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1.
Molecules ; 29(17)2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39275059

RESUMEN

Carbon dots (CDs) have garnered extensive interest in basic physical chemistry as well as in biomedical applications due to their low cost, good biocompatibility, and great aqueous solubility. However, the synthesis of multi-functional carbon dots has always been a challenge for researchers. Here, we synthesized novel CDs with a high quantum yield of 28.2% through the straightforward hydrothermal method using Diaminomaleonitrile and Boc-D-2, 3-diaminopropionic acid. The size, chemical functional group, and photophysical properties of the CDs were characterized by TEM, FTIR, XPS, UV, and fluorescence. It was demonstrated in this study that the prepared CDs have a high quantum yield, excellent photostability, and low cytotoxicity. Regarding the highly water-soluble property of CDs, they were proven to possess selective and sensitive behavior against Cu2+ ions (linear range = 0-9 µM and limit of detection = 1.34 µM). Moreover, the CDs were utilized in fluorescent ink in anti-counterfeiting measures. Because of their low cytotoxicity and good biocompatibility, the CDs were also successfully utilized in cell imaging. Therefore, the as-prepared CDs have great potential in fluorescence sensing, anti-counterfeiting, and bioimaging.


Asunto(s)
Carbono , Cobre , Puntos Cuánticos , Cobre/química , Cobre/análisis , Carbono/química , Puntos Cuánticos/química , Humanos , Colorantes Fluorescentes/química , Células HeLa
2.
Transl Psychiatry ; 14(1): 325, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107319

RESUMEN

Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.


Asunto(s)
Trastorno del Espectro Autista , Modelos Animales de Enfermedad , Interneuronas , Parvalbúminas , Corteza Prefrontal , Cognición Social , Trastorno del Espectro Autista/fisiopatología , Animales , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/metabolismo , Ratones , Interneuronas/metabolismo , Interneuronas/fisiología , Parvalbúminas/metabolismo , Masculino , Conducta Animal/fisiología , Conducta Social , Ratones Endogámicos C57BL , Femenino
3.
Emerg Microbes Infect ; 13(1): 2387439, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39139051

RESUMEN

Avian influenza viruses (AIVs) are the origin of multiple mammal influenza viruses. The genetic determinants of AIVs adapted to humans have been widely elucidated, however, the molecular mechanism of cross-species transmission and adaptation of AIVs to canines are still poorly understood. In this study, two H3N2 influenza viruses isolated from a live poultry market (A/environment/Guangxi/13431/2018, GX13431) and a swab sample from a canine (A/canine/Guangdong/0601/2019, GD0601) were used to investigate the possible molecular basis that determined H3N2 AIV adapting to canine. We found that GD0601 exhibited more robust polymerase activity in cells and higher pathogenicity in mice compared with its evolution ancestor H3N2 AIV GX13431. A series of reassortments of the ribonucleoprotein (RNP) complex showed that the PB2 subunit was the crucial factor that conferred high polymerase activity of GD0601, and the substitution of I714S in the PB2 subunit of GD0601 attenuated the replication and pathogenicity in mammal cells and the mouse model. Mechanistically, the reverse mutation of I714S in the PB2 polymerase subunit which was identified in AIV GX13431 reduced the nuclear import efficiency of PB2 protein and interfered with the interactions of PB2-PA/NP that affected the assembly of the viral RNP complex. Our study reveals amino acid mutation at the position of 714 in the nuclear localization signal (NLS) area in PB2 plays an important role in overcoming the barrier from poultry to mammals of the H3N2 canine influenza virus and provides clues for further study of mammalian adaptation mechanism of AIVs.


Asunto(s)
Subtipo H3N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , ARN Polimerasa Dependiente del ARN , Ribonucleoproteínas , Proteínas Virales , Animales , Perros , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/fisiología , Ratones , Proteínas Virales/genética , Proteínas Virales/metabolismo , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Infecciones por Orthomyxoviridae/virología , Humanos , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Transporte Activo de Núcleo Celular , Replicación Viral , Mutación , Células de Riñón Canino Madin Darby , Enfermedades de los Perros/virología , Ratones Endogámicos BALB C , Células HEK293 , Virus Reordenados/genética
4.
Sci Adv ; 10(35): eadp5935, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39213361

RESUMEN

The unique bacterial infection microenvironment (IME) usually requires complicated design of nanomaterials to adapt to IME for enhancing antibacterial therapy. Here, an alternative IME adaptative nitrite reductase-mimicking nanozyme is constructed by in situ growth of ultrasmall copper sulfide clusters on the surface of a nanofibrillar lysozyme assembly (NFLA/CuS NHs), which can temporally regulate nitric oxide (NO) gradient concentration to kill bacteria initially and promote tissue regeneration subsequently. Benefiting from a copper nitrite reductase (CuNIR)-inspired structure with CuS cluster as active center and NFLA as skeleton, NFLA/CuS NHs efficiently boost the catalytic reduction of nitrite to NO. The inherent supramolecular fibrillar networks displays excellent bacterial capture capability, facilitating initial high-concentration NO attacks on the bacteria. The subsequent catalytic release of low-concentration NO by NFLA/CuS NHs-mediated nitrite reduction remarkably promotes cell migration and angiogenesis. This work paves the way for dynamically eliminating MDR bacterial infection and promoting tissue regeneration in a simple and smart way through CuNIR-mimicking catalysis.


Asunto(s)
Antibacterianos , Óxido Nítrico , Nitrito Reductasas , Animales , Humanos , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Catálisis , Cobre/química , Cobre/metabolismo , Muramidasa/metabolismo , Muramidasa/química , Óxido Nítrico/metabolismo , Nitrito Reductasas/metabolismo , Nitrito Reductasas/química , Nitritos/metabolismo
5.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39129365

RESUMEN

Enzymatic reaction kinetics are central in analyzing enzymatic reaction mechanisms and target-enzyme optimization, and thus in biomanufacturing and other industries. The enzyme turnover number (kcat) and Michaelis constant (Km), key kinetic parameters for measuring enzyme catalytic efficiency, are crucial for analyzing enzymatic reaction mechanisms and the directed evolution of target enzymes. Experimental determination of kcat and Km is costly in terms of time, labor, and cost. To consider the intrinsic connection between kcat and Km and further improve the prediction performance, we propose a universal pretrained multitask deep learning model, MPEK, to predict these parameters simultaneously while considering pH, temperature, and organismal information. Through testing on the same kcat and Km test datasets, MPEK demonstrated superior prediction performance over the previous models. Specifically, MPEK achieved the Pearson coefficient of 0.808 for predicting kcat, improving ca. 14.6% and 7.6% compared to the DLKcat and UniKP models, and it achieved the Pearson coefficient of 0.777 for predicting Km, improving ca. 34.9% and 53.3% compared to the Kroll_model and UniKP models. More importantly, MPEK was able to reveal enzyme promiscuity and was sensitive to slight changes in the mutant enzyme sequence. In addition, in three case studies, it was shown that MPEK has the potential for assisted enzyme mining and directed evolution. To facilitate in silico evaluation of enzyme catalytic efficiency, we have established a web server implementing this model, which can be accessed at http://mathtc.nscc-tj.cn/mpek.


Asunto(s)
Aprendizaje Profundo , Enzimas , Cinética , Enzimas/metabolismo , Enzimas/química , Algoritmos , Biología Computacional/métodos
6.
ACS Appl Mater Interfaces ; 16(28): 36354-36362, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38955841

RESUMEN

Sodium-ion batteries (SIBs), owing to their abundant resources and cost-effectiveness, have garnered considerable interest in the realm of large-scale energy storage. The properties of cathode materials profoundly affect the cycle stability and specific capacity of batteries. Herein, a series of Cu-doped spherical P2-type Na0.7Fe0.23-xCuxMn0.77O2 (x = 0, 0.05, 0.09, and 0.14, x-NFCMO) was fabricated using a convenient hydrothermal method. The successful doping of Cu efficaciously mitigated the Jahn-Teller effect, augmented the electrical conductivity of the material, and diminished the resistance to charge transfer. The distinctive spherical structure remained stable and withstood considerable volumetric strain, thereby improving the cyclic stability of the material. The optimized 0.09-NFCMO cathode exhibited a high specific capacity of 168.6 mAh g-1 at 100 mA g-1, a superior rate capability (90.9 mAh g-1 at 2000 mA g-1), and a good cycling stability. This unique structure design and doping approach provides new insights into the design of advanced electrode materials for sodium-ion batteries.

7.
Mater Today Bio ; 26: 101107, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38952538

RESUMEN

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

9.
Polymers (Basel) ; 16(11)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38891531

RESUMEN

HPAM/PEI gel is a promising material for conformance control in hydrocarbon reservoirs. However, its use in low-permeability reservoirs is limited by the high polymer concentrations present. In this study, the gelation performance of an HPAM/PEI system with HPAM < 2.0 wt.% was systematically investigated. The gelation time for HPAM concentrations ranging from 0.4 to 2.0 wt.% varied from less than 1 h to 23 days, with the highest gel strength identified as grade H. The hydrodynamic radius manifested the primary effect of HPAM on the gelation performance. Branched PEI provided superior gelation performance over linear PEI, and the gelation performance was only affected when the molecular weight of the PEI varied significantly. The optimal number ratio of the PEI-provided imine groups and the HPAM-provided carboxylic acid functional groups was approximately 1.6:1~5:1. Regarding the reservoir conditions, the temperature had a crucial effect on the hydrodynamic radius of HPAM. Salts delayed the gelation process, and the order of ionic influence was Ca2+ > Na+ > K+. The pH controlled the crosslinking reaction, primarily due to the protonation degree of PEI and the hydrolysis degree of HPAM, and the most suitable pH was approximately 10.5. Plugging experiments based on a through-type fracture showed that multi-slug plugging could significantly improve the plugging performance of the system, being favorable for its application in fractured low-permeability reservoirs.

10.
ACS Nano ; 18(28): 18503-18521, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38941540

RESUMEN

Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many studies have presented improved effect of printing skin substitutes in wound healing, using hydrogel inks to fabricate 3D bioprinting architectures with complicated structures, mimicking mechanical properties, and appropriate cellular environments is still challenging. Inspired by collagen nanofibers withstanding stress and regulating cell behavior, a patterned nanofibrous film was introduced to the printed hydrogel scaffold to fabricate a composite artificial skin substitute (CASS). The artificial dermis was printed using gelatin-hyaluronan hybrid hydrogels containing human dermal fibroblasts with gradient porosity and integrated with patterned nanofibrous films simultaneously, while the artificial epidermis was formed by seeding human keratinocytes upon the dermis. The collagen-mimicking nanofibrous film effectively improved the tensile strength and fracture resistance of the CASS, making it sewable for firm implantation into skin defects. Meanwhile, the patterned nanofibrous film also provided the biological cues to guide cell behavior. Consequently, CASS could effectively accelerate the regeneration of large-area skin defects in mouse and pig models by promoting re-epithelialization and collagen deposition. This research developed an effective strategy to prepare composite bioprinting architectures for enhancing mechanical property and regulating cell behavior, and CASS could be a promising skin substitute for treating large-area skin defects.


Asunto(s)
Bioimpresión , Nanofibras , Impresión Tridimensional , Piel Artificial , Humanos , Nanofibras/química , Animales , Ratones , Porcinos , Hidrogeles/química , Fibroblastos/citología , Ingeniería de Tejidos , Queratinocitos/citología , Andamios del Tejido/química , Ácido Hialurónico/química , Gelatina/química
11.
ACS Omega ; 9(24): 26213-26221, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38911735

RESUMEN

Accurate and rapid evaluation of density is crucial for evaluating the packing and combustion characteristics of high-energy-density fuels (HEDFs). This parameter is pivotal in the selection of high-performance HEDFs. Our study leveraged a polycyclic compound density data set and quantum chemical (QC) descriptors to establish a correlation with the target properties using the XGBoost algorithm. We utilized a recursive feature elimination method to simplify the model and developed a concise and interpretable density prediction model incorporating only six QC descriptors. The model demonstrated robust performance, achieving coefficients of determination (R 2) of 0.967 and 0.971 for internal and external test sets, respectively, and root-mean-square errors (RMSE) of 0.031 and 0.027 g/cm3, respectively. Compared to the other two mainstream methods, the marginal discrepancy between the predicted and actual molecular densities underscores the model's superior predictive ability and more usefulness for energy density calculation. Furthermore, we developed a web server (SesquiterPre, https://sespre.cmdrg.com/#/) that can simultaneously calculate the density, enthalpy of combustion, and energy density of sesquiterpenoid HEDFs, which greatly facilitates the use of researchers and is of great significance for accelerating the design and screening of novel sesquiterpenoid HEDFs.

12.
J Vasc Surg Venous Lymphat Disord ; 12(5): 101905, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38761979

RESUMEN

OBJECTIVE: Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, supraclavicular vascularized lymph node transfer (SC-VLNT) is a favored approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction. METHODS: A cohort of 35 patients with GC-LEL was examined, comprising 13 patients who underwent single lymph nodes flap with a skin paddle (SLNF+P), 12 who received single lymph nodes flap without a skin paddle (SLNF), and 10 who accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and postoperative variables. RESULTS: The median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patients noted subjective improvements in Lymphedema Quality of Life scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage Ⅱ). The median follow-up time was 16 months (range, 12-36 months), with no reported severe postoperative complications. CONCLUSIONS: For advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization.


Asunto(s)
Neoplasias de los Genitales Femeninos , Lipectomía , Extremidad Inferior , Ganglios Linfáticos , Linfedema , Humanos , Femenino , Persona de Mediana Edad , Lipectomía/efectos adversos , Lipectomía/métodos , Linfedema/cirugía , Linfedema/etiología , Linfedema/diagnóstico por imagen , Linfedema/fisiopatología , Extremidad Inferior/irrigación sanguínea , Resultado del Tratamiento , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de los Genitales Femeninos/complicaciones , Anciano , Adulto , Ganglios Linfáticos/trasplante , Estudios Retrospectivos , Factores de Tiempo , Colgajos Quirúrgicos/efectos adversos
13.
Clin Cancer Res ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691100

RESUMEN

PURPOSE: Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that dendritic cells (cDC) maintain Treg we sought to identify and target cDC signaling to block Treg infiltration after radiation. EXPERIMENTAL DESIGN: Transcriptomics and high dimensional flow cytometry revealed changes in murine tumor cDC that not only mediate Treg infiltration after RT, but associate with worse survival in human cancer datasets. Antibodies perturbing a cDC-CCL22-Treg axis were tested in syngeneic murine tumors. A prototype interferon-anti-epidermal growth factor receptor fusion protein (αEGFR-IFNα) was examined to block Treg infiltration and promote a CD8+ T cell response after RT. RESULTS: Radiation expands a population of mature cDC1 enriched in immunoregulatory markers that mediates Treg infiltration via the Treg-recruiting chemokine CCL22. Blocking CCL22 or Treg depletion both enhanced RT efficacy. αEGFR-IFNα blocked cDC1 CCL22 production while simultaneously inducing an antitumor CD8+ T cell response to enhance RT efficacy in multiple EGFR-expressing murine tumor models, including following systemic administration. CONCLUSIONS: We identify a previously unappreciated cDC mechanism mediating Treg tumor infiltration after RT. Our findings suggest blocking the cDC1-CCL22-Treg axis augments RT efficacy. αEGFR-IFNα added to RT provided robust antitumor responses better than systemic free interferon administration, and may overcome clinical limitations to interferon therapy. Our findings highlight the complex behavior of cDC after RT and provide novel therapeutic strategies for overcoming RT-driven immunosuppression to improve RT efficacy.

14.
J Exp Med ; 221(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38771260

RESUMEN

The majority of cancer patients receive radiotherapy during the course of treatment, delivered with curative intent for local tumor control or as part of a multimodality regimen aimed at eliminating distant metastasis. A major focus of research has been DNA damage; however, in the past two decades, emphasis has shifted to the important role the immune system plays in radiotherapy-induced anti-tumor effects. Radiotherapy reprograms the tumor microenvironment, triggering DNA and RNA sensing cascades that activate innate immunity and ultimately enhance adaptive immunity. In opposition, radiotherapy also induces suppression of anti-tumor immunity, including recruitment of regulatory T cells, myeloid-derived suppressor cells, and suppressive macrophages. The balance of pro- and anti-tumor immunity is regulated in part by radiotherapy-induced chemokines and cytokines. Microbiota can also influence radiotherapy outcomes and is under clinical investigation. Blockade of the PD-1/PD-L1 axis and CTLA-4 has been extensively investigated in combination with radiotherapy; we include a review of clinical trials involving inhibition of these immune checkpoints and radiotherapy.


Asunto(s)
Neoplasias , Radioterapia , Microambiente Tumoral , Humanos , Neoplasias/radioterapia , Neoplasias/inmunología , Neoplasias/terapia , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de la radiación , Animales , Radioterapia/métodos , Inmunidad Innata/efectos de la radiación , Antígeno CTLA-4/inmunología , Antígeno CTLA-4/metabolismo , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/inmunología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Inmunidad Adaptativa
15.
J Cheminform ; 16(1): 48, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38685101

RESUMEN

Previous studies have shown that the three-dimensional (3D) geometric and electronic structure of molecules play a crucial role in determining their key properties and intermolecular interactions. Therefore, it is necessary to establish a quantum chemical (QC) property database containing the most stable 3D geometric conformations and electronic structures of molecules. In this study, a high-quality QC property database, called QuanDB, was developed, which included structurally diverse molecular entities and featured a user-friendly interface. Currently, QuanDB contains 154,610 compounds sourced from public databases and scientific literature, with 10,125 scaffolds. The elemental composition comprises nine elements: H, C, O, N, P, S, F, Cl, and Br. For each molecule, QuanDB provides 53 global and 5 local QC properties and the most stable 3D conformation. These properties are divided into three categories: geometric structure, electronic structure, and thermodynamics. Geometric structure optimization and single point energy calculation at the theoretical level of B3LYP-D3(BJ)/6-311G(d)/SMD/water and B3LYP-D3(BJ)/def2-TZVP/SMD/water, respectively, were applied to ensure highly accurate calculations of QC properties, with the computational cost exceeding 107 core-hours. QuanDB provides high-value geometric and electronic structure information for use in molecular representation models, which are critical for machine-learning-based molecular design, thereby contributing to a comprehensive description of the chemical compound space. As a new high-quality dataset for QC properties, QuanDB is expected to become a benchmark tool for the training and optimization of machine learning models, thus further advancing the development of novel drugs and materials. QuanDB is freely available, without registration, at https://quandb.cmdrg.com/ .

16.
Vet Microbiol ; 293: 110083, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38593623

RESUMEN

Campylobacter spp., such as Campylobacter jejuni and Campylobacter coli, are important zoonotic Gram-negative pathogens that cause acute intestinal diseases in humans. In this study, a retrospective analysis was conducted on previously collected Campylobacter isolates from antimicrobial resistance surveillance. A total of 29 optrA-positive C. coli strains were identified and subjected to second-generation sequencing. Multilocus sequence typing and single nucleotide polymorphism analyses demonstrated that the 29 optrA-positive isolates were genetically homogeneous. Notably, among the 29 isolated strains, the ΔoptrA variants exhibit a nonsense mutation at position 979 where the base C is substituted by T, leading to the formation of a premature termination codon. The alignment of sequences and genetic environmental characteristics suggested that ΔoptrA located on a chromosomally carried multidrug-resistant genomic island. There are other resistant genes on the multidrug resistance genomic island, such as aph(2'')-If, aph(3')-III, aadE, tet(O), tet(L), cat, erm(A), optrA and blaOXA-61. As a result, the 29 ΔoptrA-positive strains displayed susceptibility to both florfenicol and linezolid. The ΔoptrA gene is linked to the erm(A) gene, resulting in the formation of translocatable unit (TU) that are encompassed by two copies of IS1216 mobile elements. Multiple occurrences of similar TUs have been documented in numerous C. coli and provided evidence for the significance of TUs in facilitating the transfer of drug resistance genes in C. coli.


Asunto(s)
Antibacterianos , Infecciones por Campylobacter , Campylobacter coli , Pollos , Farmacorresistencia Bacteriana Múltiple , Islas Genómicas , Campylobacter coli/genética , Campylobacter coli/efectos de los fármacos , Islas Genómicas/genética , Pollos/microbiología , Animales , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Infecciones por Campylobacter/microbiología , Infecciones por Campylobacter/veterinaria , Estudios Retrospectivos , Proteínas Bacterianas/genética , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Enfermedades de las Aves de Corral/microbiología , Polimorfismo de Nucleótido Simple
17.
Cell Rep ; 43(3): 113873, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38427557

RESUMEN

Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.


Asunto(s)
Cartílago , Pez Cebra , Animales , Pez Cebra/metabolismo , Cartílago/metabolismo , Diferenciación Celular/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Condrogénesis/genética
18.
Int J Biol Macromol ; 265(Pt 1): 130709, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38462120

RESUMEN

Versatile nanoplatform equipped with chemo-photodynamic therapeutic attributes play an important role in improving the effectiveness of tumor treatments. Herein, we developed multifunctional nanoparticles based on chondroitin sulfate A (CSA) for the targeted delivery of chlorin e6 (Ce6) and doxorubicin (DOX), in a combined chemo-photodynamic therapy against triple-negative breast cancer. CSA was chosen for its hydrophilic properties and its affinity to CD44 receptor-overexpressed tumor cells. The CSA-ss-Ce6 (CSSC) conjugate was synthesized utilizing a disulfide linker. Subsequently, DOX-loaded CSSC (CSSC-D) nanoparticles were fabricated, showcasing a nearly spherical shape with an average particle size of 267 nm. In the CSSC-D nanoparticles, the chemically attached Ce6 constituted 1.53 %, while the physically encapsulated DOX accounted for 8.11 %. Both CSSC-D and CSSC nanoparticles demonstrated a reduction-sensitive release of DOX or Ce6 in vitro. Under near-infrared (NIR) laser irradiation, CSSC-D showed the enhanced generation of reactive oxygen species (ROS), improving cytotoxic effects against triple-negative breast cancer 4T1 and MDA-MB-231 cells. Remarkably, the CSSC-D with NIR exhibited the most potent tumor growth inhibition in comparison to other groups in the 4T1-bearing Balb/c mice model. Overall, this CSSC-D nanoplatform shows significant promise as a powerful tool for a synergetic approach in chemo-photodynamic therapy in triple-negative breast cancer.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Porfirinas , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Sulfatos de Condroitina , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Doxorrubicina/farmacología , Doxorrubicina/química , Nanopartículas/química , Porfirinas/farmacología , Porfirinas/química , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química
19.
Clin Cancer Res ; 30(9): 1945-1958, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38427437

RESUMEN

PURPOSE: Radiotherapy (RT) is a widely employed anticancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. The purpose of this study is to investigate immune suppressive factors of radiotherapy. EXPERIMENTAL DESIGN: We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated. RESULTS: Through analysis of PD-L1 expression and myeloid-derived suppressor cells (MDSC) frequencies using patient peripheral blood mononuclear cells and murine two-tumor and metastasis models, we report that local irradiation can induce a systemic increase in MDSC, as well as PD-L1 expression on dendritic cells and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, nonirradiated tissue. In a mouse model using two distinct tumors, we found that PD-L1 induction by ionizing radiation was dependent on elevated chemokine CXCL10 signaling. Inhibiting PD-L1 or MDSC can potentially abrogate RT-induced metastasis and improve clinical outcomes for patients receiving RT. CONCLUSIONS: Blockade of PD-L1/CXCL10 axis or MDSC infiltration during irradiation can enhance abscopal tumor control and reduce metastasis.


Asunto(s)
Antígeno B7-H1 , Células Supresoras de Origen Mieloide , Animales , Antígeno B7-H1/metabolismo , Ratones , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Humanos , Metástasis de la Neoplasia , Línea Celular Tumoral , Femenino , Modelos Animales de Enfermedad , Quimiocina CXCL10/metabolismo
20.
Fa Yi Xue Za Zhi ; 40(1): 59-63, 2024 Feb 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38500462

RESUMEN

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.


Asunto(s)
Enfermedad de la Arteria Coronaria , Trombosis Coronaria , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/patología , Trombosis Coronaria/complicaciones , Trombosis Coronaria/patología , Factores de Riesgo , Enfermedad de la Arteria Coronaria/complicaciones , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología
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