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BACKGROUND: Gallstone disease (GSD), nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and metabolic syndrome (MetS) are common medical disorders worldwide. This study aimed to ascertain how NAFLD, MAFLD, MetS, and other factors affect the development of GSD, and how the GSD-associated factors influence patient recovery after laparoscopic cholecystectomy (LC). METHODS: We included 200 patients who were diagnosed with GSD and underwent LC between January 2017 and February 2022. A total of 200 subjects without GSD and "non-calculous causes" during the same period were also included as controls. We compared the metabolic disorder differences between GSD patients and controls. Furthermore, we sub-grouped patients based on the comorbidities of preoperative NAFLD, MAFLD, and MetS, and compared the impacts of these comorbidities on short-term post-LC functional recovery of the patients. RESULTS: The prevalence of NAFLD and MetS were higher in GSD patients (P < 0.05). Based on multivariate logistic regression analysis, hyperglycemia [odds ratio (OR) = 2.2, 95% confidence interval (CI): 1.4-3.4, P = 0.001] and low high-density lipoprotein cholesterol (HDL-C) level (OR = 1.8, 95% CI: 1.1-3.1, P = 0.048) were linked to GSD. NAFLD and MetS linked to liver enzymes after LC (P < 0.05). MetS also linked to the levels of inflammatory indicators after LC (P < 0.05). The obesity, hyperlipidemia, low HDL-C level, and hyperglycemia linked to liver enzymes after LC (P < 0.05). Hyperlipidemia, low HDL-C level, and hypertension linked to inflammation after LC (P < 0.05). CONCLUSIONS: The prevalence of GSD may be linked to NAFLD and MetS. Hyperglycemia and low HDL-C level were independent risk factors of GSD.
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Arithmetic fluency is considered considers highly rely on language processing, encompassing essential skills. However, the independent predictive power of phonetic, semantic, or orthographic skills in relation to arithmetic fluency remains an unresolved query. This study introduces the common component hypothesis to elucidate the inconsistent findings in previous research. The hypothesis posits that significant correlations between language and mathematics hinge on whether the language and mathematics utilized in a given task share a common component. According to this hypothesis, processing skills for each of the three fundamental language elements (i.e., phonetic, semantic, orthographic) should correlate with arithmetic fluency, as these elements are also integral to simple arithmetic processing. A cohort of one hundred and ninety-eight primary school students participated in the study, undertaking a battery of tests assessing general cognitive abilities, psycholinguistic elements, and arithmetic fluency. The results showed that orthographic, phonetic, and semantic abilities independently predicted arithmetic fluency, even after accounting for all other cognitive predictors. These findings substantiate the common component hypothesis, providing empirical support for explaining the association between language and mathematics. This evidence contributes to addressing the interplay between language and mathematics in educational contexts.
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BACKGROUND AND OBJECTIVES: Lexical tone presents challenges to cochlear implant (CI) users especially in noise conditions. Bimodal hearing utilizes residual acoustic hearing in the contralateral side and may offer benefits for tone recognition in noise. The purpose of the present study was to evaluate tone recognition in both steady-state noise and multi-talker babbles by the prelingually-deafened, Mandarin-speaking children with unilateral CIs or bimodal hearing. METHODS: Fifty-three prelingually-deafened, Mandarin-speaking children who received CIs participated in this study. Twenty-two of them were unilateral CI users and 31 wore a hearing aid (HA) in the contralateral ear (i.e., bimodal hearing). All subjects were tested for Mandarin tone recognition in quiet and in two types of maskers: speech-spectrum-shaped noise (SSN) and two-talker babbles (TTB) at four signal-to-noise ratios (-6, 0, +6, and +12 dB). RESULTS: While no differences existed in tone recognition in quiet between the two groups, the Bimodal group outperformed the Unilateral CI group under noise conditions. The differences between the two groups were significant at SNRs of 0, +6, and +12 dB in the SSN conditions (all p < 0.05), and at SNRs of +6 and +12 dB of TTB conditions (both p < 0.01), but not significant at other conditions (p > 0.05). The TTB exerted a greater masking effect than the SSN for tone recognition in the Unilateral CI group as well as in the Bimodal group at all SNRs tested (all p < 0.05). Among demographic or audiometric variables, only age at implantation showed a weak but significant correlation with the mean tone recognition performance under the SSN conditions (r = -0.276, p = 0.045). However, when Bonferroni correction was applied to the correlation analysis results, the weak correlation became not significant. CONCLUSION: Prelingually-deafened children with CIs face challenges in tone perception in noisy environments, especially when the noise is fluctuating in amplitude such as the multi-talker babbles. Wearing a HA on the contralateral side when residual hearing permits is beneficial for tone recognition in noise.
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Implantes Cocleares , Ruído , Percepção da Fala , Humanos , Masculino , Feminino , Percepção da Fala/fisiologia , Criança , Pré-Escolar , Surdez/cirurgia , Auxiliares de Audição , Implante Coclear/métodos , IdiomaRESUMO
Metastatic skin cutaneous melanoma (MSCM) is the most rapidly progressing/invasive skin-based malignancy, with median survival rates of about 12 months. It appears that metabolic disorders accelerate disease progression. However, correlations between metabolism-linked genes (MRGs) and prognosis in MSCM are unclear, and potential mechanisms explaining the correlation are unknown. The Cancer Genome Atlas (TCGA) was utilized as a training set to develop a genomic signature based on the differentially expressed MRGs (DE-MRGs) between primary skin cutaneous melanoma (PSCM) and MSCM. The Gene Expression Omnibus (GEO) was utilized as a validation set to verify the effectiveness of genomic signature. In addition, a nomogram was established to predict overall survival based on genomic signature and other clinic-based characteristics. Moreover, this study investigated the correlations between genomic signature and tumor micro-environment (TME). This study established a genomic signature consisting of 3 genes (CD38, DHRS3, and TYRP1) and classified MSCM patients into low and high-risk cohorts based on the median risk scores of MSCM cases. It was discovered that cases in the high-risk cohort had significantly lower survival than cases in the low-risk cohort across all sets. Furthermore, a nomogram containing this genomic signature and clinic-based parameters was developed and demonstrated high efficiency in predicting MSCM case survival times. Interestingly, Gene Set Variation Analysis results indicated that the genomic signature was involved in immune-related physiological processes. In addition, this study discovered that risk scoring was negatively correlated with immune-based cellular infiltrations in the TME and critical immune-based checkpoint expression profiles, indicating that favorable prognosis may be influenced in part by immunologically protective micro-environments. A novel 3-genomic signature was found to be reliable for predicting MSCM outcomes and may facilitate personalized immunotherapy.
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Melanoma , Neoplasias Cutâneas , Microambiente Tumoral , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/mortalidade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Prognóstico , Masculino , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Feminino , Nomogramas , Pessoa de Meia-Idade , Melanoma Maligno Cutâneo , Imunoterapia/métodos , Biomarcadores Tumorais/genética , IdosoRESUMO
Frequent removal and reapplication of wound dressings can cause mechanical disruption to the healing process and significant physical discomfort for patients. In response to this challenge, a dynamic covalent hydrogel has been developed to advance wound care strategies. This system comprises aldehyde functionalized chondroitin sulfate (CS-CHO) and thiolated hyaluronic acid (HA-SH), with the distinct ability to form in situ via thiol-aldehyde addition and dissolve on-demand via the thiol-hemithioacetal exchange reaction. Although rarely reported, the dynamic covalent reaction of thiol-aldehyde addition holds great promise for the preparation of dynamic hydrogels due to its rapid reaction kinetics and easy reversible dissociation. The thiol-aldehyde addition chemistry provides the hydrogel system with highly desirable characteristics of rapid gelation (within seconds), self-healing, and on-demand dissolution (within 30 min). The mechanical and dissolution properties of the hydrogel can be easily tuned by utilizing CS-CHO materials of different aldehyde functional group contents. The chemical structure, rheology, self-healing, swelling profile, degradation rate, and cell biocompatibility of the hydrogels are characterized. The hydrogel possesses excellent biocompatibility and proves to be significant in promoting cell proliferation in vitro when compared to a commercial hydrogel (HyStem® Cell Culture Scaffold Kit). This study introduces the simple fabrication of a new dynamic hydrogel system that can serve as an ideal platform for biomedical applications, particularly in wound care treatments as an on-demand dissolvable wound dressing.
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Perovskite semiconductor materials have attracted significant attention in the fields of photovoltaics and luminescence due to their excellent photoelectric properties, such as high carrier mobility, high absorption coefficient, and high fluorescence quantum yield. In particular, low-dimensional metal-halide perovskite microcrystalline materials have been reported to exhibit low-dimensional lasing phenomena and laser devices due to their high gain and widely tunable bandgap. In this Letter, one-dimensional (1-D) ZnO microwires with their ultraviolet lasing emissions are utilized as an excitation source to pump CsPbBr3 microwire on hybrid ZnO-CsPbBr3 microscale structures. At higher excitation, the amplified spontaneous emission (ASE) behaviors from CsPbBr3 microwire are realized with ultralow threshold by indirect pumping from the ZnO lasing emission for the first time, to the best of our knowledge. In comparison, the ASE behaviors from the CsPbBr3 microwire directly pumped by Nd:YAG Q-switched laser and continuous wave laser are also performed at room temperature. There are also no multimode lasing behaviors observed. The paper provides a new method to achieve a low threshold on-chip microlaser by a high-quality perovskite micro-nano structure.
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This study aims to explore the mechanism of Shoutai Pills in treating threatened abortion. According to the random number table method, ICR female mice were randomized into a normal group, a model group, a dydrogesterone group, and a Shoutai Pills group, with 15 mice in each group. Mice were administrated with normal saline(normal and model groups) or the suspension of Shoutai Pills or dydrogesterone by gavage at 9:00 am every day. At 16:00 every day, mice in the normal group were administrated with an equal volume of distilled water, while those in the model, Shoutai Pills, and dydrogesterone groups were administrated with hydrocortisone solution by gavage for 4 consecutive days. ICR female and male mice were caged in a ratio of 2â¶1 during the pre-estrous or estrous period. From the first day of pregnancy, drug administration was continued for 5 consecutive days. On day 6, mice were administrated with mifepristone by gavage to establish the model of kidney deficiency-induced abortion. On day 6 of pregnancy, 10 female ICR mice were randomly selected from each group, and the uterus was collected for observation of the pathological changes of trophoblasts at the maternal-fetal interface by hematoxylin-eosin(HE) staining. The protein levels of key enzymes of glycolysis, hexokinase 2(HK2), enolase 1(ENO1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A(LDHA), were determined by Western blot and immunofluorescence. The expression of apoptosis-related proteins including B cell lymphoma-2(Bcl-2), Bcl-2-associated protein X(Bax), and cysteinyl aspartate-specific proteinase-3(caspase-3) was determined by Western blot and real-time PCR. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling was employed to examine apoptosis. The embryo loss rate of the remaining five female mice was calculated by trypan blue staining method on day 14 of pregnancy. On day 14 of pregnancy, the embryo loss rate of the normal group was 5.00%, which was lower than that(27.78%) in the model group(P<0.05). Dydrogesterone and Shoutai Pills groups showed reduced embryo loss rates(10.26% and 7.50%, respectively) compared with the model group. On day 6 of pregnancy, compared with the normal group, the model group showed down-regulated expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and up-regulated expression of Bax and caspase-3(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills up-regulated the expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and down-regulated the expression of Bax and caspase-3(P<0.05). Compared with that in the normal group, the apoptosis rate in the model group increased(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills reduced the apoptosis rate(P<0.05). In conclusion, Shoutai Pills can reduce the embryo loss rate and protect embryos by promoting aerobic glycolysis at the maternal-fetal interface and inhibiting the apoptosis of trophoblasts in mice.
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Apoptose , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos ICR , Animais , Feminino , Camundongos , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Gravidez , Ameaça de Aborto/tratamento farmacológico , Ameaça de Aborto/metabolismo , Glicólise/efeitos dos fármacos , Masculino , Modelos Animais de Doenças , HumanosRESUMO
Nanoporous aerogel fibers enjoy the luxury of being one of the most attractive nanomaterials. However, the representative fabrication pathways have faced up with low production rates due to significant speed mismatch between slow sol-gel transition and as fast as possible spinning in the same period. Herein, a novel gas-blows-liquid spinning (GS) strategy with a spinning speed of 300-700 m s-1 is developed to get the high-speed and high-efficiency production of aerogel fibers/fabrics. The spinning speed of the GS strategy is 900 times higher than various techniques reported for aerogel fibers. The resulting aerogel fibers exhibit a high specific surface area (180 m2 g-1). In comparison, the aerogel fiber possesses the highest tensile strength (58.7±3.9 MPa) among its counterparts and aerogel fabric with surprising water-absorption and microparticle-blocking performances exhibits the application prospect for better hemostasis than that of commercial gauze and cotton ball. Besides, the GS aerogel fabrics with hierarchical aligned structures show better thermal insulation (≈0.035 Wm-1K-1) than wet spinning aerogel fabric and commercial insulation felts. This work has provided inspiration for fast fabricating more aerogel fibers/fabrics with this GS strategy, and the resulting aerogel fibers/fabrics may find significant application in the fields of 5G smart phones, wound hemostasis, etc.
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Although biochar application to soils has been found to increase soil quality and crop yield, the biochar dispersion extent and its impacts on native soil organic carbon (SOC) has received relatively little attention. Here, the vertical and lateral migration of fine, intermediate and coarse-sized biochar (<0.5, 0.5-1 and 1-5 mm, respectively), applied at low and high doses (1.5-2 and 3-4% w/w, respectively), was tracked using stable isotope methods, along with its impact on native SOC stocks. Biochar was homogeneously mixed into the surface layer (0-7 cm depth) of a loamy sandy Acrisol in Zambia. After 4.5 y, 38-75% of the biochar carbon (BC) was lost from the applied layer and 4-25% was detected in lower soil layers (7-30 cm). Estimating BC mineralization to be no more than 8%, 25-60% was likely transported laterally out of the experimental plots. This conclusion was supported by observations of BC in the control plot and in soils up to 2 m outside of the experimental plots. These processes were likely progressive as recovery of BC in similar plots 1 year after application was greater in both surface and lower soil layers than after 4.5 y. Fine and intermediate-sized BC displayed the greatest downward migration (25.3 and 17.9%, respectively), particularly when applied at lower doses, suggesting its movement through soil inter-particle spaces. At higher dosages, fine and intermediate-sized particles may have clogged pore, so coarse biochar displayed the greatest downward migration when biochar was applied at higher doses. In the BC treatment plot soil profiles, native SOC stocks were reduced by 2.8 to 24.5% (18.4% on average), i.e. positive priming. However, some evidence suggested that the soils may switch to negative priming over time. The dispersion of biochar in soil should be considered when evaluating biochar's agronomic benefits and environmental effects.
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Carbono , Solo , Carvão Vegetal , Agricultura/métodosRESUMO
Navy escorts are considered crucial in countering illegal piracy attacks. In this paper, a novel approach is developed to investigate the effect of navy escorts on piracy incidents by models based on two enhanced Tree-Augmented Naïve (TAN) Bayesian networks. This approach offers a systematic investigation into the various factors that influence pirate activities, and helps to identify changes in piracy attack behaviors when confronted by navy escorts and assess the effectiveness of anti-piracy measures. An empirical study is conducted utilizing a unique data set compiled from multiple sources from 2000 to 2019. The empirical evidence shows that there was a gradual reduction in the incidence of piracy attacks in East Africa following the implementation of navy escorts in 2009, but with a surge in 2010 and 2011. The data set is, thus, divided into two time periods at the point of 2009 to facilitate a robust and comprehensive analysis, resulting in the development of two TAN models. Meanwhile, the geographical distribution of pirate attacks has shifted from international waters to port areas and territorial waters. We argue that the surge and geographical shift could be attributed to the calculating behavior of pirates when they encounter external pressures. Finally, a Shapely approach is introduced to evaluate the potential effectiveness of the implemented risk management strategies from a Game Theory perspective. This study offers new insights into the promotion of navy escorts and contributes to the development of a framework for assessing piracy risks in uncertain and dynamic anti-piracy environments.
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Conventional techniques for the closure of wounds, such as sutures and staples, have significant drawbacks that can negatively impact wound healing. Tissue adhesives have emerged as promising alternatives, but poor adhesion, low mechanical properties, and toxicity have hindered their widespread clinical adoption. In this work, a dual modified, aldehyde and methacrylate hyaluronic acid (HA) biopolymer (HA-MA-CHO) has been synthesized through a simplified route for use as a double cross-linked network (DCN) hydrogel (HA-MA-CHO-DCN) adhesive for the effective closure and sealing of wounds. HA-MA-CHO-DCN cross-links in two stages: initial cross-linking of the aldehyde functionality (CHO) of HA-MA-CHO using a disulfide-containing cross-linker, 3,3'-dithiobis (propionic hydrazide) (DTPH), leading to the formation of a self-healing injectable gel, followed by further cross-linking via ultraviolet (UV) initiated polymerization of the methacrylate (MA) functionality. This hydrogel adhesive shows a stable swelling behavior and remarkable versatility as the storage modulus (G') has shown to be highly tunable (103-105 Pa) for application to many different wound environments. The new HA-MA-CHO-DCN hydrogel showed excellent adhesive properties by surpassing the burst pressure and lap-shear strength for the widely used bovine serum albumin-glutaraldehyde (BSAG) glue while maintaining excellent cell viability.
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Ácido Hialurônico , Hidrogéis , Hidrogéis/química , Ácido Hialurônico/química , Adesivos , Glutaral , MetacrilatosRESUMO
X-ray scintillators have gained significant attention in medical diagnostics and industrial applications. Despite their widespread utility, scintillator development faces a significant hurdle when exposed to elevated temperatures, as it usually results in reduced scintillation efficiency and diminished luminescence output. Here we report a molecular design strategy based on a hybrid perovskite (TpyBiCl5) that overcomes thermal quenching through multi-excited state switching. The structure of perovskite provides a platform to modulate the luminescence centers. The rigid framework constructed by this perovskite structure stabilized its triplet states, resulting in TpyBiCl5 exhibiting an approximately 12â times higher (45 % vs. 3.8 %) photoluminescence quantum yield of room temperature phosphorescence than that of its organic ligand (Tpy). Most importantly, the interactions between the components of this perovskite enable the mixing of different excited states, which has been revealed by experimental and theoretical investigations. The TpyBiCl5 scintillator exhibits a detection limit of 38.92â nGy s-1 at 213â K and a detection limit of 196.31â nGy s-1 at 353â K through scintillation mode switching between thermally activated delayed fluorescence and phosphorescence. This work opens up the possibility of solving the thermal quenching in X-ray scintillators by tuning different excited states.
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Microfluidic deprotonation approach is proposed to realize continuous, scalable, efficient, and uniform production of aramid nanofibers (ANFs) by virtue of large specific surface area, high mixing efficiency, strong heat transfer capacity, narrow residence time distribution, mild laminar-flow process, and amplification-free effect of the microchannel reactor. By means of monitoring capabilities endowed by the high transparency of the microchannel, the kinetic exfoliation process of original aramid particles is in situ observed and the corresponding exfoliation mechanism is established quantificationally. The deprotonated time can be reduced from the traditional several days to 7 min for the final colloidal dispersion due to the synergistic effect between enhanced local shearing/mixing and the rotational motion of aramid particles in microchannel revealed by numerical simulations. Furthermore, the cascade microfluidic processing approach is used to make various ANF colloidal aerogels including aerogel fibers, aerogel films, and 3D-printed aerogel articles. Comprehensive characterizations show that these cascade-microfluidic-processed colloidal aerogels have identical features as those prepared in batch-style mode, revealing the versatile use value of these ANFs. This work achieves significant progress toward continuous and efficient production of ANFs, bringing about appreciable prospects for the practical application of ANF-based materials and providing inspiration for exfoliating any other nano-building blocks.
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BACKGROUND: Continuous positive airway pressure (CPAP) has failed to reduce cardiovascular risk in obstructive sleep apnoea (OSA) in randomized trials. CPAP increases angiopoietin-2, a lung distension-responsive endothelial proinflammatory marker associated with increased cardiovascular risk. We investigated whether CPAP has unanticipated proinflammatory effects in patients with OSA and cardiovascular disease. METHODS: Patients with OSA (apnoea-hypopnea index [AHI] ≥15 events/h without excessive sleepiness) in the Randomized Intervention with CPAP in Coronary Artery Disease and OSA study were randomized to CPAP or usual care following coronary revascularization. Changes in plasma levels of biomarkers of endothelial (angiopoietin-2, Tie-2, E-selectin, vascular endothelial growth factor [VEGF-A]) and lung epithelial (soluble receptor of advanced glycation end-products [sRAGE]) function from baseline to 12-month follow-up were compared across groups and associations with cardiovascular morbidity and mortality assessed. FINDINGS: Patients with OSA (n = 189; 84% men; age 66 ± 8 years, BMI 28 ± 3.5 kg/m2, AHI 41 ± 23 events/h) and 91 patients without OSA participated. Angiopoietin-2 remained elevated whereas VEGF-A declined significantly over 12 months in the CPAP group (n = 91). In contrast, angiopoietin-2 significantly declined whereas VEGF-A remained elevated in the usual care (n = 98) and OSA-free groups. The changes in angiopoietin-2 and VEGF-A were significantly different between CPAP and usual care, whereas Tie-2, sRAGE and E-selectin were similar. Greater 12-month levels of angiopoietin-2 were associated with greater mortality. Greater CPAP levels were associated with worse cardiovascular outcomes. INTERPRETATION: Greater CPAP levels increase proinflammatory, lung distension-responsive angiopoietin-2 and reduce cardioprotective angiogenic factor VEGF-A compared to usual care, which may counteract the expected cardiovascular benefits of treating OSA. FUNDING: National Institutes of Health/National Heart, Lung, and Blood Institute; Swedish Research Council; Swedish Heart-Lung Foundation; ResMed Foundation.
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Apneia Obstrutiva do Sono , Fator A de Crescimento do Endotélio Vascular , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Angiopoietina-2 , Selectina E , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapiaRESUMO
Among non-viral gene delivery vectors, poly(ß-amino ester)s (PAEs) are one of the most versatile candidates because of their wide monomer availability, high polymer flexibility, and superior gene transfection performance both in vitro and in vivo. Over two decades, PAEs have evolved from linear to highly branched structures, significantly enhancing gene delivery efficacy. Building on the proven efficient sets of monomers in highly branched PAEs (HPAEs), this work introduced a new class of cyclic PAEs (CPAEs) constructed via an A2 + B4 + C2 cyclization synthesis strategy and identified their markedly improved gene transfection capabilities in gene delivery applications. Two sets of cyclic PAEs (CPAEs) with rings of different sizes and topologies were obtained. Their chemical structures were confirmed via two-dimensional nuclear magnetic resonance and the photoluminescence phenomena, and their DNA delivery behaviours were investigated and compared with the HPAE counterparts. In vitro assessments demonstrated that the CPAEs with a macrocyclic architecture (MCPAEs), significantly enhanced DNA intracellular uptake and facilitated efficient gene expression while maintaining perfect biocompatibility. The top-performance MCPAEs have been further employed to deliver a plasmid coding dual single guide RNA-guided CRISPR-Cas9 machinery to delete COL7A1 exon 80 containing the c.6527dupC mutation. In recessive dystrophic epidermolysis bullosa (RDEB) patient-derived epidermal keratinocytes, MCPAEs facilitated the CRISPR plasmid delivery and achieved efficient targeted gene editing in multiple colonies.
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Ésteres , Edição de Genes , Polímeros , Humanos , Edição de Genes/métodos , Ciclização , RNA Guia de Sistemas CRISPR-Cas , DNA/metabolismo , Sistemas CRISPR-Cas/genética , Colágeno Tipo VII/genéticaRESUMO
PURPOSE: The purpose of this study was to evaluate the auditory performance and speech perception of 104 children with isolated large vestibular aqueduct syndrome (LVAS) and 523 children with no inner ear malformation (IEM) for 5 years after cochlear implantation, in order to explore whether isolated LVAS can affect the long-term hearing and speech rehabilitation of deaf children after cochlear implantation. METHOD: A cohort study was established consisting of 627 children who underwent cochlear implantation at Beijing Tongren Hospital from 1999 to 2016. The children were examined at 0, 6, 12, 24, 36, 48, and 60 months after cochlear implantation to assess their auditory performance and speech perception using the Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) questionnaires. RESULTS: The CAP scores of the isolated LVAS group increased significantly during the baseline to the 24th month, after which they gradually rose until reaching the plateau during the 24th to the 60th month. The CAP scores of the non-IEM group increased significantly during the baseline to the 36th month and then increased steadily. The SIR scores went up significantly during the baseline to the 48th month, and increased in a gradual manner in other stages of isolated LVAS evaluation. In comparison, The SIR scores of non-IEM group grew remarkably from the baseline to the 60th month. There were no significant differences in the CAP or SIR scores between isolated LVAS and non-IEM groups in each stage of evaluation, with the only exception being the CAP score at baseline month after cochlear implantation. CONCLUSIONS: The CAP and SIR questionnaires are helpful tools for quantifying the early hearing and speech skills of younger prelingually deafened cochlear implant recipients. This long-term follow-up study shows that the speech and hearing development of children in isolated LVAS and non-IEM groups follow similar patterns, and isolated LVAS does not affect the long-term rehabilitation of deaf children after cochlear implantation.
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Gene therapy holds great potential for treating Lung Cystic Fibrosis (CF) which is a fatal hereditary condition arising from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in dysfunctional CFTR protein. However, the advancement and clinical application of CF gene therapy systems have been hindered due to the absence of a highly efficient delivery vector. In this work, we introduce a new generation of highly branched poly(ß-amino ester) (HPAE) gene delivery vectors for CF treatment. Building upon the classical chemical composition of HPAE, a novel backbone cationization strategy was developed to incorporate additional functional amine groups into HPAE without altering their branching degree. By carefully adjusting the type, proportion, and backbone distribution of the added cationic groups, a series of highly effective HPAE gene delivery vectors were successfully constructed for CF disease gene therapy. In vitro assessment results showed that the backbone cationized HPAEs with randomly distributed 10% proportion of 1-(3-aminopropyl)-4-methylpiperazine (E7) amine groups exhibited superior transfection performance than their counterparts. Furthermore, the top-performed backbone cationized HPAEs, when loaded with therapeutic plasmids, successfully reinstated CFTR protein expression in the CFBE41o- disease model, achieving levels 20-23 times higher than that of normal human bronchial epithelial (HBE) cells. Their therapeutic effectiveness significantly surpassed that of the currently advanced commercial vectors, Xfect and Lipofectamine 3000.
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Regulador de Condutância Transmembrana em Fibrose Cística , Terapia Genética , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Polímeros/química , Aminas , Vetores Genéticos/genéticaRESUMO
Recent developments in real-time, in vivo micro-imaging have allowed for the visualization of tissue pathological changes, facilitating rapid diagnosis. However, miniaturization, magnification, the field of view, and in vivo image stabilization remain challenging factors to reconcile. A key issue for this technology is ensuring it is user friendly for surgeons, enabling them to use the device manually and obtain instantaneous information necessary for surgical decision-making. This descriptive study introduces a handheld, actively stabilized, miniaturized epi-fluorescence widefield microscope (MEW-M) for real-time observation in vivo with high resolution. The methodology of MEW-M system includes high resolution microscopy miniaturization technology, thousandfold shaking suppression (actively stabilized), ultra-photosensitivity, and tailored image signal processing cell image capture and processing technology, which support for the excellent real-time imaging performance of MEW-M system in brain, mammary, liver, lung, and kidney tissue imaging of rats in vivo. With a single-objective and high-frame-rate imaging, the MEW-M system facilitates roving image acquisition, enabling contiguous analysis of large tissue areas. RESEARCH HIGHLIGHTS: A handheld, actively stabilized MEW-M system was introduced. Excellent real-time, in vivo imaging with high resolution and active stabilization in brain, mammary, liver, lung, and kidney tissue of rats.
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Microscopia de Fluorescência , Ratos , Animais , Microscopia de Fluorescência/métodos , MiniaturizaçãoRESUMO
Ginseng Radix et Rhizoma Rubra (Panax ginseng C.A. Mey, Hongshen, in Chinese) and Ophiopogonis Radix (Ophiopogon japonicus (L.f) Ker-Gawl., Maidong, in Chinese) are traditional Chinese herbal pairs, which were clinically employed to enhance the immune system of cancer patients. This study employed the pharmacokinetic and pharmacodynamic (PK-PD) spectrum-effect association model to investigate the antitumor active substances of P. ginseng and O. japonicus (PG-OJ). The metabolic processes of 20 major bioactive components were analyzed using Ultra-Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (UPLC-MS/MS) in the lung tissue of tumor-bearing mice treated with PG-OJ. The ELISA method was employed to detect the levels of TGF-ß1, TNF-α, and IFN-γ in the lung tissue of mice at various time points, and to analyze their changes after drug administration. The results showed that all components presented a multiple peaks absorption pattern within 0.083 to 24 h post-drug administration. The tumor inhibition rate of tumor and repair rate of IFN-γ, TNF-α, and TGF-ß1 all increased, indicating a positive therapeutic effect of PG-OJ on A549 tumor-bearing mice. Finally, a PK-PD model based on the GBDT algorithm was developed for the first time to speculate that Methylophiopogonanone A, Methylophiopogonanone B, Ginsenoside Rb1, and Notoginsenoside R1 are the main active components in PG-OJ for lung cancer treatment.