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1.
Nat Commun ; 15(1): 3475, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658552

RESUMO

Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: 'pseudo-diploid' cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias da Próstata , Análise de Célula Única , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Aneuploidia , Próstata/patologia , Próstata/metabolismo , Células Clonais , Diploide , Idoso
2.
Small ; : e2400958, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644328

RESUMO

Quantum dots (QDs) colloidal nanocrystals are attracting enduring interest by scientific communities for solar energy conversion due to generic physicochemical merits including substantial light absorption coefficient, quantum confinement effect, enriched catalytically active sites, and tunable electronic structure. However, photo-induced charge carriers of QDs suffer from ultra-short charge lifespan and poor stability, rendering controllable vectorial charge modulation and customizing robust and stable QDs artificial photosystems challenging. Herein, tailor-made oppositely charged transition metal chalcogenides quantum dots (TMCs QDs) and MXene quantum dots (MQDs) are judiciously harnessed as the building blocks for electrostatic layer-by-layer assembly buildup on the metal oxides (MOs) framework. In these exquisitely designed LbL assembles MOs/(TMCs QDs/MQDs)n heterostructured photoanodes, TMCs QDs layer acts as light-harvesting antennas, and MQDs layer serves as electron-capturing mediator to relay cascade electrons from TMCs QDs to the MOs substrate, thereby yielding the spatially ordered tandem charge transport chain and contributing to the significantly boosted charge separation over TMCs QDs and solar water oxidation efficiency of MOs/(TMCs QDs/MQDs)n photoanodes. The relationship between interface configuration and charge transfer characteristics is unambiguously unlocked, by which photoelectrochemical mechanism is elucidated. This work would provide inspiring ideas for precisely mediating interfacial charge transfer pathways over QDs toward solar energy conversion.

3.
ACS Biomater Sci Eng ; 10(4): 2235-2250, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38445959

RESUMO

The use of exosomes to relieve skin injuries has received considerable attention. The PluronicF-127 hydrogel (PF-127 hydrogel) is a novel biomaterial that can be used to carry biomolecules. This study sought to investigate the impact of exosomes originating from human mesenchymal stem cells (MSCs) developed from adipose tissue (hADSC-Exos) combined with a PF-127 hydrogel on tissue repair and explore the underlying mechanism using in vitro and in vivo experiments. miR-148a-3p is the most expressed microRNA (miRNA) in hADSC-Exos. We found that exosomes combined with the PF-127 hydrogel had a better efficacy than exosomes alone; moreover, miR-148a-3p knockdown lowered its efficacy. In vitro, we observed a significant increase in the tumor-like ability of HUVECs after exosome treatment, which was attenuated after miR-148a-3p knockdown. Furthermore, the effects of miR-148a-3p on hADSC-Exos were achieved through the prevention of PTEN and the triggering of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. In conclusion, our results demonstrated that hADSC-Exos can promote angiogenesis and skin wound healing by delivering miR-148a-3p and have a better effect when combined with the PF-127 hydrogel, which may be an alternative strategy to promote wound healing.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Humanos , Hidrogéis/farmacologia , Fosfatidilinositol 3-Quinases/genética , MicroRNAs/genética , Cicatrização/genética
4.
Burns Trauma ; 12: tkae001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434722

RESUMO

Background: Adipose mesenchymal stem cell-derived exosomes (ADSC-Exos) have great potential in the field of tissue repair and regenerative medicine, particularly in cases of refractory diabetic wounds. Interestingly, autophagy plays a role in wound healing, and recent research has demonstrated that exosomes are closely associated with intracellular autophagy in biogenesis and molecular signaling mechanisms. Therefore, this study aimed to investigate whether ADSC-Exos promote the repair of diabetic wounds by regulating autophagy to provide a new method and theoretical basis for the treatment of diabetic wounds. Methods: Western blot analysis and autophagy double-labelled adenovirus were used to monitor changes in autophagy flow in human immortalized keratinocyte cell line (HaCaT) cells. ADSC-Exos were generated from ADSC supernatants via ultracentrifugation. The effectiveness of ADSC-Exos on HaCaT cells was assessed using a live-cell imaging system, cell counting kit-8 and cell scratch assays. The cells were treated with the autophagy inhibitor bafilomycin A1 to evaluate the effects of autophagy on cell function. The recovery of diabetic wounds after ADSC-Exo treatment was determined by calculating the healing rates and performing histological analysis. High-throughput transcriptome sequencing was used to analyze changes in mRNA expression after the treatment of HaCaT cells with ADSC-Exos. Results: ADSC-Exos activated autophagy in HaCaT cells, which was inhibited by high glucose levels, and potentiated their cellular functions. Moreover, ADSC-Exos in combination with the autophagy inhibitor bafilomycin A1 showed that autophagy defects further impaired the biological function of epidermal cells under high-glucose conditions and partially weakened the healing effect of ADSC-Exos. Using a diabetes wound model, we found that ADSC-Exos promoted skin wound healing in diabetic mice, as evidenced by increased epidermal autophagy and rapid re-epithelialization. Finally, sequencing results showed that increased expression of autophagy-related genes nicotinamide phosphoribosyltransferase (NAMPT), CD46, vesicle-associated membrane protein 7 (VAMP7), VAMP3 and eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) may contribute to the underlying mechanism of ADSC-Exo action. Conclusions: This study elucidated the molecular mechanism through which ADCS-Exos regulate autophagy in skin epithelial cells, thereby providing a new theoretical basis for the treatment and repair of skin epithelial damage by ADSC-Exos.

5.
Water Res ; 254: 121440, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479170

RESUMO

The ultraviolet/monochloramine (UV/NH2Cl) process is an emerging advanced oxidation process with promising prospects in water treatment. Previous studies developed kinetic models of UV/NH2Cl for simulating radical concentrations and pollutant degradation. However, the reaction rate constants of Cl2•- with bicarbonate and carbonate (kCl2•-, HCO3- and kCl2•-, CO32-) were overestimated in literature. Consequently, when dosing 1 mM chloride and 1 mM bicarbonate, the current models of UV/NH2Cl severely under-predicted the experimental concentrations of three important radicals (i.e., hydroxyl radical (HO•), chlorine radical (Cl•), and dichloride radical (Cl2•-)) with great deviations (> 90 %). To investigate this issue, the transformation reactions among these three radicals in UV/NH2Cl were systematically studied. For the first time, it was found that in addition to Cl•, Cl2•- was also an important parent radical of HO• in the presence of chloride, and chloride could effectively compensate the inhibitory effect of bicarbonate on HO• generation in the system. Moreover, reactions and rate constants in current models were scrutinized from corresponding literature, and the reaction rate constants of Cl2•- with bicarbonate and carbonate (kCl2•-, HCO3- and kCl2•-, CO32-) were reevaluated to be 1.47 × 105 and 3.78 × 106 M-1s-1, respectively, by laser flash photolysis. With the newly obtained rate constants, the refined model could accurately simulate concentrations of all three radicals under different chloride and bicarbonate dosages with satisfactory deviations (< 30 %). Meanwhile, the refined model performed much better in predicting pollutant degradation and radical contribution compared with the unrefined model (with the previously estimated kCl2•-, HCO3- and kCl2•-, CO32-). The results of this study enhanced the accuracy and applicability of the kinetic model of UV/NH2Cl, and deepened the understanding of radical transformation in the process.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Bicarbonatos , Cloretos , Raios Ultravioleta , Poluentes Químicos da Água/análise , Cloro , Carbonatos , Cinética , Oxirredução
6.
J Hazard Mater ; 469: 133982, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38460256

RESUMO

Enhancing Fe(VI) oxidation ability by generating high-valent iron-oxo species (Fe(IV)/Fe(V)) has attracted continuous interest. This work for the first time reports the efficient activation of Fe(VI) by a well-known aza-aromatic chelating agent 2,2'-bipyridyl (BPY) for micropollutant degradation. The presence of BPY increased the degradation constants of six model compounds (i.e., sulfamethoxazole (SMX), diclofenac (DCF), atenolol (ATL), flumequine (FLU), 4-chlorophenol (4-CP), carbamazepine (CBZ)) with Fe(VI) by 2 - 6 folds compared to those by Fe(VI) alone at pH 8.0. Lines of evidence indicated the dominant role of Fe(IV)/Fe(V) intermediates. Density functional theory calculations suggested that the binding of Fe(III) to one or two BPY molecules initiated the oxidation of Fe(III) to Fe(IV) by Fe(VI), while Fe(VI) was reduced to Fe(V). The increased exposures of Fe(IV)/Fe(V) were experimentally verified by the pre-generated Fe(III) complex with BPY and using methyl phenyl sulfoxide as the probe compound. The presence of chloride and bicarbonate slightly affected model compound degradation by Fe(VI) in the presence of BPY, while a negative effect of humic acid was obtained under the same conditions. This work demonstrates the potential of N-donor heterocyclic ligand to activate Fe(VI) for micropollutant degradation, which is instructive for the Fe(VI)-based oxidation processes.

7.
Cancers (Basel) ; 16(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38539418

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely recommended for unfit patients with newly diagnosed acute myeloid leukemia (AML). Patient survival can improve with venetoclax plus azacitidine (VEN plus AZA). However, the long-term outcome of this treatment strategy is still unsatisfactory. The high response and low treatment toxicity rates of patients receiving VEN plus AZA can provide an opportunity for HSCT among unfit patients. Nevertheless, the outcomes and complications of VEN plus AZA, followed by HSCT, remain unclear. METHODS: This single-center retrospective study aimed to compare patients with newly diagnosed AML receiving VEN plus AZA as induction therapy (n = 27) to those receiving the conventional I3A7 regimen as induction therapy (n = 34). RESULT: The 1-year overall survival, relapse, and non-relapse mortality rates in the two groups were similar. The cytogenetic risks and the hematopoietic cell transplantation-specific comorbidity index are the most significant predictive factors of overall survival. CONCLUSION: In older patients unfit for intensive chemotherapy, a low-intensity regimen with VEN plus AZA is a suitable bridge therapy. Furthermore, allo-HSCT is feasible and can be a curative option.

8.
Front Endocrinol (Lausanne) ; 15: 1281622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524630

RESUMO

Background: CXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4. Methods: This study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis. Results: 100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P<0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P<0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively). Conclusion: Differential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis.


Assuntos
Carcinoma Neuroendócrino , Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Receptores CXCR4 , Estudos Retrospectivos , Neoplasias Intestinais/patologia , Neoplasias Gástricas/patologia , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/patologia , Carcinoma Neuroendócrino/patologia
9.
Int J Biochem Cell Biol ; 169: 106557, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460905

RESUMO

There is growing evidence of an elevated risk of lung cancer in patients with rheumatoid arthritis. The poor prognosis of rheumatoid arthritis-associated lung cancer and the lack of therapeutic options pose an even greater challenge to the clinical management of patients. This study aimed to identify potential molecular targets associated with the progression of rheumatoid arthritis-associated lung cancer and examine the efficacy of naringenin nanoparticles targeting cyclin B1. Mendelian randomizatio analysis revealed that rheumatoid arthritis has a positive correlation with the risk of lung cancer. Cyclin B1 was significantly upregulated in patients with rheumatoid arthritis-associated lung cancer and was significantly overexpressed in synovial tissue fibroblasts. Furthermore, the overexpression of cyclin B1 in rheumatoid arthritis fibroblast-like synoviocytes, which promotes their proliferation and fibroblast-to-myofibroblast transition, can significantly contribute to the growth and infiltration of lung cancer cells. Importantly, our prepared naringenin nanoparticles targeting cyclin B1 effectively attenuated proliferation and fibroblast-to-myofibroblast transition by blocking cells at the G2/M phase. In vivo experiments, naringenin nanoparticles targeting cyclin B1 significantly alleviated the development of collagen-induced arthritis and lung orthotopic tumors. Collectively, our results reveal that naringenin nanoparticles targeting cyclin B1 can suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition. These findings provide new insights into the treatment of rheumatoid arthritis-associated lung cancer therapy.


Assuntos
Artrite Reumatoide , Flavanonas , Neoplasias Pulmonares , Humanos , Ciclina B1/genética , Ciclina B1/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Miofibroblastos/patologia , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Fibroblastos/patologia , Proliferação de Células , Células Cultivadas
10.
Orthop Surg ; 16(4): 953-964, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38389204

RESUMO

OBJECTIVE: Surgical treatment with internal fixation, specifically percutaneous fixation with three cannulated compression screws (CCSs), is the preferred choice for young and middle-aged patients. The mechanical advantage of the optimal spatial configuration with three screws provides maximum dispersion and cortical support. We suspect that the spatial proportion of the oblique triangle configuration (OTC) in the cross-section of the femoral neck isthmus (FNI) may significantly improve shear and fatigue resistance of the fixed structure, thereby stabilizing the internal fixation system in femoral neck fracture (FNF). This study aims to explore the mechanical features of OTC and provide a mechanical basis for its clinical application. METHODS: Twenty Sawbone femurs were prepared as Pauwels type III FNF models and divided equally into two fixation groups: OTC and inverted equilateral triangle configuration (IETC). Three 7.3 mm diameter cannulated compression screws (CCSs) were used for fixation. The specimens of FNF after screw internal fixation were subjected to static loading and cyclic loading tests, respectively, with five specimens for each test. Axial stiffness, 5 mm failure load, ultimate load, shear displacement, and frontal rotational angle of two fragments were evaluated. In the cyclic loading test, the load sizes were 700 N, 1400 N, and 2100 N, respectively, and the fracture end displacement was recorded. Results were presented as means ± SD. Data with normal distributions were compared by the Student's t test. RESULTS: In the static loading test, the axial stiffness, ultimate load, shear displacement, and frontal rotational angle of two fragments were (738.64 vs. 620.74) N/mm, (2957.61 vs. 2643.06) N, (4.67 vs. 5.39) mm, and (4.01 vs. 5.52)° (p < 0.05), respectively. Comparison between the femoral head displacement after 10,000 cycles of 700N cyclic loading and total displacement after 20,000 cycles of 700-1400N cyclic loading showed the OTC group was less than the IETC group (p < 0.05). A comparison of femoral head displacement after 10,000 cycles of 1400N and 2100N cycles and total displacement after 30,000 cycles of 700-2100N cycles showed the OTC group was less than another group, but the difference was not significant (p > 0.05). CONCLUSION: When three CCSs are inserted in parallel to fix FNF, the OTC of three screws has obvious biomechanical advantages, especially in shear resistance and early postoperative weight-bearing, which provides a mechanical basis for clinical selection of ideal spatial configuration for unstable FNF.


Assuntos
Fraturas do Colo Femoral , Colo do Fêmur , Pessoa de Meia-Idade , Humanos , Colo do Fêmur/cirurgia , Fenômenos Biomecânicos , Fraturas do Colo Femoral/cirurgia , Parafusos Ósseos , Fêmur , Fixação Interna de Fraturas/métodos
11.
J Acad Nutr Diet ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38408566

RESUMO

BACKGROUND: There is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. OBJECTIVE: The aim of this study was to determine the effect of vitamin D3-fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 µg/L [to convert µg/L ferritin to ng/mL, multiply by 1]). DESIGN: An 8-week double-blind randomized controlled trial was conducted. SUBJECTS/SETTING: A total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. INTERVENTION: Subjects were randomly assigned to receive either vitamin D3-fortified fruit drink or a placebo. MAIN OUTCOME MEASURES: Measurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. STATISTICAL ANALYSES: A mixed model, repeated measures analysis of variance was used to analyze the intervention effect. RESULTS: Attrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3-fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by .4] vs Δ -1.3 [10.7] nmol/L; P = .001) and serum ferritin concentrations (Δ 2.2 [4.2] µg/L vs Δ -0.3 [3.4] µg/L; P = .048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. CONCLUSIONS: Our study found that daily vitamin D3-fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations.

12.
Oncogene ; 43(14): 1019-1032, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38366145

RESUMO

Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer.


Assuntos
Neoplasias da Mama , Proteína I de Ligação a Poli(A) , RNA Longo não Codificante , Feminino , Humanos , Autofagia/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteína I de Ligação a Poli(A)/genética , Proteína I de Ligação a Poli(A)/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética
13.
Am J Hematol ; 99(4): 615-624, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38343151

RESUMO

Venetoclax-azacitidine is approved for treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy based on the interim overall survival (OS) analysis of the VIALE-A study (NCT02993523). Here, long-term follow-up is presented to address survival benefit and long-term outcomes with venetoclax-azacitidine. Patients with newly diagnosed AML who were ineligible for intensive chemotherapy were randomized 2:1 to receive venetoclax-azacitidine or placebo-azacitidine. OS was the primary endpoint; complete remission with/without blood count recovery (CR/CRi) was a key secondary endpoint. This final analysis was conducted when 100% of the predefined 360 OS events occurred. In VIALE-A, 431 patients were enrolled to venetoclax-azacitidine (n = 286) or placebo-azacitidine (n = 145). At 43.2 months median follow-up, median OS was 14.7 months (95% confidence interval [CI], 12.1-18.7) with venetoclax-azacitidine, and 9.6 months (95% CI, 7.4-12.7) with placebo-azacitidine (hazard ratio, 0.58 [95% CI, 0.47-0.72], p < .001); the estimated 24-month OS rate was 37.5% and 16.9%, respectively. Median OS for patients with IDH1/2 mutations and those with measurable residual disease responses was reached in this final analysis. CR/CRi rate was similar to interim analysis. Any-grade hematologic and gastrointestinal adverse events were most common in venetoclax-azacitidine and placebo-azacitidine arms, including thrombocytopenia (47% and 42%) and neutropenia (43% and 29%). No new safety signals were identified. Long-term efficacy and safety confirm venetoclax-azacitidine is an improvement in standard-of-care for patients with AML who are not eligible for intensive chemotherapy because of advanced age or comorbidities.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda , Neutropenia , Sulfonamidas , Humanos , Seguimentos , Leucemia Mieloide Aguda/tratamento farmacológico , Azacitidina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
14.
Sci Rep ; 14(1): 4460, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396186

RESUMO

As smartphones become increasingly prevalent worldwide, the relationship between smartphone addiction and subjective well-being has become a focal point in academic circles. Prior research predominantly delved into the direct correlation between smartphone addiction and subjective well-being, yet there remains a dearth in exploring its underlying mechanisms. This study investigated the mediating role of loneliness in the relationship between smartphone addiction and subjective well-being among Chinese university students. Conducted across 16 universities in eight provinces and municipalities in China, this study encompassed 1527 university students. Data collection utilized scales measuring smartphone addiction, loneliness, and subjective well-being. The findings revealed that: (1) demographic variables such as place of origin, educational level, and family income influenced university students' subjective well-being; (2) a significant negative correlation existed between smartphone addiction and subjective well-being among university students, coupled with a significant positive correlation between smartphone addiction and loneliness, indicating the significant negative predictive effect of smartphone addiction on subjective well-being; (3) loneliness partially mediated the relationship between smartphone addiction and subjective well-being among university students, suggesting that smartphone addiction could directly impact university students' subjective well-being, or indirectly through its effect on loneliness.


Assuntos
Comportamento Aditivo , Estudantes , Humanos , Solidão , Transtorno de Adição à Internet , Inquéritos e Questionários , Smartphone
15.
Artigo em Inglês | MEDLINE | ID: mdl-38416632

RESUMO

This paper presents a reconfigurable near-sensor anomaly detection processor to real-time monitor the potential anomalous behaviors of amputees with limb prostheses. The processor is low-power, low-latency, and suitable for equipment on the prostheses and comprises a reconfigurable Variational Autoencoder (VAE), a scalable Self-Organizing Map (SOM) Array, and a window-size-adjustable Markov Chain, which can implement an integrated miniaturized anomaly detection system. With the reconfigurable VAE, the proposed processor can support up to 64 sensor sampling channels programmable by global configuration, which can meet the anomaly detection requirements in different scenarios. A scalable SOM array allows for the selection of different sizes based on the complexity of the data. Unlike traditional time accumulation-based anomaly detection methods, the Markov Chain is utilized to detect time-series-based anomalous data. The processor is designed and fabricated in a UMC 40-nm LP technology with a core area of 1.49 mm2 and a power consumption of 1.81 mW. It achieves real-time detection performance with 0.933 average F1 Score for the FSP dataset within 24.22 µs, and 0.956 average F1 Score for the SFDLA-12 dataset within 30.48 µs, respectively. The energy dissipation of detection for each input feature is 43.84 nJ with the FSP dataset, and 55.17 nJ with the SFDLA-12 dataset. Compared with ARM Cortex-M4 and ARM Cortex-M33 microcontrollers, the processor achieves energy and area efficiency improvements ranging from 257×, 193× and 11×, 8×, respectively.

16.
Animals (Basel) ; 14(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38396560

RESUMO

The economic efficiency of sheep breeding can be improved by enhancing sheep productivity. A recent genome-wide association study (GWAS) unveiled the potential impact of the MAST4 gene on prolificacy traits in Australian White sheep (AUW)). Herein, whole-genome sequencing (WGS) data from 26 different sheep breeds worldwide (n = 1507), including diverse meat, wool, milk, or dual-purpose sheep breed types from China, Europe, and Africa, were used. Moreover, polymerase chain reaction (PCR) genotyping of the MAST4 gene polymorphisms in (n = 566) Australian white sheep (AUW) was performed. The 3 identified polymorphisms were not homogeneously distributed across the 26 examined sheep breeds. Findings revealed prevalent polymorphisms (P3-ins-29 bp and P6-del-21 bp) with varying frequencies (0.02 to 0.97) across 26 breeds, while P5-del-24 bp was presented in 24 out of 26 breeds. Interestingly, the frequency of the P3-ins-29 bp variant was markedly higher in Chinese meat or dual-purpose sheep breeds, while the other two variants also showed moderate frequencies in meat breeds. Notably, association analysis indicated that all InDels were associated with AUW sheep litter size (p < 0.05). These results suggest that these InDels within the MAST4 gene could be useful in marker-assisted selection in sheep breeding.

17.
BMC Cancer ; 24(1): 244, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389061

RESUMO

BACKGROUND: Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. METHODS: A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. RESULTS: Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580-0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. CONCLUSION: Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Tireoidite Autoimune , Humanos , Nomogramas , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Fatores de Risco
18.
Nutrients ; 16(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38337681

RESUMO

Serum 25(OH)D deficiency consistently demonstrated molecular mechanisms through which chronic inflammation is associated with the risk of nasopharyngeal carcinoma (NPC). This study aimed to determine the association between serum 25(OH)D and NPC. A matched case-control study was conducted at two local hospitals. A total of 300 histologically confirmed NPC cases were matched with controls for age, gender, and ethnicity, and assessed for vitamin D status and other nutritional factors. Mean Vitamin D concentration was significantly lower among cases compared to controls (63.17 ± 19.15 nmol/L and 67.34 ± 23.06 nmol/L) (t = -2.41, p = 0.016). Multiple conditional logistic regression analysis indicated that higher levels of serum 25(OH)D were associated with reduced odds of NPC (AOR = 0.73, 95% CI = 0.57-0.94, p = 0.016) controlling for confounders including BMI, physical activity, smoking status, alcohol consumption, consumption of food high in vitamin D, salted fish consumption, and family history of NPC. There was a significant association between inadequate serum 25(OH)D status with accumulation of four risk factors and increased odds of getting NPC using polynomial regression analysis. Increased NPC odds ratios were observed after sequential accumulation of additional risk factors with the presence of inadequate serum 25(OH)D status (OR = 0.54, 95% CI = 0.27, 4.77, p = 0.322, OR = 1.04, 95% CI = 0.64, 1.72, p = 0.267, OR = 1.15, 95% CI = 0.73, 1.80, p = 0.067, OR = 1.93, 95% CI = 1.13, 3.31, p = 0.022, and OR = 5.55, 95% CI = 1.67, 10.3, p < 0.001 respectively). Future research in Malaysia should involve both prospective cohort studies and randomized controlled trials to confirm and further clarify the role of vitamin D in NPC outcomes.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Deficiência de Vitamina D , Humanos , Calcifediol , Estudos de Casos e Controles , Malásia/epidemiologia , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Masculino , Feminino
19.
Inorg Chem ; 63(5): 2562-2568, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38268414

RESUMO

Layered hybrid perovskites show significant advantages in the field of optoelectronics. However, the low quantum efficiency and complex preparation methods limit their applications. In this work, we developed a series of perovskite powders with a two-dimensional (2D) layered structure of organic-inorganic hybrid metal halides M2CdCl4:x%Mn (M = CH3NH3+, C2H8N+, C3H10N+) via facile mechanochemical methods. The prepared manganese Mn-doped MA2CdCl4 produces orange emission at 605 nm under both 254 and 420 nm excitation, which originates from a dual excitation channel competition mechanism, and its excitation channel could be changed with the increase of Mn2+ ion concentration. Typically, MA2CdCl4:20%Mn powder exhibits high photoluminescence quantum yield (PLQY) close to 90% at 605 nm due to the organic amine ions enlarging the Mn-Mn interlayer distances. In addition, we prepared MA2CdCl4:x%Mn@PVA flexible films, which also exhibit good luminescence at 254 nm excitation and were unexpectedly found to have a better response to Cs+, which could be a candidate for anticounterfeiting applications.

20.
J Orthop Surg Res ; 19(1): 41, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184651

RESUMO

OBJECTIVE: This study aims to identify potential independent risk factors for residual low back pain (LBP) in patients with thoracolumbar osteoporotic vertebral compression fractures (OVCFs) following percutaneous kyphoplasty (PKP) treatment. Additionally, we aim to develop a nomogram that can accurately predict the occurrence of residual LBP. METHODS: We conducted a retrospective review of the medical records of thoracolumbar OVCFs patients who underwent PKP treatment at our hospital between July 2021 and December 2022. Residual LBP was defined as the presence of moderate or greater pain (VAS score ≥ 4) in the low back one day after surgery, and patients were divided into two groups: the LBP group and the non-LBP group. These patients were then randomly allocated to either a training or a validation set in the ratio of 7:3. To identify potential risk factors for residual LBP, we employed lasso regression for multivariate analysis, and from this, we constructed a nomogram. Subsequently, the predictive accuracy and practical clinical application of the nomogram were evaluated through a receiver operating characteristic (ROC) curve, a calibration curve, and a decision curve analysis (DCA). RESULTS: Our predictive model revealed that five variables-posterior fascial oedema, intravertebral vacuum cleft, time from fracture to surgery, sarcopenia, and interspinous ligament degeneration-were correlated with the presence of residual LBP. In the training set, the area under the ROC was 0.844 (95% CI 0.772-0.917), and in the validation set, it was 0.842 (95% CI 0.744-0.940), indicating that the model demonstrated strong discriminative performance. Furthermore, the predictions closely matched actual observations in both the training and validation sets. The decision curve analysis (DCA) curve suggested that the model provides a substantial net clinical benefit. CONCLUSIONS: We have created a novel numerical model capable of accurately predicting the potential risk factors associated with the occurrence of residual LBP following PKP in thoracolumbar OVCFs patients. This model serves as a valuable tool for guiding specific clinical decisions for patients with OVCFs.


Assuntos
Fraturas por Compressão , Cifoplastia , Dor Lombar , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/etiologia , Fraturas por Compressão/cirurgia , Cifoplastia/efeitos adversos , Dor Lombar/etiologia , Dor Lombar/cirurgia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Coluna Vertebral
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