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The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.
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Background: Deep brain stimulation (DBS) is a potential treatment for improving movement disorder. However, few large-sample studies can reveal its efficacy and safety. This study aims to initially explore the efficacy and safety of DBS in the mesencephalic locomotor region (MLR) on motor function in patients with post-stroke hemiplegia. Methods/design: This multicenter, prospective, double-blind, randomized crossover clinical trial aims to assess the safety and effectiveness of Deep Brain Stimulation (DBS) in the mesencephalic locomotor region (MLR) for patients with moderate to severe post-stroke hemiplegia. Sixty-two patients with stable disease after a year of conservative treatment will be enrolled and implanted with deep brain electrodes. Post-surgery, patients will be randomly assigned to either the DBS group or the control group, with 31 patients in each. The DBS group will receive electrical stimulation 1 month later, while the control group will undergo sham stimulation. Stimulation will be discontinued after 3 and 6 months, followed by a 2-week washout period. Subsequently, the control group will receive electrical stimulation, while the DBS group will undergo sham stimulation. Both groups will resume electrical stimulation at the 9th and 12th-month follow-ups. Post-12-month follow-up, motor-related scores will be collected for analysis, with the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) as the primary metric. Secondary outcomes include balance function, neuropsychiatric behavior, fall risk, daily living activities, and quality of life. This study aims to provide insights into the therapeutic benefits of DBS for post-stroke hemiplegia patients. Result/conclusion: We proposed this study for the first time to comprehensively explore the effectiveness and safety of DBS in improving motor function for post-stroke hemiplegia, and provide evidence for DBS in the treatment of post-stroke hemiplegia. Study limitations are related to the small sample size and short study period. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05968248.
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BACKGROUND: Graft-versus-host disease (GVHD) is a recognized complication among individuals undergoing bone marrow transplantation (BMT). There is a requirement for supplementary data regarding the in-patient outcomes of GVHD in individuals who have undergone BMT. Our analysis seeks to assess the healthcare burden and outcomes associated with GVHD in hospitalized patients who have undergone BMT. METHOD: In this retrospective study, we used data from the National Inpatient Sample (NIS) database spanning from 2016 to 2019. Utilizing ICD-10 codes, we distinguished hospitalizations related to BMT and grouped them into two categories: those with GVHD and those without GVHD. Our areas of focus included in-hospital mortality, length of stay, charges, and associations related to GVHD. Unadjusted odds ratios/coefficients were computed through univariable analysis, followed by adjusted odds ratios (aORs)/coefficients from multivariable analysis that considered potential confounding factors. RESULTS: From 2016 to 2019, data were collected from 13,999 hospitalizations with bone marrow transplants. Among them, 836 had GVHD cases. Patient characteristics showed slight differences in mean age and demographics between the two groups, with GVHD patients having a mean age of 51.61 years and higher percentages of males and whites. Analyzing outcomes, patients with GVHD experienced significantly longer hospital stays (41.4 days vs. 21.3 days) and higher total hospital charges ($824,058 vs. $335,765). Adjusting for confounding factors, GVHD posed a substantial risk. The aOR for mortality in GVHD hospitalizations was 7.20 (95% CI: 5.54-9.36, p < .001). The coefficient for the length of stay was 19.36 days (95% CI: 17.29-21.42, p < .001), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889, p < .001) in GVHD cases. Furthermore, GVHD in patients was associated with elevated risks of various medical conditions. The aORs for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in GVHD patients were 2.79 (95% CI: 2.28-3.41, p < .001), 3.30 (95% CI: 2.57-4.24, p < .001), 5.10 (95% CI: 4.01-6.49, p < .001), 4.88 (95% CI: 3.75-6.34, p < .001), 1.45 (95% CI: 1.13-1.86, p = .003), and 3.57 (95% CI: 2.97-4.29, p < .001). CONCLUSION: GVHD in individuals undergoing BMT is linked to elevated mortality rates, prolonged hospitalization, and higher healthcare costs. Moreover, they face a significantly increased risk of developing complications, such as sepsis, pneumonia, acute respiratory failure, C. difficile infection, and AKI. These results underscore the critical need for vigilant monitoring and effective GVHD management to improve patient outcomes and reduce the complications associated with BMT. Nevertheless, further prospective studies are essential to obtain a more profound understanding and a comprehensive assessment of outcomes in these hospitalized patients.
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Background: Necrotizing soft-tissue infection (NSTI) is a rare and serious disease with high morbidity and mortality. Standard therapeutic concepts have included urgent surgical intervention, broad-spectrum antibiotic treatment, and intensive care. Hyperbaric oxygen therapy (HBOT) is used as adjuvant therapy in some centers, but its benefits remain controversial. Methods: A retrospective analysis was conducted in which 98 patients with a clinical diagnosis of NSTI were treated with standard treatments plus HBOT. The clinical outcomes were wound healing, performance status, hospital length, complication rate, recurrence rate, morbidity (amputation rate), and mortality. Primary or secondary outcomes were compared between the time interval of HBOT and the clinical outcomes. Results: The average times from diagnosis of NSTI to initial HBO treatment and from initial surgery to initial HBO treatment were both significantly longer in dead patients than in surviving patients (P = 0.031; P = 0.020). These two time intervals were both significantly longer in amputated patients than in preserved patients (P = 0.031; P = 0.037). Conclusions: Using combined treatment with early surgical debridement combined with HBOT, it is possible to reduce hospital stay, intensive care unit stay, number of debridements, improve complete wound healing rate, and lower amputation and mortality rates among patients with NSTI. The early onset of HBOT soon after diagnosis, especially during critical conditions, is proved to be associated with higher survival and preservation rates.
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Mutations in the γ-amino butyric acid type A (GABAA) receptor γ2 subunit gene, GABRG2, have been associated with refractory epilepsy. Increasing evidence indicates that suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone acetyltransferases (HDACs) inhibitor, can inhibit seizure onset. However, the mechanisms involved remains unknown. The present study aimed to explore the anti-epileptic effect and underlying mechanisms of SAHA in the treatment of refractory epilepsy induced by GABRG2 mutation. In the zebrafish line expressing human mutant GABRG2(F343L), Tg(hGABRG2F343L), SAHA was found to reduce seizure onset, swimming activity, and neuronal activity. In both Tg(hGABRG2F343L) zebrafish and HEK293T cells transfected with GABAA receptor subunits, SAHA could improve the pan-acetylation level and reduce the expression of HDAC1/10. The decreased expressions of GABAA receptor subunits could be rescued by SAHA treatment both in vivo and in vitro, which might be the result of increased gene transcription and protein trafficking. The up-regulated acetylation of histone H3 and H4 as well as Bip expression might be involved in the process. Taken together, our data proved that both histone and non-histone acetylation might contribute to the anti-epileptic effect of SAHA in refractory epilepsy caused by GABRG2(F343L) mutation, demonstrating SAHA as a promising therapeutic agent for refractory epilepsy.
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Mutação , Receptores de GABA-A , Vorinostat , Peixe-Zebra , Animais , Humanos , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Células HEK293 , Vorinostat/farmacologia , Vorinostat/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/genética , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Animais Geneticamente ModificadosRESUMO
Myelin sheath plays important roles in information conduction and nerve injury repair in the peripheral nerve system (PNS). Enhancing comprehension of the structure and components of the myelin sheath in the PNS during development would contribute to a more comprehensive understanding of the developmental and regenerative processes. In this research, the structure of sciatic nerve myelin sheath in C57BL/6 mice from embryonic day 14 (E14) to postnatal 12 months (12M) was observed with transmission electron microscopy. Myelin structure appeared in the sciatic nerve as early as E14, and the number and thickness of myelin lamellar gradually increased with the development until 12M. Transcriptome analysis was performed to show the expressions of myelin-associated genes and transcriptional factors involved in myelin formation. The genes encoding myelin proteins (Mag, Pmp22, Mpz, Mbp, Cnp and Prx) showed the same expression pattern, peaking at postnatal day 7 (P7) and P28 after birth, whereas the negative regulators of myelination (c-Jun, Tgfb1, Tnc, Cyr61, Ngf, Egr1, Hgf and Bcl11a) showed an opposite expression pattern. In addition, the expression of myelin-associated proteins and transcriptional factors was measured by Western blot and immunofluorescence staining. The protein expressions of MAG, PMP22, MPZ, CNPase and PRX increased from E20 to P14. The key transcriptional factor c-Jun co-localized with the Schwann cells Marker S100ß and decreased after birth, whereas Krox20/Egr2 increased during development. Our data characterized the structure and components of myelin sheath during the early developmental stages, providing insights for further understanding of PNS development.
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Camundongos Endogâmicos C57BL , Bainha de Mielina , Nervo Isquiático , Animais , Bainha de Mielina/metabolismo , Nervo Isquiático/metabolismo , Nervo Isquiático/crescimento & desenvolvimento , Nervo Isquiático/ultraestrutura , Camundongos , Proteínas da Mielina/metabolismo , Proteínas da Mielina/genéticaRESUMO
In this work, a novel and sensitive fluorescence sensing system for alkaline phosphatase (ALP) was constructed using a bifunctional copper metal-organic framework (Cu@MOF) nanozyme, which had excellent oxidase-mimetic activity and fluorescence properties. Owing to the presence of 2-amino-1,4-benzenedicarboxylic acid (1,4-BDC-NH2) ligand, Cu@MOF displays excellent fluorescence performance at 444 nm. Additionally, Cu2+ endows the oxidase-like activity of Cu@MOF, which could trigger p-phenylenediamine (PPD) to be oxidized to a brown product (PPDox) and quench the photoluminescence of Cu@MOF through the inner filtration effect (IFE). As the preferential affinity of ATP for Cu2+, the catalytic activity of Cu@MOF was significantly reduced once ATP was added, thus PPD could not be oxidized and fluorescence was recovered. In the presence of ALP, ATP was hydrolyzed to adenosine and Pi, which allowed Cu@MOF to regain its catalytic activity and continued to catalyze the generation of PPDox. The fluorescence of Cu@MOF was therefore weakened once again. The ALP activity was directly proportional to the degree of decrease in fluorescence intensity. Thus, this novel fluorescence sensing strategy had a linear range of 0.5-60 U/L and the limit of detection was 0.14 U/L. The established sensing method could also be used to for ALP inhibitors screening, and achieved satisfactory results in determining the level of ALP activity in human serum.
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Fosfatase Alcalina , Cobre , Estruturas Metalorgânicas , Espectrometria de Fluorescência , Cobre/química , Fosfatase Alcalina/antagonistas & inibidores , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/química , Fosfatase Alcalina/sangue , Estruturas Metalorgânicas/química , Humanos , Espectrometria de Fluorescência/métodos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fluorescência , Limite de DetecçãoRESUMO
AIM: Our study aims to provide an updated estimate of age- and sex-specific deaths and disability-adjusted life years (DALYs) associated with high body mass index (BMI) from 1990 to 2019 at the global, regional and national levels, and to forecast the global burden of disease attributed to high BMI from 2020 to 2035. METHODS: We used the data for the number of deaths, DALYs, age-standardized rate (per 100 000 population), percentage change and population attributable fraction from the Global Burden of Disease Study 2019 (GBD 2019) to examine the disease burden attributable to high BMI. We further applied an autoregressive integrated moving average (ARIMA) model to predict the disease burden for the period 2020-2035. RESULTS: From 1990 to 2019, the deaths and DALYs attributable to high BMI increased by 148% and 155.86% for men, and by 111.67% and 121.78% for women, respectively. In 2019, high BMI directly accounted for 8.52% [95% uncertainty intervals (UI) 0.05, 0.12] of all-cause deaths and 5.89% (95% UI 0.04, 0.08) of global DALYs. The highest death rates were observed in men aged 65-69 and women aged 75-79. The highest DALY rates were observed in the age group of 60-64 for both sexes. In 2019, the highest age-standardized deaths and DALY rates were observed in the Central Asia region [163.15 (95% UI 107.72, 223.58) per 100 000 people] and the Oceania region [4643.33 (95% UI 2835.66, 6902.6) per 100 000 people], respectively. Fiji [319.08 (95% UI 213.77, 444.96) per 100 000 people] and Kiribati [10 000.58 (95% UI 6266.55, 14159.2) per 100 000 people] had the highest age-standardized deaths and DALY rates, respectively. In 2019, the highest age-standardized rates of high BMI-related deaths and DALYs were observed in the middle-high socio-demographic index quintile and in the middle socio-demographic index quintile. The age-standardized deaths and DALY rates attributable to high BMI are projected to increase in both sexes from 2020 to 2035. The death rates are projected to rise from 62.79 to 64.31 per 100 000 people, while the DALY rates are projected to rise from 1946 to 2099.54 per 100 000 people. CONCLUSIONS: High BMIs significantly contribute to the global disease burden. The projected rise in deaths and DALY rates attributable to high BMI by 2035 highlights the critical need to address the impact of obesity on public health. Our study provides policymakers with up-to-date and comprehensive information.
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Índice de Massa Corporal , Carga Global da Doença , Obesidade , Humanos , Masculino , Carga Global da Doença/tendências , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Obesidade/epidemiologia , Obesidade/mortalidade , Anos de Vida Ajustados por Deficiência/tendências , Saúde Global/estatística & dados numéricos , Previsões , Idoso de 80 Anos ou mais , Adulto Jovem , Anos de Vida Ajustados por Qualidade de Vida , Causas de Morte , Adolescente , Mortalidade/tendências , Sobrepeso/epidemiologia , Sobrepeso/mortalidadeRESUMO
Trichosanthes kirilowii (T. kirilowii) is a valuable plant used for both medicinal and edible purposes. It belongs to the Cucurbitaceae family. However, its phylogenetic position and relatives have been difficult to accurately determine due to the lack of mitochondrial genomic information. This limitation has been an obstacle to the potential applications of T. kirilowii in various fields. To address this issue, Illumina and Nanopore HiFi sequencing were used to assemble the mitogenome of T. kirilowii into two circular molecules with sizes of 245,700 bp and 107,049 bp, forming a unique multi-branched structure. The mitogenome contains 61 genes, including 38 protein-coding genes (PCGs), 20 tRNAs, and three rRNAs. Within the 38 PCGs of the T. kirilowii mitochondrial genome, 518 potential RNA editing sites were identified. The study also revealed the presence of 15 homologous fragments that span both the chloroplast and mitochondrial genomes. The phylogenetic analysis strongly supports that T. kirilowii belongs to the Cucurbitaceae family and is closely related to Luffa. Collinearity analysis of five Cucurbitaceae mitogenomes shows a high degree of structural variability. Interestingly, four genes, namely atp1, ccmFC, ccmFN, and matR, played significant roles in the evolution of T. kirilowii through selection pressure analysis. The comparative analysis of the T. kirilowii mitogenome not only sheds light on its functional and structural features but also provides essential information for genetic studies of the genus of Cucurbitaceae.
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Genoma Mitocondrial , Filogenia , Plantas Medicinais , Trichosanthes , Trichosanthes/genética , Trichosanthes/química , Genoma Mitocondrial/genética , Plantas Medicinais/genética , Evolução Molecular , Medicina Tradicional ChinesaRESUMO
Our understanding of how visual cortex neural processes mature during infancy and toddlerhood is limited. Using magnetoencephalography (MEG), the present study investigated the development of visual evoked responses (VERs) in both cross-sectional and longitudinal samples of infants and toddlers 2 months to 3 years. Brain space analyses focused on N1m and P1m latency, as well as the N1m-to-P1m amplitude. Associations between VER measures and developmental quotient (DQ) scores in the cognitive/visual and fine motor domains were also examined. Results showed a nonlinear decrease in N1m and P1m latency as a function of age, characterized by rapid changes followed by slower progression, with the N1m latency plateauing at 6-7 months and the P1m latency plateauing at 8-9 months. The N1m-to-P1m amplitude also exhibited a non-linear decrease, with strong responses observed in younger infants (â¼2-3 months) and then a gradual decline. Associations between N1m and P1m latency and fine motor DQ scores were observed, suggesting that infants with faster visual processing may be better equipped to perform fine motor tasks. The present findings advance our understanding of the maturation of the infant visual system and highlight the relationship between the maturation of visual system and fine motor skills. Highlights: The infant N1m and P1m latency shows a nonlinear decrease.N1m latency decreases precede P1m latency decreases.N1m-to-P1m amplitude shows a nonlinear decrease, with stronger responses in younger than older infants.N1m and P1m latency are associated with fine motor DQ.
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In this work, a novel double-chamber system (PFC-Fenton), combined photocatalytic fuel cell (PFC) with Fenton, was constructed for tetracycline hydrochloride (TCH) and hexavalent chromium (Cr(VI)) removal and electricity production. Therein, Zn5(OH)6(CO3)2/Fe2O3/BiVO4/fluorine-doped SnO2 (ZIO/BiVO4/FTO) and carboxylated carbon nanotubes/polypyrrole/graphite felt (CCNTs/Ppy/GF) were served as photoanode and cathode, respectively. Under light irradiation, the removal efficiencies of TCH and Cr(VI) with the addition of H2O2 (2 mL) could reach 93.1% and 80.4%, respectively. Moreover, the first-order kinetic constants (7.37 × 10-3 min-1 of TCH and 3.94 × 10-3 min-1 of Cr(VI)) were 5.26 and 5.57 times as much as the absence of H2O2. Simultaneously, the maximum power density could be obtained 0.022 mW/cm2 at a current density of 0.353 mA/cm2. Therein, the main contribution of TCH degradation was ·OH and holes in anode chamber. The synergistic effect of photoelectrons, generated ·O2-, and H2O2 played a crucial role in the reduction of Cr(VI) in cathode chamber. The high-performance liquid chromatography-mass spectrometry indicated that TCH could be partially mineralized into CO2 and H2O. X-ray photoelectron spectroscope and X-ray absorption near-edge structure spectra showed that Cr(VI) could be reduced to Cr(III). After 5 times of cycling, the removal efficiencies of TCH and Cr(VI) were still greater than 70%, indicating the remarkable stability of the PFC-Fenton system. Overall, this system could remove TCH/Cr(VI) and generate power simultaneously without iron sludge formation, demonstrating a promising method to further develop PFC-Fenton technology.
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Cromo , Peróxido de Hidrogênio , Tetraciclina , Cromo/química , Tetraciclina/química , Peróxido de Hidrogênio/química , Catálise , Ferro/químicaRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third most malignant tumor in the world. 5-fluorouracil (5FU) -based chemotherapy is the first-line chemotherapy scheme for CRC, whereas acquired drug resistance poses a huge obstacle to curing CRC patients and the mechanism is still obscure. Therefore, identification of genes associated with 5FU chemotherapy and seeking second-line treatment are necessary means to improve survival and prognosis of patients with CRC. METHODS: The Cancer Therapeutics Response Portal (CTRP) database and Genomics of Drug Sensitivity in Cancer (GDSC) database were used to identify CRC-related genes and potential second-line therapies for 5-FU-resistant CRC. The single-cell RNA sequencing data for CRC tissues were obtained from a GEO dataset. The relationship between ITGA2 and 5-FU-resistant was investigated in vitro and in vivo models. RESULTS: ACOX1 and ITGA2 were identified as risk biomarkers associated with 5-FU-resistance. We developed a risk signature, consisting of ACOX1 and ITGA2, that was able to distinguish well between 5-FU-resistance and 5-FU-sensitive. The single-cell sequencing data showed that ITGA2 was mainly enriched in malignant cells. ITGA2 was negatively correlated with IC50 values of most small molecule inhibitors, of which selumetinib had the highest negative correlation. Finally, knocking down ITGA2 can make 5-FU-resistant CRC cells sensitive to 5-FU and combining with selumetinib can improve the therapeutic effect of 5-FU resistant cells. CONCLUSION: In summary, our findings demonstrated the critical role of ITGA2 in enhancing chemotherapy resistance in CRC cells and suggested that selumetinib can restore the sensitivity of chemotherapy-resistant CRC cells to 5-FU by inhibiting ITGA2 expression.
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Benzimidazóis , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Fluoruracila , Integrina alfa2 , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/uso terapêutico , Fluoruracila/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Integrina alfa2/genética , Integrina alfa2/metabolismo , Animais , Benzimidazóis/uso terapêutico , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Severe combined immunodeficiency (SCID) is the most fatal form of inherited primary immunodeficiency disease. Known molecular defect mutations occur in most children with SCID. METHODS: Herein, we report Adenosine Deaminase-SCID (ADA-SCID) using whole-exome sequencing (WES), explore exome mutational landscape and significance for 17 SCID samples, and verify the mutated exon genes using the Gene Expression Omnibus (GEO) datasets. A total of 250 patients, who were hospitalized at the Neonatal Intensive Care Unit (NICU) of The Seventh Medical Center of the PLA General Hospital for 3 years (from 2017 to 2020), were screened for SCID. We collected mutated genes from the WES data of 17 SCID children. GSE609 and GSE99176 cohorts were used to identify the expressions of mutated exon genes and molecular features in SCID. Gene set variation analyses (GSVA) and correlation analyses were performed. RESULTS: The detection rate with approximately 6.8 % (17/250) of SCID is high in the NICU. A total of 16 genes were identified among 17 SCID samples, of which the Top 2 genes (MUC6 and RP11-683L23.1) might be crucial in the progression of SCID with 94 % mutation frequency. Furthermore, CNN2 and SCGB1C1 had significant co-mutations and may cooperate to affect SCID development. Importantly, the phylogenetic tree classification results of 17 SCID samples are more correlated to MUC6 with the most significant mutations. Expression profiles of seven mutated genes and five mutated genes were documented in GSE609 and GSE99176 cohorts based on microarray, respectively. Several immune-related pathways were significantly enriched, and Foxd4, differing from the other four mutated genes, was inversely correlated with the GSVA-enriched pathway. CONCLUSION: Due to its high detection rate (6.8%) and fatality rate (100%), the inclusion of SCID in newborn screening (NBS) is urgent for children in China. The WES successfully identified several common exonic variants (e.g., MUC6) and depicted the feature of mutations and evolution, which will help develop new diagnostic methods for SCID.
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Sequenciamento do Exoma , Triagem Neonatal , Imunodeficiência Combinada Severa , Humanos , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/diagnóstico , Recém-Nascido , China , Masculino , Feminino , Éxons/genética , Mutação , Adenosina Desaminase/genéticaRESUMO
Background: Evidence suggests that type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD), sharing similar pathophysiological traits like impaired insulin signaling. Objective: To test the association between plasma insulin and cerebrospinal fluid (CSF) AD pathology. Methods: A total of 304 participants were included in the Alzheimer's Disease Neuroimaging Initiative, assessing plasma insulin and CSF AD pathology. We explored the cross-sectional and longitudinal associations between plasma insulin and AD pathology and compared their associations across different AD clinical and pathological stages. Results: In the non-demented group, amyloid-ß (Aß)+ participants (e.g., as reflected by CSF Aß42) exhibited significantly lower plasma insulin levels compared to non-demented Aß-participants (pâ<â0.001). This reduction in plasma insulin was more evident in the A+T+ group (as shown by CSF Aß42 and pTau181 levels) when compared to the A-T- group within the non-dementia group (pâ=â0.002). Additionally, higher plasma insulin levels were consistently associated with more normal CSF Aß42 levels (pâ<â0.001) across all participants. This association was particularly significant in the Aß-group (pâ=â0.002) and among non-demented individuals (pâ<â0.001). Notably, baseline plasma insulin was significantly correlated with longitudinal changes in CSF Aß42 (pâ=â0.006), whereas baseline CSF Aß42 did not show a similar correlation with changes in plasma insulin over time. Conclusions: These findings suggest an association between plasma insulin and early Aß pathology in the early stages of AD, indicating that plasma insulin may be a potential predictor of changes in early Aß pathology.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Insulina , Fragmentos de Peptídeos , Proteínas tau , Humanos , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Masculino , Feminino , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Insulina/sangue , Idoso , Estudos Transversais , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano , Estudos Longitudinais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Idoso de 80 Anos ou mais , Pessoa de Meia-IdadeRESUMO
Depression and Alzheimer's disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression-AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients' distinct needs.
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In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (P2m measured using magnetoencephalography, MEG) in a cross-sectional (2 to 24 months) as well as longitudinal cohort (2 to 29 months) of typically developing infants and toddlers. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. After removing the variance associated with age in both P2m latency and auditory radiation diffusion measures, auditory radiation still accounted for significant variance in P2m latency. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for a contribution of auditory radiation white matter to rapid cortical auditory encoding processes in infants.
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The highly reversible plating/stripping of Zn is plagued by dendrite growth and side reactions on metallic Zn anodes, retarding the commercial application of aqueous Zn-ion batteries. Herein, a distinctive nano dual-phase diamond (NDPD) comprised of an amorphous-crystalline heterostructure is developed to regulate Zn deposition and mechanically block dendrite growth. The rich amorphous-crystalline heterointerfaces in the NDPD endow modified Zn anodes with enhanced Zn affinity and result in homogeneous nucleation. In addition, the unparalleled hardness of the NDPD effectively overcomes the high growth stress of dendrites and mechanically impedes their proliferation. Moreover, the hydrophobic surfaces of the NDPD facilitate the desolvation of hydrate Zn2+ and prevent water-mediated side reactions. Consequently, the Zn@NDPD presents an ultrastable lifespan exceeding 3200 h at 5 mA cm-2 and 1 mAh cm-2. The practical application potential of Zn@NDPD is further demonstrated in full cells. This work exhibits the great significance of a chemical-mechanical synergistic anode modification strategy in constructing high-performance aqueous Zn-ion batteries.
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With the increase of hexavalent Cr(VI) wastewater discharged from industrial production, it seriously pollutes water bodies and poses a risk to human health. Adsorption is used as an effective means to treat Cr(VI), but its effectiveness is affected by pH, and the adsorption performance decreases when acidity is strong. Furthermore, research on the mechanism of Cr(VI) adsorption using DFT calculations needs to be developed. This study focuses on the development of magnetically responsive core-shell nano-ion imprinted materials (Fe3O4@GO@IIP) through magnetic separation and surface imprinting techniques. Characterization techniques including FT-IR, XRD, and EDS confirmed the core-shell nanostructure of Fe3O4@GO@IIP. Batch adsorption experiments and model simulations demonstrated the exceptional adsorption capacity of Fe3O4@GO@IIP for Cr(VI) in strongly acidic solutions (pH = 1), reaching a maximum of 89.18 mg/g. The adsorption mechanism was elucidated through XPS and DFT calculations, revealing that Fe3O4@GO@IIP operates through electrostatic interactions and chemical adsorption, with charge transfer dynamics quantified during the process. This research provides new insights for addressing Cr(VI) treatment in highly acidic environments.
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Jujube (Ziziphus jujuba) exhibits a rich diversity in fruit shape, with natural occurrences of gourd-like, flattened, and other special shapes. Despite the ongoing research into fruit shape, studies integrating elliptical Fourier descriptors (EFDs) with both Short Time-series Expression Miner (STEM) and weighted gene co-expression network analysis (WGCNA) for gene discovery remain scarce. In this study, six cultivars of jujube fruits with distinct shapes were selected, and samples were collected from the fruit set period to the white mature stage across five time points for shape analysis and transcriptome studies. By combining EFDs with WGCNA and STEM, the study aimed to identify the critical periods and key genes involved in the formation of jujube fruit shape. The findings indicated that the D25 (25 days after flowering) is crucial for the development of jujube fruit shape. Moreover, ZjAGL80, ZjABI3, and eight other genes have been implicated to regulate the shape development of jujubes at different periods of fruit development, through seed development and fruit development pathway. In this research, EFDs were employed to precisely delineate the shape of jujube fruits. This approach, in conjunction with transcriptome, enhanced the precision of gene identification, and offered an innovative methodology for fruit shape analysis. This integration facilitates the advancement of research into the morphological characteristics of plant fruits, underpinning the development of a refined framework for the genetic underpinnings of fruit shape variation.
RESUMO
Temperature is one of the seven fundamental physical quantities. The ability to measure temperatures approaching absolute zero has driven numerous advances in low-temperature physics and quantum physics. Currently, millikelvin temperatures and below are measured through the characterization of a certain thermal state of the system as there is no traditional thermometer capable of measuring temperatures at such low levels. In this study, we develop a kind of diamond with sp2-sp3 composite phase to tackle this problem. The synthesized composite phase diamond (CPD) exhibits a negative temperature coefficient, providing an excellent fit across a broad temperature range, and reaching a temperature measurement limit of 1 mK. Additionally, the CPD demonstrates low magnetic field sensitivity and excellent thermal stability, and can be fabricated into probes down to 1 micron in diameter, making it a promising candidate for the manufacture of next-generation cryogenic temperature sensors. This development is significant for the low-temperature physics researches, and can help facilitate the transition of quantum computing, quantum simulation, and other related technologies from research to practical applications.