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1.
ACS Sens ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350515

RESUMO

Transition metal oxide semiconductors have great potential for use in H2 sensors, but in recent years, the strange phenomena about gas-sensitive performance associated with their special properties have been more widely discussed in research. In some cases, the resistance of transition metal oxide gas sensors will emerge with some changes contrary to their intrinsic semiconductor characteristics, especially in gas sensor research of WO3. Based on the hydrothermal synthesis of WO3, our work focuses on the abnormal change of tungsten oxide resistance to different gases at low temperature (80-200 °C) and high temperature (above 200 °C). Through in situ FT-IR and in situ XPS, combined with density functional theory calculations, a new reasonable explanation of WO3 is proposed for the abnormal resistance change caused by temperature and the strange response due to gas concentration. The occurrence of these findings can be attributed to the synergistic effect resulting from the presence of two contributing factors. One of them is attributed to the alteration in the surface valence state of WO3 induced by gas, resulting in the reduction of W6+. The other one is due to the reaction between gas and adsorbed oxygen on the surface of WO3. This work presents a novel and rational concept for addressing the reaction mechanism between gas and transition metal oxide semiconductors, thereby paving the way for the development of highly efficient gas sensors based on transition metal oxide semiconductors.

2.
PeerJ ; 12: e17922, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221280

RESUMO

The family Diogenidae Ortmann, 1892 is a diverse and abundance group of hermit crabs, but their systematics and phylogenetic relationships are highly complex and unresolved. Herein, we gathered nucleotide sequence data from two mitochondrial (16S rRNA and COI) and two nuclear (NaK and PEPCK) genes for a total of 2,308 bp in length across 38 species from six extant diogenid genera. Molecular data were combined with 41 morphological characters to estimate the largest phylogeny of diogenid hermit crabs to date with the aim of testing the proposed taxonomic scheme of Diogenidae and addressing intergeneric relationships within this family. Despite conflicts between mitochondrial and nuclear DNA trees, the combined-data tree reflects the contributions of each dataset, and improves tree resolution and support for internal nodes. Contrary to traditional classification, our total evidence revealed a paraphyletic Diogenidae based on internally nested representatives of Coenobitidae Dana, 1851. Within Diogenidae, the studied diogenid hermit crabs were split between two clades with high support, which contradicts recent morphological classification scheme for Diogenidae sensu lato based on fossil records. The genus Diogenes Dana, 1851 was found nested inside Paguristes Dana, 1851, which formed a clade being separated from the remainder, pointing towards paraphyly in Paguristes. In another clade, Dardanus Paulson, 1875 occupied a basal position relative to the other diogenids, while Calcinus Dana, 1851 and Clibanarius Dana, 1852 showed sister relationships and formed a cluster with Ciliopagurus Forest, 1995. Among the morphological characters examined, carapace shield and telson were identified as phylogenetically significant for grouping diogenid genera, while phylogenetic insignificance of gill number was evidenced by its mosaic pattern in diogenid phylogeny. The present study sheds light on the controversial generic phylogeny of Diogenidae and highlights the necessity for thorough taxonomic revisions of this family as well as some genera (e.g., Paguristes) to reconcile current classifications with phylogenetic relationships.


Assuntos
Anomuros , Filogenia , Animais , Anomuros/genética , Anomuros/anatomia & histologia , RNA Ribossômico 16S/genética , DNA Mitocondrial/genética
3.
BMC Med Inform Decis Mak ; 24(1): 251, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251987

RESUMO

OBJECTIVE: To analyze primary angle closure suspect (PACS) patients' anatomical characteristics of anterior chamber configuration, and to establish artificial intelligence (AI)-aided diagnostic system for PACS screening. METHODS: A total of 1668 scans of 839 patients were included in this cross-sectional study. The subjects were divided into two groups: PACS group and normal group. With anterior segment optical coherence tomography scans, the anatomical diversity between two groups was compared, and anterior segment structure features of PACS were extracted. Then, AI-aided diagnostic system was constructed, which based different algorithms such as classification and regression tree (CART), random forest (RF), logistic regression (LR), VGG-16 and Alexnet. Then the diagnostic efficiencies of different algorithms were evaluated, and compared with junior physicians and experienced ophthalmologists. RESULTS: RF [sensitivity (Se) = 0.84; specificity (Sp) = 0.92; positive predict value (PPV) = 0.82; negative predict value (NPV) = 0.95; area under the curve (AUC) = 0.90] and CART (Se = 0.76, Sp = 0.93, PPV = 0.85, NPV = 0.92, AUC = 0.90) showed better performance than LR (Se = 0.68, Sp = 0.91, PPV = 0.79, NPV = 0.90, AUC = 0.86). In convolutional neural networks (CNN), Alexnet (Se = 0.83, Sp = 0.95, PPV = 0.92, NPV = 0.87, AUC = 0.85) was better than VGG-16 (Se = 0.84, Sp = 0.90, PPV = 0.85, NPV = 0.90, AUC = 0.79). The performance of 2 CNN algorithms was better than 5 junior physicians, and the mean value of diagnostic indicators of 2 CNN algorithm was similar to experienced ophthalmologists. CONCLUSION: PACS patients have distinct anatomical characteristics compared with health controls. AI models for PACS screening are reliable and powerful, equivalent to experienced ophthalmologists.


Assuntos
Aprendizado Profundo , Glaucoma de Ângulo Fechado , Humanos , Glaucoma de Ângulo Fechado/diagnóstico por imagem , Glaucoma de Ângulo Fechado/diagnóstico , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Masculino , Tomografia de Coerência Óptica , Idoso , Segmento Anterior do Olho/diagnóstico por imagem , Algoritmos
4.
J Alzheimers Dis ; 101(3): 1015-1025, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39240644

RESUMO

Background: The widespread exposure to plastic products and the increasing number of individuals with cognitive impairments have imposed a heavy burden on society. Objective: This study aims to investigate the relationship between plastic product exposure in daily life and cognitive function in older Chinese individuals. Methods: Data were obtained from the 2023 Ningxia Older Psychological Health Cohort, comprising 4045 participants aged 60 and above. Cognitive function was assessed using the Mini-Mental State Examination scale. A population-based plastic exposure questionnaire was used to calculate plastic exposure scores (PES). Binary logistic regression was employed to analyze the relationship between PES and cognitive function, while restricted cubic splines were used to examine the dose-response relationship between PES and cognitive function. Latent profile analysis (LPA) was employed to explore the potential patterns of plastic exposure, and logistic regression was used to investigate the relationship between different exposure patterns and cognitive function. A linear regression model was utilized to investigate the relationship between PES and different dimensions of cognitive function. Results: Among the 4045 participants, 1915 individuals were assessed with mild cognitive impairment (MCI). After adjusting for all covariates, PES (OR = 1.04, 95% CI 1.02-1.06) was significantly associated with the risk of MCI and exhibited a dose-response relationship. LPA identified two potential categories of plastic exposure, with a higher risk of MCI observed in the group using plastic utensils. Conclusions: This study indicates a positive correlation between plastic exposure levels and MCI risk, particularly among individuals who frequently use plastic tableware.


Assuntos
Cognição , Disfunção Cognitiva , Plásticos , Humanos , Feminino , Masculino , Idoso , Disfunção Cognitiva/epidemiologia , China/epidemiologia , Pessoa de Meia-Idade , Exposição Ambiental/efeitos adversos , Testes de Estado Mental e Demência , Idoso de 80 Anos ou mais , Estudos de Coortes , Inquéritos e Questionários , População do Leste Asiático
5.
ACS Appl Mater Interfaces ; 16(38): 51738-51747, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39263994

RESUMO

Oxygen vacancies (VO) in metal oxide semiconductors play an important role in improving gas-sensing performance of chemiresistive gas sensors. Nonetheless, there is still a lack of clear understanding of the inherent mechanism of the influence of oxygen vacancies on gas sensing due to generally focusing on the concentration of VO. Herein, oxygen vacancies were rationally modulated in WO3 nanoflower structures via an annealing process, resulting in a transformation of VO from neutral (VO0) to a doubly ionized (VO2+) state. Density functional theory (DFT) calculations indicate that VO2+ is significantly more efficient than VO0 for NO2 detection in competition with atmospheric O2. Benefiting from a high concentration of VO2+, the WO3-450 (WO3 annealed at 450 °C) sensor exhibits excellent sensing performance with an ultrahigh sensitivity (3674.1 to 5 ppm NO2), superior selectivity, and long-term stability (one month). Furthermore, the sensor with the wide range of concentration detection not only can detect NO2 gas with parts per million (ppm) but also can detect NO2 with parts per billion (ppb) level concentration, with a high sensibility reaching 2.8 to 25 ppb NO2 and over 100 to 100 ppb NO2. This study elucidates the oxygen vacancy mediated sensing mechanism toward NO2 and provides an effective strategy for the rational design of gas sensors with high sensing performance.

6.
Materials (Basel) ; 17(16)2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39203263

RESUMO

This study aimed to decipher the influence of red mud on the mechanical properties, pore structure, and microstructure of basic magnesium sulfate cements (BMSCs). The results showed that BMSC prepared with an appropriate addition of red mud exhibited improved mechanical properties and yielded the highest compressive strength of 94.54 MPa after curing for 28 days. Adding red mud reduced the total porosity and optimized the pore structure of BMSC. The microstructure and hydration products of the specimens were examined using X-ray diffraction, scanning electron microscopy, and energy-dispersive spectroscopy. The results illustrate that the addition of 50% red mud did not affect the amount of the main strength phase 5-1-7 produced in BMSC. It could also reduce the residual amount of MgO and the generation of Mg(OH)2. The red mud and the M-S-H gel generated by the reaction between active SiO2 and α-MgO in the red mud together filled the pore structure of BMSC, making its microstructure denser and higher-strength. This study aims to improve the comprehensive use of red mud, and the results show that red mud can improve the mechanical properties of BMSCs, protecting the environment and simultaneously reducing BMSC production costs to create good economic benefits.

7.
Toxics ; 12(8)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39195633

RESUMO

Nanoplastics (NPs) cause serious contamination of drinking water and potential damage to human health. This study aimed to investigate the effects of NPs with different particle sizes and concentrations on the reproductive function of male mice. In this study, free drinking water exposure was used to expose male BALB/C mice to PS-NPs (20 nm, 200 nm, and 1000 nm) at 0.1 mg/L, 1 mg/L, and 5 mg/L for 4 months. The male reproductive function of the mice was assessed after NPs exposure, and fecal and blood samples were collected for macrogenomics and metabolomics. The results showed that PS-NPs resulted in mice with reduced testicular organ coefficients, decreased sperm quality, altered testicular tissue structure, disturbed sex hormone levels, and abnormal levels of inflammatory factors and oxidative stress. Furthermore, this study found that NP exposure affected the alteration of gut communities and metabolic pathways related to male reproduction, such as Clostridium and glutathione metabolism. Importantly, we found an effect of NP particle size on reproductive function. In the future, more attention should be paid to the smaller particle sizes of NPs.

8.
iScience ; 27(8): 110503, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39108715

RESUMO

[This corrects the article DOI: 10.1016/j.isci.2024.110255.].

9.
Sci Rep ; 14(1): 18111, 2024 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103500

RESUMO

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors, with childhood trauma recognized as a contributing factor to its pathophysiology. This study aimed to delineate brain functional aberrations in OCD patients and explore the association between these abnormalities and childhood trauma, to gain insights into the neural underpinnings of OCD. Forty-eight drug-naive OCD patients and forty-two healthy controls (HC) underwent resting-state functional magnetic resonance imaging and clinical assessments, including the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Compared to HCs, OCD patients exhibited significantly decreased amplitude of low-frequency fluctuations (ALFF) in the right cerebellum, decreased regional homogeneity (ReHo) in the right cerebellum and right superior occipital lobes (FWE-corrected p < 0.05), which negatively correlated with Y-BOCS scores (p < 0.05). Furthermore, cerebellar ALFF negatively correlated with the CTQ emotional abuse subscale (r = - 0.514, p < 0.01). Mediation analysis revealed that cerebellar ALFF mediated the relationship between CTQ-emotional abuse and Y-BOCS (good model fit: R2 = 0.231, MSE = 14.311, F = 5.721, p < 0.01; direct effect, c' = 0.153, indirect effect, a*b = 0.191). Findings indicated abnormal spontaneous and regional cerebellar activity in OCD, suggesting childhood trauma impacts OCD symptoms through cerebellar neural remodeling, highlighting its importance for clinical treatment selection.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Masculino , Feminino , Adulto , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Mapeamento Encefálico , Adulto Jovem , Estudos de Casos e Controles
10.
Nat Commun ; 15(1): 6234, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39043688

RESUMO

Zn-I2 flow batteries, with a standard voltage of 1.29 V based on the redox potential gap between the Zn2+-negolyte (-0.76 vs. SHE) and I2-posolyte (0.53 vs. SHE), are gaining attention for their safety, sustainability, and environmental-friendliness. However, the significant growth of Zn dendrites and the formation of dead Zn generally prevent them from being cycled at high current density (>80 mA cm-2). In addition, the crossover of Zn2+ across cation-exchange-membrane also limits their cycle stability. Herein, we propose a chelated Zn(P2O7)26- (donated as Zn(PPi)26-) negolyte, which facilitates dendrite-free Zn plating and effectively prevents Zn2+ crossover. Remarkably, the utilization of chelated Zn(PPi)26- as a negolyte shifts the Zn2+/Zn plating/stripping potential to -1.08 V (vs. SHE), increasing cell voltage to 1.61 V. Such high voltage Zn-I2 flow battery shows a promising stability over 250 cycles at a high current density of 200 mA cm-2, and a high power density up to 606.5 mW cm-2.

11.
iScience ; 27(7): 110255, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39021794

RESUMO

The effect on catalytic behavior induced by different morphology of NiO supports has been investigated using the example of gold-catalyzed CO oxidation. Three NiO-supported nanogold consisting of nanogold deposited onto NiO nanorods (NiO-R), nanosheet (NiO-S), and nanodiscs (NiO-D) were prepared. Transmission electron microscopy(TEM)/Scanning transmission electron microscopy(STEM) investigations indicated that Au particles dominantly exposed Au(111) facets virtually independent of NiO architectures. Au/NiO-S displayed a normal Arrhenius-type behavior. Au/NiO-R and Au/NiO-D showed an atypical behavior, characterized by a U-shaped curve of activity vs. temperature, which is attributed to the carbonate accumulation on whose catalytically active sites. On Au/NiO-R, a stable CO-conversion rate of 1.78 molCO gAu -1 h-1 at 30°C was achieved, which is among the higher rates reported so far for supported Au-based systems. DRIFTS measurement identified Auδ+ species as crucial CO adsorption sites promoting CO oxidation, and the catalytic CO oxidation should obey Mars-van Krevelen (<200°C) and Eley-Rideal mechanism (>240°C).

12.
Paediatr Int Child Health ; 44(2): 68-72, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39011794

RESUMO

The early diagnosis of tuberculosis (TB) in infants is challenging owing to the non-specific clinical manifestations in infancy, particularly preterm infants. Two cases in preterm infants are reported. Case 1, conceived by in vitro fertilization (IVF), was born at 27 + 1 weeks gestational age weighing 880 g. He presented on Day 85 with intermittent fever. Following a course of systemic broadspectrum antibiotics, he deteriorated, developing acute respiratory distress syndrome (ARDS). TB Xpert polymerase chain reaction (PCR) of the sputum obtained by laryngeal aspiration confirmed Mycobacterium TB (MTB) on Day 97. He responded well to anti-tuberculosis treatment. His mother had a fever and headache and was diagnosed with COVID-19 79 days after delivery. The fever persisted for nearly 10 days after empirical treatment. She was eventually diagnosed with miliary TB and tuberculous meningitis 92 days after delivery. Case 2 was conceived by IVF and born at 36 + 6 weeks gestation weighing 2430 g. She presented on Day 15 with intermittent fever and abdominal distention. Chest and abdominal radiography demonstrated severe diffuse inflammatory changes. She had received BCG vaccination, and there was no history of contact with active TB. TB PCR of the sputum obtained by laryngeal aspiration confirmed MTB on Day 19. The asymptomatic mother was subsequently diagnosed with pulmonary and genital TB. TB should be considered as a differential diagnosis in infants with unexpected respiratory distress and fever. Women evaluated for infertility should be routinely screened for TB before receiving assisted reproductive treatment, particularly where TB is prevalent.Abbreviations: ARDS: acute respiratory distress syndrome; BPD: bronchopulmonary dysplasia; CPAP: continuous positive airway pressure; CSF: cerebrospinal fluid; HIV: human immunodeficiency virus; IVF: in vitro fertilization; KMC: Kangaroo mother care; MDR: multidrug-resistant; MTB: Mycobacterium tuberculosis; NICU: neonatal intensive care unit; PCR: polymerase chain reaction; PS: pulmonary surfactant; SIMV: synchronised intermittent mandatory ventilation; TB: tuberculosis; CT: computed tomography; HREZ: isoniazid, rifampin, ethambutol and pyrazinamide; IGRA: interferon-γ release assay; IVF: in vitro fertilization; PCR: polymerase chain reaction; TB: tuberculosis.


Assuntos
Fertilização in vitro , Recém-Nascido Prematuro , Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Feminino , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Recém-Nascido , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Antituberculosos/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico
13.
Adv Sci (Weinh) ; 11(30): e2401314, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38877663

RESUMO

Organic anodes have emerged as a promising energy storage medium in proton ion batteries (PrIBs) due to their ability to reversibly accommodate non-metallic proton ions. Nevertheless, the currently available organic electrodes often encounter dissolution issues, leading to a decrease in long-cycle stability. In addition, the inherent potential of the organic anode is generally relatively high, resulting in low cell voltage of assembled PrIBs (<1.0 V). To address these challenges, a novel long-period stable, low redox potential biphenylzine derivative, [2,2'-biphenazine]-7,7'-tetraol (BPZT) is explored, from the perspective of molecular symmetry and solubility, in conjunction with the effect of the molecular frontier orbital energy levels on its redox potential. Specifically, BPZT exhibited a low potential of 0.29 V (vs SHE) and is virtually insoluble in 2 m H2SO4 electrolyte during cycling. When paired with MnO2@GF or PbO2 cathodes, the resulting PrIBs achieve cell voltages of 1.07 V or 1.44 V, respectively, and maintain a high capacity retention of 90% over 20000 cycles. Additionally, these full batteries can operate stably at a high mass loading of 10 mgBPZT cm-2, highlighting their potential toward long-term energy storage applications.

14.
Small ; : e2401996, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829026

RESUMO

Visible-blind ultraviolet (UV) light detection has a wide application range in scenes like space environment monitoring and medical imaging. To realize miniaturized UV detectors with high performance and high integration ability, new device structures without bulky light filters need to be developed based on advanced mechanisms. Here the unipolar barrier van der Waals heterostructure (UB-vdWH) photodetector is reported that realizes filter-free visible-blind UV detection with good stability, robustness, selectivity, and high detection performance. The UB-vdWH shows a responsivity of 2452 A W-1, a photo on-off ratio of 2.94 × 105 and a detectivity of 1.26 × 1015 Jones as a UV detector, owing to the intentionally designed barrier height that suppresses dark current and photoresponse to visible light during the transport process. The good performance remains intact during 104 test cycles or even under high temperatures, which proves the stability, and robustness of the UB-vdWH, thus shows the huge potential for a wider application range.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(5): 450-455, 2024 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-38802903

RESUMO

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.


Assuntos
Acidente Vascular Cerebral , Humanos , Masculino , Recém-Nascido , Feminino , China/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Prognóstico , Eletroencefalografia , Incidência , Imageamento por Ressonância Magnética
16.
Front Immunol ; 15: 1410457, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765013

RESUMO

Introduction: CM313 is currently under clinical investigation for treatments of multiple myeloma, systemic lupus erythematosus, and immune thrombocytopenia. We aimed to report the preclinical profile of the novel therapeutic anti-CD38 monoclonal antibody (mAb) CM313, with an emphasis on the difference with other CD38-targeting mAb. Methods: The binding of CM313 to CD38 recombinant protein across species was assessed using ELISA. The binding of CM313 to CD38-positive (CD38+) cells was detected using flow cytometry assays. CM313-induced complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and apoptosis on different CD38+ cells were assessed by LDH release assays or flow cytometry assays. The effect of CM313 on CD38 enzymatic activity was measured using fluorescence spectroscopy. CM313 immunotoxicity in human blood was assessed using flow cytometry assays, ELISA, and LDH release assays. Anti-tumor activity of CM313 was assessed in multiple mouse xenograft models. Safety profile of CM313 were evaluated in cynomolgus monkeys and human CD38 transgenic (B-hCD38) mice. Results: There exist unique sequences at complementarity-determining regions (CDR) of CM313, which facilitates its affinity to CD38 is consistently higher across a spectrum of CD38+ cell lines than daratumumab. In vitro studies showed that CM313 induces comparable killing activity than daratumumab, including ADCC, CDC, ADCP, apoptosis induced by Fc-mediated cross-linking, and effectively inhibited the enzymatic activity of CD38. However, CM313 showed more potent CDC than isatuximab. In vivo, CM313 dose-dependently inhibited xenograft tumor growth, both as a monotherapy and in combination with dexamethasone or lenalidomide. Furthermore, CM313 was well tolerated with no drug-related clinical signs or off-target risks, as evidenced by 4-week repeat-dose toxicology studies in cynomolgus monkeys and B-hCD38 mice, with the later study showing no observed adverse effect level (NOAEL) of 300mg/kg once weekly. Discussion: CM313 is a novel investigational humanized mAb with a distinct CDR sequence, showing comparable killing effects with daratumumab and stronger CDC activity than isatuximab, which supports its clinical development.


Assuntos
ADP-Ribosil Ciclase 1 , Anticorpos Monoclonais , Citotoxicidade Celular Dependente de Anticorpos , Animais , Feminino , Humanos , Camundongos , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/imunologia , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Antineoplásicos Imunológicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Macaca fascicularis , Glicoproteínas de Membrana , Camundongos Transgênicos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Psychiatry Investig ; 21(5): 464-474, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38810995

RESUMO

OBJECTIVE: We aimed to predict the possible mechanism of obsessive-compulsive disorder (OCD) by integrating and analyzing mRNA sequencing results from two datasets and to provide direction for future studies into the pathogenesis of OCD. METHODS: Two OCD datasets, GSE78104 and GSE60190, were obtained, and the intersection of the two gene sets with differential expression in OCD samples was selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment and Gene Ontology (GO) analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) online analysis website for the genes at the intersection, and the data were mapped using http://www.bioinformatics.com.cn. After genes with p≤0.05 had been screened out, protein-protein interaction (PPI) interaction analysis was conducted using Metascape to screen the key Molecular Complex Detection (MCODE) genes. MCODE genes were then enriched using the KEGG signaling pathway and GO classification. RESULTS: A total of 3,449 differentially expressed genes (DEGs) were obtained from the GSE78104 and GSE60190 datasets. KEGG, GO, and Gene Set Enrichment Analysis analyses of DEGs showed that the onset of OCD was related to oxidative phosphorylation and other metabolic processes, which may have a similar pathogenesis to other neurodegenerative diseases. Single-gene PPI analysis of SAPAP3 revealed that the mechanism by which SAPAP3 knockout induces OCD may also be caused by affecting oxidative phosphorylation. CONCLUSION: The mechanism of SAPAP3 knockout-induced OCD in mice may be due to the oxidative phosphorylation process in the body. Future studies on the neural circuit mechanism of OCD should be conducted.

18.
Plant Cell Rep ; 43(5): 132, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687389

RESUMO

KEY MESSAGE: Salt tolerance, selenium accumulation and expression of the responsive genes were analyzed in the wheat high selenium mutants. Selenium is an essential trace element for the human body, and its deficiency can lead to various diseases such as Keshan disease and large bone disease. Wheat, being a major staple crop, plays a crucial role in providing dietary selenium supplementation to combat this deficiency. Despite progress in understanding the molecular regulation of selenium accumulation in certain crops, the molecular mechanisms governing selenium accumulation-related gene expression in wheat plants remain poorly understood. In this study, three mutant wheat lines with elevated selenium content were identified. Under the treatment of Na2SeO3 or NaCl, the selenium-rich wheat mutants exhibited decreased sensitivity to both selenium and NaCl compared to the wild type. Additionally, there was an increase in the activities of SOD and POD, while the content of MDA decreased. Through qRT-PCR analysis, the expression of selenium-related genes was affected, revealing that some of these genes not only regulate the response of wheat to salt stress, but also play a role in the process of selenium accumulation. The transcriptome results revealed that the important genes encoding glutathione S-transferases, peroxidases, superoxide dismutases, and UDP-glucosyltransferases may function in the regulation of salt tolerance and selenium accumulation in wheat. These findings significantly contribute to the current understanding of the molecular regulation of selenium accumulation in wheat crops, while also offering novel germplasm resources for cultivating selenium-rich and salt-tolerant wheat lines.


Assuntos
Regulação da Expressão Gênica de Plantas , Mutação , Selênio , Triticum , Triticum/genética , Triticum/metabolismo , Selênio/metabolismo , Tolerância ao Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cloreto de Sódio/farmacologia , Genes de Plantas , Transcriptoma/genética , Perfilação da Expressão Gênica
19.
Drugs R D ; 24(2): 145-154, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38644462

RESUMO

BACKGROUND AND OBJECTIVE: Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters. PATIENTS AND METHODS: Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed study and the fasted study. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to evaluate ornidazole contents. maximum plasma concentration (Cmax), time to Cmax (Tmax), the area under the curve (AUC) from t = 0 to infinity (AUC0-∞), AUC from t = 0 to the last quantifiable concentration (AUC0-t), half-life (t1/2), and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure). RESULTS: For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 100.97% (99.12-102.85%), 99.88% (90.63-110.08%), and 101.12% (99.17-103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 103.00% (100.94-105.11%), 101.90% (99.63-104.22%), and 102.99% (100.87-105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (Cmax, AUC0-72, and AUC0-∞) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00-125.00% for both the fasting and fed states. Both treatments have comparable safety profiles. CONCLUSION: The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated among healthy Chinese participants under both fasting and fed conditions. The results indicated that both formulations were bioequivalent and generally well tolerated; besides, the interaction between food and drug may affect drug pharmacokinetics. TRIAL REGISTRATION: CTR20212873, registered on 15 November 2021; ChiCTR2300069098, registered on 7 March 2023.


Assuntos
Área Sob a Curva , Estudos Cross-Over , Jejum , Voluntários Saudáveis , Ornidazol , Comprimidos , Equivalência Terapêutica , Humanos , Adulto , Masculino , Ornidazol/farmacocinética , Ornidazol/administração & dosagem , Ornidazol/efeitos adversos , Adulto Jovem , Feminino , Espectrometria de Massas em Tandem , Povo Asiático , Meia-Vida
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