vivo real-time imaging and inhibition of Aß-fibril formation using a complex of Ru polypyridine with organic fluorophores (N,N-dimethylaniline) and hydrophobic peptides (KLVFF). DLS and TEM studies have shown that Ru-YH has an inhibitory effect on the fibrotic aggregation of Aß. Both in vivo and in vitro studies have shown that Ru-WJ and Ru-YH can quickly cross the blood-brain barrier and successfully detect Aß in early (2.5-month old) transgenic mouse models. In summary, we have explored the potential of Ru complex based biological probes for early diagnosis and inhibition of AD.
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Doença de Alzheimer , Camundongos , Animais , Barreira Hematoencefálica/patologiaRESUMO
Nucleosomes represent hubs in chromatin organization and gene regulation and interact with a plethora of chromatin factors through different modes. In addition, alterations in histone proteins such as cancer mutations and post-translational modifications have profound effects on histone/nucleosome interactions. To elucidate the principles of histone interactions and the effects of those alterations, we developed histone interactomes for comprehensive mapping of histone-histone interactions (HHIs), histone-DNA interactions (HDIs), histone-partner interactions (HPIs) and DNA-partner interactions (DPIs) of 37 organisms, which contains a total of 3808 HPIs from 2544 binding proteins and 339 HHIs, 100 HDIs and 142 DPIs across 110 histone variants. With the developed networks, we explored histone interactions at different levels of granularities (protein-, domain- and residue-level) and performed systematic analysis on histone interactions at a large scale. Our analyses have characterized the preferred binding hotspots on both nucleosomal/linker DNA and histone octamer and unraveled diverse binding modes between nucleosome and different classes of binding partners. Last, to understand the impact of histone cancer-associated mutations on histone/nucleosome interactions, we complied one comprehensive cancer mutation dataset including 7940 cancer-associated histone mutations and further mapped those mutations onto 419,125 histone interactions at the residue level. Our quantitative analyses point to histone cancer-associated mutations' strongly disruptive effects on HHIs, HDIs and HPIs. We have further predicted 57 recurrent histone cancer mutations that have large effects on histone/nucleosome interactions and may have driver status in oncogenesis.
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Neoplasias , Nucleossomos , Humanos , Nucleossomos/genética , Histonas/genética , Histonas/metabolismo , DNA/química , Mutação , Neoplasias/genéticaRESUMO
Background: Lymphomas originating in bone but not involving visceral or regional lymph nodes are diagnosed as primary bone lymphoma (PBL). Few case reports of anaplastic large-cell lymphoma (ALCL) originating in bone have been reported. The purpose of this report is to describe the difficulty in diagnosing and complete treatment process of this rare type of bone lymphoma. Case Description: We describe a case of anaplastic lymphoma kinase positive (ALK+) ALCL patient with primary multiple bone lesions. The patient was initially in the local hospital due to lumbosacral pain and was diagnosed with multiple myeloma. However, after receiving two cycles of bortezomib, lenalidomide and dexamethasone (VRD) chemotherapy, the patient's pain increased. After discussion with the patient and his family, the patient finally agreed to accept the biopsy of the T10 and L2 vertebral bodies and diagnosed as ALK+ ALCL stage IV with primary bone involvement. After receiving multiple cycles of chemotherapy, local bone radiotherapy and denosumab treatment, the patient's bone pain and osteolytic lesions were improved. Regular follow-up shows that the patient's bone pain has been controlled and he is generally in good condition. Conclusions: ALK+ ALCL originating primarily in the bone may be easily misdiagnosed and hence require appropriate evaluation in the upfront setting. In consideration of the lack of relevant experience due to the rarity of the disease, choosing a suitable treatment regimen requires comprehensive consideration. In the next clinical work, we must observe relevant cases to summarize the treatment experience better.
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Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression. Through meticulous in vivo and in vitro experiments, we reveal that depletion of SMYD3 curtails cell proliferation, migration, and invasion capabilities, leading to compromised non-homologous end joining repair (NHEJ) and heightened sensitivity of EC cells to radiation. Furthermore, our pathway enrichment analysis underscores the pivotal involvement of the DNA damage repair pathway in regulating EC progression. Mechanistically, in response to DNA damage, SMYD3 is recruited to these sites in a PARP1-dependent manner, specifically methylating LIG4. This methylation sets off a sequential assembly of the LIG4/XRCC4/XLF complex, actively participating in the NHEJ pathway and thereby fostering EC progression. Notably, our findings highlight the promise of SMYD3 as a crucial player in NHEJ repair and its direct correlation with EC progression. Intriguingly, pharmacological intervention targeting SMYD3 with its specific inhibitor, BCI-121, emerges as a potent strategy, markedly suppressing the tumorigenicity of EC cells and significantly enhancing the efficacy of radiotherapy. Collectively, our comprehensive data position SMYD3 as a central factor in NHEJ repair and underscore its potential as a promising pharmacological target for endometrial cancer therapy, validated through both in vitro and in vivo systems.
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This study investigated the effect of varying magnetic field intensities (ranging from 0 to 10 mT) on the quality characteristics of dough with 40 % potato pulp substitution (DPP). The results indicated that the DPP fermented with a 4 mT magnetic field exhibited a significant enhancement in the combination of water and substrate, thereby elevating the viscoelastic properties of DPP through reinforcing the stability of gluten network. Meanwhile, DPP treated with a 4 mT magnetic field exhibited the highest amount of disulfide bonds (11.64 µmol SS/g sample). This is accompanied by a prominent cross-linkage structure, as evidenced by SDS-PAGE and CLSM. Notably, the application of a magnetic field substantially augments the dough's capacity to retain gas during fermentation. In addition, the application of magnetic field significantly increased the wet gluten content (20.85 %, P < 0.05) in DPP, which improved tensile properties and an acceptable color profile. The introduction of a magnetic field induces gluten aggregation, which in turn results in heightened particle size distribution and ζ-potential values. In conclusion, this study emphasize the potential of magnetic field technology as a viable method to enhance the overall quality attributes of dough enriched with potato pulp substitution.
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Glutens , Solanum tuberosum , Glutens/química , Farinha , PãoRESUMO
The underlying mechanisms of bright light therapy (BLT) in the prevention of individuals with subthreshold depression symptoms are yet to be elucidated. The goal of the study was to assess the correlation between midbrain monoamine-producing nuclei treatment-related functional connectivity (FC) changes and depressive symptom improvements in subthreshold depression. This double-blind, randomized, placebo-controlled clinical trial was conducted between March 2020 and June 2022. A total of 74 young adults with subthreshold depression were randomly assigned to receive 8-week BLT (N = 38) or placebo (N = 36). Depression severity was measured using the Hamilton Depression Rating Scale (HDRS). The participants underwent resting-state functional magnetic resonance imaging at baseline and after treatment. The dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and habenula seed-based whole-brain FC were analyzed. A multivariate regression model examined whether baseline brain FC was associated with changes in scores on HDRS during BLT treatment. BLT group displayed significantly decreased HDRS scores from pre- to posttreatment compared to the placebo group. BLT increased the FC between the DRN and medial prefrontal cortex (mPFC) and between the left VTA and right superior frontal gyrus (SFG). Altered VTA-SFG connectivity was associated with HDRS changes in the BLT group. Moreover, the baseline FC between DRN and mPFC could predict HDRS changes in BLT. These results suggested that BLT improves depressive symptoms and increases midbrain monoamine-producing nuclei and frontal cortex connectivity in subthreshold depression, which raises the possibility that pretreatment FC of DRN-mPFC could be used as a biomarker for improved BLT treatment in depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Transtorno Depressivo Maior , Adulto Jovem , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Depressão , Fototerapia/métodos , Córtex Pré-Frontal , Mesencéfalo , Imageamento por Ressonância Magnética/métodosRESUMO
ABSTRACT: Aims: Targeted temperature management is recommended for at least 24 h in comatose survivors of in-hospital cardiac arrest (IHCA) after the return of spontaneous circulation; however, whether an extension for 72 h leads to better neurological outcomes is uncertain. Methods: We included data from the Qilu Hospital of Shandong University between July 20, 2019, and June 30, 2022. Unconscious patients who had return of spontaneous circulation lasting >20 consecutive min and received endovascular cooling (72 h) or normothermia treatment were compared in terms of survival-to-discharge and favorable neurological survival. Propensity score matching was used to formulate balanced 1:3 matched patients. Results: In total, 2,084 patients were included. Sixteen patients received extended endovascular cooling and 48 matched controls received normothermia therapy. Compared with the normothermia group, patients who received prolonged endovascular cooling had a higher survival-to-discharge rate. However, good neurological outcomes did not differ significantly. Before matching, Cox regression analysis, using mortality as the event, showed that extended endovascular cooling independently affected the survival of IHCA patients. Conclusions: Among comatose patients who had been resuscitated from IHCA, the use of endovascular cooling for 72 h might confer a benefit on survival-to-discharge.