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1.
J Obstet Gynaecol Can ; : 102585, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38878822

RESUMEN

OBJECTIVES: This study investigates experiences of medical students across Canada related to consent for educational sensitive (i.e., pelvic, rectal) exams under anesthesia (EUAs). METHODS: A bilingual online questionnaire was developed and distributed to medical students across Canada. RESULTS: Of 134 respondents, 63% had performed a pelvic EUA, 35% a rectal EUA, and 11% another sensitive EUA during their training. For those who had performed pelvic EUA, 28% were unsure if consent had taken place, 26% reported no specific consent, 20% reported specific consent, and 25% had mixed experiences of consent. For rectal EUAs, 48% reported no specific consent, 37% were unsure if consent had taken place, 13% reported that there had been specific consent, and 2% reported mixed experiences. Most respondents were uncomfortable (36%) or not sure if they were comfortable (32%) with how the consent process was handled for student pelvic EUAs; 31% were comfortable. In open-ended responses, respondents described experiences related to variability, discomfort, and authority. CONCLUSIONS: Non-consensual educational sensitive EUAs continue to take place in medical training across Canada, although practices of consent are highly variable. The majority of respondents reported being uncomfortable or unsure if they were comfortable with how consent for educational sensitive EUAs was practised during their training, and some respondents struggled to express their discomfort given the power dynamics at play.

2.
Biomacromolecules ; 25(6): 3566-3582, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38780026

RESUMEN

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes mellitus, may result in an amputation. Natural and renewable hydrogels are desirable materials for DFU dressings due to their outstanding biosafety and degradability. However, most hydrogels are usually only used for wound repair and cannot be employed to monitor motion because of their inherent poor mechanical properties and electrical conductivity. Given that proper wound stretching is beneficial for wound healing, the development of natural hydrogel patches integrated with wound repair properties and motion monitoring was expected to achieve efficient and accurate wound healing. Here, we designed a dual-network (chitosan and sodium alginate) hydrogel embedded with lignin-Ag and quercetin-melanin nanoparticles to achieve efficient wound healing and motion monitoring. The double network formed by the covalent bond and electrostatic interaction confers the hydrogel with superior mechanical properties. Instead of the usual chemical reagents, genipin extracted from Gardenia was used as a cross-linking agent for the hydrogel and consequently improved its biosafety. Furthermore, the incorporation of lignin-Ag nanoparticles greatly enhanced the mechanical strength, antibacterial efficacy, and conductivity of the hydrogel. The electrical conductivity of hydrogels gives them the capability of motion monitoring. The motion sensing mechanism is that stretching of the hydrogel induced by motion changes the conductivity of the hydrogel, thus converting the motion into an electrical signal. Meanwhile, quercetin-melanin nanoparticles confer exceptional adhesion, antioxidant, and anti-inflammatory properties to the hydrogels. The system ultimately achieved excellent wound repair and motion monitoring performance and was expected to be used for stretch-assisted safe and accurate wound repair in the future.


Asunto(s)
Quitosano , Conductividad Eléctrica , Hidrogeles , Cicatrización de Heridas , Hidrogeles/química , Cicatrización de Heridas/efectos de los fármacos , Quitosano/química , Animales , Quercetina/química , Quercetina/farmacología , Melaninas/química , Plata/química , Pie Diabético/terapia , Pie Diabético/tratamiento farmacológico , Ratones , Alginatos/química , Nanopartículas del Metal/química , Humanos , Antibacterianos/química , Antibacterianos/farmacología , Iridoides
3.
Nat Chem Biol ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720107

RESUMEN

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

4.
Phytomedicine ; 129: 155613, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38703659

RESUMEN

BACKGROUND: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism. PURPOSE: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH). METHODS: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling. RESULTS: The present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation. CONCLUSION: Our findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention.


Asunto(s)
Medicamentos Herbarios Chinos , Hepatocitos , Peroxidación de Lípido , Fosfolípidos , Estrés Psicológico , Animales , Medicamentos Herbarios Chinos/farmacología , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Masculino , Estrés Psicológico/tratamiento farmacológico , Ratones , Peroxidación de Lípido/efectos de los fármacos , Fosfolípidos/metabolismo , Humanos , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Araquidonato 15-Lipooxigenasa/metabolismo , Factores de Transcripción ARNTL/metabolismo , Ritmo Circadiano/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos
5.
Int J Biol Macromol ; 268(Pt 2): 131678, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38657921

RESUMEN

BACKGROUND: Glia maturation factor beta (GMFB) is a growth and differentiation factor that acts as an intracellular regulator of signal transduction pathways. The small ubiquitin-related modifier (SUMO) modification, SUMOylation, is a posttranslational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. However, the relationship between GMFB and SUMOylation is unclear. RESULTS: Here, we report for the first time that GMFB and SUMO1 are markedly increased in retinal pigment epithelial (RPE) cells at the early stage of diabetes mellitus (DM) under hyperglycemia. The GMFΒ protein could be mono-SUMOylated by SUMO1 at the K20, K35, K58 or K97 sites. SUMOylation of GMFB led to its increased protein stability and subcellular translocation. Furthermore, deSUMOylation of GMFΒ downregulates multiple signaling pathways, including the Jak-STAT signaling pathway, p38 pathway and NF-kappa B signaling pathway. CONCLUSIONS: This work provides novel insight into the role of SUMOylated GMFB in RPE cells and provides a novel therapeutic target for diabetic retinopathy (DR).


Asunto(s)
Hiperglucemia , Estabilidad Proteica , Epitelio Pigmentado de la Retina , Transducción de Señal , Sumoilación , Humanos , Línea Celular , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Células Epiteliales/metabolismo , Hiperglucemia/metabolismo , FN-kappa B/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Proteína SUMO-1/metabolismo , Factor de Maduración de la Glia
6.
J Med Internet Res ; 26: e47017, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557504

RESUMEN

The mortality rate in intensive care units (ICUs) is notably high, with patients often relying on surrogates for critical medical decisions due to their compromised state. This paper provides a comprehensive overview of eHealth. The challenges of applying eHealth tools, including economic disparities and information inaccuracies are addressed. This study then introduces eHealth literacy and the assessment tools to evaluate users' capability and literacy levels in using eHealth resources. A clinical scenario involving surrogate decision-making is presented. This simulated case involves a patient with a hemorrhagic stroke who has lost consciousness and requires medical procedures such as tracheostomy. However, due to the medical surrogate's lack of familiarity with eHealth devices and limited literacy in using eHealth resources, difficulties arise in assisting the patient in making medical decisions. This scenario highlights challenges related to eHealth literacy and solution strategies are proposed. In conclusion, effective ICU decision-making with eHealth tools requires a careful balance between efficiency with inclusivity. Tailoring communication strategies and providing diverse materials are essential for effective eHealth decision resources in the ICU setting. Health professionals should adopt a patient-centered approach to enhance the decision-making experience, particularly for individuals with limited eHealth literacy.


Asunto(s)
Alfabetización en Salud , Telemedicina , Humanos , Toma de Decisiones , Unidades de Cuidados Intensivos , Comunicación , Personal de Salud
7.
J Genet Genomics ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38570113

RESUMEN

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy.

8.
Phytomedicine ; 128: 155475, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38492368

RESUMEN

BACKGROUND: The intricate interactions between chronic psychological stress and susceptibility to breast cancer have been recognized, yet the underlying mechanisms remain unexplored. Danzhi Xiaoyao Powder (DZXY), a traditional Chinese medicine (TCM) formula, has found clinical utility in the treatment of breast cancer. Macrophages, as the predominant immune cell population within the tumor microenvironment (TME), play a pivotal role in orchestrating tumor immunosurveillance. Emerging evidence suggests that lipid oxidation accumulation in TME macrophages, plays a critical role in breast cancer development and progression. However, a comprehensive understanding of the pharmacological mechanisms and active components of DZXY related to its clinical application in the treatment of stress-aggravated breast cancer remains elusive. PURPOSE: This study sought to explore the plausible regulatory mechanisms and identify the key active components of DZXY contributing to its therapeutic efficacy in the context of breast cancer. METHODS: Initially, we conducted an investigation into the relationship between the phagocytic capacity of macrophages damaged by psychological stress and phospholipid peroxidation using flow cytometry and LC-MS/MS-based phospholipomics. Subsequently, we evaluated the therapeutic efficacy of DZXY based on the results of the tumor size, tumor weight, the phospholipid peroxidation pathway and phagocytosis of macrophage. Additionally, the target-mediated characterization strategy based on binding of arachidonate 15-lipoxygenase (ALOX15) to phosphatidylethanolamine-binding protein-1 (PEBP1), including molecular docking analysis, microscale thermophoresis (MST) assay, co-immunoprecipitation analysis and activity verification, has been further implemented to reveal the key bio-active components in DZXY. Finally, we evaluated the therapeutic efficacy of isochlorogenic acid C (ICAC) based on the results of tumor size, tumor weight, the phospholipid peroxidation pathway, and macrophage phagocytosis in vivo. RESULTS: The present study demonstrated that phospholipid peroxides, as determined by LC-MS/MS-based phospholipidomics, triggered in macrophages, which in turn compromised their capacity to eliminate tumor cells through phagocytosis. Furthermore, we elucidate the mechanism behind stress-induced PEBP1 to form a complex with ALOX15, thereby mediating membrane phospholipid peroxidation in macrophages. DZXY, demonstrates potent anti-breast cancer therapeutic effects by disrupting the ALOX15/PEBP1 interaction and inhibiting phospholipid peroxidation, ultimately enhancing macrophages' phagocytic capability towards tumor cells. Notably, ICAC emerged as a promising active component in DZXY, which can inhibit the ALOX15/PEBP1 interaction, thereby mitigating phospholipid peroxidation in macrophages. CONCLUSION: Collectively, our findings elucidate stress increases the susceptibility of breast cancer by driving lipid peroxidation of macrophages and suggest the ALOX15/PEBP1 complex as a promising intervention target for DZXY.


Asunto(s)
Araquidonato 15-Lipooxigenasa , Medicamentos Herbarios Chinos , Peroxidación de Lípido , Macrófagos , Fosfolípidos , Microambiente Tumoral , Medicamentos Herbarios Chinos/farmacología , Microambiente Tumoral/efectos de los fármacos , Animales , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Femenino , Ratones , Araquidonato 15-Lipooxigenasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Estrés Psicológico/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Fagocitosis/efectos de los fármacos , Ratones Endogámicos BALB C , Células RAW 264.7
9.
Free Radic Biol Med ; 216: 46-49, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38458392

RESUMEN

Since the discovery of tocopherols a century ago, α-tocopherol has been distinguished for its unique biological functions. In this study, we aim to elucidate the unique characteristics of α-tocopherol from a chemical perspective. Utilizing density functional theory (DFT) calculations, we evaluated the thermodynamic and kinetic properties of tocopherols, tocotrienols and their oxidation products. Our findings highlight the superior thermodynamic and kinetic properties of α-tocopherol. Although tocopherol substrates generally exhibit similar reactivities, α-tocopherol is distinguished by a larger gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in intermediates, indicating a potential for greater energy release and favoring reaction progression. Moreover, α-tocopherol shows enhanced efficiency in quenching radical intermediates, especially when combined with vitamin C. All these dates provide valuable support for the naming of vitamin E.


Asunto(s)
Antioxidantes , Tocotrienoles , Antioxidantes/química , Vitamina E , alfa-Tocoferol , Tocoferoles
10.
Front Med (Lausanne) ; 11: 1382100, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38545507

RESUMEN

Purpose: To present the outcomes of a new technique for intrascleral fixation of a flanged three-piece foldable intraocular lens (IOL) without a conjunctival incision. Materials and methods: We retrospectively reviewed a consecutive series of 12 eyes of 12 patients who underwent scleral IOL fixation using this technique. Results: The follow-up period ranged 3-12 months. There was a significant improvement in best-corrected visual acuity, from 0.8 (1.6) logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.45 (0.8) logMAR at the final postoperative follow-up (p = 0.012). Notable complications included one case of pupillary IOL capture and increased intraocular pressure. Conclusion: Our novel technique is a viable solution for managing secondary IOL fixation, enabling the use of a wider variety of IOLs and simplifying the reposition process for dislocated three-piece IOLs. This approach has the potential to lower complication rates and enhance patients' recovery.

11.
Nutr Metab Cardiovasc Dis ; 34(6): 1571-1580, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38418351

RESUMEN

BACKGROUND AND AIM: The present study aimed to investigate whether the mitochondrial KATP channel contributes to angiotensin II (Ang II)-induced vascular dysfunction, the development of hypertension, and atherosclerosis. METHODS AND RESULTS: ApoE (-/-) mice fed a high-fat diet were chronically infused with Ang II for eight weeks and concomitantly treated with losartan (ARB), apocynin, or 5-hydroxy decanoate (5-HD), or 3-methyladenine (3-MA). Systolic blood pressure was measured, and pathological changes of aortic or liver tissue were observed. Nitric oxide (NO), superoxide dismutase 2 (SOD2) levels and vasorelaxation rate were measured, and protein and mRNA expressions were examined by western blot and RT-PCR. Ang II-induced development of hypertension was suppressed not only by ARB, and apocynin but also by 5-HD or 3-MA. Ang II infusion decreased aortic NO production and relaxation, as well as SOD2 activity in liver, which were improved by all treatments. In addition, Ang II-induced activation of autophagy was suppressed by 5-HD in aortic tissue, furthermore, Ang II increases the atherosclerotic index in plasma and exacerbates the development of atherosclerosis by increases of fat deposition in the aorta and liver. Lipid metabolism-related mRNA expressions (LXR-α, LDLR, SRBI, Acca, and FASN) were changed by Ang II. Similarly, not only ARB, and apocynin, but also 5-HD and 3-MA suppressed Ang II-induced these changes. CONCLUSIONS: Our present findings evidence that mitochondrial KATP channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis.


Asunto(s)
Angiotensina II , Aterosclerosis , Autofagia , Hipertensión , Óxido Nítrico , Superóxido Dismutasa , Animales , Autofagia/efectos de los fármacos , Masculino , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Hipertensión/fisiopatología , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/patología , Óxido Nítrico/metabolismo , Aterosclerosis/inducido químicamente , Aterosclerosis/patología , Aterosclerosis/metabolismo , Aterosclerosis/genética , Aterosclerosis/fisiopatología , Ratones Noqueados para ApoE , Ratones Endogámicos C57BL , Aorta/efectos de los fármacos , Aorta/patología , Aorta/metabolismo , Aorta/fisiopatología , Presión Sanguínea/efectos de los fármacos , Ratones , Modelos Animales de Enfermedad , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Dieta Alta en Grasa , Canales de Potasio
12.
iScience ; 27(1): 108690, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38235340

RESUMEN

Prenatal stress has been extensively documented as a contributing factor to adverse cardiac development and function in fetuses and infants. The release of glucocorticoids (GCs), identified as a significant stressor, may be a potential factor inducing cardiac hypertrophy. However, the underlying mechanism remains largely unknown. Herein, we discovered that corticosterone (CORT) overload induced cardiac hypertrophy in embryonic chicks and fetal mice in vivo, as well as enlarged cardiomyocytes in vitro. The impaired mitochondria dynamics were observed in CORT-exposed cardiomyocytes, accompanied by dysfunction in oxidative phosphorylation and ATP production. This phenomenon was found to be linked to decreased mitochondrial fusion protein mitofusin 2 (MFN2). Subsequently, we found that CORT facilitated the ubiquitin-proteasome-system-dependent degradation of MFN2 with an enhanced binding of appoptosin to MFN2, serving as the underlying cause. Collectively, our findings provide a comprehensive understanding of the mechanisms by which exposure to stress hormones induces cardiac hypertrophy in fetuses.

13.
Nat Commun ; 15(1): 112, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168034

RESUMEN

Chronic spontaneous urticaria (CSU) comes with gut dysbiosis, but its relevance remains elusive. Here we use metagenomics sequencing and short-chain fatty acids metabolomics and assess the effects of human CSU fecal microbial transplantation, Klebsiella pneumoniae, Roseburia hominis, and metabolites in vivo. CSU gut microbiota displays low diversity and short-chain fatty acids production, but high gut Klebsiella pneumoniae levels, negatively correlates with blood short-chain fatty acids levels and links to high disease activity. Blood lipopolysaccharide levels are elevated, link to rapid disease relapse, and high gut levels of conditional pathogenic bacteria. CSU microbiome transfer and Klebsiella pneumoniae transplantation facilitate IgE-mediated mast cell(MC)-driven skin inflammatory responses and increase intestinal permeability and blood lipopolysaccharide accumulation in recipient mice. Transplantation of Roseburia hominis and caproate administration protect recipient mice from MC-driven skin inflammation. Here, we show gut microbiome alterations, in CSU, may reduce short-chain fatty acids and increase lipopolysaccharide levels, respectively, and facilitate MC-driven skin inflammation.


Asunto(s)
Urticaria Crónica , Dermatitis , Microbioma Gastrointestinal , Humanos , Ratones , Animales , Lipopolisacáridos/farmacología , Ácidos Grasos Volátiles/metabolismo , Inflamación , Disbiosis/microbiología
14.
J Chem Inf Model ; 64(3): 785-798, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38262973

RESUMEN

The allosteric modulation of the homodimeric H10-03-6 protein to glycan ligands L1 and L2, and the STAB19 protein to glycan ligands L3 and L4, respectively, has been studied by molecular dynamics simulations and free energy calculations. The results revealed that the STAB19 protein has a significantly higher affinity for L3 (-11.38 ± 2.32 kcal/mol) than that for L4 (-5.51 ± 1.92 kcal/mol). However, the combination of the H10-03-6 protein with glycan L2 (1.23 ± 6.19 kcal/mol) is energetically unfavorable compared with that of L1 (-13.96 ± 0.35 kcal/mol). Further, the binding of glycan ligands L3 and L4 to STAB19 would result in the significant closure of the two CH2 domains of the STAB19 conformation with the decrease of the centroid distances between the two CH2 domains compared with the H10-03-6/L1/L2 complex. The CH2 domain closure of STAB19 relates directly to the formation of new hydrogen bonds and hydrophobic interactions between the residues Ser239, Val240, Asp265, Glu293, Asn297, Thr299, Ser337, Asp376, Thr393, Pro395, and Pro396 in STAB19 and glycan ligands L3 and L4, which suggests that these key residues would contribute to the specific regulation of STAB19 to L3 and L4. In addition, the distance analysis revealed that the EF loop in the H10-03-6/L1/L2 model presents a high flexibility and partial disorder compared with the stabilized STAB19/L3/L4 complex. These results will be helpful in understanding the specific regulation through the asymmetric structural characteristics in the CH2 and CH3 domains of the H10-03-6 and STAB19 proteins.


Asunto(s)
Fragmentos Fc de Inmunoglobulinas , Simulación de Dinámica Molecular , Fragmentos Fc de Inmunoglobulinas/química , Fragmentos Fc de Inmunoglobulinas/metabolismo , Isotipos de Inmunoglobulinas , Conformación Molecular , Polisacáridos
15.
Ther Adv Neurol Disord ; 17: 17562864231219151, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38288324

RESUMEN

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.

16.
Plant Cell Environ ; 47(5): 1575-1591, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38269615

RESUMEN

The spike growth phase is critical for the establishment of fertile floret (grain) numbers in wheat (Triticum aestivum L.). Then, how to shorten the spike growth phase and increase grain number synergistically? Here, we showed high-resolution analyses of floret primordia (FP) number, morphology and spike transcriptomes during the spike growth phase under three light regimens. The development of all FP in a spike could be divided into four distinct stages: differentiation (Stage I), differentiation and morphology development concurrently (Stage II), morphology development (Stage III), and polarization (Stage IV). Compared to the short photoperiod, the long photoperiod shortened spike growth and stimulated early flowering by shortening Stage III; however, this reduced assimilate accumulation, resulting in fertile floret loss. Interestingly, long photoperiod supplemented with red light shortened the time required to complete Stages I-II, then raised assimilates supply in the spike and promoted anther development before polarization initiation, thereby increasing fertile FP number during Stage III, and finally maintained fertile FP development during Stage IV until they became fertile florets via a predicted dynamic gene network. Our findings proposed a light regimen, critical stages and candidate regulators that achieved a shorter spike growth phase and a higher fertile floret number in wheat.


Asunto(s)
Flores , Triticum , Flores/fisiología , Triticum/fisiología , Perfilación de la Expresión Génica , Grano Comestible/genética , Fertilidad , Transcriptoma/genética
17.
Int J Biol Macromol ; 264(Pt 1): 129762, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38281535

RESUMEN

Lignin, as an amorphous three-dimensional aromatic polymer, was able to self-assemble into lignin nanoparticles (LNPs) to realize valorization of lignin. Here, lignin-xylan extractives were extracted from grape seed (GS) and poplar by acidic THF at room temperature, and effectively produced lignin-xylan nanospheres via spin evaporation. The morphology and chemical properties of nanospheres were determined by its natural origins, consequently influencing its application. For the lignin-xylan extractive from grape seed, the lignin was composed of guaiacyl (G) and p-hydroxylphenyl (H) units and the hollowed nanospheres (GS-LNPs) with 362.72 nm diameter was produced. The extractive from poplar was composed of G-syringyl (S) typed lignin (80.30 %) and xylan (12.33 %), that can assemble into LNPs with smaller size (229.87 nm), better PDI (0.1), and light color. The hybrid particles showed the qualities of lignin and xylan, that properties led to the LNPs@PVA composite films with UV-blocking capability, strong mechanical strength and hydrophobicity, and transparency ability of visible light. P-LNPs showed better performance as the film additives, due to its lower particles size and high content of unconjugated -OH from xylan. Xylan was significant in the composite films, and lowering the xylan content resulted in the decrease of the composite film's mechanical properties and hydrophobicity.


Asunto(s)
Lignina , Nanosferas , Lignina/química , Xilanos/química , Polímeros
18.
J Exp Bot ; 75(7): 1967-1981, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38069503

RESUMEN

Within a spike of wheat, the central spikelets usually generate three to four fertile florets, while the basal spikelets generate zero to one fertile floret. The physiological and transcriptional mechanism behind the difference in fertility between the basal and central spikelets is unclear. This study reports a high temporal resolution investigation of transcriptomes, number and morphology of floret primordia, and physiological traits. The W6.5-W7.5 stage was regarded as the boundary to distinguish between fertile and abortive floret primordia; those floret primordia reaching the W6.5-W7.5 stage during the differentiation phase (3-9 d after terminal spikelet stage) usually developed into fertile florets in the next dimorphism phase (12-27 d after terminal spikelet stage), whereas the others aborted. The central spikelets had a greater number of fertile florets than the basal spikelets, which was associated with more floret primordia reaching the W6.5-W7.5 stage. Physiological and transcriptional results demonstrated that the central spikelets had a higher sucrose content and lower abscisic acid (ABA) and jasmonic acid (JA) accumulation than the basal spikelets due to down-regulation of genes involved in ABA and JA synthesis. Collectively, we propose a model in which ABA and JA accumulation is induced under limiting sucrose availability (basal spikelet) through the up-regulation of genes involved in ABA and JA synthesis; this leads to floret primordia in the basal spikelets failing to reach their fertile potential (W6.5-W7.5 stage) during the differentiation phase and then aborting. This fertility repression model may also regulate spikelet fertility in other cereal crops and potentially provides genetic resources to improve spikelet fertility.


Asunto(s)
Ácido Abscísico , Ciclopentanos , Flores , Oxilipinas , Sulfonamidas , Flores/genética , Triticum/genética , Sacarosa , Fertilidad/genética
19.
Bioresour Technol ; 394: 130242, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38145760

RESUMEN

Brewer's spent grain (BSG) is a major low-value by-product of beer industry. To realize the high value application of BSG, this work proposed a strategy to produce single cell protein (SCP) with oligosaccharide prebiotics from BSG, via ammoniation pretreatment, enzymatic hydrolysis, and fermentation. The optimum conditions of ammoniation pretreatment obtained by response surface method were 11 % ammonia dosage (w/w), 63 °C for 26 h. Suitable enzyme and yeast were screened to enhance the conversion of cellulose and hemicellulose in BSG into sugars and maximize the SCP yield. It was shown that using lignocellulolytic enzyme SP from Penicillium oxalicum and Trichosporon cutaneum, about 310 g of SCP with 80 g of arabinoxylo-oligosaccharides were obtained from 1000 g of BSG. This process is low cost, high efficiency, and easy to implement, which has good industrial application prospects.


Asunto(s)
Celulosa , Proteínas en la Dieta , Grano Comestible , Fermentación , Grano Comestible/metabolismo , Celulosa/metabolismo , Saccharomyces cerevisiae/metabolismo
20.
Signal Transduct Target Ther ; 8(1): 432, 2023 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-37949875

RESUMEN

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.


Asunto(s)
COVID-19 , Microbiota , Neumonía , Humanos , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2/genética , Respiración Artificial , Pulmón , Neumonía/metabolismo , Bacterias
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