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Ginseng (Panax ginseng C. A. Mey.) is an important and valuable medicinal plant species used in traditional Chinese medicine, and its metabolite ginsenoside is the primary active ingredient. The FAR1/FHY3 gene family members play critical roles in plant growth and development as well as participate in a variety of physiological processes, including plant development and signaling of hormones. Studies have indicated that methyl jasmonate treatment of ginseng adventitious roots resulted in a significant increase in the content of protopanaxadiol ginsenosides. Therefore, it is highly significant to screen the FAR1/FHY3 gene family members in ginseng and preliminarily investigate their expression patterns in response to methyl jasmonic acid signaling. In this study, we screened and identified the FAR1/FHY3 family genes in the ginseng transcriptome databases. And then, we analyzed their gene structure and phylogeny, chromosomal localization and expression patterns, and promoter cis-acting elements, and made GO functional annotations on the members of this family. After that, we treated the ginseng adventitious roots with 200 mM methyl jasmonate and investigated the trend of the expression of four genes containing the largest number of methyl jasmonate cis-acting elements at different treatment times. All four genes were able to respond to methyl jasmonate, the most significant change was in the PgFAR40 gene. This study provides data support for subsequent studies of this family member in ginseng and provides experimental reference for subsequent validation of the function of this family member under methyl jasmonic acid signaling.
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Acetatos , Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Oxilipinas , Panax , Filogenia , Proteínas de Plantas , Oxilipinas/farmacología , Ciclopentanos/farmacología , Panax/genética , Panax/metabolismo , Panax/efectos de los fármacos , Acetatos/farmacología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Perfilación de la Expresión Génica , Genes de Plantas , GinsenósidosRESUMEN
Panax ginseng is an important medicinal plant, and ginsenosides are the main bioactive molecules of ginseng. The TCP (TBI, CYC, PCF) family is a group of transcription factors (TFs) that play an important role in plant growth and development, hormone signalling and synthesis of secondary metabolites. In our study, 78 PgTCP transcripts were identified from the established ginseng transcriptome database. A phylogenetic tree analysis showed that the 67 PgTCP transcripts with complete open reading frames were classified into three subfamilies, including CIN, PCF, and CYC/TB1. Protein structure analysis showed that PgTCP genes had bHLH structures. Chromosomal localization analysis showed that 63 PgTCP genes were localized on 17 of the 24 chromosomes of the Chinese ginseng genome. Expression pattern analysis showed that PgTCP genes differed among different lineages and were spatiotemporally specific. Coexpression network analysis indicated that PgTCP genes were coexpressed and involved in plant activities or metabolic regulation in ginseng. The expression levels of PgTCP genes from class I (PCF) were significantly downregulated, while the expression levels of PgTCP genes from class II (CIN and CYC/TB1) were upregulated, suggesting that TCP genes may be involved in the regulation of secondary metabolism in ginseng. As the PgTCP26-02 gene was found to be related to ginsenoside synthesis, its predicted protein structure and expression pattern were further analysed. Our results provide new insights into the origin, differentiation, evolution and function of the PgTCP gene family in ginseng, as well as the regulation of plant secondary metabolism.
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Ginsenósidos , Panax , Ginsenósidos/metabolismo , Panax/genética , Panax/metabolismo , Filogenia , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcriptoma , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/metabolismoRESUMEN
BACKGROUND: Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. METHODS: We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. RESULTS: Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (ß -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). CONCLUSION: Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Isquemia Miocárdica , Masculino , Humanos , Femenino , Persona de Mediana Edad , Prueba de Esfuerzo , Isquemia Miocárdica/diagnóstico , Angiografía CoronariaRESUMEN
Background: Although pulmonary vein isolation (PVI) remains the mainstream way of atrial fibrillation (AF) ablation. The left atrial posterior wall (LAPW) may contributes to the development of AF as an arrhythmogenic substrate. The efficacy of additional left atrial posterior wall isolation (LAPWI) beyond PVI is in AF patients remains undefined. This study explored the influence of posterior wall isolation (PWI) on clinical outcomes in AF patients. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for studies comparing the outcomes of AF with and without PWI. The efficacy outcomes were recurrence of all atrial arrhythmia (AA), atrial fibrillation (AF), and atrial flutter (AFL)/atrial tachycardia (AT). The safety outcomes were mainly focused on procedural adverse events. Results: A total of 16 studies (7 randomized controlled trials (RCTs), 3 prospective studies and 6 retrospective analyses) with 3340 AF patients were enrolled (1550 patients in PVI with PWI group and 1790 in PVI alone group). 12 studies included persistent atrial fibrillation patients, 3 studies with paroxysmal AF patients and 1 study with paroxysmal AF and persistent AF concurrently. Mean follow-up period was 16.56 months. In AF patients, adjunctive PWI obviously reduced the recurrence of all atrial arrhythmias (risk ratio (RR) 0.78 [95% CI 0.64-0.95], I 2 = 79%, p = 0.01) and the recurrence of AF (RR 0.68 [95% CI 0.53-0.88], I 2 = 75%, p = 0.004); Meanwhile, additional PWI left no impact substantially on lower recurrence of AFL/AT (RR 1.23 [95% CI 0.94-1.60], I 2 = 49%, p = 0.12). The results seemed to be no significant differences in occurrence rate of procedural complications between the PVI only and PWI+PVI (RR 1.19 [95% CI 0.80-1.79], I 2 = 0%, p = 0.39). In subgroup analyses, the benefit of adjunctive PWI compared with PVI only was more distinct in persistent AF group and cryoballoon ablation group. Notably, adjunctive PWI with radiofrequency ablation may induce a slight increase of recurrent AFL/AT compared with PVI only (RR 1.56 [95% CI 1.02-2.39], I 2 = 30%, p = 0.04). Conclusions: Compared with PVI alone, additional PWI to PVI appeared to be associated with decreased recurrence of AF and atrial arrhythmias without an increased occurrence of procedural complications, especially in persistent AF patients. Cryoballoon ablation seemed more suitable for PWI compared with radiofrequency ablation. More RCTs are needed to verify the conclusion.
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Although multiple purinergic receptors mediate the analgesic effects of acupuncture, it remains unclear whether there is mutual interaction between purinergic receptors to jointly mediate the electroacupuncture inhibition of peripheral sensitization in visceral pain. Visceral hypersensitivity was induced by intracolonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rat. The antinociception effect of electroacupuncture on visceral pain was evaluated by morphology, behaviors, neuroelectrophysiology and molecular biology techniques. After labeling the colon-related primary sensory neurons with neural retrograde tracer and employing neuropharmacology, neuroelectrophysiology, and molecular biotechnology, the mechanisms of P2X7R, P2Y1R, and P2X3R in colon-related dorsal root ganglion (DRG) neurons alleviating visceral hypersensitivity of irritable bowel syndrome (IBS) by electroacupuncture at Zusanli and Sanyinjiao acupoints.were elucidated from the perspective of peripheral sensitization. Electroacupuncture significantly inhibited TNBS-induced colonic hypersensitivity in rats with IBS, and Satellite Glial Cells (SGCs) in DRG were found to be involved in electroacupuncture-mediated regulation of the electrophysiological properties of neurons. P2X7R was found to play a pain-inducing role in IBS visceral hypersensitivity by affecting P2X3R, and electroacupuncture exerted an analgesic effect by inhibiting P2X7R activation. P2Y1R was found to play an analgesic role in the process of visceral pain, mediating electroacupuncture to relieve visceral hypersensitivity. P2Y1R relieved visceral pain by inhibiting P2X3R in neurons associated with nociception, with P2X7R identified as upstream of P2Y1R up-regulation by electroacupuncture. Our study suggests that the P2X7R â P2Y1R â P2X3R inhibitory pathway in DRG mediates the inhibition of peripheral sensitization by electroacupuncture in rats with IBS visceral hypersensitivity.
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A simple twin-core D-shape photonic crystal fiber sensor based on surface plasmon resonance (SPR) is designed for the measurement of refractive indices (RI). The twin-core D-shape structure enhances the SPR effect, and the M g F 2-Au dual-layer film narrows the linewidth in the loss spectrum, consequently improving both the sensitivity and figure of merit (FOM). The properties of the sensor are analyzed by the finite element method. In the RI range of 1.32-1.42, the maximum wavelength sensitivity, FOM, and resolution are 62,000 nm/RIU, 1281R I U -1, and 1.61×10-6, respectively.
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Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe-loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence.
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Vesículas Extracelulares , Inmunoterapia , Macrófagos , Ratones Endogámicos BALB C , Fotoquimioterapia , Fármacos Fotosensibilizantes , Animales , Inmunoterapia/métodos , Vesículas Extracelulares/química , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Línea Celular Tumoral , Femenino , Liposomas/química , Concentración de Iones de Hidrógeno , Microambiente Tumoral/efectos de los fármacos , Humanos , Ferroptosis/efectos de los fármacos , Nanopartículas/químicaRESUMEN
This quasi-experimental study investigated the impact of traditional Chinese culture-based life-and-death education on 38 ICU nurses. Participants underwent 14 hours of training, and data were collected before and after the intervention using various questionnaires. Frequency and percentage were used for categorical data; mean and standard deviation for measurement data; and paired-sample t test for comparison of teaching effects before and after the intervention of life-and-death education programs. Results indicated significant improvements in understanding of death, reduced death anxiety, enhanced death coping abilities, and increased search for meaning (p < .05). However, there was no statistically significant change in attitude toward death (p > .05). Life-and-death education rooted in traditional Chinese culture positively influenced ICU nurses, fostering improved death cognition, reduced death anxiety, enhanced coping skills, and a heightened sense of meaning in life. Subsequent research will explore the relationship and distinctions between explicit and implicit death attitudes.
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Esophageal cancer (EC) is a deadly malignancy. Small extracellular vesicles (sEVs) with programmed death ligand 1 (sEV-PDL1) induce immune escape to promote tumor progression. Furthermore, the imbalance between circulating follicular helper T (Tfh) and circulating follicular regulatory T (Tfr) cells is related to the progression of many malignant tumors. However, the role of the EC-derived sEV-PDL1 in circulating Tfh/Tfr is unknown. Circulating Tfh and Tfr cells were detected by flow cytometry. sEVs were isolated through differential centrifugation and cultured for cell expansion assays. Naïve CD4+ T cells were isolated, stimulated, and cultured with sEVs to evaluate the frequencies, phenotypes, and functions of Tfh and Tfr cells. The proportion of circulating Tfh in patients with EC was lower than that in healthy donors (HDs), whereas that of circulating Tfr was higher. The EC group showed significantly lower circulating Tfh/Tfr and a higher level of sEV-PDL1 than HDs. Notably, sEV-PDL1 was negatively correlated with circulating Tfh/Tfr in the EC group. In vitro assays, sEV-PDL1 inhibited Tfh expansion, enhanced the cytotoxic T lymphocyte-associated antigen 4+ (CTLA4+) Tfh cell percentage, decreased the levels of interleukin (IL)-21 and interferon-γ, and increased IL-10. sEV-PDL1 promoted the expansion and immunosuppressive functions of circulating Tfr; the increased percentages of CTLA4+ Tfr and inducible T cell co-stimulator+ Tfr were accompanied with high IL-10. However, applying an anti-PDL1 antibody significantly reversed this. Our results suggest a novel mechanism of sEV-PDL1-mediated immunosuppression in EC. Inhibiting sEV-PDL1 to restore circulating Tfh/Tfr balance provides a novel therapeutic approach for EC.
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Neoplasias Esofágicas , Vesículas Extracelulares , Humanos , Linfocitos T Colaboradores-Inductores , Células T Auxiliares Foliculares , Interleucina-10 , Antígeno CTLA-4 , Antígeno B7-H1 , Linfocitos T Reguladores , Terapia de InmunosupresiónRESUMEN
Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.
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Neoplasias Óseas , Exosomas , Vesículas Extracelulares , Neoplasias de la Próstata , Masculino , Humanos , Exosomas/metabolismo , Neoplasias de la Próstata/patología , Neoplasias Óseas/patología , Comunicación Celular , Vesículas Extracelulares/metabolismo , Microambiente Tumoral , Metástasis de la NeoplasiaRESUMEN
OBJECTIVES: Our study aimed to elucidate the possible relationship between endogenous circulating testosterone and the beginning and development of stress urinary incontinence (SUI) in postmenopausal women. PATIENTS AND METHODS: The clinical data of female patients with SUI who underwent surgery at our hospital from January 2014 to February 2023 and healthy female volunteers recruited during the same period were retrospectively analyzed according to age and body mass index (BMI). Venous blood samples were taken from all subjects, and levels of estradiol, luteinizing hormone, prolactin, follicle-stimulating hormone, progesterone, and testosterone were measured by radioimmunoassay. After adjusting for age, BMI, hypertension, mode of delivery, hysterectomy, and profession, multiple logistic regression analysis was used to determine the relationship between SUI and serum testosterone levels in postmenopausal women. RESULTS: Serum testosterone levels were significantly lower in women with SUI than in healthy control women (0.92 ± 0.67 vs. 1.28 ± 1.10; P < 0.05). Further comparison of testosterone levels between postmenopausal SUI women and healthy postmenopausal women in postmenopausal subjects revealed that testosterone levels were significantly lower in postmenopausal SUI women than in healthy postmenopausal women (0.84 ± 0.64 vs. 1.23 ± 1.10; P < 0.05). This difference in testosterone levels remained significant after controlling for age, BMI, hypertension, mode of delivery, hysterectomy, and profession in postmenopausal women. CONCLUSION: The results of the present study indicate that low levels of serum testosterone are associated with an increased likelihood of stress urinary incontinence in women. Low serum testosterone levels may be a risk factor for SUI in postmenopausal women.
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Hipertensión , Incontinencia Urinaria de Esfuerzo , Femenino , Humanos , Posmenopausia , Estudios Retrospectivos , TestosteronaRESUMEN
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with Ca2+ leak predominantly caused by ryanodine receptor 2 (RyR2) mutations. We identified a R1760W-RyR2 mutation located between the N-terminal domain and the central domain of RyR2 in a CPVT patient by DNA sequencing. Recombinant mutant RyR2-2801mcherry plasmid generated by the overlap extension polymerase chain reaction and seamless cloning was transfected in HEK293 cells for the cell model. Single-cell luminal and cytosolic Ca2+ imaging was measured by endoplasmic reticulum (ER) luminal Ca2+ -sensitive protein D1ER and Fura-2 AM on a confocal laser scanning microscope, respectively. We found that in RyR2 mutant cells, the propensity for store-overload-induced Ca2+ release (SOICR) was enhanced representing increased Ca2+ oscillations, reduced activation and termination thresholds of spontaneous Ca2+ release; and the sensitivity to cytosolic Ca2+ activation was increased manifesting reduced steady state ER Ca2+ levels. Our results indicated that R1760W-RyR2 mutation induced calcium leak, representing a gain of function. Further, antiarrhythmic drugs propafenone and flecainide significantly suppressed SOICR caused by the R1760W-RyR2 mutation at a concentration of 20 µM, which was lower than the concentration at which carvedilol suppressed SOICR.
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Mutación con Ganancia de Función , Canal Liberador de Calcio Receptor de Rianodina , Humanos , Células HEK293 , Canal Liberador de Calcio Receptor de Rianodina/genéticaRESUMEN
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an ion channelopathy, caused by mutations in genes coding for calcium-handling proteins. It can coexist with left ventricular non-compaction. We aim to investigate the clinical and genetic characteristics of this co-phenotype. METHODS: Medical records of 24 patients diagnosed with catecholaminergic polymorphic ventricular tachycardia in two Chinese hospitals between September, 2005, and January, 2020, were retrospectively reviewed. We evaluated their clinical and genetic characteristics, including basic demographic data, electrocardiogram parameters, medications and survival during follow-up, and their gene mutations. We did structural analysis for a novel variant ryanodine receptor 2-E4005V. RESULTS: The patients included 19 with catecholaminergic polymorphic ventricular tachycardia mono-phenotype and 5 catecholaminergic polymorphic ventricular tachycardia-left ventricular non-compaction overlap patients. The median age of onset symptoms was 9.0 (8.0,13.5) years. Most patients (91.7%) had cardiac symptoms, and 50% had a family history of syncope. Overlap patients had lower peak heart rate and threshold heart rate for ventricular tachycardia and ventricular premature beat during the exercise stress test (p < 0.05). Sudden cardiac death risk may be higher in overlap patients during follow-up. Gene sequencing revealed 1 novel ryanodine receptor 2 missense mutation E4005V and 1 mutation previously unreported in catecholaminergic polymorphic ventricular tachycardia, but no left ventricular non-compaction-causing mutations were observed. In-silico analysis showed the novel mutation E4005V broke down the interaction between two charged residues. CONCLUSIONS: Catecholaminergic polymorphic ventricular tachycardia overlapping with left ventricular non-compaction may lead to ventricular premature beat/ventricular tachycardia during exercise stress test at lower threshold heart rate than catecholaminergic polymorphic ventricular tachycardia alone; it may also indicate a worse prognosis and requires strict follow-up. ryanodine receptor 2 mutations disrupted interactions between residues and may interfere the function of ryanodine receptor 2.
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BACKGROUND: It is important to understand how the perception of death affects the competence to cope with death. OBJECTIVES: To explore whether the perception of death has an indirect effect on competence to cope with death through the mediation of attitude toward death and meaning of life. METHODS: A total of 786 nurses from Hunan Province, China, selected by random sampling method and asked to complete an online electronic questionnaire between October and November 2021 were included in the study. RESULTS: The nurses' scored 125.39 ± 23.88 on the competence to cope with death. There was a positive correlation among perception of death, competence to cope with death, the meaning of life, and attitude toward death. There were three mediating pathways: the separate mediating effect of natural acceptance and meaning of life, and the chain mediating effect of natural acceptance and meaning of life. CONCLUSION: The nurses' competence to cope with death was moderate. Perception of death could indirectly and positively predict nurses' competence to cope with death by enhancing natural acceptance or sense of meaning in life. In addition, perception of death could improve natural acceptance and then enhance the sense of meaning in life to positively predict nurses' competence to cope with death.
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To explore nurses' ability to cope with death and its relationship with death cognition and meaning in life in the context of Chinese traditional culture. 1146 nurses from six tertiary hospitals were recruited. Participants completed the Coping with Death Scale, the Meaning in Life Questionnaire, and the self-made Death Cognition Questionnaire. Multiple regression analysis revealed that the search for meaning, the understanding of "good death", receiving education related to life-and-death, cultural aspect, the presence of meaning, and the number of patient deaths experienced in career explained 20.3% of the variance in the ability to cope with death. Lacking a correct understanding of death, nurses are not sufficiently prepared to deal with death and their ability to cope with death is influenced by the unique cognition of death and the sense of the meaning in life in the context of Chinese traditional culture.
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Vanadium-based oxides with high theoretical specific capacities and open crystal structures are promising cathodes for aqueous zinc-ion batteries (AZIBs). In this work, the confined synthesis can insert metal ions into the interlayer spacing of layered vanadium oxide nanobelts without changing the original morphology. Furthermore, we obtain a series of nanomaterials based on metal-confined nanobelts, and describe the effect of interlayer spacing on the electrochemical performance. The electrochemical properties of the obtained Al2.65 V6 O13 â 2.07H2 O as cathodes for AZIBs are remarkably improved with a high initial capacity of 571.7â mAh â g-1 at 1.0â A g-1 . Even at a high current density of 5.0â A g-1 , the initial capacity can still reach 205.7â mAh g-1 , with a high capacity retention of 89.2 % after 2000â cycles. This study demonstrates that nanobelts confined with metal ions can significantly improve energy storage applications, revealing new avenues for enhancing the electrochemical performance of AZIBs.
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BACKGROUND: Mitochondrial dysfunction is an important pathogenic event in acute kidney injury (AKI). GCN5L1 is a specific acetyltransferase in mitochondria, which regulates glucose and fatty acid metabolism. However, the role of GCN5L1 in mitochondrial dysfunction and the pathogenesis of ischemic AKI are not fully understood. METHODS: The protein level of GCN5L1 was detected by western blot assay. Acetylated proteomics was used to explore the level of acetylated TFAM. Duolink proximity ligation assay and co-immunoprecipitation were used to detect the interaction of TFAM and translocase of outer membrane 70 (TOM70). mtDNA copy number, the expression of mitochondrial electron transport chain complexes, the number and morphology of mitochondria were measured. The renal injury of AKI mice was reflected by the levels of creatinine and urea nitrogen and the pathological changes of renal tissue. RESULTS: We showed that GCN5L1 was highly expressed in vivo and in vitro and renal tubules specific knockdown of GCN5L1 could effectively attenuate AKI-induced mitochondrial impairment. Besides, acetylated proteomics revealed that acetylated TFAM was significantly upregulated in AKI mice kidney, which reminded us that TFAM might be an acetylating substrate of GCN5L1. Mechanistically, we evidenced that GCN5L1 could acetylate TFAM at its K76 site and subsequently inhibited its binding to TOM70, thereby reducing TFAM import into mitochondria and mitochondrial biogenesis. Clinically, GCN5L1 and acetylated TFAM were positively correlated with disease severity (all p < 0.05). CONCLUSIONS: In sum, these data demonstrated an unrecognized regulating mechanism of GCN5L1 on TFAM acetylation and its intracellular trafficking, and a potential intervening target for AKI associated mitochondrial disorders as well.
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Lesión Renal Aguda , Biogénesis de Organelos , Ratones , Animales , Proteínas de Unión al ADN , Proteínas del Grupo de Alta Movilidad/genéticaRESUMEN
Broadband and switchable versatile polarization metamaterial is crucial in the applications of imaging, sensing and communication, especially in the terahertz frequency. Here, we investigated versatile polarization manipulation in a hybrid terahertz metamaterial with bilayer rectangular rods and a complementary vanadium dioxide (VO2) layer. The VO2 phase transition enables a flexible switching from dual-band asymmetric transmission to dual-band reflective half-wave plate. The full width half maximum (FWHM) bandwidths of dual-band asymmetric transmission are 0.77 and 0.21 THz, respectively. The polarization conversion ratio (PCR) of the reflective metamaterial is over 0.9 in the frequency ranges of 1.01-1.17 THz and 1.47-1.95 THz. Angular dependences of multiple polarization properties are studied. The proposed switchable polarization metamaterial is important to the development of multifunctional polarization devices and multichannel polarization detection.
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BACKGROUND: T long-term effects of cognitive therapy and behavior therapy (CTBT) for menopausal symptoms are unknown, and whether the effects are different between natural menopause and treatment-induced menopause are currently unclear. Therefore, we sought to conduct an accurate estimate of the efficacy of CTBT for menopausal symptoms. METHODS: We conducted searches of Cochrane Library, EMBASE, PsycINFO, PubMed, and Web of Science databases for studies from 1 January 1977 to 1 November 2021. Randomized controlled trials (RCTs) comparing intervention groups to control groups for menopausal symptoms were included. Hedge's g was used as the standardized between-group effect size with a random-effects model. RESULTS: We included 14 RCTs comprising 1618 patients with a mean sample size of 116. CTBT significantly outperformed control groups in terms of reducing hot flushes [g = 0.39, 95% confidence interval (CI) 0.23-0.55, I2 = 45], night sweats, depression (g = 0.50, 95% CI 0.34-0.66, I2 = 51), anxiety (g = 0.38, 95% CI 0.23-0.54, I2 = 49), fatigue, and quality of life. Egger's test indicated no publication bias. CONCLUSIONS: CTBT is an effective psychological treatment for menopausal symptoms, with predominantly small to moderate effects. The efficacy is sustained long-term, although it declines somewhat over time. The efficacy was stronger for natural menopause symptoms, such as vasomotor symptoms, than for treatment-induced menopause symptoms. These findings provide support for treatment guidelines recommending CTBT as a treatment option for menopausal symptoms.
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Terapia Cognitivo-Conductual , Sofocos , Femenino , Sofocos/terapia , Humanos , Menopausia , Calidad de VidaRESUMEN
Rare diseases, also known as orphan diseases, are a group of diseases that affect a relatively small number of people. Low incidence rates, atypical symptoms, imperfect diagnosis criteria and few treatment options impose medical, psychological and financial stress on the local healthcare system. The spectrum of liver diseases in China has changed in the past decades due to successful control of once highly prevalent viral hepatitis B and C. Furthermore, the increased awareness and improved availability of specific laboratory tests have also facilitated the diagnosis of rare diseases such as autoimmune, cholestatic and genetic liver diseases. Finally, considering the huge population, the total number of many rare liver diseases in China is not as rare as once deemed. In this mini-review article, we will outline the current clinical and epidemiological profiles of some rare liver diseases that are no longer rare in China.