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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.
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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 ControlesRESUMO
[This corrects the article DOI: 10.1016/j.isci.2024.110255.].
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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.
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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).
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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.
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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/diagnósticoRESUMO
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.
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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.
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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.
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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 XenoenxertoRESUMO
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.
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Acidente Vascular Cerebral , Humanos , Masculino , Recém-Nascido , Feminino , China/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Prognóstico , Eletroencefalografia , Incidência , Imageamento por Ressonância MagnéticaRESUMO
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.
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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.
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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-VidaRESUMO
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.
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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 GênicaRESUMO
There was an error in the original publication [...].
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A synthetic flocculant of aluminum (Al) and iron (Fe) extracted from red mud (RM) has been widely used in sewage treatment, while the remaining RM residue has been ignored. This study aimed to synthesize polymeric aluminum ferric sulfate (PAFS) flocculant from RM by acid leaching and then use the acidified RM residue to produce an acid RM-based ceramsite (ARMC) by mixing bentonite, hydroxypropyl methylcellulose, and starch. Our results showed that sintering, reaction temperature, H2SO4 concentration, reaction time, and liquid-to-solid ratio had an obvious effect on the leaching of Al and Fe in RM, which was a necessary prerequisite for the efficient PAFS flocculants. At a PAFS dosage of 60 mg/L, turbidity and phosphate removal rates were 95.21 ± 0.64% and 89.17 ± 0.52%, respectively. When the pH value was 8.0, the turbidity and phosphate removal efficiency were 99.22 ± 0.66% and 95.98 ± 1.63%, respectively. Considering the adsorption capacity and mechanical properties, the best conditions for ARMC production included using 60% ARM and ceramsite calcination at 600 °C, with the BET surface area 56.16 m2/g and a pore volume of 0.167 cm3/g. Thermogravimetric analysis indicated that 400 °C was a reasonable preheating temperature to enhance the ARMC mechanical strength, as this temperature allows the removal of surface-adsorbed and constituent water. Under a scanning electron microscope, the ARMC appeared rough before adsorption, while relatively uniform pores occupied it after adsorption. Our conclusion will help to improve the zero-waste strategy of RM and speed up the industrial production of RM in flocculants as well as utilizing ARMC as a new type of adsorbent for phosphorus adsorption in sewage treatment.
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Myasthenia gravis (MG) is an autoimmune disease which can impact pregnancy. We describe a transient neonatal myasthenia gravis (TNMG) born to an asymptomatic mother aged 26. The newborn presented cyanosis and generalized muscular weakness quickly after birth. Nasal continuous positive airway pressure (nCPAP) ventilation was performed immediately. On day 3, detailed family history showed that the neonate's 50-year-old maternal grandmother was diagnosed as ocular MG at the age of 40. Ryanodine receptor calcium release channel antibody (RyR-Ab) and acetylcholine receptor antibody (AChR-Ab) tested on day 5 were positive. However, neostigmine tests were negative for the neonate. Intravenous immunoglobulin (IVIG) and oral pyridostigmine were administered. The infant was weaned from the ventilator on day 7. On day 10, the neonate's asymptomatic mother was confirmed to have positive AChR-Ab either. The neonate regained the capability of bottle feeding on day 17 and discharged on day 26. Asymptomatic pregnant women with MG family history can also deliver infants who develop TNMG. Testing AChR antibodies in pregnant women with a family history of MG should be necessary as TNMG was a life-threatening disease. With timely diagnosis and accurate treatment, TNMG can be effectively relieved.
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Silicon nanowire field effect (SiNW-FET) biosensors have been successfully used in the detection of nucleic acids, proteins and other molecules owing to their advantages of ultra-high sensitivity, high specificity, and label-free and immediate response. However, the presence of the Debye shielding effect in semiconductor devices severely reduces their detection sensitivity. In this paper, a three-dimensional stacked silicon nanosheet FET (3D-SiNS-FET) biosensor was studied for the high-sensitivity detection of nucleic acids. Based on the mainstream Gate-All-Around (GAA) fenestration process, a three-dimensional stacked structure with an 8 nm cavity spacing was designed and prepared, allowing modification of probe molecules within the stacked cavities. Furthermore, the advantage of the three-dimensional space can realize the upper and lower complementary detection, which can overcome the Debye shielding effect and realize high-sensitivity Point of Care Testing (POCT) at high ionic strength. The experimental results show that the minimum detection limit for 12-base DNA (4 nM) at 1 × PBS is less than 10 zM, and at a high concentration of 1 µM DNA, the sensitivity of the 3D-SiNS-FET is approximately 10 times higher than that of the planar devices. This indicates that our device provides distinct advantages for detection, showing promise for future biosensor applications in clinical settings.
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Técnicas Biossensoriais , Nanofios , Ácidos Nucleicos , Silício/química , Transistores Eletrônicos , DNA , Técnicas Biossensoriais/métodos , Nanofios/químicaRESUMO
A new species of the subfamily Stegocephalinae, Stegocephaluscarolussp. nov., is described from a seamount in the Caroline Plate. Two related species, S.cascadiensis (Moore, 1992) and S.longicornis (Gurjanova, 1962), were previously reported in the North Pacific. Important morphological characters which differentiate S.carolussp. nov. from S.cascadiensis are found in antenna 1, the mouthparts, pereopod 7 and the length of rami of uropods 2 and 3. The new species differs from S.longicornis by characters of antenna 1, the mouthparts and the shape of epimeral plate 3. Additionally, the morphological differences between the new species and the remaining seven species of Stegocephalus are also presented.
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The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an "active PC" to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of "passive PCs" formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.
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Nanopartículas , Coroa de Proteína , Feminino , Humanos , Enterócitos/metabolismo , Coroa de Proteína/metabolismo , Transcitose , Muco/metabolismo , Transferrinas/metabolismo , Transferrinas/farmacologia , Transferrina/metabolismoRESUMO
To determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5-g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268-01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 1:1 ratio, followed by a 7-day rest interval before the administration of the alternative formulation. After taking the capsules, plasma samples were taken for 48 hours, and using liquid chromatography-tandem mass spectrometry, the calcium dobesilate level was determined. The PK parameters evaluated in the study included the maximum serum concentration (Cmax), area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration, AUC from time 0 to infinity, half-life, time to Cmax, and terminal elimination rate constant. In addition, the safety evaluation encompassed monitoring fluctuations in vitals (temperature, pulse, and blood pressure) and laboratory tests (urinalysis, hepatic function, blood biochemistry, and hematology), as well as recording the emergence of adverse events (AEs). The geometric mean ratio (GMR) of the test/reference medications was used to assess bioequivalence by determining if the 90% confidence intervals of the GMR fell within the predefined range of 80%-125%. AEs were assessed as safety end points. The study included 48 healthy Chinese volunteers (with n = 24 each for the fasting and the fed conditions), and no subjects dropped out for any reason. The differences in the PK metrics for the test and reference drugs for both conditions were insignificant (P > .05). For bioequivalence, irrespective of whether the food was consumed or not, the range of the 90% confidence intervals of the GMR for Cmax, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity was between 80% and 125%. In the experiment, no serious AEs were recorded. Our findings revealed that the calcium dobesilate capsules used as the reference and the test drugs were both bioequivalent. Irrespective of whether the healthy Chinese volunteers consumed food or not, the PK and safety profiles were comparable.
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Dobesilato de Cálcio , Humanos , Área Sob a Curva , Disponibilidade Biológica , China , Estudos Cross-Over , Jejum , Equivalência Terapêutica , Voluntários , População do Leste AsiáticoRESUMO
The purpose of this study was to compare the blood concentration and pharmacokinetic (PK) parameters of 2 formulations under fasting and ed conditions in healthy Chinese volunteers and to evaluate whether the 2 preparations were bioequivalent. This trial screened 170 subjects. Thirteen subjects were assigned to the fasting trial and 18 subjects to the fed trial; 1 subject in the fed trial group was automatically withdrawn for personal reasons. Two cycles had a 14-day washout period. This clinical study was a bioequivalence study, with PK parameters as end point indicators. The bioequivalence PK parameters were the maximal concentration (Cmax ), area under the blood drug concentration-time curve from 0 to 72 hours (AUC0-72 h ), and the time to peak plasma concentration (tmax ) which were determined in human plasma by the liquid chromatography-tandem mass spectrometry method, and nonatrioventricular model analysis was used to determine Cmax , AUC0-72 h , tmax , and other PK parameters. The incidence of adverse events was calculated on the basis of System Organ Classification and Preferred Terms. The results showed that the amlodipine besylate tablets met the equivalence range requirements of bioequivalence in the guidelines for human bioavailability and bioequivalence testing under fasting and fed conditions, compared to the fasting test; the tmax of the fed test was almost unchanged; and the Cmax and AUC0-72 h showed no difference between fasting and fed conditions. It was confirmed that both formulations were well tolerated, and no new safety signals were observed.