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1.
J Colloid Interface Sci ; 674: 841-851, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38955015

RESUMO

Due to the complexity of regulatory networks of disease-related biomarkers, developing simple, sensitive, and accurate methods has remained challenging for precise diagnosis. Herein, an "AND" logic gates DNA molecular machine (LGDM) was constructed, which was powered by the catalytic hairpin assembly (CHA). It was coupled with dual-emission CdTe quantum dots (QDs)-based cation exchange reaction (CER) for label-free, sensitive, and ratiometric fluorescence detection of APE1 and miRNA biomarkers. Benefiting from synergistic signal amplification strategies and a ratiometric fluorometric output mode, this LGDM enables accurate logic computing with robust and significant output signals from weak inputs. It offers improved sensitivity and selectivity even in cell extracts. Using dual-emission spectra CdTe QDs, with a ratiometric signal output mode, ensured good stability and effectively prevented false-positive signals from intrinsic biological interferences compared to the approach relying on a single signal output mode, which enabled the LGDM to achieve rapid, efficient, and accurate natural drug screening against APE1 inhibitors in vitro and cells. The developed method provides impetus to streamline research related to miRNA and APE1, offering significant promise for widespread application in drug development and clinical analysis.

2.
Nat Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956195

RESUMO

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

3.
Mol Plant ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956872

RESUMO

The discovery of a wild abortive-type cytoplasmic male sterile line and the breeding of its restorer line have led to the commercialization of three-line hybrid rice, which has contributed greatly to global food security. However, the molecular mechanisms underlying fertility abortion and the restoration of wild abortive-type cytoplasmic male sterile lines largely remain elusive. In this study, we cloned a restorer gene, Rf20, following a genome-wide association study analysis of the core parent lines of three-line hybrid rice. We found that Rf20 was present in all core parental lines, but different haplotypes and structural variants of its gene resulted in differences in Rf20 expression levels between sterile and restored lines. Rf20 could restore fertility in the wild abortive-type cytoplasmic male sterile line and was found to be responsible for fertility restoration in some cytoplasmic male sterile lines under high temperature. In addition, we found that Rf20 encodes a pentatricopeptide repeat protein that competes with WA352 for binding with COX11. This interaction enhances COX11's function as a scavenger of reactive oxygen species, which in turn restores pollen fertility. In this study, a new model of pentatricopeptide repeat proteins involved in the fertility recovery of cytoplasmic male sterile lines was proposed, which provides an important theoretical basis for the breeding of strong restorer lines and for overcoming high-temperature fertility recovery of some three-line sterile lines.

4.
J Leukoc Biol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38952265

RESUMO

Aryl hydrocarbon receptor (AhR) is a key transcription factor that modulates the differentiation of T helper 17 (Th17) cells. How AhR is regulated at the post-translational level in Th17 cells remains largely unclear. Here we identify USP21 as a newly defined deubiquitinase of AhR. We demonstrate that USP21 interacts with and stabilizes AhR by removing the K48-linked polyubiquitin chains from AhR. Interestingly, USP21 inhibits the transcriptional activity of AhR in a deubiquitinating-dependent manner. USP21 deubiquitinates AhR at the K432 residue, and the maintenance of ubiquitination on this site is required for the intact transcriptional activity of AhR. Moreover, the deficiency of USP21 promotes the differentiation of Th17 cells both in vitro and in vivo. Consistently, adoptive transfer of USP21 deficient naïve CD4+ T cells elicits more severe colitis in Rag1-/- recipients. Therefore, our study reveals a novel mechanism in which USP21 deubiquitinates AhR and negatively regulates the differentiation of Th17 cells.

5.
Ecol Evol ; 14(7): e11641, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957699

RESUMO

Although brood parasitism has been well documented among bird species, interspecific alloparenting, which is parenting behavior of adult individuals of one species toward the progeny of another species, is increasingly being reported. However, compared with the many reports of interspecific alloparenting behavior in North America and Europe, this phenomenon is less well known in China, with only two prior cases of interspecific alloparenting behavior in birds having been recorded. On June 23, 2022, we observed an instance of interspecific alloparental care provided by a mountain bulbul (Ixos mcclellandii) towards silver-eared mesia (Leiothrix argentauris) nestlings in Caihu Village, Jingdong County, Yunnan Province, southwestern China. We recorded 19.5 h of footage during the period in which the mountain bulbul provided care for the nestlings with the aim of documenting detailed observations of interspecific alloparenting to contribute to our overall understanding of this behavior. The alloparenting behavior of the mountain bulbul lasted for at least 5 days. During this period, both silver-eared mesia parents fed their nestlings 157 times and removed their nestlings' fecal sacs 5 times, while the mountain bulbul fed the nestlings 30 times and removed the nestlings' fecal sacs 4 times. In addition, the male silver-eared mesia parent chased the mountain bulbul away during nestling feeding. As there was no life history information for the mountain bulbul at that time, we were unable to directly determine why it exhibited interspecific alloparental care. Regardless of the reason for the mountain bulbul's behavior, these findings provide valuable information for future studies on the reproductive ecology of these two bird species.

6.
Front Microbiol ; 15: 1418959, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962124

RESUMO

In recent years, porcine diarrhea-associated viruses have caused significant economic losses globally. These viruses present similar clinical symptoms, such as watery diarrhea, dehydration, and vomiting. Co-infections with porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are common. For the rapid and on-site preliminary diagnosis on the pig farms, this study aimed to develop a colloidal gold immunochromatography assay (GICA) strip for the detection of PEDV and TGEV simultaneously. The GICA kit showed that there was no cross-reactivity with the other five common porcine viruses. With visual observation, the lower limits were approximately 104 TCID50/mL and 104 TCID50/mL for PEDV and TGEV, respectively. The GICA strip could be stored at 4°C or 25°C for 12 months without affecting its efficacy. To validate the GICA strip, 121 clinical samples were tested. The positive rates of PEDV and TGEV were 42.9 and 9.9%, respectively, and the co-infection rate of the two viruses was 5.8% based on the duplex GICA strip. Thus, the established GICA strip is a rapid, specific, and stable tool for on-site preliminary diagnosis of PEDV- and TGEV-associated diarrhea.

7.
J Med Genet ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38964834

RESUMO

BACKGROUND: IFIH1 variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether IFIH1 variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive. METHODS: Trio-based whole-exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype-phenotype associations. RESULTS: Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure-free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C-terminal domain led to seizures with normal neurodevelopment, suggesting a sub-molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype-phenotype correlation. IFIH1 is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients. CONCLUSIONS: IFIH1 variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub-molecular implication and genotype-phenotype association help explain phenotype variations of IFIH1 variants.

8.
BMC Public Health ; 24(1): 1780, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965513

RESUMO

BACKGROUND: Nosocomial infections with heavy disease burden are becoming a major threat to the health care system around the world. Through long-term, systematic, continuous data collection and analysis, Nosocomial infection surveillance (NIS) systems are constructed in each hospital; while these data are only used as real-time surveillance but fail to realize the prediction and early warning function. Study is to screen effective predictors from the routine NIS data, through integrating the multiple risk factors and Machine learning (ML) methods, and eventually realize the trend prediction and risk threshold of Incidence of Nosocomial infection (INI). METHODS: We selected two representative hospitals in southern and northern China, and collected NIS data from 2014 to 2021. Thirty-nine factors including hospital operation volume, nosocomial infection, antibacterial drug use and outdoor temperature data, etc. Five ML methods were used to fit the INI prediction model respectively, and to evaluate and compare their performance. RESULTS: Compared with other models, Random Forest showed the best performance (5-fold AUC = 0.983) in both hospitals, followed by Support Vector Machine. Among all the factors, 12 indicators were significantly different between high-risk and low-risk groups for INI (P < 0.05). After screening the effective predictors through importance analysis, prediction model of the time trend was successfully constructed (R2 = 0.473 and 0.780, BIC = -1.537 and -0.731). CONCLUSIONS: The number of surgeries, antibiotics use density, critical disease rate and unreasonable prescription rate and other key indicators could be fitted to be the threshold predictions of INI and quantitative early warning.


Assuntos
Infecção Hospitalar , Aprendizado de Máquina , Humanos , Infecção Hospitalar/epidemiologia , Medição de Risco/métodos , China/epidemiologia , Fatores de Risco , Incidência
9.
Behav Brain Funct ; 20(1): 18, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965529

RESUMO

BACKGROUND: Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated. METHODS: In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests. RESULTS: We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects. CONCLUSIONS: This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.


Assuntos
Ansiedade , Grelina , Núcleo Accumbens , Ratos Sprague-Dawley , Receptores de Grelina , Transdução de Sinais , Estresse Psicológico , Animais , Grelina/metabolismo , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Masculino , Ansiedade/metabolismo , Ansiedade/psicologia , Receptores de Grelina/metabolismo , Receptores de Grelina/genética , Ratos , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Comportamento Animal/efeitos dos fármacos
10.
Plast Reconstr Surg ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38967627

RESUMO

BACKGROUND: Survival and regeneration mechanisms of large (>250 mL) fat grafts remain incompletely understood. In fat grafts from volunteers with megavolume fat transfer breast augmentation, neovascularization and inflammatory cell infiltration decreased within 7 days according to histological analysis. We further investigated this phenomenon using a nude mouse model. METHODS: To simulate clinical contexts, chambers containing 1 mL human fat were implanted into nude mice. Chambers allowed selective transfer of tissue fluid from recipient nude mice into chambers, but not capillaries or macrophages. Seven days later, fat was removed from the chamber and reimplanted into a new nude mouse in the open-chambered fat group (OCFG, n=45). Adipose samples from volunteers and explanted grafts from OCFG were subjected to histological analyses. Graft weight, vascularization, and immune response were also compared between the OCFG and conventional direct fat grafting (control group (CG)). RESULTS: Percent tissue integrity, percent fibrosis, adipocyte viability, and neovascularization did not significantly differ between volunteer samples and OCFG grafts at day 7. On day 90, OCFG retention rate was decreased relative to CG and the fibrosis area was larger in the OCFG than in the CG. However, the macrophage and capillary counts were lower in the OCFG group relative to CG at days 7 and 14 after transplantation. CONCLUSIONS: The present study provides histological analyses of megavolume fat grafts sampled from clinical breast augmentation tissues and a xenograft nude mouse model. However, these preliminary results in a small clinical cohort should be further assessed in large allogeneic animal models.

11.
Environ Res ; 259: 119523, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960352

RESUMO

Strengthening rhizosphere effects to enhance pollutant removal is a hotspot of constructed wetlands (CWs) research in recent years, and improving the root traits and metabolic capacity of macrophytes is crucial for strengthening rhizosphere effects. In the field experiment, two types of subsurface flow (SSF) CWs (CW10 and CW20, with substrate depths of 10 and 20 cm, respectively) under the vertical spatial stress of roots (VSSR) and two types of non-VSSR SSF CWs (CW40 and CW60) were adopted with Typha orientalis as cultivated plants to investigate the variability of root development, metabolism, and pollutant removal at different substrate depths. VSSR induced substantial redundant root development, which significantly increased root-shoot ratio, fine and lateral root biomass, root porosity, and root activity, with lateral and fine root biomass of CW20 reaching 409.17 and 237.42 g/m2, respectively, which were 3.18 and 5.28 times those of CW60. The radical oxygen loss (ROL) and dissolved organic carbon (DOC) levels of CW20 single plant were 1.36 and 4.57 times higher than those of CW60, respectively, and more types of root exudates were determined (e.g., aldehydes, ketones and amides). More aerobic heterotrophs (e.g., Massilia, Planomicrobium), nitrification bacteria (e.g., Ellin6067, Nitrospira), aerobic denitrification bacteria (e.g., Bacillu, Chryseobacterium, Pseudomonas) and denitrification phosphorus accumulating organisms (e.g., Flavobacterium) were enriched in the rhizosphere of CW20. This changed the main transformation pathways of pollutants and enhanced the removal of pollutants, with the COD, TN and TP average removal rates of CW20 increasing by 9.99%, 13.28% and 8.92%, respectively, compared with CW60. The ideotype root system architecture CW (RSACW; CW20) constructed in this study, which consists of a large number of fine and lateral roots, can stimulate more efficient rhizosphere effects stably and continuously.

12.
Br J Surg ; 111(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960881

RESUMO

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).


Oesophageal cancer often requires complex surgery. Recently, minimally invasive techniques like robot- and video-assisted surgery have emerged to improve outcomes. This study compared robot- and video-assisted surgery for oesophageal cancer, focusing on removing lymph nodes near a critical nerve. Patients with a specific oesophageal cancer type were assigned randomly to robot- or video-assisted surgery at three Asian hospitals. Robot-assisted surgery had a higher success rate in removing lymph nodes near the important nerve without permanent damage. It also had shorter operating times, more lymph nodes removed, and faster drain removal after surgery. In summary, for oesophageal cancer surgery, the robotic approach may provide better lymph node removal and less nerve injury than video-assisted techniques.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Excisão de Linfonodo , Procedimentos Cirúrgicos Robóticos , Cirurgia Torácica Vídeoassistida , Humanos , Esofagectomia/métodos , Esofagectomia/efeitos adversos , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Feminino , Pessoa de Meia-Idade , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Neoplasias Esofágicas/cirurgia , Excisão de Linfonodo/métodos , Excisão de Linfonodo/efeitos adversos , Idoso , Carcinoma de Células Escamosas do Esôfago/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Nervo Laríngeo Recorrente/cirurgia , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Adulto
13.
BMC Med Genomics ; 17(1): 180, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970023

RESUMO

BACKGROUND: There is an association between migraine and dementia, however, their causal relationship remains unclear. This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationship between migraine and dementia and its subtypes: Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). METHODS: Summary-level statistics data were obtained from publicly available genome-wide association studies (GWAS) for both migraine and five types of dementia. Single nucleotide polymorphisms (SNPs) associated with migraine and each dementia subtype were selected. MR analysis was conducted using inverse variance weighting (IVW) and weighted median (WM) methods. Sensitivity analyses included Cochran's Q test, MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, the intercept of MR-Egger, and leave-one-out analysis. RESULTS: Migraine showed a significant causal relationship with AD and VaD, whereas no causal relationship was observed with all-cause dementia, FTD, or DLB. Migraine may be a potential risk factor for AD (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 0.02-0.14; P = 0.007), while VaD may be a potential risk factor for migraine (OR: 1.04; 95% CI: 0.02-0.06; P = 7.760E-5). Sensitivity analyses demonstrated the robustness of our findings. CONCLUSION: Our study suggest that migraine may have potential causal relationships with AD and VaD. Migraine may be a risk factor for AD, and VaD may be a risk factor for migraine. Our study contributes to unraveling the comprehensive genetic associations between migraine and various types of dementia, and our findings will enhance the academic understanding of the comorbidity between migraine and dementia.


Assuntos
Demência , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos de Enxaqueca , Polimorfismo de Nucleotídeo Único , Humanos , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/complicações , Demência/genética , Predisposição Genética para Doença
14.
Clin Chim Acta ; 562: 119850, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977167

RESUMO

OBJECTIVE: The receptor-interacting protein kinase 3 (RIPK3) is a pivotal component for triggering necroptosis. We intended to investigate predictive effects of serum RIPK3 levels on early hematoma growth (EHG) and poor neurological outcome after acute intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study, 183 ICH patients and 100 controls were enrolled for measuring serum RIPK3 levels. National Institutes of Health Stroke Scale (NIHSS) and hematoma volume were recorded as the severity indicators. EHG and poststroke 6-month unfavorable outcome (modified Rankin Scale scores of 3-6) were registered as the two prognostic parameters. Multivariate analyses were implemented to discern relevance of serum RIPK3 to ICH severity and prognosis. RESULTS: Serum RIPK3 levels of patients, which were dramatically higher than those of controls, were independently related to NIHSS scores, hematoma volume, EHG, 6-month mRS scores and unfavorable outcome. Risks of EHG and unfavorable outcome were linearly pertinent to and efficiently discriminated by RIPK3 levels under restricted cubic spline and receiver operating characteristic curve respectively. RIPK3 levels nonsignificantly interacted with age, gender, hypertension, etc. Predictive ability of RIPK3 levels resembled those of NIHSS scores and hematoma volume. The prediction models, in which serum RIPK3, NIHSS scores and hematoma volume were integrated, were visually displayed via nomograms. The models' predictive capabilities substantially surpassed that of serum RIPK3, NIHSS scores and hematoma volumes alone. The models kept stable under calibration curve. CONCLUSION: A profound increase of serum RIPK3 levels after ICH is tightly relevant to severity, EHG and poor neurological outcomes, assuming that serum RIPK3 may emerge as a valuable prognostic predictor of ICH.

15.
Sci Adv ; 10(28): eadn2829, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38985865

RESUMO

Piezoelectric actuators have been extensively utilized as micro-displacement devices because of their advantages of large output displacement, high sensitivity, and immunity to electromagnetic interference. Here, we propose a straightforward approach to design <110>-oriented defect dipoles by introducing A-site vacancies and oxygen vacancies in (K0.48Na0.52)0.99NbO2.995 ceramics. As a result, we achieve ultrahigh electrostrains of 0.7% at 20 kV cm-1 (with an effective piezoelectric strain coefficient d33* = 3500 pm V-1), outperforming the performance of existing piezoelectric ceramics at the same driving field. The exceptional electrostrain is primarily attributed to the large stretching of defect dipoles when subjected to an applied electric field, a phenomenon that has been experimentally confirmed. Moreover, the strong interaction between these defect dipoles and <110> spontaneous polarizations plays a critical role in minimizing hysteresis and ensuring excellent fatigue resistance. Our findings present a practical and effective strategy for developing high-performance piezoelectric materials tailored for advanced actuator applications.

16.
Neurology ; 103(3): e209658, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-38991203

RESUMO

BACKGROUND AND OBJECTIVES: Posterior cerebral artery involvement (PCAi) has been identified as an important factor related to poor prognosis in moyamoya disease (MMD). This study summarized the characteristics of children with MMD and PCAi, clarified the clinical course, identified prognostic predictors, and investigated the long-term effect of encephaloduroarteriosynangiosis for posterior circulation (EDAS-p). METHODS: We retrospectively reviewed all our pediatric MMD cases with follow-up angiograms from November 2003 to December 2016. PCAi was classified as early-onset at initial diagnosis and delayed-onset after anterior circulation revascularization. Multivariable data including clinical features, radiographic findings, and surgical outcomes were analyzed. RESULTS: Among 570 children with MMD, 246 (43.2%) had PCAi, with 176 (30.9%) classified as early-onset PCAi. During a median follow-up period of 10 years, 17.8% (70/394) of patients without initial PCAi developed delayed-onset PCAi. The median time to detection of a new PCA lesion was 15.5 (range 7-110) months from initial diagnosis, with a median age of 10.5 (3-22). Younger age at onset, familial occurrence, advanced Suzuki stages, and preoperative infarctions were predictors of delayed-onset PCAi. EDAS-p was performed on 294 hemispheres of 195 patients with PCAi. Stroke-free survival was significantly higher in the EDAS-p group than in the non-EDAS-p group (99.0% vs 90.2%; p < 0.001 [Breslow test]; p = 0.001 [log-rank test]; median follow-up: 101 months). DISCUSSION: PCAi is not uncommon in children with MMD, underscoring the need for long-term close clinical monitoring, especially in patients with high-risk factors for PCA progression. EDAS-p may be a safe and effective procedure for preventing subsequent stroke in children with MMD and PCAi.


Assuntos
Doença de Moyamoya , Artéria Cerebral Posterior , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/complicações , Doença de Moyamoya/cirurgia , Doença de Moyamoya/terapia , Masculino , Criança , Feminino , Estudos Retrospectivos , Pré-Escolar , Adolescente , Artéria Cerebral Posterior/diagnóstico por imagem , Resultado do Tratamento , Revascularização Cerebral/métodos , Seguimentos , Adulto Jovem , Lactente , Prognóstico
17.
Food Chem ; 458: 140287, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38991240

RESUMO

Procyanidin B2 (Pac B2) has attracted much attention due to its strong antioxidant activity, but poor in vivo stability limits its wide application in food and medicine. In this paper, composite nanoparticles (NPs) were constructed using abietic acid (AA) as a carrier, which significantly enhanced Pac B2 stability. A spherical morphology and average diameter of 396.05 nm were observed in AA-Pac B2 NPs synthesized by solvent co-precipitation. Pac B2 encapsulation was 11.28 %, and thermal stability is improved. Infrared, Ultraviolet spectrum, and MD (molecular dynamics) spectroscopy revealed hydrogen bonding and hydrophobic interaction between AA and Pac B2. For up to 2 h at 37 °C, Pac B2 can be sustainably released in simulated gastric and intestinal fluids. In vitro, AA-Pac B2 NPs at the same concentration exhibited higher bioavailability and uptake efficiency than free Pac B2. The data demonstrate the potential of AA NPs for improving polyphenol thermal stability and bioavailability.

18.
Org Lett ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995672

RESUMO

Selective dehydrogenative C-H silylation is one of the most powerful tools to synthesize silacycles. Herein, we developed Ru-catalyzed sequential hydrosilylation/C-H silylation of allyl-indoles and dehydrogenative O-H/C-H silylation of pyrrole phenols. Both six-membered indole silacycles and pyrrole silyl ether cycles were successfully synthesized with good functional group tolerance. Furthermore, the RuHCl(CO)(PPh3)3 catalyst exhibited high reaction compatibility in hydrosilylation of alkene, dehydrogenative O-H silylation, and C-H silylation.

19.
Heliyon ; 10(12): e32782, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975204

RESUMO

Purpose: The intimate connection between long noncoding RNA (lncRNA) and autophagy has been established in cartilage degeneration. However, their roles in meniscal degeneration remain ambiguous. This study aimed to identify the key autophagy-related lncRNA and its associated regulatory network in meniscal degeneration in the context of osteoarthritis (OA). Methods: RNA sequencing was performed to identify differentially expressed lncRNAs (DELs) and mRNAs (DEMs), which were then conducted to enrichment analyses using the DAVID database and Metascape. Autophagy-related DEMs were identified by combining DEMs with data from the Human Autophagy Database. Three databases were used to predict miRNA, and the DIANA LncBase Predicted database was utilized to predict miRNA-lncRNA interactions. Based on these predictions, comprehensive competitive endogenous RNA (ceRNA) network were constructed. The expression levels of the classical autophagy markers and autophagy-related ceRNA network were validated. Additionally, Gene Set Enrichment Analysis (GSEA) was performed using autophagy-related DEMs. Results: 310 DELs and 320 DEMs were identified, with five upregulated and one downregulated autophagy-related DEMs. Through reverse prediction of miRNA, paired miRNA-lncRNA interactions, and verification using RT-qPCR, two lncRNAs (PCAT19, CLIP1-AS1), two miRNA (has-miR-3680-3p and has-miR-4795-3p) and two mRNAs (BAG3 and HSP90AB1) were included in the constructed ceRNA regulatory networks. GSEA indicated that the increased expression of autophagy-related mRNAs inhibited glycosaminoglycan biosynthesis in the degenerative meniscus. Conclusion: This study presented the first construction of regulatory ceRNA network involving autophagy-related lncRNA-miRNA-mRNA interactions in OA meniscus. These findings offered valuable insights into the mechanisms underlying meniscal degeneration and provided potential targets for therapeutic intervention.

20.
Front Immunol ; 15: 1420847, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975339

RESUMO

High-grade serous ovarian cancer (HGSOC) presents significant challenges due to its heterogeneity and late-stage diagnoses. Using single-cell and spatial transcriptomics to elucidate the complex landscape of HGSOC to understand its underlying mechanism. Our analysis reveals significant inter- and intra-tumoral diversity, manifested through distinct cellular subpopulations and varied microenvironmental niches. Notably, our findings highlight a widespread immunosuppressive environment, marked by complex networks of cell-cell interactions, particularly evident in areas of elevated tumor cell density within metastatic samples. We identify the exclusive presence of COL14A1+ neoplastic cells in metastatic specimens, alongside a strong correlation between CD8A+ NKT cells and poor prognosis, and elevated CHODL expression in HGSOC metastasis tissues. Furthermore, knockdown experiments targeting CHODL demonstrate its role in reducing migration and invasion abilities in HGSOC cells. A pivotal discovery of our study is the delineation of specific cellular signatures correlated with adverse outcomes, notably a subset of CHODL+ neoplastic cells characterized by a distinct metabolic phenotype with a predilection for lipid metabolism. The therapeutic targeting of this metabolic pathway with existing inhibitors appears promising in curbing tumor proliferation. These findings enhance our understanding of HGSOC heterogeneity and reveal potential therapeutic targets, promising more effective management strategies for this aggressive cancer subtype.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Análise de Célula Única , Microambiente Tumoral , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Microambiente Tumoral/genética , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Perfilação da Expressão Gênica , Transcriptoma , Linhagem Celular Tumoral , Gradação de Tumores , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Biomarcadores Tumorais/genética , Prognóstico
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