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1.
Cell ; 174(2): 259-270.e11, 2018 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-29937224

RESUMEN

Many community- and hospital-acquired bacterial infections are caused by antibiotic-resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) predisposes humans to invasive infections that are difficult to eradicate. We designed a closed-loop gene network programming mammalian cells to autonomously detect and eliminate bacterial infections. The genetic circuit contains human Toll-like receptors as the bacterial sensor and a synthetic promoter driving reversible and adjustable expression of lysostaphin, a bacteriolytic enzyme highly lethal to S. aureus. Immunomimetic designer cells harboring this genetic circuit exhibited fast and robust sense-and-destroy kinetics against live staphylococci. When tested in a foreign-body infection model in mice, microencapsulated cell implants prevented planktonic MRSA infection and reduced MRSA biofilm formation by 91%. Notably, this system achieved a 100% cure rate of acute MRSA infections, whereas conventional vancomycin treatment failed. These results suggest that immunomimetic designer cells could offer a therapeutic approach for early detection, prevention, and cure of pathogenic infections in the post-antibiotic era.


Asunto(s)
Biomimética/métodos , Staphylococcus aureus Resistente a Meticilina/fisiología , Infecciones Estafilocócicas/prevención & control , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Pruebas Antimicrobianas de Difusión por Disco , Femenino , Células HEK293 , Humanos , Receptores de Lipopolisacáridos/genética , Lisostafina/metabolismo , Lisostafina/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Plásmidos/genética , Plásmidos/metabolismo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/veterinaria , Receptor Toll-Like 1/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 6/genética , Factor de Transcripción AP-1/metabolismo
2.
J Am Chem Soc ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847794

RESUMEN

Traditional Li-ion intercalation chemistry into graphite anodes exclusively utilizes the cointercalation-free or cointercalation mechanism. The latter mechanism is based on ternary graphite intercalation compounds (t-GICs), where glyme solvents were explored and proved to deliver unsatisfactory cyclability in LIBs. Herein, we report a novel intercalation mechanism, that is, in situ synthesis of t-GIC in the tetrahydrofuran (THF) electrolyte via a spontaneous, controllable reaction between binary-GIC (b-GIC) and free THF molecules during initial graphite lithiation. The spontaneous transformation from b-GIC to t-GIC, which is different from conventional cointercalation chemistry, is characterized and quantified via operando synchrotron X-ray and electrochemical analyses. The resulting t-GIC chemistry obviates the necessity for complete Li-ion desolvation, facilitating rapid kinetics and synchronous charge/discharge of graphite particles, even under high current densities. Consequently, the graphite anode demonstrates unprecedented fast charging (1 min), dendrite-free low-temperature performance, and ultralong lifetimes exceeding 10 000 cycles. Full cells coupled with a layered cathode display remarkable cycling stability upon a 15 min charging and excellent rate capability even at -40 °C. Furthermore, our chemical strategies are shown to extend beyond Li-ion batteries to encompass Na-ion and K-ion batteries, underscoring their broad applicability. Our work contributes to the advancement of graphite intercalation chemistry and presents a low-cost, adaptable approach for achieving fast-charging and low-temperature batteries.

3.
Bioorg Chem ; 150: 107569, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38905886

RESUMEN

Erianin, a natural compound derived from Dendrobium, has shown significant anticancer properties against a wide range of cancer cells. Despite the identification of multiple mechanisms of action for erianin, none of these mechanisms fully account for its broad-spectrum effect. In this study, we aimed to identify the cellular target and underlying mechanism responsible for the broad-spectrum antitumor effects of erianin. We found that erianin effectively inhibited tubulin polymerization in cancer cells and purified tubulin. Through competition binding assays and X-ray crystallography, it was revealed that erianin bound to the colchicine site of ß-tubulin. Importantly, the X-ray crystal structure of the tubulin-erianin complex was solved, providing clear insight into the orientation and position of erianin in the colchicine-binding site. Erianin showed activity against paclitaxel-resistant cells, evidenced by G2/M cell cycle arrest, apoptosis-related PARP and Caspase-3 cleavage, and in vivo xenograft studies. The study concluded that erianin bound reversibly to the colchicine site of ß-tubulin, inhibited tubulin polymerization, and displayed anticancer activity against paclitaxel-resistant cells, offering valuable insights for further exploration as potential anticancer agents.

4.
J Invertebr Pathol ; 203: 108067, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38278342

RESUMEN

Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs.


Asunto(s)
Monoterpenos Ciclohexánicos , Insectos , Rabdítidos , Animales , Rabdítidos/fisiología
5.
Nano Lett ; 23(9): 3716-3723, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37125916

RESUMEN

Out-of-plane (OP) exciton-based emitters in two-dimensional semiconductor materials are attractive candidates for novel photonic applications, such as radially polarized sources, integrated photonic chips, and quantum communications. However, their low quantum efficiency resulting from forbidden transitions limits their practicality. In this work, we achieve a giant enhancement of up to 34000 for OP exciton emission in indium selenide (InSe) via a designed Ag nanocube-over-Au film plasmonic nanocavity. The large photoluminescence enhancement factor (PLEF) is attributed to the induced OP local electric field (Ez) within the nanocavity, which facilitates effective OP exciton-plasmon interaction and subsequent tremendous enhancement. Moreover, the nanoantenna effect resulting from the effective interaction improves the directivity of spontaneous radiation. Our results not only reveal an effective photoluminescence enhancement approach for OP excitons but also present an avenue for designing on-chip photonic devices with an OP dipole orientation.

6.
J Am Chem Soc ; 145(30): 16538-16547, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37466049

RESUMEN

Solid-electrolyte interphases (SEIs) in advanced rechargeable batteries ensure reversible electrode reactions at extreme potentials beyond the thermodynamic stability limits of electrolytes by insulating electrons while allowing the transport of working ions. Such selective ion transport occurs naturally in biological cell membranes as a ubiquitous prerequisite of many life processes and a foundation of biodiversity. In addition, cell membranes can selectively open and close the ion channels in response to external stimuli (e.g., electrical, chemical, mechanical, and thermal), giving rise to "gating" mechanisms that help manage intracellular reactions. We wondered whether the chemistry and structure of SEIs can mimic those of cell membranes, such that ion gating can be replicated. That is, can SEIs realize a reversible switching between two electrochemical behaviors, i.e., the ion intercalation chemistry of batteries and the ion adsorption of capacitors? Herein, we report such SEIs that result in thermally activated selective ion transport. The function of open/close gate switches is governed by the chemical and structural dynamics of SEIs under different thermal conditions, with precise behaviors as conducting and insulating interphases that enable battery and capacitive processes within a finite temperature window. Such an ion gating function is synergistically contributed by Arrhenius-activated ion transport and SEI dissolution/regrowth. Following the understanding of this new mechanism, we then develop an electrochemical method to heal the SEI layer in situ. The knowledge acquired in this work reveals the possibility of hitherto unknown biomimetic properties of SEIs, which will guide us to leverage such complexities to design better SEIs for future battery chemistries.

7.
Proc Biol Sci ; 290(1995): 20230159, 2023 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-36946117

RESUMEN

Humans exhibit a broad range of post-marital residence patterns and there is growing recognition that post-marital residence predicts women's reproductive success; however, the nature of the relationship is probably dependent on whether co-resident kin are cooperators or competitors. Here, we explore this relationship in a Tibetan population, where couples practice a mixture of post-marital residence patterns, co-residing in the same village with the wife's parents, the husband's parents or endogamously with both sets of parents. Using detailed demographic data from 17 villages we find that women who live with only their own parents have an earlier age at first birth (AFB) and age at last birth (ALB) than women who live with only their parents-in-law. Women who co-reside with both sets of parents have the earliest AFB and ALB. However, those with co-resident older siblings postponed reproduction, suggestive of competition-related delay. Shifts to earlier reproductive timing were also observed in relation to the imposition of family planning policies, in line with Fisherian expectations. Our study provides evidence of the costs and benefits to women's direct fitness of co-residing with different kin, against a backdrop of adaptive responses to cultural constraints on completed fertility.


Asunto(s)
Composición Familiar , Matrimonio , Femenino , Humanos , Factores Socioeconómicos , Reproducción , Fertilidad
8.
Cytotherapy ; 25(2): 210-219, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36443171

RESUMEN

BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer; however, there is no consensus on the manufacturing processes. Cell type heterogeneity in products manufactured by various methods is understudied and may elicit safety concerns from the regulatory perspective. METHODS: We characterized the cell type composition of a recently developed DC vaccine, CUD-002, consisting of DCs loaded with mRNA encoding personalized tumor neoantigens (NCT05270720). RESULTS: Using single-cell transcriptomic analysis as an unbiased approach, we found that >80% cells in the final product were DCs and the rest primarily comprised myelocytes and lymphocytes. Subsequent fluorescence-activated cell sorting analyses confirmed these cellular identities. These results indicate that unintended cells originate from leukapheresis, the first step of the manufacturing process, and thus likely safe. Consistently, no overt toxicity or tumorigenicity was observed in mice inoculated with CUD-002. CONCLUSIONS: Considering that leukapheresis is a widely used procedure for collecting diverse peripheral blood cell types to manufacture various cytotherapies, this study establishes a workflow to analyze and address regulatory considerations on cell type heterogeneity.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Vacunas , Animales , Ratones , Vacunas contra el Cáncer/genética , Células Dendríticas , Inmunoterapia/métodos , Neoplasias/terapia , Análisis de Secuencia de ARN , Vacunas/metabolismo , Estudios Clínicos como Asunto
9.
Eur J Nucl Med Mol Imaging ; 50(2): 475-485, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36269382

RESUMEN

PURPOSE: Heart failure (HF) is a chronic progressive clinical syndrome associated with structural and/or functional heart abnormalities. Active fibroblasts and ventricular remodelling play an essential role in HF progression. 68Ga-labelled fibroblast activation protein (FAP) inhibitor (68Ga-FAPI) binds to FAP. This study aimed to examine the feasibility of using 68Ga-FAPI positron emission tomography (PET)/computed tomography (CT) to visualize changes in cardiac fibrosis and function over time in the HF setting. METHODS: After establishing an isoproterenol (ISO)-induced HF rat model (14 consecutive days of intraperitoneal ISO injections), echocardiography and 68Ga-FAPI PET/CT were performed weekly in experimental and control groups. Rat hearts were examined weekly for biodistribution analysis; autoradiography; and haematoxylin and eosin, FAP immunofluorescence and Masson's trichrome staining analysis. Rat blood was sampled weekly for enzyme-linked immunosorbent assay analysis of various plasma indicators. A preliminary clinical study was also performed in seven HF patients who underwent both 13N-amino (NH3) perfusion and 68Ga-FAPI cardiac PET imaging. RESULTS: In the animal experiments, myocardial 68Ga-FAPI uptake, expression of FAP and myocardial contractility peaked on day 7 after the initial ISO injection. Only slight fibrotic changes were observed on histopathological examination. 68Ga-FAPI uptake and ventricular wall motion decreased over time as cardiac fibrosis and degree of myocardial injury gradually increased. In the human HF patient study, 68Ga-FAPI PET imaging identified varying degrees of 68Ga-FAPI uptake in the myocardium that did not precisely match with 13N-NH3 myocardial perfusion. CONCLUSION: As HF progresses, 68Ga-FAPI uptake is high in the early stages and then gradually decreases. Although preliminary, our findings suggest that 68Ga-FAPI PET can be used to demonstrate active myocardial fibrosis. Active myocardial FAP expression is followed by myocardial remodelling and fibrosis. Detection of early active FAP expression may assist treatment decision making in HF patients. CLINICAL TRIAL REGISTRATION: NCT04982458.


Asunto(s)
Insuficiencia Cardíaca , Tomografía Computarizada por Tomografía de Emisión de Positrones , Animales , Humanos , Ratas , Radioisótopos de Galio , Insuficiencia Cardíaca/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Distribución Tisular
10.
Nature ; 543(7647): 690-694, 2017 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-28297708

RESUMEN

A zeolite with structure type MFI is an aluminosilicate or silicate material that has a three-dimensionally connected pore network, which enables molecular recognition in the size range 0.5-0.6 nm. These micropore dimensions are relevant for many valuable chemical intermediates, and therefore MFI-type zeolites are widely used in the chemical industry as selective catalysts or adsorbents. As with all zeolites, strategies to tailor them for specific applications include controlling their crystal size and shape. Nanometre-thick MFI crystals (nanosheets) have been introduced in pillared and self-pillared (intergrown) architectures, offering improved mass-transfer characteristics for certain adsorption and catalysis applications. Moreover, single (non-intergrown and non-layered) nanosheets have been used to prepare thin membranes that could be used to improve the energy efficiency of separation processes. However, until now, single MFI nanosheets have been prepared using a multi-step approach based on the exfoliation of layered MFI, followed by centrifugation to remove non-exfoliated particles. This top-down method is time-consuming, costly and low-yield and it produces fragmented nanosheets with submicrometre lateral dimensions. Alternatively, direct (bottom-up) synthesis could produce high-aspect-ratio zeolite nanosheets, with improved yield and at lower cost. Here we use a nanocrystal-seeded growth method triggered by a single rotational intergrowth to synthesize high-aspect-ratio MFI nanosheets with a thickness of 5 nanometres (2.5 unit cells). These high-aspect-ratio nanosheets allow the fabrication of thin and defect-free coatings that effectively cover porous substrates. These coatings can be intergrown to produce high-flux and ultra-selective MFI membranes that compare favourably with other MFI membranes prepared from existing MFI materials (such as exfoliated nanosheets or nanocrystals).

11.
Molecules ; 28(5)2023 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-36903428

RESUMEN

In this study, a series of Al-doped metal-organic frameworks (AlxZr(1-x)-UiO-66) were synthesized through a one-step solvothermal method. Various characterization techniques, including X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and N2 sorption measurement, suggested that the Al doping was uniform and barely influenced the crystallinity, chemical stability, and thermal stability of the materials. Two cationic dyes, safranine T (ST) and methylene blue (MB), were selected for investigating the adsorption performances of Al-doped UiO-66 materials. Al0.3Zr0.7-UiO-66 exhibited 9.63 and 5.54 times higher adsorption capacities than UiO-66, 498 mg/g and 251 mg/g for ST and MB, respectively. The improved adsorption performance can be attributed to π-π interaction, hydrogen bond, and the coordination between the dye and Al-doped MOF. The pseudo-second-order and Langmuir models explained the adsorption process well, which indicated that the dye adsorption on Al0.3Zr0.7-UiO-66 mostly occurred through chemisorption on homogeneous surfaces. A thermodynamic study indicated the adsorption process was spontaneous and endothermic. The adsorption capacity did not decrease significantly after four cycles.

12.
Water Sci Technol ; 88(10): 2694-2705, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38017686

RESUMEN

Groundwater reservoirs play an important role in regional water volume balance. In order to ensure the efficiency of a groundwater reservoir and obtain its maximum value, it is necessary to figure out its characteristics, such as minimum water level, normal water level, and maximum water level. The characteristics not only determined the storage capacity but also influenced the water allocation and utilization. Therefore, this paper took a groundwater reservoir built in an alluvial fan as an example to assess its storage capacity and the influence on water dynamic control. The alluvial fan was located in the front of Lao River, where there were an alluvial-diluvial fan, groundwater storage space, and natural impervious boundary. Therefore, it was an ideal place for constructing a groundwater reservoir. Through theoretical analysis and numerical simulation, the storage capacity was determined, and the influence of groundwater reservoir characteristics on water dynamic control was analyzed. On this basis, the water-supply method in the research area was confirmed. This paper will present a new method for repairing the groundwater system and protecting the ecological environment.


Asunto(s)
Agua Subterránea , Contaminantes Químicos del Agua , Agua/análisis , Agua Subterránea/análisis , Abastecimiento de Agua , Ríos , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente/métodos
13.
Small ; 18(44): e2204120, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36135780

RESUMEN

Colloidal semiconductor CdSe nanoplatelets (NPLs) feature ultranarrow and anisotropic emissions. However, the optical performance of blue-emitting NPLs is deteriorated by trap states, currently exhibiting tainted emissions and inferior photoluminescence quantum yields (PLQYs). Here, near trap-free blue-emitting NPLs are achieved by the controlled growth of the core/crown. Deep trap states in NPLs can be partially suppressed with the asymmetrical crown growth and are further suppressed with the growth of the small core and the alloyed symmetrical crown, yielding NPLs with pure blue emissions and near-unity PLQYs. Exciton dynamic research based on these NPLs indicates that the trap emission stems from surface traps. Besides, light-emitting diodes exhibiting ultranarrow emission centered around 461 nm with full-width-at-half-maximums down to 11 nm are fabricated using these NPLs.

14.
J Virol ; 95(12)2021 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-33789997

RESUMEN

Enteroviruses belong to the genus Enterovirus of the family Picornaviridae and include four human enterovirus groups (EV-A to -D): the epidemic of enteroviruses such as human enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) is a threat to global public health. Enteroviral protein 2C is the most conserved nonstructural protein among all enteroviruses and possesses RNA helicase activity that plays pivotal roles during enteroviral life cycles, which makes 2C an attractive target for developing antienterovirus drugs. In this study, we designed a peptide, named 2CL, based on the structure of EV-A71 2C. This peptide effectively impaired the oligomerization of EV-A71 2C protein and inhibited the RNA helicase activities of 2C proteins encoded by EV-A71 and CVA16, both of which belong to EV-A, and showed potent antiviral efficacy against EV-A71 and CVA16 in cells. Moreover, the 2CL treatment elicited a strong in vivo protective efficacy against lethal EV-A71 challenge. In addition, the antiviral strategy of targeting the 2C helicase activity can be applied to inhibit the replication of EV-B. Either 2CL or B-2CL, the peptide redesigned based on the 2CL-corresponding sequence of EV-Bs, could exert effective antiviral activity against two important EV-Bs, coxsackievirus B3 and echovirus 11. Together, our findings demonstrated that targeting the helicase activity of 2C with a rationally designed peptide is an efficient antiviral strategy against enteroviruses, and 2CL and B-2CL show promising clinical potential to be further developed as broad-spectrum antienterovirus drugs.IMPORTANCE Enteroviruses are a large group of positive-sense single-stranded RNA viruses and include numerous human pathogens, such as enterovirus A71 (EV-A71), coxsackieviruses, and echoviruses. However, no approved EV antiviral drugs are available. Enteroviral 2C is the most conserved nonstructural protein among all enteroviruses and contains the RNA helicase activity critical for the viral life cycle. Herein, according to the structure of EV-A71 2C, we designed a peptide that effectively inhibited the RNA helicase activities of EV-A71- and coxsackievirus A16 (CVA16)-encoded 2C proteins. Moreover, this peptide exerted potent antiviral effects against EV-A71 and CVA16 in cells and elicited therapeutic efficacy against lethal EV-A71 challenge in vivo Furthermore, we demonstrate that the strategy of targeting the 2C helicase activity can be used for other relevant enteroviruses, including coxsackievirus B3 and echovirus 11. In summary, our findings provide compelling evidence that the designed peptides targeting the helicase activity of 2C could be broad-spectrum antivirals for enteroviruses.


Asunto(s)
Antivirales/farmacología , Proteínas Portadoras/antagonistas & inhibidores , Enterovirus Humano A/efectos de los fármacos , Infecciones por Enterovirus/tratamiento farmacológico , Péptidos/farmacología , ARN Helicasas/antagonistas & inhibidores , Proteínas no Estructurales Virales/antagonistas & inhibidores , Animales , Antivirales/química , Antivirales/uso terapéutico , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , Línea Celular , Diseño de Fármacos , Enterovirus Humano A/química , Enterovirus Humano A/fisiología , Enterovirus Humano B/efectos de los fármacos , Enterovirus Humano B/fisiología , Infecciones por Enterovirus/virología , Humanos , Ratones , Ratones Endogámicos ICR , Péptidos/química , Péptidos/uso terapéutico , ARN Helicasas/metabolismo , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/metabolismo , Replicación Viral/efectos de los fármacos
15.
BMC Neurol ; 22(1): 424, 2022 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-36371153

RESUMEN

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an inflammatory disease of the central nervous system (CNS) in which antibodies within the serum and cerebrospinal fluid (CSF) target NMDA receptors. Glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease affecting the central nervous system (CNS). Meningoencephalitis can affect any anatomical region rostrocaudally, from the optic nerve to the spinal cord. The clinical implications of NMDAR antibodies overlapping with other antibodies against glial or neuronal cell surface proteins have not been investigated. CASE PRESENTATION: A 35-year-old male presented with headaches along with amnesia, slurred and awkward speech, psychiatric symptoms, cognitive decline, and insomnia. His medical history revealed ankylosing spondylitis for six months. Ancillary findings included CSF pleocytosis and elevated protein levels. T2-weighted fluid attenuation inversion recovery was used to image high-intensity lesions of the bilateral paraventricular, radiate corona, semioval centre, and right subcortical regions. The CSF was positive for NMDAR and GFAP antibodies through transfected cell-based assays. A diagnosis of anti-GFAP encephalitis was made, although the prominent clinical features were of anti-NMDAR encephalitis. CONCLUSIONS: Herein, we describe a case of anti-NMDAR encephalitis with overlapping symptoms of GFAP antibody positivity. Patients with unusual symptoms of anti-NMDAR encephalitis should also be tested for anti-GFAP antibodies. However, because this was a single case study, caution should be exercised when interpreting the observations. Since the patient was diagnosed with autoimmune encephalitis, intravenous methylprednisolone was administered, which yielded a positive outcome.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Enfermedad de Hashimoto , Masculino , Humanos , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Autoanticuerpos , Receptores de N-Metil-D-Aspartato , Inmunoglobulina G
16.
Bioorg Chem ; 128: 106053, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35964504

RESUMEN

A hydroxamic acid based microtubule-destabilizing agent (MDA) SKLB-14b was discovered in this study, which was derived from shortening the linker length of the HDAC6 and microtubule dual-target inhibitor SKLB-23bb. SKLB-14b exhibited low nanomolar IC50 values on a wide spectrum of human cancer cell lines including both sensitive and multidrug-resistant cell lines. Surprisingly, its anti-proliferative activity relied on the presence of the hydroxamic acid group but lost inhibitory activity against HDACs. SKLB-14b bound to the colchicine site of tubulin and could inhibit tubulin polymerization. It exhibited good metabolic stability in liver microsomes, no inhibitory effect on CYP450 isoenzymes and high oral bioavailability. In vivo experiments revealed that SKLB-14b was potent in both sensitive (A2780S, HCT116) and resistant (A2780/T) xenograft mice models. Furthermore, in the patient-derived tumor xenograft (PDX) models of osimertinib resistant non-small cell lung cancer (NSCLC), 50 mg/kg of SKLB-14b administered every twodays inhibited tumor growth by 70.6% without obvious toxicity, better than the 59.7% inhibition rate of paclitaxel. Mechanistically, we found that SKLB-14b exerted anti-tumor and anti-multidrug resistance effects in vitro and in vivo through cell cycle arrest and pro-apoptotic activities, as well as vascular disrupting activities. Therefore, we discovered that SKLB-14b, as a novel MDA based on hydroxamic acid, could serve as a potential drug candidate for cancer therapy which deserves further investigation.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Ováricas , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Ácidos Hidroxámicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Microtúbulos , Neoplasias Ováricas/tratamiento farmacológico , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Andrologia ; 54(6): e14403, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35233797

RESUMEN

Leukocytospermia is one of the common causes of male infertility, and its effects on the clinical outcomes of assisted reproduction are controversial. There are no recommendations for the management of leukocytospermia in cases of assisted reproductive technology (ART). To investigate the impact of leukocytospermia on ART, we retrospectively compared the clinical outcomes in ART couples with or without leukocytospermia and further analysed the impact of the insemination method itself by split insemination treatment in ART couples with leukocytospermia. In this study, leukocytospermia was detected in 133 patients, namely 63 in the conventional in vitro fertilization (IVF) group, 38 in the intracytoplasmic sperm injection (ICSI) group and 32 in the split insemination group. Leukocytospermia has a negative influence on the parameters of semen samples; however, leukocytospermia did not affect the clinical outcomes of IVF or ICSI. Different insemination methods did not affect the fertilization, clinical pregnancy or live birth rates. In the split insemination study, no significant differences in clinical pregnancy and live birth rates between the IVF and ICSI groups were found; however, the numbers of two pronuclei (2PN), available embryos and good-quality embryos in the ICSI group were higher than those in the IVF group. Leukocytospermia may be a risk factor affecting semen parameters, and more attention should be given to IVF insemination. Leukocytospermia has no significant negative effect on the outcomes of ART. ICSI may obtain better embryos than IVF, but it cannot improve the clinical pregnancy and live birth rates.


Asunto(s)
Técnicas Reproductivas Asistidas , Inyecciones de Esperma Intracitoplasmáticas , Tasa de Natalidad , Femenino , Fertilización In Vitro , Humanos , Masculino , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/métodos
18.
J Integr Neurosci ; 21(1): 27, 2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35164463

RESUMEN

Background: To investigate the safety and efficacy of endovascular embolization of very tiny (≤2 mm) intracranial aneurysms with single coil and summarize experience. Methods: A retrospective analysis was performed for 15 consecutive patients with very tiny aneurysms treated by coil embolization alone or stent-assisted coil embolization between January 2017 and January 2020. 15 patients with six unruptured aneurysms and nine ruptured aneurysms were included in this study. There were eight males and seven females with a mean age of 50.0 ± 5.2 years (range 41 to 57 years old). Intraoperative complications, imaging outcomes, clinical outcomes and follow-up data were analyzed. Results: All aneurysms were embolized with a single coil. Lvis stents were used in all coil assisted embolizations. The embolization success rate was 100%. The average volume embolization ratio (VER) of aneurysm embolization was 53.7 ± 25.5%. An intraoperative aneurysm re-rupture complication occurred in one patient (6.7%). 11 patients (73.3%) had immediate complete occlusion after embolization. After a mean follow-up period of 6.7 ± 1.4 months, 13 patients (86.7%) had complete occlusion. No patients had aneurysm re-rupture, an ischemic event or recurrence during follow-up. All patients achieved favorable clinical outcomes with a modified rankin scale (MRS) of 0-2. Conclusions: This study demonstrates that endovascular embolization of very tiny intracranial aneurysms with a single coil is safe and effective. However, the follow-up period was not long enough and studies with larger numbers of patients are required. The summary of experience reported here is expected to provide significant patient benefits.


Asunto(s)
Embolización Terapéutica , Aneurisma Intracraneal/terapia , Evaluación de Procesos y Resultados en Atención de Salud , Adulto , Embolización Terapéutica/instrumentación , Embolización Terapéutica/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents
19.
Heart Surg Forum ; 25(5): E676-E679, 2022 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-36317900

RESUMEN

Giant atrial septal defect (ASD) often is associated with atrial arrhythmia, such as atrial fibrillation (AF). The recovery rate of AF is very low. Moreover, it is difficult for the intervention of a giant atrial septal defect, and it also is more difficult to perform atrial septal puncture and left atrial appendage (LAA) closure after ASD occlusion. Here, we report a case of a giant ASD and permanent AF. We find that the AF is significantly improved after atrial septal defect (ASD) occlusion and left atrial appendage (LAA) occlusion, which is manifested by spontaneous restoration and maintenance of normal sinus rhythm.


Asunto(s)
Fibrilación Atrial , Procedimientos Quirúrgicos Cardíacos , Ablación por Catéter , Defectos del Tabique Interatrial , Humanos , Fibrilación Atrial/complicaciones , Defectos del Tabique Interatrial/cirugía
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(4): 701-706, 2022 Jul.
Artículo en Zh | MEDLINE | ID: mdl-35871744

RESUMEN

Objective: To evaluate the pregnancy outcomes and neurodevelopment prognosis of subjects prenatally diagnosed with fetal ventriculomegaly (VM). Methods: All the subjects with VM diagnosed by ultrasound and were admitted and treated at West China Second Hospital, Sichuan University between March 2011 and September 2020 were retrospectively enrolled for a chohort study, while non-VM subjects of the same period were selected with a random number table to form the control group. Pregnancy outcomes of the two groups were compared, and the fetuses of both groups were followed up after birth for further assessment and comparison of their neurodevelopmental prognosis. Results: The live birth rate of the VM group was lower than that of the control group (77.63% [229/295] vs. 94.31% [265/281], P<0.001). Furthermore, the proportion of subjects that were transferred to NICU for monitoring and observation after birth was higher in the VM group than that of the control group (20.96% [48/229] vs. 4.53% [12/265], P<0.001). During the follow-up, it was found that the rate of neurodevelopmental abnormalities of the VM group was significantly higher than that of the control group (11.79% [27/229] vs. 1.90% [5/265], P<0.001). Moreover, neurodevelopmental abnormalities of VM fetuses were correlated to the following factors, the degree of VM ( P=0.010), intrauterine progression of VM ( P=0.024), and whether the postnatal cranial ultrasound result was suggestive of VM ( P=0.001). In addition, postnatal cranial ultrasound suggestive of VM was found to be an independent risk factor for neurodevelopmental abnormalities ( OR=9.434, 95% CI: 1.791-49.688, P=0.008). Conclusion: VM reduces the fetal live birth rate and may increase the risks of neurodevelopmental abnormalities after birth. All VM fetuses should be closely followed up for neurodevelopment status after birth, especially those with severe VM, intrauterine progression, and postnatal cranial ultrasound indicative of VM.


Asunto(s)
Hidrocefalia , Resultado del Embarazo , Femenino , Feto/diagnóstico por imagen , Humanos , Hidrocefalia/diagnóstico por imagen , Imagen por Resonancia Magnética , Embarazo , Pronóstico , Estudios Retrospectivos , Ultrasonografía Prenatal
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