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1.
Genome Biol ; 25(1): 117, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715110

RESUMEN

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.


Asunto(s)
Preeclampsia , Trofoblastos , Remodelación Vascular , Preeclampsia/genética , Embarazo , Femenino , Humanos , Trofoblastos/metabolismo , Remodelación Vascular/genética , Placenta/metabolismo , Metilación de ADN , Epigénesis Genética , Células Endoteliales/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Impresión Genómica , Factor de Crecimiento Transformador beta/metabolismo , Retardo del Crecimiento Fetal/genética , Placentación/genética , Proteínas de Unión al ARN , Proteínas Reguladoras de la Apoptosis
2.
Sensors (Basel) ; 24(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38732835

RESUMEN

Ultrasonic guided wave (UGW) inspection is an emerging non-destructive testing(NDT) technique for rail flaw detection, where weak UGW signals under strong noise backgrounds are difficult to detect. In this study, a UGW signal identification model based on a chaotic oscillator is established. The approach integrates the UGW response into the critical state of the Duffing system to serve as a disturbance control variable. By evaluating the system's motion state before and after introducing the UGW response, identification of UGW signals can be realized. Thus, the parameters defining the critical state of Duffing oscillators are determined by Ke. Moreover, an electromagnetic transducer was specifically devised to enable unidirectional excitation for UGWs targeted at both the rail base and rail head. Experimental studies showed that the proposed methodology effectively detected and located a 0.46 mm notch at the rail base and a 1.78 mm notch at the rail head. Furthermore, Ke was directly proportional to the notch size, which could be used as a quantitative index to characterize the rail flaw.

3.
Int Immunol ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38708774

RESUMEN

Persistent immunoglobulin G (IgG) production (PIP) provides long-term vaccine protection. While variations in the duration of protection have been observed with vaccines prepared from different pathogens, little is known about the factors that determine PIP. Here, we investigated the impact of three parameters on the duration of anti-peptide IgGs production, namely amino acid sequences, protein carriers, and immunization programs. We show that anti-peptide IgGs production can be transformed from transient IgG production (TIP) to PIP, by placing short peptides (Pi) containing linear B cell epitopes in different competitive environments using bovine serum albumin (BSA) conjugates instead of the original viral particles. When goats were immunized with the peste des petits ruminants (PPR) live-attenuated vaccine (containing Pi as the constitutive component) and BSA-Pi conjugate, anti-Pi IgGs production exhibited TIP (duration <60 days) and PIP (duration >368 days), respectively. Further, this PIP was unaffected by subsequent immunization with the PPR live-attenuated vaccine in the same goat. When goats were co-immunized with PPR live-attenuated vaccine and BSA-Pi, the induced anti-Pi IgGs production showed a slightly extended TIP (from ~60 days to ~100 days). This discovery provides new perspectives for studying the fate of plasma cells in humoral immune responses and developing peptide vaccines related to linear neutralizing epitopes from various viruses.

4.
Front Microbiol ; 15: 1387309, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716170

RESUMEN

Senecavirus A (SVA) is an important emerging swine pathogen that causes vesicular lesions in swine and acute death in newborn piglets. VP2 plays a significant role in the production of antibodies, which can be used in development of diagnostic tools and vaccines. Herein, the aim of the current study was to identify B-cell epitopes (BCEs) of SVA for generation of epitope-based SVA marker vaccine. Three monoclonal antibodies (mAbs), named 2E4, 1B8, and 2C7, against the SVA VP2 protein were obtained, and two novel linear BCEs, 177SLGTYYR183 and 266SPYFNGL272, were identified by peptide scanning. The epitope 177SLGTYYR183 was recognized by the mAb 1B8 and was fully exposed on the VP2 surface, and alanine scanning analysis revealed that it contained a high continuity of key amino acids. Importantly, we confirmed that 177SLGTYYR183 locates on "the puff" region within the VP2 EF loop, and contains three key amino acid residues involved in receptor binding. Moreover, a single mutation, Y182A, blocked the interaction of the mutant virus with the mAb 1B8, indicating that this mutation is the pivotal point for antibody recognition. In summary, the BCEs that identified in this study could be used to develop diagnostic tools and an epitope-based SVA marker vaccine.

5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(4): 303-310, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38710514

RESUMEN

Objective To clarify the relationship between astrocyte activation patterns and disease progression in epidemic encephalitis B (Japanese encephalitis). Methods First, a mouse model of epidemic encephalitis B was constructed by foot-pad injection of Japanese encephalitis virus (JEV), and the expression of viral protein NS3 in different brain regions was detected by immunofluorescence assay (IFA). Next, IFA, RNA sequencing (RNA-seq) and real-time quantitative PCR (qRT-PCR) were used to clarify the changes in the astrocyte activation patterns at different stages of epidemic encephalitis B. Finally, intracerebroventricular administration of irisin was conducted to regulate the proportion of activation in complement C3-positive A1 astrocytes and S100A10-positive A2 astrocytes, investigating whether it could improve the body mass, behavioral scores, and brain tissue damage in a mouse model. Results NS3 protein was detected by IFA predominantly in the M1/M2 region of the motor cortex and the hippocampus. The number and volume of GFAP-positive astrocytes significantly increased in JEV-infected brain regions, in which the expression of multiple genes associated with A1/A2 astrocyte activation was significantly enhanced. Although intracerebroventricular or intraperitoneal injection of irisin did not improve the prognosis of epidemic encephalitis B, it inhibited the activation of A1 astrocytes and ameliorate neuroinflammation. Conclusion Neurons in the M1/M2 motor cortex and hippocampus are susceptible to JEV infection, in which the abnormal astrocyte activation contributes to the neuroinflammatory injury. Irisin administration may restrain A1 astrocyte activation and alleviate neuroinflammation following JEV infection.


Asunto(s)
Astrocitos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Astrocitos/metabolismo , Astrocitos/virología , Ratones , Encefalitis Japonesa/inmunología , Virus de la Encefalitis Japonesa (Especie)/fisiología , Encéfalo/metabolismo , Encéfalo/virología , Encéfalo/patología , Masculino , Fibronectinas/metabolismo , Fibronectinas/genética
6.
Adv Mater ; : e2400502, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38651254

RESUMEN

Chemotherapy of glioblastoma (GBM) has not yielded success due to inefficient blood-brain barrier (BBB) penetration and poor glioma tissue accumulation. Aerobic glycolysis, as the main mode of energy supply for GBM, safeguards the rapid growth of GBM while affecting the efficacy of radiotherapy and chemotherapy. Therefore, to effectively inhibit aerobic glycolysis, increase drug delivery efficiency and sensitivity, a novel temozolomide (TMZ) nanocapsule (ApoE-MT/siPKM2 NC) is successfully designed and prepared for the combined delivery of pyruvate kinase M2 siRNA (siPKM2) and TMZ. This drug delivery platform uses siPKM2 as the inner core and methacrylate-TMZ (MT) as the shell component to achieve inhibition of glioma energy metabolism while enhancing the killing effect of TMZ. By modifying apolipoprotein E (ApoE), dual targeting of the BBB and GBM is achieved in a "two birds with one stone" style. The glutathione (GSH) responsive crosslinker containing disulfide bonds ensures "directional blasting" cleavage of the nanocapsules to release MT and siPKM2 in the high GSH environment of glioma cells. In addition, in vivo experiments verify that ApoE-MT/siPKM2 NC has good targeting ability and prolongs the survival of tumor-bearing nude mice. In summary, this drug delivery system provides a new strategy for metabolic therapy sensitization chemotherapy.

7.
J Am Chem Soc ; 146(15): 10908-10916, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38579155

RESUMEN

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38682804

RESUMEN

In the fields of photolithographic patterning, optical anticounterfeiting, and information encryption, reversible photochromic materials with solid-state fluorescence are emerging as a potential class of systems. A design strategy for reversible photochromic materials has been proposed and synthesized through the introduction of photoactive thiophene groups into the molecular backbone of aryl vinyls, compounds with unique aggregation-induced emission properties, and solid-state reversible photocontrollable fluorescence and color-changing properties. This work develops novel photochromic inks, films, and cellulose hydrogels for enhancing the security of information encryption and anticounterfeiting technologies. They achieve rapid and reversible color change under ultraviolet light irradiation. Dependent upon the rate of color change, higher levels of time-resolved security can be achieved. This feature is important for enhancing the confidentiality of encrypted information and the reliability of security labels. Color-changing cellulose hydrogels, inks, and films consisting of three photochromic fluorescent molecules have quick photoactivity, great photoreversibility and photostability, and good processability, making them ideal for time-delayed anticounterfeiting and smart encryption. Furthermore, specialized algorithms are used to construct convolutional neural networks, and image analysis is performed on these systems, thus solving the current problem of the time-consuming information decryption process. This artificial intelligence method offers new opportunities for enhanced data encryption.

9.
Sensors (Basel) ; 24(8)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38676232

RESUMEN

Identifying the structural state without baseline data is an important engineering problem in the field of structural health monitoring, which is crucial for assessing the safety condition of structures. In the context of limited accelerometers available, this paper proposes a correlation-based damage identification method using Variational Autoencoder neural networks. The approach involves initially constructing a Variational Autoencoder network model for bridge damage detection, optimizing parameters such as loss functions and learning rates for the model, and ultimately utilizing response data from limited sensors for model training analysis to determine the structural state. The contribution of this paper lies in the ability to identify structural damage without baseline data using response data from a small number of sensors, reducing sensor costs and enhancing practical applications in engineering. The effectiveness of the proposed method is demonstrated through numerical simulations and experimental structures. The results show that the method can identify the location of damage under different damage conditions, exhibits strong robustness in detecting multiple damages, and further enhances the accuracy of identifying bridge structures.

10.
Molecules ; 29(6)2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38542983

RESUMEN

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.


Asunto(s)
Stemonaceae , Stemonaceae/química , Stemonaceae/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo
11.
Heliyon ; 10(4): e26450, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38434036

RESUMEN

In the realm of significant technological research and innovation within the marine economy, enterprises and academic research institutions often grapple with a lack of innovation motivation due to financial constraints. This paper introduces the factor of "capital constraints" into the marine innovation chain, establishing a technological innovation chain within the marine economy. Utilizing a three-party evolutionary game model, the study delves into the strategy selection and evolution of financial institutions, marine enterprises, and academic research institutions. In contrast to previous studies, this paper categorizes technological innovation cooperation into two types: "cooperative tackling type" and "market-oriented promotion type." Additionally, it posits that collaboration between academic research institutions and marine enterprises establishes an implicit guarantee relationship, facilitating access to higher loan amounts for both parties. The research reveals that the behavior of governments and marine enterprises is influenced by the initial willingness of participants. Higher basic benefits of cooperation and innovation between academic research institutions and marine enterprises lead to a quicker attainment of an evolutionary stable state. Moreover, in collaborations between marine enterprises and research institutions, an excessively high proportion of funds occupied by marine enterprises proves disadvantageous. The paper suggests that pure market-oriented promotion innovation cooperation could serve as a supplementary approach to traditional cooperation and innovation. Finally, numerical examples are presented to elucidate the outcomes of the theoretical model, accompanied by policy suggestions.

12.
NPJ Vaccines ; 9(1): 28, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341504

RESUMEN

Hantaan virus (HTNV) is a pathogenic orthohantavirus prevalent in East Asia that is known to cause hemorrhagic fever with severe renal syndrome (HFRS), which has a high fatality rate. However, a Food and Drug Administration (FDA)-approved vaccine is not currently available against this virus. Although inactivated vaccines have been certified and used in endemic regions for decades, the neutralizing antibody (NAb) titer induced by inactivated vaccines is low and the immunization schedule is complicated, requiring at least three injections spanning approximately 6 months to 1 year. Replication-competent vesicular stomatitis virus (VSV)-based vaccines provide prolonged protection after a single injection. In this study, we successfully engineered the HTNV glycoprotein (GP) in the VSV genome by replacing the VSV-G open reading frame. The resulting recombinant (r) rVSV-HTNV-GP was rescued, and the immunogenicity of GP was similar to that of HTNV. BALB/c mice immunized with rVSV-HTNV-GP showed a high titer of NAb against HTNV after a single injection. Notably, the cross-reactive NAb response induced by rVSV-HTNV-GP against Seoul virus (an orthohantavirus) was higher than that induced by three sequential injections of inactivated vaccines. Upon challenge with HTNV, rVSV-HTNV-GP-immunized mice showed a profoundly reduced viral burden in multiple tissues, and inflammation in the lungs and liver was nearly undetectable. Moreover, a single injection of rVSV-HTNV-GP established a prolonged immunological memory status as the NAbs were sustained for over 1 year and provided long-term protection against HTNV infection. The findings of our study can support further development of an rVSV-HTNV-GP-based HTNV vaccine with a simplified immunization schedule.

13.
J Hazard Mater ; 468: 133809, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38387178

RESUMEN

Given the extensive need for the detection of hydrazine (N2H4) in the biomedical and chemical-pharmaceutical sectors, there is a necessity to devise a fast, sensitive, specific, and portable technique for precisely quantifying hydrazine at environmental levels. In our work, an "OFF-ON" type fluorescent probe namely 2-(4-(10-(naphthalen-2-yl)anthracen-9-yl)phenyl)isoindole-1,3-dione (NAP), which was inspired by the "Gabriel" reaction, was synthesized. The NAP fluorescent cellulose film successfully achieved the detection of hydrazine vapor with a LOD = 0.658 ppm. Compared to previous qualitative methods for detecting hydrazine, this study successfully achieved quantitative identification of hydrazine at low concentrations. In addition, a portable sensor device based on NAP cellulose film was successfully integrated, enabling ultra-sensitive, wireless, remote, and real-time detection of N2H4 vapor. It was determined that the probe (NAP) exhibited excellent detection performance when applied to various environmental samples including distilled water, tap water, creek water, soil and plants. This study introduces a potentially effective approach for detecting hydrazine in real-world settings.

14.
Sensors (Basel) ; 24(4)2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38400362

RESUMEN

In this study, a quantitative detection method of pipeline cracks based on a one-dimensional convolutional neural network (1D-CNN) was developed using the time-domain signal of ultrasonic guided waves and the crack size of the pipeline as the input and output, respectively. Pipeline ultrasonic guided wave detection signals under different crack defect conditions were obtained via numerical simulations and experiments, and these signals were input as features into a multi-layer perceptron and one-dimensional convolutional neural network (1D-CNN) for training. The results revealed that the 1D-CNN performed better in the quantitative analysis of pipeline crack defects, with an error of less than 2% in the simulated and experimental data, and it could effectively evaluate the size of crack defects from the echo signals under different frequency excitations. Thus, by combining the ultrasonic guided wave detection technology and CNN, a quantitative analysis of pipeline crack defects can be effectively realized.

15.
J Virol ; 98(1): e0135023, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38169284

RESUMEN

Epitranscriptomic RNA modifications can regulate the stability of mRNA and affect cellular and viral RNA functions. The N4-acetylcytidine (ac4C) modification in the RNA viral genome was recently found to promote viral replication; however, the mechanism by which RNA acetylation in the host mRNA regulates viral replication remains unclear. To help elucidate this mechanism, the roles of N-acetyltransferase 10 (NAT10) and ac4C during the infection and replication processes of the alphavirus, Sindbis virus (SINV), were investigated. Cellular NAT10 was upregulated, and ac4C modifications were promoted after alphavirus infection, while the loss of NAT10 or inhibition of its N-acetyltransferase activity reduced alphavirus replication. The NAT10 enhanced alphavirus replication as it helped to maintain the stability of lymphocyte antigen six family member E mRNA, which is a multifunctional interferon-stimulated gene that promotes alphavirus replication. The ac4C modification was thus found to have a non-conventional role in the virus life cycle through regulating host mRNA stability instead of viral mRNA, and its inhibition could be a potential target in the development of new alphavirus antivirals.IMPORTANCEThe role of N4-acetylcytidine (ac4C) modification in host mRNA and virus replication is not yet fully understood. In this study, the role of ac4C in the regulation of Sindbis virus (SINV), a prototype alphavirus infection, was investigated. SINV infection results in increased levels of N-acetyltransferase 10 (NAT10) and increases the ac4C modification level of cellular RNA. The NAT10 was found to positively regulate SINV infection in an N-acetyltransferase activity-dependent manner. Mechanistically, the NAT10 modifies lymphocyte antigen six family member E (LY6E) mRNA-the ac4C modification site within the 3'-untranslated region (UTR) of LY6E mRNA, which is essential for its translation and stability. The findings of this study demonstrate that NAT10 regulated mRNA stability and translation efficiency not only through the 5'-UTR or coding sequence but also via the 3'-UTR region. The ac4C modification of host mRNA stability instead of viral mRNA impacting the viral life cycle was thus identified, indicating that the inhibition of ac4C could be a potential target when developing alphavirus antivirals.


Asunto(s)
Infecciones por Alphavirus , Antígenos de Superficie , Proteínas Ligadas a GPI , Acetiltransferasas N-Terminal , Virus Sindbis , Replicación Viral , Humanos , Infecciones por Alphavirus/genética , Antígenos de Superficie/genética , Citidina/análogos & derivados , Proteínas Ligadas a GPI/genética , ARN Mensajero/genética , Virus Sindbis/fisiología , Línea Celular , Acetiltransferasas N-Terminal/genética , Estabilidad del ARN
16.
Clin. transl. oncol. (Print) ; 26(1): 147-154, jan. 2024.
Artículo en Inglés | IBECS | ID: ibc-229153

RESUMEN

Purpose To study the clinical diagnostic value of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer. Methods The clinical data of 120 patients consistent with pulmonary cancer admitted to the First Affiliated Hospital of Hebei North University from March 2019 to December 2019 were selected for retrospective analysis, and they were divided into the bone metastasis group (n = 58) and non-bone metastasis group (n = 62) according to comprehensive evaluation result of X-ray, CT, MRI and clinical follow-up. The CT values of patients were obtained by SPECT/CT bone imaging to compare serum levels of ALP (alkaline phosphatase belongs to phosphoric monoester hydrolases, as a specific phosphatase, mainly in body tissues and body fluid) and BAP (bone alkaline phosphatase is formed by different modification and processing of alkaline phosphatase, and is mainly released by osteoblasts) and CT values of patients in both groups, using receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy of single detection and combined detection. Results SPECT/CT bone imaging in patients with bone metastasis from pulmonary cancer showed abnormal radioactive accumulation in spine, pelvis and bilateral ribs. Serum ALP, BAP and CT values in bone metastasis group were overtly higher than the non-bone metastasis group (P < 0.001). Logistic regression analysis showed that serum ALP, BAP and CT value were independent risk factors for bone metastasis from pulmonary cancer. The AUC value and Youden index of combined diagnosis were higher than those of single diagnosis. Conclusion SPECT/CT bone imaging combined with serum detection of ALP and BAP in patients with pulmonary cancer is helpful for early diagnosis of bone metastasis, which provides more basis for the formulation and selection of clinical treatment options (AU)


Asunto(s)
Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estudios Retrospectivos
17.
Nat Commun ; 15(1): 438, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200007

RESUMEN

Hantaan virus (HTNV) is asymptomatically carried by rodents, yet causes lethal hemorrhagic fever with renal syndrome in humans, the underlying mechanisms of which remain to be elucidated. Here, we show that differential macrophage responses may determine disparate infection outcomes. In mice, late-phase inactivation of inflammatory macrophage prevents cytokine storm syndrome that usually occurs in HTNV-infected patients. This is attained by elaborate crosstalk between Notch and NF-κB pathways. Mechanistically, Notch receptors activated by HTNV enhance NF-κB signaling by recruiting IKKß and p65, promoting inflammatory macrophage polarization in both species. However, in mice rather than humans, Notch-mediated inflammation is timely restrained by a series of murine-specific long noncoding RNAs transcribed by the Notch pathway in a negative feedback manner. Among them, the lnc-ip65 detaches p65 from the Notch receptor and inhibits p65 phosphorylation, rewiring macrophages from the pro-inflammation to the pro-resolution phenotype. Genetic ablation of lnc-ip65 leads to destructive HTNV infection in mice. Thus, our findings reveal an immune-braking function of murine noncoding RNAs, offering a special therapeutic strategy for HTNV infection.


Asunto(s)
FN-kappa B , Roedores , Humanos , Animales , Ratones , Reacciones Cruzadas , Inflamación , Macrófagos , Receptores Notch
18.
Chemistry ; 30(5): e202302950, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-37950682

RESUMEN

We herein describe the synthesis of a new class of axially chiral aza/boracyclophanes (BDN1, BXN1, BDB1 and BXB1) using binaphthyls as chiral building blocks and the main-group (B/N) chemistry with tunable electronic effects. All macrocycles substituted with triarylamine donors or triarylborane acceptors are strongly luminescent. These macrocycles showed two distinct meta and para π-conjugation pathways, leading to the formation of quasi figure-of-eight and square-shaped conformations. Interestingly, comparison of such structural models revealed that the former type of macrocycles BXN1 and BXB1 gave higher racemization barriers relative to the other ones. The results reported here may provide a new approach to engineer the optical stability of π-conjugated chiral macrocycles by controlling π-substitution patterns. The ring constraints induced by macrocyclization were also demonstrated to contribute to the configurational persistence as compared with the open-chain analogues p-BTT and m-BTT.

19.
Clin Transl Oncol ; 26(1): 147-154, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37269491

RESUMEN

PURPOSE: To study the clinical diagnostic value of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer. METHODS: The clinical data of 120 patients consistent with pulmonary cancer admitted to the First Affiliated Hospital of Hebei North University from March 2019 to December 2019 were selected for retrospective analysis, and they were divided into the bone metastasis group (n = 58) and non-bone metastasis group (n = 62) according to comprehensive evaluation result of X-ray, CT, MRI and clinical follow-up. The CT values of patients were obtained by SPECT/CT bone imaging to compare serum levels of ALP (alkaline phosphatase belongs to phosphoric monoester hydrolases, as a specific phosphatase, mainly in body tissues and body fluid) and BAP (bone alkaline phosphatase is formed by different modification and processing of alkaline phosphatase, and is mainly released by osteoblasts) and CT values of patients in both groups, using receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy of single detection and combined detection. RESULTS: SPECT/CT bone imaging in patients with bone metastasis from pulmonary cancer showed abnormal radioactive accumulation in spine, pelvis and bilateral ribs. Serum ALP, BAP and CT values in bone metastasis group were overtly higher than the non-bone metastasis group (P < 0.001). Logistic regression analysis showed that serum ALP, BAP and CT value were independent risk factors for bone metastasis from pulmonary cancer. The AUC value and Youden index of combined diagnosis were higher than those of single diagnosis. CONCLUSION: SPECT/CT bone imaging combined with serum detection of ALP and BAP in patients with pulmonary cancer is helpful for early diagnosis of bone metastasis, which provides more basis for the formulation and selection of clinical treatment options.


Asunto(s)
Neoplasias Óseas , Neoplasias Pulmonares , Humanos , Fosfatasa Alcalina , Estudios Retrospectivos , Tomografía Computarizada de Emisión de Fotón Único , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X
20.
Microorganisms ; 11(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37894092

RESUMEN

The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein-peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient's recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease.

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