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1.
PLoS One ; 19(7): e0305275, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38950026

RESUMEN

Acute compartment syndrome (ACS) is a syndrome in which local circulation is affected due to increased pressure within the compartment. We previously found in patients with calf fractures, the pressure of fascial compartment could be sharply reduced upon the appearance of tension blisters. Deep fascia, as the important structure for compartment, might play key role in this process. Therefore, the aim of the present study was to examine the differences in gene profile in deep fascia tissue in fracture patients of the calf with or without tension blisters, and to explore the role of fascia in pressure improvement in ACS. Patients with lower leg fracture were enrolled and divided into control group (CON group, n = 10) without tension blister, and tension blister group (TB group, n = 10). Deep fascia tissues were collected and LC-MS/MS label-free quantitative proteomics were performed. Genes involved in fascia structure and fibroblast function were further validated by Western blot. The differentially expressed proteins were found to be mainly enriched in pathways related to protein synthesis and processing, stress fiber assembly, cell-substrate adhesion, leukocyte mediated cytotoxicity, and cellular response to stress. Compared with the CON group, the expression of Peroxidasin homolog (PXDN), which promotes the function of fibroblasts, and Leukocyte differentiation antigen 74 (CD74), which enhances the proliferation of fibroblasts, were significantly upregulated (p all <0.05), while the expression of Matrix metalloproteinase-9 (MMP9), which is involved in collagen hydrolysis, and Neutrophil elastase (ELANE), which is involved in elastin hydrolysis, were significantly reduced in the TB group (p all <0.05), indicating fascia tissue underwent microenvironment reconstruction during ACS. In summary, the ACS accompanied by blisters is associated with the enhanced function and proliferation of fibroblasts and reduced hydrolysis of collagen and elastin. The adaptive alterations in the stiffness and elasticity of the deep fascia might be crucial for pressure release of ACS.


Asunto(s)
Síndromes Compartimentales , Fascia , Proteómica , Humanos , Proteómica/métodos , Síndromes Compartimentales/metabolismo , Masculino , Fascia/metabolismo , Fascia/patología , Persona de Mediana Edad , Adulto , Femenino , Enfermedad Aguda , Anciano
2.
Artículo en Inglés | MEDLINE | ID: mdl-38986604

RESUMEN

Developing extracellular matrix-derived hydrogel with a fast self-healing capacity to provide a sustainable moist environment able to accelerate wound healing is highly desired for full-thickness skin wound repair. In this study, a fast self-healing hyaluronic acid hydrogel with a dual dynamic network was constructed through a primary reversible acylhydrazone bond formed between aldehyde-modified hyaluronic acid, 3,3'-dithiobis (propionyl hydrazide) (DTP), and secondary dynamic ionic interactions between κ-carrageenan (KC) and K+. Because of the presence of various dynamic covalent bonds such as the acylhydrazone bond, disulfide bond, and noncovalent bonds including hydrogen bonding and ionic interactions, as well as the notable thermoreversible nature of KC, the resultant hydrogel could be self-healed rapidly within 30 min under physiological temperature with a self-healing efficiency of 100%, which was significantly better than other hyaluronic acid hydrogels, as reported previously. Besides, the hydrogel displayed excellent cytocompatibility. According to this study, the hydrogel was administered into the wounds and achieved a superior performance of promoting full-thickness skin wound healing by increasing granulation tissue formation, deposition of collagen as well as the acceleration of re-epithelialization and neovascularization, compared to commercial products, e.g., gauze and 3 M hydrocolloid. We also anticipate that this strategy of double-dynamic network cross-linking can be adopted to fabricate self-healing materials for multiple applications.

3.
FASEB J ; 38(13): e23794, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38967258

RESUMEN

Obesity is often associated with low-grade inflammation. The incidence of obesity has increased annually worldwide, which seriously affects human health. A previous study indicated that long noncoding RNA SNHG12 was downregulated in obesity. Nevertheless, the role of SNHG12 in obesity remains to be elucidated. In this study, qRT-PCR, western blot, and ELISA were utilized to examine the gene and protein expression. Flow cytometry was employed to investigate the M2 macrophage markers. RNA pull-down assay and RIP were utilized to confirm the interactions of SNHG12, hnRNPA1, and HDAC9. Eventually, a high-fat diet-fed mouse model was established for in vivo studies. SNHG12 overexpression suppressed adipocyte inflammation and insulin resistance and promoted M2 polarization of macrophages that was caused by TNF-α treatment. SNHG12 interacted with hnRNPA1 to downregulate HDAC9 expression, which activated the Nrf2 signaling pathway. HDAC9 overexpression reversed the effect of SNHG12 overexpression on inflammatory response, insulin resistance, and M2 phenotype polarization. Overexpression of SNHG12 improved high-fat diet-fed mouse tissue inflammation. This study revealed the protective effect of SNHG12 against adipocyte inflammation and insulin resistance. This result further provides a new therapeutic target for preventing inflammation and insulin resistance in obesity.


Asunto(s)
Adipocitos , Dieta Alta en Grasa , Histona Desacetilasas , Inflamación , Resistencia a la Insulina , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2 , Obesidad , ARN Largo no Codificante , Proteínas Represoras , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratones , Inflamación/metabolismo , Inflamación/genética , Adipocitos/metabolismo , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Dieta Alta en Grasa/efectos adversos , Masculino , Obesidad/metabolismo , Obesidad/genética , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Transducción de Señal , Macrófagos/metabolismo
4.
Cell Signal ; : 111302, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025344

RESUMEN

Liver fibrosis is a pathological process caused by a variety of chronic liver diseases. Currently, therapeutic options for liver fibrosis are very limited, highlighting the urgent need to explore new treatment approaches. Epigenetic modifications and epitranscriptomic modifications, as reversible regulatory mechanisms, are involved in the development of liver fibrosis. In recent years, researches in epitranscriptomics and epigenetics have opened new perspectives for understanding the pathogenesis of liver fibrosis. Exploring the epigenetic mechanisms of liver fibrosis may provide valuable insights into the development of new therapies for chronic liver diseases. This review primarily focus on the regulatory mechanisms of N6-methyladenosine (m6A) modification, non-coding RNA, and DNA methylation in organ fibrosis. It discusses the interactions between m6A modification and DNA methylation, as well as between m6A modification and non-coding RNA, providing a reference for understanding the interplay between epitranscriptomics and epigenetics.

5.
Small ; : e2404099, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940444

RESUMEN

The chemically pre-intercalated lattice engineering is widely applied to elevate the electronic conductivity, expand the interlayer spacing, and improve the structural stability of layered oxide cathodes. However, the mainstream unitary metal ion pre-intercalation generally produces the cation/vacancy ordered superstructure, which astricts the further improvement of lattice respiration and charge-carrier ion storage and diffusion. Herein, a multiple metal ions pre-intercalation lattice engineering is proposed to break the cation/vacancy ordered superstructure. Taking the bilayer V2O5 as an example, Ni, Co, and Zn ternary ions are simultaneously pre-intercalated into its interlayer space (NiCoZnVO). It is revealed that the Ni─Co neighboring characteristic caused by Ni(3d)-O(2p)-Co(3d) orbital coupling and the Co-Zn/Ni-Zn repulsion effect due to chemical bond incompatibility, endow the NiCoZnVO sample with the cation/vacancy disordered structure. This not only reduces the Li+ diffusion barrier, but also increases the diffusion dimension of Li+ (from one-dimension to two-dimension). Particularly, Ni, Co, and Zn ions co-pre-intercalation causes a prestress, which realizes a quasi-zero-strain structure at high-voltage window upon charging/discharging process. The functions of Ni ion stabilizing the lattice structure and Co or Zn ions activating more Li+ reversible storage reaction of V5+/V4+ are further revealed. The cation/vacancy disordered structure significantly enhances Li+ storage properties of NiCoZnVO cathode.

6.
Food Chem ; 457: 140143, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38901339

RESUMEN

The Hippophae rhamnoides L. pomace was generated in the production process for juice, wine of food industry. To expand the application of pomace, the extraction process optimization, enrichment and identification of triterpene acids were performed in this study. The extraction yield was 14.87% under optimal ultrasound-assisted extraction techniques performed via response surface methodology. The extract was subsequently purified to obtain the triterpenoid acid enrichment fraction (TPF) with the content of 75.23% ± 1.45%. 13 triterpenoid acids were identified via UPLC-Triple-TOF MS/MS and further semi-quantified through comparison with triterpenoid acid standards. TPF exhibited a strong inhibitory effect on α-glucosidase with IC50 value of 5.027 ± 0.375 µg/mL, as determined via enzyme inhibition experiment and molecular docking. Additionally, the TPF significantly reduced postprandial glucose levels, as revealed via carbohydrate tolerance tests, as well as ameliorate serum lipid profiles. Therefore, pomace may be a promising resource of functional food components with therapeutic and commercial values.

7.
BMC Med ; 22(1): 223, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831366

RESUMEN

BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Humanos , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Niño , Adolescente , Masculino , Femenino , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Neuroimagen , Estudios de Cohortes
8.
Mol Cell Biochem ; 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38879838

RESUMEN

As the world's aging population increases, cardiovascular diseases (CVDs) associated with aging deserve increasing attention. CVD in association with age is considered a major cause of morbidity and mortality worldwide. In this review, we provide an overview of the key molecular pathways, cellular processes such as autophagy, oxidative stress, inflammatory responses, myocardial remodeling and ischemia-refocused injury that accompany CVD as well as the natural products of targeting these mechanisms and some of the dietary habits that have been studied in cardiovascular-related diseases. The potential preventive and therapeutic avenues resulting from these dietary habits and natural products related to animal models and clinical studies can help us to better understand the processes involved in cardiovascular diseases and provide recommendations to reduce the cardiovascular burden associated with aging heart.

9.
Ultrasonics ; 142: 107359, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38823151

RESUMEN

Conventional surface acoustic wave (SAW) atomizers require a direct water supply on the surface, which can be complex and cumbersome. This paper presents a novel SAW atomizer that uses lateral acoustic wetting to achieve atomization without a direct water supply. The device works by simply pressing a piece of wetted paper strip against the bottom of an excited piezoelectric transducer. The liquid then flows along the side to the unmodified surface edge, where it is atomized into a well-converging mist in a stable and sustainable manner. We identified this phenomenon as the edge effect, using numerical simulation results of surface displacement mode. The feasibility of the prototype design was demonstrated by observing and investigating the integrated process of liquid extraction, transport, and atomization. We further explored the hydrodynamic principles of the change and breakup in liquid film geometry under different input powers. Experiments demonstrate that our atomizer is capable of generating high-quality fine liquid particles stably and rapidly even at very high input power. Compared to conventional SAW atomizer, the dispersion of mist width can be scaled down by 70%, while the atomization rate can be increased by 37.5%. Combined with the advantages of easy installation and robustness, the edge effect-based atomizer offers an attractive alternative to current counterparts for applications requiring high efficiency and miniaturization, such as simultaneous synthesis and encapsulation of nanoparticles, pulmonary drug delivery and portable inhalation therapy.

10.
Int J Biol Macromol ; 272(Pt 2): 132930, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38848843

RESUMEN

The rapid absorption of water from the blood to concentrate erythrocytes and platelets, thus triggering quick closure, is important for hemostasis. Herein, expansion-clotting chitosan fabrics are designed and fabricated by ring spinning of polylactic acid (PLA) filaments as the core layer and highly hydrophilic carboxyethyl chitosan (CECS) fibers as the sheath layer, and subsequent knitting of obtained PLA@CECS core spun yarns. Due to the unidirectional fast-absorption capacity of CECS fibers, the chitosan fabrics can achieve erythrocytes and platelets aggregate quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the loop structure of coils formed in the knitted fabric can help them to expand by absorbing water to close their pores, providing effective sealing for bleeding. Besides, They have enough mechanical properties, anti-penetrating ability, and good tissue-adhesion ability in wet conditions, which can form a physical barrier to resist blood pressure during hemostasis and prevent them from falling off the wound, thus enhancing hemostasis synergistically. Therefore, the fabrics exhibit superior hemostatic performance in the rabbit liver, spleen, and femoral artery puncture injury model compared to the gauze group. This chitosan fabric is a promising hemostatic material for hemorrhage control.


Asunto(s)
Quitosano , Hemorragia , Hemostáticos , Quitosano/química , Animales , Hemorragia/tratamiento farmacológico , Hemorragia/prevención & control , Conejos , Hemostáticos/química , Hemostáticos/farmacología , Poliésteres/química , Textiles , Coagulación Sanguínea/efectos de los fármacos , Hemostasis/efectos de los fármacos
11.
Chem Biodivers ; 21(7): e202400145, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38738490

RESUMEN

As a medicinal and edible resource, Hippophae rhamnoides Linn. subsp. sinensis Rousi is rich in bioactive secondary metabolites, including flavonoids and their derivatives, which offer protective effects against oxidative damage. This study reported the isolation of three new kaempferol derivatives from the seed residue of H. rhamnoides - Hippophandine A, B, and C (compounds 1-3). Their structures were elucidated by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR), and chemical analyses. The compounds were evaluated for their ability to mitigate hydrogen peroxide (H2O2)-induced cell death in SH-SY5Y cells. The results elucidated that Hippophandine A-C at concentrations of 1, 5, and 10 µM reduced the levels of malondialdehyde (MDA) and increased the activity of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Furthermore, they significantly altered the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1), which is an indicator of redox detection in H2O2-induced SH-SY5Y.


Asunto(s)
Hippophae , Peróxido de Hidrógeno , Quempferoles , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Regulación hacia Arriba , Humanos , Quempferoles/farmacología , Quempferoles/química , Quempferoles/aislamiento & purificación , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Hippophae/química , Factor 2 Relacionado con NF-E2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Relación Estructura-Actividad , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga
12.
Nat Commun ; 15(1): 4303, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773073

RESUMEN

Uncontrollable zinc (Zn) plating and hydrogen evolution greatly undermine Zn anode reversibility. Previous electrolyte designs focus on suppressing H2O reactivity, however, the accumulation of alkaline byproducts during battery calendar aging and cycling still deteriorates the battery performance. Here, we present a direct strategy to tackle such problems using a strong Brønsted acid, bis(trifluoromethanesulfonyl)imide (HTFSI), as the electrolyte additive. This approach reformulates battery interfacial chemistry on both electrodes, suppresses continuous corrosion reactions and promotes uniform Zn deposition. The enrichment of hydrophobic TFSI- anions at the Zn|electrolyte interface creates an H2O-deficient micro-environment, thus inhibiting Zn corrosion reactions and inducing a ZnS-rich interphase. This highly acidic electrolyte demonstrates high Zn plating/stripping Coulombic efficiency up to 99.7% at 1 mA cm-2 ( > 99.8% under higher current density and areal capacity). Additionally, Zn | |ZnV6O9 full cells exhibit a high capacity retention of 76.8% after 2000 cycles.

13.
BMC Psychol ; 12(1): 286, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778400

RESUMEN

BACKGROUND: Mothers of children with autism reported higher levels of anxiety than mothers of typical children. This study revealed the relationship between parent-child conflict, children's problem behavior, parenting stress, and maternal anxiety from the perspective of the relationship within the family. METHODS: The State-Trait Anxiety Inventory (STAI) and Caregiver Strain Questionnaire (CGSQ) were used to measure maternal anxiety and parenting stress respectively from 102 mothers of children with autism. We also collected information on parent-child relationships and children's problem behaviors by using the Child-Parent Relationship Scale (CPRS) and Conners Parent Symptom Questionnaire (PSQ). RESULTS: Parent-child conflict positively predicted state and trait anxiety in mothers of children with autism. The severity of children's psychosomatic disorders fully mediated the positive association between parent-child conflict and state-trait anxiety in mothers of children with autism. Parenting stress significantly moderated the impact of parent-child conflict on maternal state anxiety and trait anxiety. CONCLUSION: In the case of children with autism spectrum disorders, parent-child conflict can directly affect maternal anxiety levels, especially when mothers have low levels of parenting stress. Parent-child conflict can also affect children's problem behaviors and thus indirectly affect maternal anxiety. Therefore, this study is of great significance for the alleviation of anxiety of mothers of autistic children and the family intervention for the early rehabilitation of autistic children.


Asunto(s)
Ansiedad , Madres , Estrés Psicológico , Humanos , Femenino , Ansiedad/psicología , Madres/psicología , Masculino , Adulto , Niño , Estrés Psicológico/psicología , Responsabilidad Parental/psicología , Preescolar , Trastorno Autístico/psicología , China , Encuestas y Cuestionarios , Relaciones Madre-Hijo/psicología , Relaciones Padres-Hijo , Problema de Conducta/psicología , Persona de Mediana Edad , Pueblos del Este de Asia
14.
Nephrology (Carlton) ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716715

RESUMEN

AIM: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients. METHODS: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non-rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed. RESULTS: IgAN-rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P = .016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P = .025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P = .037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non-rTMA group (χ2 = 18.467, P = .000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P = .037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P = .027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P = .041) were identified as independent risk factors for the development of end-stage renal disease (ESRD). CONCLUSION: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN.

15.
Small ; : e2400408, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709208

RESUMEN

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

16.
J Am Chem Soc ; 146(27): 18210-18217, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38788197

RESUMEN

Molecular rearrangement occupies a pivotal position among fundamental transformations in synthetic chemistry. Radical translocation has emerged as a prevalent synthetic tool, efficiently facilitating the migration of diverse functional groups. In contrast, the development of di-π-methane rearrangement remains limited, particularly in terms of the translocation of cyano functional groups. This is primarily attributed to the energetically unfavorable three-membered-ring transition state. Herein, we introduce an unprecedented di-π-ethane rearrangement enabled by energy-transfer catalysis under visible light conditions. This innovative open-shell rearrangement boasts broad tolerance toward a range of functional groups, encompassing even complex drug and natural product derivatives. Overall, the reported di-π-ethane rearrangement represents a complementary strategy to the development of radical translocation enabled by energy-transfer catalysis.

17.
Cancer Lett ; 594: 216991, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38797232

RESUMEN

Genetic interactions (GIs) refer to two altered genes having a combined effect that is not seen individually. They play a crucial role in influencing drug efficacy. We utilized CGIdb 2.0 (http://www.medsysbio.org/CGIdb2/), an updated database of comprehensively published GIs information, encompassing synthetic lethality (SL), synthetic viability (SV), and chemical-genetic interactions. CGIdb 2.0 elucidates GIs relationships between or within protein complex models by integrating protein-protein physical interactions. Additionally, we introduced GENIUS (GENetic Interactions mediated drUg Signature) to leverage GIs for identifying the response signature of immune checkpoint inhibitors (ICIs). GENIUS identified high MAP4K4 expression as a resistant signature and high HERC4 expression as a sensitive signature for ICIs treatment. Melanoma patients with high expression of MAP4K4 were associated with decreased efficacy and poorer survival following ICIs treatment. Conversely, overexpression of HERC4 in melanoma patients correlated with a positive response to ICIs. Notably, HERC4 enhances sensitivity to immunotherapy by facilitating antigen presentation. Analyses of immune cell infiltration and single-cell data revealed that B cells expressing MAP4K4 may contribute to resistance to ICIs in melanoma. Overall, CGIdb 2.0, provides integrated GIs data, thus serving as a crucial tool for exploring drug effects.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/inmunología , Melanoma/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología , Inmunoterapia/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Bases de Datos Genéticas
18.
Biol Psychiatry ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38718879

RESUMEN

BACKGROUND: The right middle frontal gyrus (MFG) has been proposed as a convergence site for the dorsal attention network (DAN) and ventral attention network (VAN), regulating both networks and enabling flexible modulation of attention. However, it is unclear whether the connections between the right MFG and these networks can predict changes in attention-deficit/hyperactivity disorder (ADHD) symptoms. METHODS: This study used data from the Children School Functions and Brain Development project (N = 713, 56.2% boys). Resting-state functional magnetic resonance imaging was employed to analyze the connections of the right MFG with the DAN/VAN; connectome-based predictive modeling was applied for longitudinal prediction, and ADHD polygenic risk scores were used for genetic analysis. RESULTS: ADHD symptoms were associated with the connections between the right MFG and DAN subregion, including the frontal eye field, as well as the VAN subregions, namely the inferior parietal lobule and inferior frontal gyrus. Furthermore, these connections of the right MFG with the frontal eye field, the inferior parietal lobule, and the inferior frontal gyrus could significantly predict changes in ADHD symptoms over 1 year and mediate the prediction of ADHD symptom changes by polygenic risk scores for ADHD. Finally, the validation samples confirmed that the functional connectivity between the right MFG and the frontal eye field/inferior parietal lobule in patients with ADHD was significantly weaker than that in typically developing control participants, and this difference disappeared after medication. CONCLUSIONS: The connection of the right MFG with the DAN and VAN can serve as a predictive indicator for changes in ADHD symptoms over the following year, while also mediating the prediction of ADHD symptom changes by a polygenic risk score for ADHD. These findings hold promise as potential biomarkers for early identification of children who are at risk of developing ADHD.

19.
Sci Data ; 11(1): 463, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714688

RESUMEN

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Asunto(s)
Encéfalo , Desarrollo Infantil , Niño , Preescolar , Humanos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , China , Cognición , Bases de Datos Factuales , Neuroimagen
20.
BMJ Open ; 14(4): e079354, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38569706

RESUMEN

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.


Asunto(s)
Terapia por Acupuntura , Diabetes Mellitus , Neuropatías Diabéticas , Electroacupuntura , Humanos , Neuropatías Diabéticas/terapia , Dolor , China , Beijing , Resultado del Tratamiento , Electroacupuntura/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
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