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1.
Ecol Evol ; 14(5): e11336, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38711485

RESUMO

The preservation or removal of apical meristem in Leymus chinensis is contingent upon grazing intensity and has a significant impact on above- and belowground biomass, nutritive value, and sustainability of L. chinensis grassland. However, this topic remains understudied. Therefore, a manipulative trial was conducted to induce grazing defoliation through mowing, where two post-grazing heights (preservation or removal of the apical meristem) and four pre-grazing plant heights (i.e., 18, 24, 31, and 35 cm) are combined factorially to create gradients of grazing intensities, resulting in a total of eight treatments. Additionally, two identical control treatments are also incorporated. Our results showed that apical meristem removal at various pre-grazing heights resulted in varying degrees of increased grazing intensities, thereby enhancing the nutritive value of L. chinensis. However, this practice also led to detrimental effects on the plant's carbohydrates reserve as well as herbage mass. The results indicated that although defoliation in treatments involving apical meristem removal resulted in the highest number of frequent cuttings, it did not confer any advantages in terms of herbage mass and nutrient preserves, except for herbage nutritive values when compared to treatments involving apical meristem preservation. The apical meristem preservation treatments demonstrated the highest CP yield over a 2-year period compared to the apical meristem removal treatments. Furthermore, within these apical meristem preservation treatments, only when the pre-grazing height is 35 cm and post-grazing height is 17 cm, there is no significant decrease in above- and belowground biomass. This establishes this specific defoliation regime as an optimal and effective management strategy for L. chinensis grassland.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 161-168, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38686711

RESUMO

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Micro-Ondas , Humanos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Laparoscopia/métodos , Masculino , Feminino , Resultado do Tratamento , Fluoruracila/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Taxa de Sobrevida
3.
BMC Geriatr ; 24(1): 348, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632503

RESUMO

BACKGROUND: Definitive chemoradiotherapy is one of the primary treatment modalities for older patients with esophageal cancer (EC). However, the evolution of prognosis over time and the factors affected non-EC deaths remain inadequately studied. We examined the conditional survival and annual hazard of death in older patients with EC after chemoradiotherapy. METHODS: We collected data from patients aged 65 or older with EC registered in the Surveillance, Epidemiology, and End Results database during 2000-2019. Conditional survival was defined as the probability of survival given a specific time survived. Annual hazard of death was defined the yearly event rate. Restricted cubic spline (RCS) analysis identified the association of age at diagnosis with mortality. RESULTS: Among 3739 patients, the 3-year conditional overall survival increased annually by 7-10%. Non-EC causes accounted for 18.8% of deaths, predominantly due to cardio-cerebrovascular diseases. The hazard of death decreased from 40 to 10% in the first 6 years and then gradually increased to 20% in the tenth year. Non-EC causes surpassed EC causes in hazard starting 5 years post-treatment. RCS indicated a consistent increase in death hazard with advancing age, following a linear relationship. The overall cohort was divided into two groups: 65-74 and ≥ 75 years old, with the ≥ 75-year-old group showing poorer survival and earlier onset of non-EC deaths (HR = 1.36, 95% CI: 1.15-1.62, P < 0.001). Patients with early-stage disease (I-II) had higher risks of death from non-EC causes (HR = 0.82, 95% CI: 0.68-0.98, P = 0.035). Tumor histology had no significant impact on non-EC death risk (HR = 1.17, 95% CI: 0.98-1.39, P = 0.081). CONCLUSIONS: Survival probability increases with time for older patients with EC treated with chemoradiotherapy. Clinicians and patients should prioritize managing and preventing age-related comorbidities, especially in older cohorts and those with early-stage disease.


Assuntos
Neoplasias Esofágicas , Humanos , Idoso , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Quimiorradioterapia/métodos , Prognóstico , Comorbidade
4.
Nat Commun ; 15(1): 3394, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649371

RESUMO

The prevalence of chirality, or, handedness in biological world is a fundamental phenomenon and a characteristic hallmark of life. Thus, understanding the origin of enantio-selection, i.e., the sense and magnitude of asymmetric induction, has been a long-pursued goal in asymmetric catalysis. Herein, we demonstrated a polarizability-derived electronic effect that was shown to be capable of rationalizing a broad range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in a ruthenium-catalyzed asymmetric transfer hydrogenations of ketones. Direct and quantitative linear free energy relationships between substrates' local polarizabilities and observed enantio-selectivity were also revealed in three widely known asymmetric catalytic systems covering both reductions and oxidations. This broadly applicable polarizability-based electronic effect, in conjunction with conventional wisdom mainly leveraging on steric effect considerations, should aid rational design of enantio-selective processes for better production of chiral substances.

5.
ACS Sens ; 9(4): 2101-2109, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38574240

RESUMO

Single-atom catalysts (SACs) hold great promise in highly sensitive and selective gas sensors due to their ultrahigh atomic efficiency and excellent catalytic activity. However, due to the extremely high surface energy of SACs, it is still a huge challenge to synthesize a stable single-atom metal on sensitive materials. Here, we report an atomic layer deposition (ALD) strategy for the elaborate synthesis of single-atom Pt on oxygen vacancy-rich Fe2O3 nanosheets (Pt-Fe2O3-Vo), which displayed ultrafast and sensitive detection to H2, achieving the stability of Pt single atoms. Gas-sensing investigation showed that the Pt-Fe2O3-Vo materials enabled a significantly enhanced response of 26.5-50 ppm of H2, which was 17-fold higher than that of pure Fe2O3, as well as ultrafast response time (2 s), extremely low detection limit (86 ppb), and improved stability. The experimental and density functional theory (DFT) studies revealed that the abundant oxygen vacancy sites of Fe2O3 contributed to stabilizing the Pt atoms via electron transfer. In addition, the stabilized Pt atoms also greatly promote the electron transfer of H2 molecules to Fe2O3, thereby achieving an excellent H2 sensing performance. This work provides a potential strategy for the development of highly selective and stable chemical sensors.


Assuntos
Compostos Férricos , Hidrogênio , Nanoestruturas , Oxigênio , Platina , Platina/química , Oxigênio/química , Hidrogênio/química , Compostos Férricos/química , Nanoestruturas/química , Teoria da Densidade Funcional , Catálise , Limite de Detecção
6.
STAR Protoc ; 5(2): 103006, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38602871

RESUMO

Exploring cell-cell communication is pivotal for understanding biological processes in multicellular life forms. Here, we present a protocol that details the use of matrix decomposition to infer cell-cell communication (MDIC3) for unsupervised cell-cell communication inference. We describe steps for using the MDIC3 Python scripts to deduce cell-cell communication and identify key ligand-receptor pairs between a specific cell type pair from a single-cell gene expression dataset. This protocol has potential application in cell-cell communication inference on any species. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

7.
Angew Chem Int Ed Engl ; : e202405255, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682659

RESUMO

Precise regulation of the active site structure is an important means to enhance the activity and selectivity of catalysts in CO2 electroreduction. Here, we creatively introduce anionic groups, which can not only stabilize metal sites with strong coordination ability but also have rich interactions with protons at active sites to modify the electronic structure and proton transfer process of catalysts. This strategy helps to convert CO2 into fuel chemicals at low overpotentials. As a typical example, a composite catalyst, CuO/Cu-NSO4/CN, with highly dispersed Cu(II)-SO4 sites has been reported, in which CO2 electroreduction to formate occurs at a low overpotential with a high Faradaic efficiency (-0.5 V vs. RHE, FEHCOO-=87.4%). Pure HCOOH is produced with an energy conversion efficiency of 44.3% at a cell voltage of 2.8 V. Theoretical modeling demonstrates that sulfate promotes CO2 transformation into a carboxyl intermediate followed by HCOOH generation, whose mechanism is significantly different from that of the traditional process via a formate intermediate for HCOOH production.

8.
ISA Trans ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38679561

RESUMO

The paper discusses the dissipative control problem of nonlinear singularly perturbed systems (SPSs) with dynamic quantization and actuator failure. The nonlinear singularly perturbed plant is described by Takagi-Sugeno (T-S) fuzzy model. The dynamic quantizer is considered to realize the effective utilization of the limited network channel bandwidth resources, and the possible transmission failure between the controller and the actuator is also considered. Based on linear matrix inequalities, sufficient design conditions for the ϵ-independent state feedback controller are given such that the constructed quantized closed-loop system is asymptotically stable and satisfies a predefined dissipative performance. Furthermore, a short search algorithm is given to search the maximum stability bound ϵ̄. Finally, two examples are provided in order to prove the feasibility and effectiveness of the proposed method.

9.
Ecotoxicol Environ Saf ; 277: 116389, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657458

RESUMO

Microplastics (MPs), recognized as an emerging environmental menace, have been extensively investigated in both marine and terrestrial fauna. This study is comprehensive to investigate how polystyrene (PS) affects ruminant animals. The experimental design comprised 24 individually housed lambs, divided into a CON group (diet without PS) and three PS-exposed (25 µm, 50 µm, 100 µm) groups, each with six lambs, the exposure of PS was 100 mg/day, and the duration of exposure was 60 days. The study yielded noteworthy results: (ⅰ) PS leads to a decrease in average daily gain along with an increase in feed conversion rate. (ⅱ) PS decreases rumen ammonia nitrogen. The rumen microbiota diversity remains consistent. However, the relative abundance of Bacteroidetes and Actinobacteria increased in the PS-exposed groups, while the relative abundance of Coriobacteriales_incertae_Sedis and Prevotellaceae_YAB2003_group decreased. (ⅲ) PS leads to decrease in hemoglobin, thrombocytocrit, and albumin levels in lamb blood, thus triggering oxidative stress accumulation, along with swelling of the kidneys and liver. (ⅳ) PS inflicts severe damage to jejunum, consequently impacting digestion and absorption. (ⅴ) PS reduces meat quality and the nutritional value. In conclusion, PS-exposure inhibited lambs' digestive function, adversely affects blood and organs' health status, reducing average daily gain and negatively influencing meat quality. PS particles of 50-100 µm bring worse damage to lambs. This research aims to fill the knowledge void concerning MPs' influences on ruminant animals, with a specific focus on the meat quality of fattening lambs.


Assuntos
Poliestirenos , Rúmen , Animais , Ovinos , Poliestirenos/toxicidade , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/veterinária , Inflamação/induzido quimicamente , Carne , Microbioma Gastrointestinal/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Microplásticos/toxicidade
10.
World J Gastroenterol ; 30(2): 158-169, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38312121

RESUMO

BACKGROUND: Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. AIM: To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. METHODS: The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. RESULTS: Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. CONCLUSION: TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Prognóstico , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Colorretais/patologia , Neoplasias do Colo/patologia
11.
Patterns (N Y) ; 5(2): 100911, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38370122

RESUMO

Crosstalk among cells is vital for maintaining the biological function and intactness of systems. Most existing methods for investigating cell-cell communications are based on ligand-receptor (L-R) expression, and they focus on the study between two cells. Thus, the final communication inference results are particularly sensitive to the completeness and accuracy of the prior biological knowledge. Because existing L-R research focuses mainly on humans, most existing methods can only examine cell-cell communication for humans. As far as we know, there is currently no effective method to overcome this species limitation. Here, we propose MDIC3 (matrix decomposition to infer cell-cell communication), an unsupervised tool to investigate cell-cell communication in any species, and the results are not limited by specific L-R pairs or signaling pathways. By comparing it with existing methods for the inference of cell-cell communication, MDIC3 obtained better performance in both humans and mice.

12.
NPJ Syst Biol Appl ; 10(1): 4, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218959

RESUMO

Knowledge bases have been instrumental in advancing biological research, facilitating pathway analysis and data visualization, which are now widely employed in the scientific community. Despite the establishment of several prominent knowledge bases focusing on signaling, metabolic networks, or both, integrating these networks into a unified topological network has proven to be challenging. The intricacy of molecular interactions and the diverse formats employed to store and display them contribute to the complexity of this task. In a prior study, we addressed this challenge by introducing a "meta-pathway" structure that integrated the advantages of the Simple Interaction Format (SIF) while accommodating reaction information. Nevertheless, the earlier Global Integrative Network (GIN) was limited to reliance on KEGG alone. Here, we present GIN version 2.0, which incorporates human molecular interaction data from ten distinct knowledge bases, including KEGG, Reactome, and HumanCyc, among others. We standardized the data structure, gene IDs, and chemical IDs, and conducted a comprehensive analysis of the consistency among the ten knowledge bases before combining all unified interactions into GINv2.0. Utilizing GINv2.0, we investigated the glycolysis process and its regulatory proteins, revealing coordinated regulations on glycolysis and autophagy, particularly under glucose starvation. The expanded scope and enhanced capabilities of GINv2.0 provide a valuable resource for comprehensive systems-level analyses in the field of biological research. GINv2.0 can be accessed at: https://github.com/BIGchix/GINv2.0 .


Assuntos
Redes e Vias Metabólicas , Transdução de Sinais , Humanos , Redes e Vias Metabólicas/genética , Bases de Conhecimento
13.
Science ; 383(6678): 81-85, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38175894

RESUMO

Isolable singlet carbenes have universally adopted a σ2π0 electronic state, making them σ-donors and π-acceptors. We present a rhodium-coordinated, cationic cyclic diphosphinocarbene with a σ0π2 ground state configuration. Nuclear magnetic resonance spectroscopy studies show a carbene carbon chemical shift below -30.0 parts per million. X-ray crystallography reveals a planar RhP2C configuration. Quantum chemical calculations rationalize how σ-electron delocalization/donation and π-electron negative hyperconjugation together stabilize the formally vacant σ orbital and the filled π orbital at the carbene center. In contrast to traditional carbene counterparts this carbene can undergo synthetic transformations with both a Lewis base and a silver salt, producing a Lewis acid/base adduct and a silver π-complex, respectively. Exhibiting ambiphilic reactivity, it can also form a ketenimine through reaction with an isocyanide.

14.
Transl Res ; 266: 49-56, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37989391

RESUMO

BACKGROUND: Patients with birth defects (BD) exhibit an elevated risk of cancer. We aimed to investigate the potential link between pediatric cancers and BDs, exploring the hypothesis of shared genetic defects contributing to the coexistence of these conditions. METHODS: This study included 1454 probands with BDs (704 females and 750 males), including 619 (42.3%) with and 845 (57.7%) without co-occurrence of pediatric onset cancers. Whole genome sequencing (WGS) was done at 30X coverage through the Kids First/Gabriella Miller X01 Program. RESULTS: 8211 CNV loci were called from the 1454 unrelated individuals. 191 CNV loci classified as pathogenic/likely pathogenic (P/LP) were identified in 309 (21.3%) patients, with 124 (40.1%) of these patients having pediatric onset cancers. The most common group of CNVs are pathogenic deletions covering the region ChrX:52,863,011-55,652,521, seen in 162 patients including 17 males. Large recurrent P/LP duplications >5MB were detected in 33 patients. CONCLUSIONS: This study revealed that P/LP CNVs were common in a large cohort of BD patients with high rate of pediatric cancers. We present a comprehensive spectrum of P/LP CNVs in patients with BDs and various cancers. Notably, deletions involving E2F target genes and genes implicated in mitotic spindle assembly and G2/M checkpoint were identified, potentially disrupting cell-cycle progression and providing mechanistic insights into the concurrent occurrence of BDs and cancers.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias , Masculino , Criança , Feminino , Humanos , Variações do Número de Cópias de DNA/genética , Sequenciamento Completo do Genoma , Neoplasias/epidemiologia , Neoplasias/genética , Comorbidade
15.
Biol Psychiatry ; 95(9): 881-887, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37865391

RESUMO

BACKGROUND: Previous studies have implicated both rare copy number variations (CNVs) and common variants in liability for attention-deficit/hyperactivity disorder (ADHD). However, how common and rare genetic variants jointly contribute to individual liability requires further investigation in larger cohorts. METHODS: This study comprises 9385 participants of European descent and 7810 participants of African American ancestry who were recruited from the greater Philadelphia area by the Children's Hospital of Philadelphia. The polygenic risk score (PRS) of each participant was estimated by linkage disequilibrium pruning and p-value thresholding (P + T) methods using PRSice-2. We investigated whether the risk of ADHD follows a polygenic liability threshold model wherein 1) the risk of ADHD requires less contribution from common variants in the presence of a rare CNV, and 2) control carriers of ADHD-associated CNVs have lower common risk allele burden than noncarriers. RESULTS: CNVs previously reported in ADHD cases were significantly associated with ADHD risk in both the European American cohort and the African American cohort. Healthy control participants carrying those same risk CNVs had lower PRSs than those without risk CNVs in the European American cohort. This result was replicated in the African American cohort. However, PRSs were not significantly different in case participants carrying risk CNVs versus those without risk CNVs. CONCLUSIONS: These findings provide evidence in support of interactive effects of PRS and ADHD-associated CNVs on disease risk and add novel insights into the genetic basis of ADHD by highlighting a protective role of low PRS in ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Variações do Número de Cópias de DNA , Criança , Humanos , Variações do Número de Cópias de DNA/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estratificação de Risco Genético , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Estudo de Associação Genômica Ampla
16.
ACS Sens ; 9(1): 388-397, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147687

RESUMO

Transition metal dichalcogenide (TMD) materials hold great promise for gas sensors working at room temperature (RT). But the low response and slow dynamics derived from pristine TMDs remain a challenge toward their real applications. In this work, we report an efficient N-doping strategy to modulate the electronic structure of MoS2 nanosheets (N-MoS2) to achieve improved detection toward NO2. The effect of N-doping on the sensor properties, which has been rarely investigated, is elucidated by both experimental and computational studies. Due to N-doping, the Fermi level of N-MoS2 decreased from -5.29 to -5.33 eV and the band gap was reduced from 1.79 to 1.65 eV. The smaller band gap indicated the reduced resistance of N-MoS2 compared to that of original MoS2. As a result, the response of the MoS2 sensor to 10 ppm of NO2 was improved from 1.23 to 2.31 at RT. The sensor also has a limit of detection (LOD) of 62.5 ppb. To explain the effect of N-doping, density functional theory (DFT) calculations were conducted to figure out the important roles played by N-doping. This work demonstrates a pathway to modulate the chemical and electronic structures of TMD materials for advanced sensors.


Assuntos
Molibdênio , Dióxido de Nitrogênio , Temperatura , Eletrônica , Limite de Detecção
17.
medRxiv ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38077063

RESUMO

Striatal dopaminergic overactivity was hypothesized as the core pathophysiology of schizophrenia. However, morphological alterations of striatum in schizophrenia remains exclusive, largely because brain regional heterogeneity limited traditional group-mean based approach. Leveraging third-party brain maps of neurotransmitter and cognition behaviours, we developed a pattern-based representation feature score (ReFS) to investigate structural spatial pattern variation in schizophrenia. Structural ReFS of subcortical regions, particularly the striatum, were linked to schizophrenia diagnosis, symptom severity, and genetic susceptibility. Dopaminergic-ReFS of striatum was increased in schizophrenia patients and reliably reproduced across 13 datasets. The pattern-based ReFS effectively captured the shared genetic pathways underlying both schizophrenia and striatum. The results provide convergent, multimodal suggest the central role of striatal spatial patterns in schizophrenia psychopathologies and and open new avenues to develop individualized treatments for psychotic disorders.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38072244

RESUMO

OBJECTIVE: Accumulative evidence indicates a critical role of mitochondrial function in autism spectrum disorders (ASD), implying that ASD risk may be linked to mitochondrial dysfunction due to DNA (mtDNA) variations. Although a few studies have explored the association between mtDNA variations and ASD, the role of mtDNA in ASD is still unclear. Here, we aimed to investigate whether mitochondrial DNA haplogroups are associated with the risk of ASD. METHOD: Two European cohorts and an Ashkenazi Jewish (AJ) cohort were analyzed, including 2,062 ASD patients in comparison with 4,632 healthy controls. DNA samples were genotyped using Illumina HumanHap550/610 and Illumina 1M arrays, inclusive of mitochondrial markers. Mitochondrial DNA (mtDNA) haplogroups were identified from genotyping data using HaploGrep2. A mitochondrial genome imputation pipeline was established to detect mtDNA variants. We conducted a case-control study to investigate potential associations of mtDNA haplogroups and variants with the susceptibility to ASD. RESULTS: We observed that the ancient adaptive mtDNA haplogroup K was significantly associated with decreased risk of ASD by the investigation of 2 European cohorts including a total of 2,006 cases and 4,435 controls (odds ratio = 0.64, P=1.79 × 10-5), and we replicated this association in an Ashkenazi Jewish (AJ) cohort including 56 cases and 197 controls (odds ratio = 0.35, P = 9.46 × 10-3). Moreover, we demonstrate that the mtDNA variants rs28358571, rs28358584, and rs28358280 are significantly associated with ASD risk. Further expression quantitative trait loci (eQTLs) analysis indicated that the rs28358584 and rs28358280 genotypes are associated with expression levels of nearby genes in brain tissues, suggesting those mtDNA variants may confer risk for ASD via regulation of expression levels of genes encoded by the mitochondrial genome. CONCLUSION: This study helps to shed light on the contribution of mitochondria in ASD and provides new insights into the genetic mechanism underlying ASD, suggesting the potential involvement of mtDNA-encoded proteins in the development of ASD.

19.
Angew Chem Int Ed Engl ; 62(52): e202315555, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37942957

RESUMO

Featuring an extra electron in the π* antibonding orbital, species with a 2-center-3-electron (2c3e) π bond without an underlying σ bond are scarcely known. Herein, we report the synthesis, isolation and characterization of a radical anion salt [K(18-C-6)]+ {[(HCNDipp)2 Si]2 P2 }⋅- (i.e. [K(18-C-6)]+ 3⋅- ) (18-C-6=18-crown-6, Dipp=2,6-diisopropylphenyl), in which 3⋅- features a perfectly planar Si2 P2 four-membered ring. This species represents the first example of a Si- and P-containing analog of a bicyclo[1.1.0]butane radical anion. The unusual bonding motif of 3⋅- was thoroughly investigated via X-ray diffraction crystallography, electron paramagnetic resonance spectroscopy (EPR), and calculations by density functional theory (DFT), which collectively unveiled the existence of a 2c3e π bond between the bridgehead P atoms and no clearly defined supporting P-P σ bond.

20.
Sci Rep ; 13(1): 18953, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919314

RESUMO

As an important risk factor for many cardiovascular diseases, hypertension requires convenient and reliable methods for prevention and intervention. This study designed a visualization risk prediction system based on Machine Learning and SHAP as an auxiliary tool for personalized health management of hypertension. We used ten Machine Learning algorithms such as random forests and 1617 anonymized health check data to build ten hypertension risk prediction models. The model performance was evaluated through indicators such as accuracy, F1-score, and ROC curve. We used the best-performing model combined with the SHAP algorithm for feature importance analysis and built a visualization risk prediction system on the web page. The LightGMB model exhibited the best predictive performance, and age, alkaline phosphatase, and triglycerides were important features for predicting the risk of hypertension. Users can obtain their risk probability of hypertension and determine the focus of intervention through the visualization system built on the web page. Our research helps doctors and patients to develop personalized prevention and intervention programs for hypertension based on health check data, which has significant clinical and public health significance.


Assuntos
Doenças Cardiovasculares , Hipertensão , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Algoritmos , Aprendizado de Máquina , Fatores de Risco
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