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In this study, we have successfully developed a glycosylation method using 1-O-(methylthio)thiocarbonyl-glycoses as donors. Such xanthate donors are easily accessible and shelf-stable. The glycosylation reaction could be promoted by cations (acidic to neutral conditions) under mild conditions, exhibiting a reactivity intermediate between that with glycosyl trichloroacetimidate as the donor and that with thioglycoside as the donor. This methodology tolerates both "armed" and "disarmed" glycosyl donors, as well as various sugar acceptors, and affords the corresponding glycosides in good to excellent yields. Based on the relative higher reactivity of such xanthate donors than thioglycoside donors under the same glycosylation conditions, a trisaccharide was further synthesized in a one-pot glycosylation strategy.
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The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.
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Organismos Acuáticos , Biodiversidad , Bioprospección , Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Organismos Acuáticos/genética , Bacterias/genética , Bacterias/clasificación , Archaea/genética , Archaea/clasificación , Genoma Bacteriano/genética , Metagenoma , Genoma Arqueal/genética , Agua de Mar/microbiología , Filogenia , Océanos y MaresRESUMEN
Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: "Graft Selection" and "Clinical Outcome Evaluation" during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive "gold standard" graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.
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Water is considered an effective microwave absorber due to its high transmittance and frequency-dispersive dielectric constant, yet it is challenging to form it into a stable state as an absorber. Herein, we developed a water-containing microwave absorber using chemical vapor deposition (CVD), namely, the bifunctional carbon/NaCl multi-interfaces hybrid with excellent water harvesting and microwave absorption performance. Carbon/NaCl exhibits remarkable water harvesting abilities from air, exceeding 210 % of its weight in 12 h. The development of the hydrophilic/hydrophobic heterojunction interface is responsible for this outstanding performance. Additionally, the interfacial polarization provided by carbon/NaCl, along with the dipole polarization induced by the internally captured water and defects, enhances its microwave absorption. The carbon/NaCl hybrid achieved a minimum reflection loss (RLmin) of -69.62 dB at 17.1 GHz with a thickness of 2.13 mm, and a maximum effective absorption bandwidth (EABmax) of 6.74 GHz at a thickness of 2.5 mm. Compared with raw NaCl (RLmin of -24.5 dB, EABmax of 3.88 GHz), the RLmin and EABmax values of the absorber increased by approximately 2.85 and 1.74 times. These results highlight the potential for bifunctional carbon/NaCl hybrid in applications within extreme environments, presenting a promising avenue for further research and development.
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Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)-Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers.
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BACKGROUND: Tuberculosis (TB) is amongst the leading causes of death from an infectious disease, with an estimated 1.3 million deaths from TB in 2022. Approximately 25% of the global population is estimated to be infected with the TB bacterium, giving rise to 10.6 million episodes of TB disease in 2022. The prevalence of diabetes influences TB incidence and TB mortality. It is associated not only with an increased risk of TB disease but also death during TB treatment, TB relapse after treatment completion and multidrug-resistant TB. Since 2011, the World Health Organization (WHO) has recommended collaborative TB and diabetes activities as outlined in the Collaborative Framework for Care and Control of TB and Diabetes. OBJECTIVES: To determine the prognostic value of diabetes mellitus (DM) in the general population of adults, adolescents and children for predicting tuberculosis disease. SEARCH METHODS: We searched the literature databases MEDLINE (via PubMed) and WHO Global Index Medicus, and the WHO International Clinical Trials Registry Platform (ICTRP) on 3 May 2023 (date of last search for all databases); we placed no restrictions on the language of publication. SELECTION CRITERIA: We included retrospective and prospective cohort studies, irrespective of publication status or language. The target population comprised adults, adolescents and children from diverse settings, encompassing outpatient and inpatient cohorts, with varying comorbidities and risk of exposure to tuberculosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and the Quality In Prognosis Studies (QUIPS) tool. Prognostic factors assessed at enrolment/baseline included diabetes, as defined by the individual studies, encompassing patient-reported status, abstracted from medical records or claims data, or diagnosed by plasma glucose/glycosylated haemoglobin. The primary outcome was the incidence of tuberculosis disease. The secondary outcome was recurrent TB disease. We performed a random-effects meta-analysis for the adjusted hazard ratios, risk ratios, or odds ratios, employing the restricted maximum likelihood estimation. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 48 cohort studies with over 61 million participants from the six WHO regions. However, the representation was variable as eight population-based studies were from South Korea and 19 from China, with overlapping study periods, and only one from the African region (Ethiopia). All studies included adults, and nine studies also included children and adolescents. Most studies diagnosed DM based on clinical records, including fasting blood glucose levels or glucose-lowering treatments. The studies did not distinguish between type 1 and type 2 DM; only one study focused on type 1 DM. Diagnosis and exclusion of TB were performed using culture or molecular WHO-recommended rapid diagnostic tests (mWRD) in only 12 studies, which could have biassed the effect estimate. The median follow-up time was five years (interquartile range 1.5 to 10, range 1 to 16.9), and the studies primarily reported an adjusted hazard ratio from a multivariable Cox-proportional hazard model. Hazard Ratios (HR) The HR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. We present 95% confidence intervals (CI) and prediction intervals, which show between-study heterogeneity represented in measuring the variability of effect sizes (i.e. the interval within which the effect size of a new study would fall considering the same population of studies included in the meta-analysis). DM may increase the risk of tuberculosis disease (HR 1.90, 95% CI 1.51 to 2.40; prediction interval 0.83 to 4.39; 10 studies; 11,713,023 participants). The certainty of the evidence is low, due to a moderate risk of bias across studies and inconsistency. Considering a risk without diabetes of 129 cases per 100,000 population, this represents 102 more (59 to 153 more) cases per 100,000. When stratified by follow-up time, the results are more consistent across < 10 years follow-up (HR 1.52, 95% CI 1.47 to 1.57; prediction interval 1.45 to 1.59; 7 studies; 10,380,872 participants). This results in a moderate certainty of the evidence due to a moderate risk of bias across studies. However, at 10 or more years of follow-up, the estimates yield a wider CI and a higher HR (HR 2.44, 95% CI 1.22 to 4.88; prediction interval 0.09 to 69.12; 3 studies; 1,332,151 participants). The certainty of the evidence is low due to the moderate risk of bias and inconsistency. Odds Ratio (OR) DM may increase the odds of tuberculosis disease (OR 1.61, 95% CI 1.27 to 2.04; prediction interval 0.96 to 2.70; 4 studies; 167,564 participants). Stratification by follow-up time was not possible as all studies had a follow-up < 10 years. The certainty of the evidence is low due to a moderate risk of bias and inconsistency. Risk Ratio (RR) The RR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. DM probably increases the risk of tuberculosis disease (RR 1.60, 95% CI 1.42 to 1.80; prediction interval 1.38 to 1.85; 6 studies; 44,058,675 participants). Stratification by follow-up time was not possible as all studies had a follow-up < 10 years. The certainty of the evidence is moderate due to a moderate risk of bias. AUTHORS' CONCLUSIONS: Diabetes probably increases the risk of developing TB disease in the short term (< 10 years) and may also increase the risk in the long term (≥ 10 years). As glycaemic control and access to care may be potential effect modifiers of the association between diabetes and the risk of TB disease, the overall estimates should be interpreted with caution when applied locally. Policies targeted at reducing the burden of diabetes are needed to contribute to the aims of ending TB. Large population-based cohorts, including those derived from high-quality national registries of exposures (diabetes) and outcomes (TB disease), are needed to provide estimates with a high certainty of evidence of this risk across different settings and populations, including low- and middle-income countries from different WHO regions. Moreover, studies including children and adolescents and currently recommended methods for diagnosing TB would provide more up-to-date information relevant to practice and policy. FUNDING: World Health Organization (203256442) REGISTRATION: PROSPERO registration: CRD42023408807.
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Diabetes Mellitus , Tuberculosis , Adolescente , Adulto , Niño , Humanos , Diabetes Mellitus/epidemiología , Incidencia , Pronóstico , Factores de Riesgo , Tuberculosis/epidemiologíaRESUMEN
As the most effective therapeutic drug for malaria, artemisinin can only be extracted from Artemisia annua L., which is sensitive to the surrounding growing habitat. Histone acetyltransferases (HATs) contain acetyl groups, which modulate mRNA transcription and thereby regulate plant environmental adaptation. Comprehensive analyses of HATs have been performed in many plants, but systematic identification of HATs in medicinal plants is lacking. In the present study, we identified 11 AaHATs and characterized these genes into four classes according to their conserved protein structures. According to the phylogenetic analysis results, potential functions of HAT genes from Arabidopsis thaliana, Oryza sativa, and A. annua were found. According to our results, AaHAT has a highly conserved evolutionary history and is rich in highly variable regions; thus, AaHAT has become a comparatively ideal object of medical plant identification and systematic study. Moreover, motifs commonly present in histone acetyltransferases in the A. annua genome may be associated with functional AaHATs. AaHATs appear to be related to gene-specific functions. AaHATs are regulated by cis-elements, and these genes may affect phytohormone responsiveness, adaptability to stress, and developmental growth. We performed expression analyses to determine the potential roles of AaHATs in response to three environmental stresses. Our results revealed a cluster of AaHATs that potentially plays a role in the response of plants to dynamic environments.
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The adiabatic connection (AC) approximation, along with its linearized variant AC0, was introduced as a method of obtaining dynamic correlation energy. When using a complete active space self-consistent field (CASSCF) wave function as a reference, the AC0 approximation is considered one of the most efficient multi-reference perturbation theories. It only involves the use of 1st- and 2nd-order reduced density matrices. However, some numerical results have indicated that the excitation energies predicted by AC0 are not as reliable as those from the second-order N-electron valence state perturbation theory (NEVPT2). In this study, we develop a spinless formulation of AC0 based on the Dyall Hamiltonian and provide a detailed comparison between AC0 and NEVPT2 approaches. We demonstrate the components within the correlation energy expressions that are common to both methods and those unique to either AC0 or NEVPT2. We investigate the role of the terms exclusive to NEVPT2 and explore the possibility of enhancing AC0's performance in this regard.
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Multicolor tuning of persistent luminescence has been extensively studied by deliberately integrating various luminescent units, known as activators or chromophores, into certain host compounds. However, it remains a formidable challenge to fine-tune the persistent luminescence spectra either in organic materials, such as small molecules, polymers, metal-organic complexes and carbon dots, or in doped inorganic crystals. Herein, we present a strategy to delicately control the persistent luminescence wavelength by engineering sub-bandgap donor-acceptor states in a series of single-phase Ca(Sr)ZnOS crystals. The persistent luminescence emission peak can be quasi-linearly tuned across a broad wavelength range (500-630 nm) as a function of Sr/Ca ratio, achieving a precision down to ~5 nm. Theoretical calculations reveal that the persistent luminescence wavelength fine-tuning stems from constantly lowered donor levels accompanying the modified band structure by Sr alloying. Besides, our experimental results show that these crystals exhibit a high initial luminance of 5.36 cd m-2 at 5 sec after charging and a maximum persistent luminescence duration of 6 h. The superior, color-tunable persistent luminescence enables a rapid, programable patterning technique for high-throughput optical encryption.
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Deep learning models have been developed for various predictions in glioma; yet, they were constrained by manual segmentation, task-specific design, or a lack of biological interpretation. Herein, we aimed to develop an end-to-end multi-task deep learning (MDL) pipeline that can simultaneously predict molecular alterations and histological grade (auxiliary tasks), as well as prognosis (primary task) in gliomas. Further, we aimed to provide the biological mechanisms underlying the model's predictions. We collected multiscale data including baseline MRI images from 2776 glioma patients across two private (FAHZU and HPPH, n = 1931) and three public datasets (TCGA, n = 213; UCSF, n = 410; and EGD, n = 222). We trained and internally validated the MDL model using our private datasets, and externally validated it using the three public datasets. We used the model-predicted deep prognosis score (DPS) to stratify patients into low-DPS and high-DPS subtypes. Additionally, a radio-multiomics analysis was conducted to elucidate the biological basis of the DPS. In the external validation cohorts, the MDL model achieved average areas under the curve of 0.892-0.903, 0.710-0.894, and 0.850-0.879 for predicting IDH mutation status, 1p/19q co-deletion status, and tumor grade, respectively. Moreover, the MDL model yielded a C-index of 0.723 in the TCGA and 0.671 in the UCSF for the prediction of overall survival. The DPS exhibits significant correlations with activated oncogenic pathways, immune infiltration patterns, specific protein expression, DNA methylation, tumor mutation burden, and tumor-stroma ratio. Accordingly, our work presents an accurate and biologically meaningful tool for predicting molecular subtypes, tumor grade, and survival outcomes in gliomas, which provides personalized clinical decision-making in a global and non-invasive manner.
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Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α's transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV.
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Coroides , Neovascularización Coroidal , Modelos Animales de Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones Endogámicos C57BL , Complejo Represivo Polycomb 1 , Factor A de Crecimiento Endotelial Vascular , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/patología , Neovascularización Coroidal/genética , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 1/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Humanos , Coroides/irrigación sanguínea , Coroides/metabolismo , Transducción de Señal/fisiología , Células Cultivadas , Western Blotting , Proliferación Celular/fisiología , Células Endoteliales/metabolismo , Regulación de la Expresión Génica , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Movimiento Celular , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
This study introduces an efficient on-column refolding and purification method for preparing nanobodies (Nbs) expressed as inclusion bodies and fusion proteins. The HisTrapTM FF system was successfully employed for the purification of the fusion protein FN1-ΔI-CM-2D5. The intein ΔI-CM cleavage activity was activated at 42 °C, followed by incubation for 4 h. Leveraging the remarkable thermal stability of Nbs, 2D5 was further purified through heat treatment at 80 °C for 1h. This method yielded up to 107.2 mg of pure 2D5 with a purity of 99.2 % from just 1L of bacterial culture grown in a shaker flask. Furthermore, this approach successfully restored native secondary structure and affinity of 2D5. Additionally, the platform was effectively applied to the refolding and purification of a polystyrene-binding nanobody (B2), which exhibited limited expression in the periplasmic and cytoplasmic spaces of E. coli. This endeavor resulted in the isolation of 53.2 mg of pure B2 Nb with a purity exceeding 99.5 % from the same volume of bacterial culture. Significantly, this approach restored the native secondary structure of the Nbs, highlighting its potential for addressing challenges associated with expressing complex Nbs in E. coli. Overall, this innovative platform provides a scientifically rigorous and reproducible method for the efficient preparation of Nbs, offering a valuable tool for antibody research and development.
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Escherichia coli , Cuerpos de Inclusión , Replegamiento Proteico , Proteínas Recombinantes de Fusión , Anticuerpos de Dominio Único , Cuerpos de Inclusión/química , Cuerpos de Inclusión/metabolismo , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/aislamiento & purificación , Anticuerpos de Dominio Único/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismoRESUMEN
In vivo mechanical characterization of skin finds broad applications in understanding skin aging, diagnosis of some skin diseases and assessing the effectiveness of diverse skin care strategies. Skin has a layered structure consisting of the epidermis, dermis and subcutaneous layers. Although much effort has been made towards mechanical characterization of skin, it remains a challenging issue to measure the mechanical properties of an individual layer in vivo. To address this issue, we here report a guided wave elastography method for layered human skin which incorporates the effect of muscle states. Both finite element simulations and phantom experiments have been performed to validate the method. For skin-mimicking phantoms with different fat layer thicknesses, the errors in the identified shear modulus of the skin layers are no more than 11 %. In vivo experiments have been carried out on 6 healthy subjects to demonstrate the potential use of the method in clinics. A statistical analysis indicates the muscle contraction contributes to the stiffening of the skin (p < 0.001). Finally, a phase diagram has been constructed to reveal the extent to which muscle sates (including both passive and active states) affect the measurement of elastic modulus of a skin layer, which may guide the application of the method in practice.
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Diagnóstico por Imagen de Elasticidad , Modelos Biológicos , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Piel/diagnóstico por imagen , Módulo de Elasticidad/fisiología , Fantasmas de Imagen , Adulto , Análisis de Elementos Finitos , Masculino , Femenino , Fenómenos Fisiológicos de la Piel , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Músculo Esquelético/diagnóstico por imagenRESUMEN
BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder in children. We aimed to investigate trends and regional disparities of burden in paediatric AD at global, regional and national levels, and to explore potential associated factors. METHODS: Based on data from Global Burden of Disease study 2019, we assessed trends in burden of AD aged <19 years from 1990 to 2019, including prevalent and incident cases, age-standardised prevalence and age-standardised incidence. For potential associated factors, correlations of above trends and indexes of socio-economic status (sociodemographic index, SDI) and health service coverage (universal health coverage index, UHCI) were evaluated. We conducted decomposition analysis to understand the net contribution of population-level factors and their contribution proportions on changes of prevalent and incident cases, including age structure, population change and epidemiological change. RESULTS: Global prevalent and incident cases of paediatric AD increased by about 5.7 and 0.7 million between 1990 and 2019, respectively. Global age-standardised prevalence and incidence decreased by -0.17% (-0.19% to -0.16%) and -0.12% (-0.13% to -0.11%) per year from 1990 to 2019, respectively. Regionally, the highest increase of prevalent and incident cases was in low SDI region (by 96.77% and 84.85%); the highest decrease of age-standardised prevalence and incidence was in high SDI regions (by -0.20% and -0.27% per year). The correlation analyses identified significant negative correlations between trends and SDI and UHCI. Population change was a major driver of case rise; epidemiological change and age structure showed negative impact of case rise. Regional disparities in contribution of three population-level factors were seen, including net contribution direction (positive or negative) and contribution proportion levels. CONCLUSION: Global paediatric AD case numbers increased, primarily due to population growth. Prevalence and incidence decreased slightly. Geographic inequalities were seen. Developing region-specific strategies targeting potential factors is essential to reduce paediatric AD burden.
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In recent years, the fully oxygen-tolerant reversible deactivation radical polymerization (RDRP) has become a highly researched area. In this contribution, a new and minimalist method is successfully employed to accomplish fully oxygen-tolerant reversible addition-fragmentation chain transfer (RAFT) polymerization using bis(trithiocarbonate) disulfides (BisTTC) as an iniferter agent, where the released sulfur-centered trithiocarbonate (TTC) radical can initiate monomer. Furthermore, polymerization kinetics revealed the typical "living" features of this polymerization system. More importantly, by high-throughput screening, it is found that dodecyl-substituted TTC is responsible for the fully oxygen-tolerant RAFT polymerization though trithiocarbonate radical initiation and R radical deoxygenation. It is believed that trithiocarbonate radical initiation strategy provides a powerful and minimalist tool for fully oxygen-tolerant RDRPs.
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BACKGROUND: Circular RNAs (circRNAs), produced by reverse splicing, act as important players in human cancers. We aimed to assess the biological functions of circRNA pituitary homeobox 1 (circ-PITX1) in non-small-cell lung cancer (NSCLC). METHODS: qRT-PCR was employed to determine RNA expression. Biological behaviors of NSCLC cells were assessed by CCK-8, colony formation, EdU assay, flow cytometry, wound healing, and transwell assays. Glutamine catabolism was examined via the measurement of glutamine consumption, α-ketoglutarate levels, as well as ATP levels. Protein levels were detected by western blot assays. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to reveal the mechanism responsible for circ-PITX1 regulating NSCLC cell malignancy. The murine xenograft model was established to investigate circ-PITX1's effect on tumor formation. RESULTS: Circ-PITX1 was overexpressed in NSCLC tissue samples and cells. Its low expression repressed NSCLC cell proliferation and motility. Moreover, our data revealed its downregulation inhibited glutamine catabolism and tumor formation and promoted cell apoptosis. In addition, circ-PITX1 bound to miR-615-5p, and its inhibitory effect on tumor cellular behaviors could be reversed after decreasing miR-615-5p expression. The miRNA targeted E26 transformation specific-1 (ETS1), whose upregulation abolished miR-615-5p overexpression-induced effects in NSCLC cells. Furthermore, circ-PITX1 positively modulated ETS1 production through interaction with miR-615-5p. CONCLUSION: Circ-PITX1 facilitated NSCLC progression via modulating miR-615-5p/ETS1 pathway.
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Marine mussels inhabit a wide range of ocean depths, necessitating unique adaptations to cope with varying hydrostatic pressures. This study investigates the transcriptomic responses and evolutionary adaptations of the deep-sea mussel Gigantidas platifrons and the shallow-water mussel Mytilus galloprovincialis to high hydrostatic pressure (HHP) conditions. By exposing atmospheric pressure (AP) acclimated G. platifrons and M. galloprovincialis to HHP, we aim to simulate extreme environmental challenges and assess their adaptive mechanisms. Through comparative transcriptomic analysis, we identified both conserved and species-specific mechanisms of adaptation, with a notable change in gene expression associated with immune system, substance transport, protein ubiquitination, apoptosis, lipid metabolism and antioxidant processes in both species. G. platifrons demonstrated an augmented lipid metabolism, whereas M. galloprovincialis exhibited a dampened immune function. Additionally, the expressed pattern of deep-sea mussel G. platifrons were more consistent than shallow-water mussel M. galloprovincialis under hydrostatic pressures changed conditions which corresponding the long-term living stable deep-sea environment. Moreover, evolutionary analysis pinpointed positively selected genes in G. platifrons that are linked to transmembrane transporters, DNA repair and replication, apoptosis, ubiquitination which are important to cell structural integrity, substances transport, and cellular growth regulation. This indicates a specialized adaptation strategy in G. platifrons to cope with the persistent HHP conditions of the deep sea. These results offer significant insights into the molecular underpinnings of mussel adaptation to varied hydrostatic conditions and enhance our comprehension of the evolutionary forces driving their depth-specific adaptations.
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Presión Hidrostática , Transcriptoma , Animales , Adaptación Fisiológica , Evolución Biológica , Mytilus/fisiología , Mytilus/genética , Bivalvos/genética , Bivalvos/fisiologíaRESUMEN
With the postponement of female reproductive age and the higher incidence of cancer in young people, fertility preservation has become increasingly important in childbearing age. Chemotherapy during pregnancy is crucial for maternal cancer treatments and fetal outcomes. It is a need to further study ovarian damage caused by chemotherapy drug combinations and long-term effects on offspring development, and a detailed understanding of side effects of chemotherapy drugs. In this study, chemotherapy drug combinations significantly impacted on ovarian function, especially epirubicin/cyclophosphamide (EC) combination led to an unbalance in the development of the left and right ovary. Exposure to EC and cisplatin/paclitaxel (TP) increased the number of progenitor follicles while decreased the count of antral follicles and corpora luteum. As to the estrus cycle, EC exposure resulted in a longer estrus period and diestrus period, while TP exposure only extended the diestrus period. EC and TP affected steroid biosynthesis by reducing the expression of SF1 and P450arom.γ-H2AX was detected in both EC and TP exposure groups. As to the impact on the offspring from 4T1 tumor-bearing pregnant mice injected with EC, no significant difference was observed in the physical and neurological development compared to the control, but the ovarian weights, estrus cycles of the offspring were significantly different. Chemotherapy drug combinations exhibit ovarian toxicity, not only causing direct damage on the follicle cells but also disrupting steroid biosynthesis. The reproductive system of offspring from maternal tumor-bearing mice exposed to chemotherapy drugs was observed disorder, but the concrete mechanism still needs further exploration.
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Cisplatino , Ciclofosfamida , Epirrubicina , Ovario , Femenino , Animales , Ciclofosfamida/toxicidad , Ciclofosfamida/efectos adversos , Embarazo , Ovario/efectos de los fármacos , Cisplatino/efectos adversos , Cisplatino/toxicidad , Epirrubicina/efectos adversos , Epirrubicina/toxicidad , Paclitaxel/efectos adversos , Paclitaxel/toxicidad , Ratones , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ratones Endogámicos BALB C , Antineoplásicos/efectos adversos , Antineoplásicos/toxicidadRESUMEN
Polystyrene nanoplastics (PS NPs) and dibutyl phthalate (DBP) pollution pose significant risks to ecosystems and contribute to bioaccumulation in plants, yet uptake mechanisms and combined toxicity are poorly understood. We used fluorescent labeling and europium-doped PS NPs to reveal the absorption and translocation of NPs by dandelions and conducted a transcriptomic analysis under PS NPs and DBP exposure. The results indicated that NPs are transported horizontally through the intercellular gaps at the root tips and primary root-lateral root junctions via the apoplastic pathway, followed by longitudinal transport through the xylem vessels under the transpiration stream. Co-exposure significantly reduced the bioconcentration factors of dandelion seedlings by 113 % but increased the NP transfer factors by 33.8 %. Transcriptomic analysis confirmed that exposure to PS NPs and DBP activated gene expression in dandelion shoots and roots. The differentially expressed genes were primarily involved in the photosynthesis, plant hormone signal transduction, and phenylpropanoid biosynthesis pathways. Weighted gene co-expression network analysis identified key genes and hub transcription factors playing crucial roles in regulating dandelion's response to combined stress. Our study provides new insights into the plant toxicity mechanism underlying the interaction between PS NPs and DBP, highlighting the adverse effects of the combined pollution on plant health.
Asunto(s)
Dibutil Ftalato , Poliestirenos , Taraxacum , Transcriptoma , Dibutil Ftalato/toxicidad , Poliestirenos/toxicidad , Taraxacum/metabolismo , Taraxacum/genética , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacosRESUMEN
Da Chuanxiong Formula (DCXF) is a traditional herbal prescription used for pain management. It consists of Chuanxiong Rhizoma (CR) and Gastrodiae Rhizoma (GR). Despite its long history of use, the underlying therapeutic mechanism of DCXF remains insufficiently understood. Therefore, in this study, key target genes were obtained through network pharmacology research methods and molecular docking techniques, including transient receptor potential vanilloid 1 (TRPV1), adenosine A2a receptor (ADORA2A), nuclear receptor subfamily 3 group C member 1 (NR3C1), and protein kinase C beta (PRKCB). Molecular dynamics simulations demonstrated the favorable binding between all four key genes and their corresponding compounds. Notably, chronic constriction injury (CCI) treatment resulted in a significant decrease in mechanical threshold and thermal latency period for rat foot contraction, which was ameliorated upon administration of DCXF. Furthermore, real-time quantitative reverse transcription PCR (RT-qPCR) and western blot (WB) analyses indicated an upregulation of TRPV1, ADORA2A, NR3C1, and PRKCB expression in the rat dorsal root ganglion following CCI, which was attenuated by treatment with DCXF. The expressions of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6), in the rat dorsal root ganglion were assessed using ELISA, confirming consistent trends with the aforementioned findings. The results of this study offer a promising theoretical foundation for the utilization of DCXF in the treatment of neuropathic pain (NP).