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BACKGROUND: Atopic dermatitis (AD) has the highest disease burden among all skin diseases. However, reports on AD prevalence trends in China are limited. This study aimed to investigate the time trends of AD prevalence in China from 1990 to 2021 and to explore the age and sex differences. METHODS: Data were obtained from the Global Burden of Disease Study, 2021. We analyzed the annual percentage change in the crude prevalence rate and age-standardized prevalence rate (ASPR) of AD from 1990 to 2021 using the Joinpoint model. We predicted the future prevalence of AD from 2022 to 2030 using the Bayesian age-period-cohort model. RESULTS: The total ASPR decreased slightly from 1990 (1357.93 per 100,000) to 2021 (1347.11 per 100,000). The ASPR of females (1457.64 per 100,000) was higher than that of males (1247.04 per 100,000) in 2021. The prevalence rate of AD was highest in the under 5 years old age group (3455.56 per 100,000) and the 5-9 years old age group (3360.31 per 100,000). By 2030, the predicted ASPR of AD will be 1394.36 (per 100,000) in males and 1603.69 in females (per 100,000). The predicted prevalence rate in the under 5 years old (3996.14 per 100,000 in males and 3990.68 per 100,000 in females) and 5-9 years old (3714.61 per 100,000 in males and 3963.96 per 100,000 in females) age groups will be higher than those in other age groups. CONCLUSION: Despite a slight decrease from 1990 to 2021, there has been an increasing trend since 2015 in the total AD burden. Given the increasing burden of AD on Chinese children and females, healthcare practitioners should enhance community education, improve disease management abilities of patients and caregivers, and reduce the burden and healthcare costs of AD.
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Dermatitis Atópica , Humanos , Dermatitis Atópica/epidemiología , Femenino , Masculino , Prevalencia , Preescolar , China/epidemiología , Niño , Adolescente , Lactante , Adulto , Adulto Joven , Persona de Mediana Edad , Recién Nacido , Factores Sexuales , Factores de Edad , Carga Global de Enfermedades , Pueblos del Este de AsiaRESUMEN
Polysaccharides are used as wall materials to extend the shelf life of lactic acid bacteria. Ice crystal formation during freezing leads to probiotic death. We prepared a series of dodecenyl succinic anhydride (DDSA)-modified rice starches with varying degrees of substitution and compared their functional properties. Fourier-transform infrared spectroscopy, X-ray diffraction analysis, and nuclear magnetic resonance results confirmed successful DDSA modification and the disruption of the long-range ordering of starch molecules. The structural changes modified the physicochemical properties of starch. For example, the apparent viscosity and viscoelastic characteristics of modified rice starch increased, and its freeze-thaw stability and emulsion capacity were remarkably improved after DDSA modification. Moreover, the modified starches exhibited promising performance for microencapsulating Pediococcus acidilactici. This study describes a rice starch derivative with excellent physicochemical properties that can be used to enhance the storage stability of bioactive probiotics.
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The formation conditions and functional property differences of esterified starch (ES) and granular esterified-pregelatinized starch (EPS) synchronously prepared by octenyl succinic anhydride (OSA) modification remain unclear. In this study, we explored the formation conditions and physicochemical properties of ES and EPS after OSA modification. The modification temperature controlled the formation amount and time for both starch types during OSA modification. Compared to ES, EPS exhibited a higher degree of substitution, cold-water swelling power, water-absorption capacity and apparent viscosity in cold water. The structural characterization confirmed the molecular weight and short/long-range molecular order of ES and EPS decreased. Moreover, scanning electron microscopy indicated EPS retained its granular morphology. The X-ray diffraction patterns confirmed the presence of more starch-lipid complexes formed in EPS than in ES. This study provides a novel method for preparing esterified and granularly esterified-pregelatinized starches that could be used as promising additives in low-energy formula foods.
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Almidón , Temperatura , Almidón/química , Almidón/análogos & derivados , Esterificación , Viscosidad , Difracción de Rayos X , Peso MolecularRESUMEN
The primary objective of this study was to explore the influence of prolonged (24 weeks) supplementary Tai Chi therapy on cognitive capabilities and immune-inflammatory pathways in subjects diagnosed with schizophrenia. A total of 90 individuals who have been clinically diagnosed with schizophrenia were assigned to two treatment groups, namely the Tai Chi treatment (TT) group and the routine treatment (RT) group. Following a 24-week duration of intervention, the data obtained from 32 patients in the TT group and 30 patients in the RT group were meticulously analyzed. At the commencement of the investigation and upon completion of the 24-week intervention, blood samples were gathered, and clinical evaluations were executed. In plasma, the identification of nine cytokines (IL-10, IFN-γ, IL-5, GM-CSF, TNF-α, IL-13, IL-4, IL-2, and IL-12) was conducted using the multiple primer suspension chip method. The clinical evaluations encompassed CGI, WHOQUOL-BREF, SOFS, PSS, BPRS, SAPS, SANS, and RBANS. In comparison to the RT group, the patients in the TT group demonstrated decreased levels of TNF-α and IL-5 (P < 0.05). Moreover, they encountered more pronounced advancements in SAPS, SANS, PSS, SOFS, and RBANS scores (P < 0.05). Additionally, a positive connection was detected between the plasma TNF-α level in the TT group and both the SANS score and the SPFS score (P < 0.05). Tai Chi has been shown to improve clinical symptoms in patients with schizophrenia as an add-on therapy, potentially through its effects on immunomodulatory pathways.
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Background: Social anxiety disorder (SAD) is one of the most prevalent psychological disorders and generally co-occurs with elevated shame levels. Previous shame-specific interventions could significantly improve outcomes in social anxiety treatments. Recent review suggests that integrating a more direct shame intervention could potentially increase the effectiveness of cognitive behavioral therapy. Web-based cognitive behavioral therapy (WCBT) has proven efficacy, sustaining benefits for 6 months to 4 years. Previous evidence indicated that shame predicted the reduction of social anxiety and mediated between engagements in exposure and changes in social anxiety during WCBT. Objective: This study aimed to design a shame intervention component through a longitudinal study and conduct a randomized controlled trial to investigate the effectiveness of a shame intervention component in reducing social anxiety symptoms and shame experience in a clinical sample of people with SAD. Methods: The development of a shame intervention component was informed by cognitive behavioral principles and insights from longitudinal data that measured the Experience of Shame Scale (ESS), the Coping Styles Questionnaire, and the Social Interaction Anxiety Scale (SIAS) in 153 participants. The psychoeducation, cognitive construct, and exposure sections were tailored to focus more on shame-related problem-solving and self-blame. A total of 1220 participants were recruited to complete questionnaires, including the ESS, the SIAS, the Social Phobia Scale (SPS), and diagnostic interviews. Following a 2-round screening process, 201 participants with SAD were randomly assigned into a shame WCBT group, a normal WCBT group, and a waiting group. After the 8-week WCBT intervention, the participants were asked to complete posttest evaluations, including the ESS, SIAS and SPS. Results: Participants in the shame WCBT group experienced significant reductions in shame levels after the intervention (ESS: P<.001; ηp2=0.22), and the reduction was greater in the shame intervention group compared to normal WCBT (P<.001; mean deviation -12.50). Participants in both the shame WCBT and normal WCBT groups experienced significant reductions in social anxiety symptoms (SIAS: P<.001; ηp2=0.32; SPS: P<.001; ηp2=0.19) compared to the waiting group after intervention. Furthermore, in the experience of social interaction anxiety (SIAS), the shame WCBT group showed a higher reduction compared to the normal WCBT group (P<.001; mean deviation -9.58). Problem-solving (SE 0.049, 95% CI 0.025-0.217) and self-blame (SE 0.082, 95% CI 0.024-0.339) mediated the effect between ESS and SIAS. Conclusions: This is the first study to design and incorporate a shame intervention component in WCBT and to validate its efficacy via a randomized controlled trial. The shame WCBT group showed a significant reduction in both shame and social anxiety after treatment compared to the normal WCBT and waiting groups. Problem-solving and self-blame mediated the effect of shame on social anxiety. In conclusion, this study supports previous findings that a direct shame-specific intervention component could enhance the efficacy of WCBT.
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Terapia Cognitivo-Conductual , Intervención basada en la Internet , Fobia Social , Vergüenza , Humanos , Masculino , Terapia Cognitivo-Conductual/métodos , Femenino , Fobia Social/terapia , Fobia Social/psicología , Adulto , Estudios Longitudinales , Resultado del Tratamiento , Adulto Joven , Persona de Mediana Edad , InternetRESUMEN
Objectives: This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants. Methods: This qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes. Results: The comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established. Conclusion: The results indicated that nursing assistants' capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant's care behaviors.
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Teoría Fundamentada , Asistentes de Enfermería , Casas de Salud , Investigación Cualitativa , Calidad de la Atención de Salud , Humanos , Casas de Salud/normas , Femenino , Masculino , Anciano , Adulto , Persona de Mediana Edad , Entrevistas como AsuntoRESUMEN
Copper nanoclusters (Cu NCs) are a new fluorescent material that is often used for determining metal ions, but most sensing systems are based on the "turn-off" model. Here, a "turn-on" model of fluorescence sensing for the detection of Cr(VI) was developed based on Cu NCs@MIL-101 composites. The Cu NCs@MIL-101 composites were synthesized from a simple mixture of Cu NCs and MIL-101(Cr), in which the Cu NCs were uniformly distributed in MIL-101(Cr). Notably, the fluorescence intensity of Cu NCs@MIL-101 was significantly weakened due to the internal filtration effect (IFE) of MIL-101. When Cr(VI) was introduced, the fluorescence of Cu NCs@MIL-101 was recovered by the guest exchange process between Cr(VI) and the Cu NCs, which overcame the IFE of Cu NCs@MIL-101. Based on this, a "turn-on" fluorescence probe was successfully constructed for the quantitative detection of Cr(VI) with two linear ranges of 0.05-1 µM and 1-20 µM, and a low detection limit of 0.05 µM. The proposed fluorescence probe possessed excellent selectivity and anti-interference ability, and was successfully applied for the detection of Cr(VI) in real water samples with satisfactory results. This study provides a new approach for the analytical application of Cu NCs.
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Some wheat-based foods require different doses of oil to moderate quality of dough during processing and the influence mechanisms remain unclear. Therefore, the effect of rapeseed oil addition on physicochemical characteristics and fine structure of dough and underlying mechanism were elucidated by rheometer, scanning microscope and molecular spectroscopic method. Results showed that compared with native dough (without exogenous rapeseed oil), the addition of rapeseed oil changed the fine structure, improved extensibility, but reduced viscoelasticity of the dough. Moreover, high addition especially 20 wt% oil (based on wheat flour) significantly changed gelatinization and retrogradation behaviors of the dough, whilst disrupted gluten network and increased random coil content (32.1%) of dough except that decreased its α-helix (21.2%), ß-sheet (23.1%), disulfide bond (7.9 µmol/g) compared with native dough which were 16.3%, 29.2%, 33.1%, 11.0 µmol/g, respectively. Results in the study could provide a certain understanding for application of vegetable oils in wheat-based products.
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Harina , Ácido Oléico , Aceite de Brassica napus , Reología , Triticum , Triticum/química , Aceite de Brassica napus/química , Harina/análisis , Ácido Oléico/química , Viscosidad , Pan/análisis , Glútenes/química , Aceites de Plantas/químicaRESUMEN
Autophagy, a self-digestion mechanism, has emerged as a promising target in the realm of cancer therapy, particularly in bladder cancer (BCa), a urological malignancy characterized by dysregulated biological processes contributing to its progression. This highly conserved catabolic mechanism exhibits aberrant activation in pathological events, prominently featured in human cancers. The nuanced role of autophagy in cancer has been unveiled as a double-edged sword, capable of functioning as both a pro-survival and pro-death mechanism in a context-dependent manner. In BCa, dysregulation of autophagy intertwines with cell death mechanisms, wherein pro-survival autophagy impedes apoptosis and ferroptosis, while pro-death autophagy diminishes tumor cell survival. The impact of autophagy on BCa progression is multifaceted, influencing metastasis rates and engaging with the epithelial-mesenchymal transition (EMT) mechanism. Pharmacological modulation of autophagy emerges as a viable strategy to impede BCa progression and augment cell death. Notably, the introduction of nanoparticles for targeted autophagy regulation holds promise as an innovative approach in BCa suppression. This review underscores the intricate interplay of autophagy with cell death pathways and its therapeutic implications in the nuanced landscape of bladder cancer.
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Autofagia , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Autofagia/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Nanopartículas , Apoptosis/efectos de los fármacos , Animales , Ferroptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacosRESUMEN
Dodecenylsuccinic anhydride (DDSA) has been widely used to obtain amphiphilic starches. In this study, we investigated the functionalities of synchronous intermissive multi-ultrasound-assisted esterified starch. Compared to native starch (NS), it was deduced that multi-ultrasound-modified starch (US), esterified starch (ES), and multi-ultrasound-assisted esterified starch (UES) exhibited increased viscosities but reduced gelatinization temperatures and thermal stabilities. The viscoelastic moduli, retrogradation behaviors and hydrophobicity of the ES and UES species significantly altered. Moreover, the results of structural characterization suggested that esterification reduced the molecular weight and structural order of starch, whereas the intermissive ultrasonication treatment did not aggravate the structural disruption of ES. Additionally, compared with NS and US, the emulsification abilities of the ES and UES specimens were improved, leading to the desirable effect of stabilizing astaxanthin. Overall, this study provides a method for preparing amphiphilic starch, which can be exploited as a potential emulsifier and emulsion stabilizer for bioactive compounds.
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Emulsiones , Interacciones Hidrofóbicas e Hidrofílicas , Almidón , Almidón/química , Emulsiones/química , Esterificación , Viscosidad , Emulsionantes/química , Peso MolecularRESUMEN
Radiation therapy (RT) not only can directly kill tumor cells by causing DNA double-strand break, but also exerts anti-tumor effects through modulating local and systemic immune responses. The immunomodulatory effects of RT are generally considered as a double-edged sword. On the one hand, RT effectively enhances the immunogenicity of tumor cells, triggers type I interferon response, induces immunogenic cell death to activate immune cell function, increases the release of proinflammatory factors, and reshapes the tumor immune microenvironment, thereby positively promoting anti-tumor immune responses. On the other hand, RT stimulates tumor cells to express immunosuppressive cytokines, upregulates the function of inhibitory immune cells, leads to lymphocytopenia and depletion of immune effector cells, and thus negatively suppresses immune responses. Nonetheless, it is notable that RT has promising abscopal effects and may achieve potent synergistic effects, especially when combined with immunotherapy in the daily clinical practice. This systematic review will provide a comprehensive profile of the latest research progress with respect to the immunomodulatory effects of RT, as well as the abscopal effect of radioimmunotherapy combinations, from the perspective of biological basis and clinical practice.
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Inmunoterapia , Radioinmunoterapia , Citocinas , Roturas del ADN de Doble Cadena , Muerte Celular InmunogénicaRESUMEN
The stomata regulate CO2 uptake and efficient water usage, thereby promoting drought stress tolerance. NAC proteins (NAM, ATAF1/2, and CUC2) participate in plant reactions following drought stress, but the molecular mechanisms underlying NAC-mediated regulation of stomatal movement are unclear. In this study, a novel NAC gene from Reaumuria trigyna, RtNAC055, was found to enhance drought tolerance via a stomatal closure pathway. It was regulated by RtMYC2 and integrated with jasmonic acid signaling and was predominantly expressed in stomata and root. The suppression of RtNAC055 could improve jasmonic acid and H2O2 production and increase the drought tolerance of transgenic R. trigyna callus. Ectopic expression of RtNAC055 in the Arabidopsis atnac055 mutant rescued its drought-sensitive phenotype by decreasing stomatal aperture. Under drought stress, overexpression of RtNAC055 in poplar promoted ROS (H2O2) accumulation in stomata, which accelerated stomatal closure and maintained a high photosynthetic rate. Drought upregulated the expression of PtRbohD/F, PtP5CS2, and PtDREB1.1, as well as antioxidant enzyme activities in heterologous expression poplars. RtNAC055 promoted H2O2 production in guard cells by directly binding to the promoter of RtRbohE, thus regulating stomatal closure. The stress-related genes RtDREB1.1/P5CS1 were directly regulated by RtNAC055. These results indicate that RtNAC055 regulates stomatal closure by maintaining the balance between the antioxidant system and H2O2 level, reducing the transpiration rate and water loss, and improving photosynthetic efficiency and drought resistance.
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Octenyl succinic anhydride (OSA)-modified starches have gained widespread interest, but the modification can produce two starches with different states ignored. Herein, the two types of starches, esterified starch (ES) and pregelatinized esterified starch (PES), prepared by OSA modification were separated, and their structural and functional characteristics were comprehensively explored. Results showed that compared with native starch (NS), ES and PES exhibited high water-holding capacity, solubility, and swelling power and significantly decreased pasting temperature and thermal stability. Dynamic rheological tests illustrated that OSA modification changed the rheological behavior of starches. Fourier transform infrared spectroscopy confirmed that PES with higher degree of substitution showed more obvious ester carbonyl and carboxylate groups than ES. Laser confocal micro-Raman spectroscopy revealed that the short-range molecular order of ES, especially PES, decreased after modification. X-ray diffraction indicated that OSA modification disrupted the crystalline structure of starch, and that more amylose-lipid complex was formed in PES. Scanning electron microscopy showed that OSA modification eroded starchs surface and reduced its smoothness, and significantly disrupted PES integrity. ES and PES could be developed as food additives for retrogradation inhibition of dough. These results provide new insights into OSA modification and expand its functional application in foods.
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Almidón , Anhídridos Succínicos , Anhídridos Succínicos/química , Almidón/química , Amilosa/química , Difracción de Rayos XRESUMEN
Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) could alleviate Alzheimer's disease (AD) defects. Additionally, engineered exosomes are more effective in treating diseases. In this study, we established an in vitro model of AD by treating SH-SY5Y cells with Aß1-40 . We observed that incubation with hucMSC-derived exosomes effectively protected SH-S5Y5 cells from Aß1-40 -induced damage. Since NEP plays a central role in suppressing AD development, we screened NEP-targeting miRNAs that are differentially expressed in control and AD patients. We identified miR-211-5p as a potent repressor of NEP expression. Exosomes purified from hucMSCs overexpressing miR-211-5p inhibitor exhibited significantly greater efficiency than control exosomes in mitigating the injury caused by Aß1-40 treatment. However, this enhanced protective effect was nullified by the knockdown of NEP. These observations demonstrate that inhibition of miR-211-5p has the potential to improve the efficacy of hucMSC-derived exosomes in AD treatment by increasing NEP expression.
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Enfermedad de Alzheimer , Exosomas , Células Madre Mesenquimatosas , MicroARNs , Neuroblastoma , Humanos , Exosomas/metabolismo , Neuroblastoma/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Células Madre Mesenquimatosas/metabolismo , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Cordón Umbilical/metabolismoRESUMEN
OBJECTIVE: The impact of inflammatory response on tumor development and therapeutic response is of significant importance in clear cell renal cell carcinoma (ccRCC). The customization of specialized prognostication approaches and the exploration of supplementary treatment options hold critical clinical implications in relation to the inflammatory response. METHODS: In the present study, unsupervised clustering was implemented on TCGA-KIRC tumors using transcriptome profiles of inflammatory response genes, which was then validated in two ccRCC datasets (E-MATB-1980 and ICGC) and two immunotherapy datasets (IMvigor210 and Liu et al.) via SubMap and NTP algorithms. Combining co-expression and LASSO analyses, inflammatory response-based scoring system was defined, which was evaluated in pan-cancer. RESULTS: Three reproducible inflammatory response subtypes (named IR1, IR2 and IR3) were determined and independently verified, each exhibiting distinct molecular, clinical, and immunological characteristics. Among these subtypes, IR2 had the best OS outcomes, followed by IR3 and IR1. In terms of anti-angiogenic agents, sunitinib may be appropriate for IR1 patients, while axitinib and pazopanib may be suitable for IR2 patients, and sorafenib for IR3 patients. Additionally, IR1 patients might benefit from anti-CTLA4 therapy. A scoring system called IRscore was defined for individual ccRCC patients. Patients with high IRscore presented a lower response rate to anti-PD-L1 therapy and worse prognostic outcomes. Pan-cancer analysis demonstrated the immunological features and prognostic relevance of the IRscore. CONCLUSION: Altogether, characterization of inflammatory response subtypes and IRscore provides a roadmap for patient risk stratification and personalized treatment decisions, not only in ccRCC, but also in pan-cancer.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/terapia , Neoplasias Renales/tratamiento farmacológico , Medicina de Precisión , Sorafenib/uso terapéutico , Axitinib/uso terapéutico , PronósticoRESUMEN
Background: Excess body mass index (BMI) plays a key role in the onset and progression of knee osteoarthritis (knee OA). However, the burden of knee OA attributable to high BMI at the global, Chinese, and regional levels have received far too little attention. The aim of this study is to provide evidence to support the design of policy by investigating long-term trends of years lived with disability (YLDs) for knee OA. Methods: To illustrate the trends of YLDs for knee OA attributable to high BMI and the temporal trends of the YLDs rate by age, period, and cohort, Joinpoint regression software and age-period-cohort (APC) were used to analyze the YLDs data of knee OA from the Global Burden of Disease (GBD) 2019. Results: In China, there were 549,963.5 YLDs for knee OA attributable to high BMI in 2019, which had increased by 460.7% since 1990. From 1990 to 2019, age-standardized disability-adjusted life year rate (ASDR) of knee OA attributable to high BMI trended upwards. The average annual percent change (AAPC) of knee OA attributable to high BMI in China and globe were 3.019, 1.419%, respectively. The longitudinal age curve of the APC model showed that the YLDs rates of knee OA due to high BMI increased with age, and YLDs rates were higher among females than males. The period rate ratios (RRs) of knee OA due to high BMI increased significantly. The cohort RRs of knee OA due to high BMI increased among those born between 1900 and 1970. The net drifts of knee OA attributable to high BMI in China and globe were above 1. Compared with global condition, the net drift values of knee OA attributable to high BMI in China was higher. Compared with females, males had higher net drift value. Countries with high socio-demographic index (SDI) have a much higher burden of knee OA caused by high BMI than countries with low SDI. Conclusion: In China, high BMI is a substantial cause of knee OA, the incidence of which has been increasing since 1990. In addition, women and the elderly are more vulnerable to knee OA caused by high BMI. The Chinese government must take the long-term impact of high BMI on knee OA into account and implement effective public health policies and resort to interventions to reduce the burden as soon as possible.
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Interleukin-1ß (IL-1ß)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1ß, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Presently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1ß-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1ß-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain (FLD) and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.
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OBJECTIVE: To study the effect of inhibitor of differentiation 3 (ID3) on radiotherapy in patients with rectal cancer and to explore its primary mechanism. METHODS: Cell proliferation and clonogenic assays were used to study the relationship between ID3 and radiosensitivity. Co-immunoprecipitation and immunofluorescence were performed to analyze the possible mechanism of ID3 in the radiosensitivity of colorectal cancer. At the same time, a xenograft tumor model of HCT116 cells in nude mice was established to study the effect of irradiation on the tumorigenesis of ID3 knockdown colorectal cancer cells in vivo. Immunohistochemistry was performed to analyze the relationship between ID3 expression and the efficacy of radiotherapy in 46 patients with rectal cancer. RESULTS: Proliferation and clonogenic assays revealed that the radiosensitivity of colorectal cancer cells decreased with ID3 depletion through p53-independent pathway. With the decrease in ID3 expression, MDC1 was downregulated. Furthermore, the expression of ID3, MDC1, and γH2AX increased and formed foci after irradiation. ID3 interacted with PPARγ and form a positive feedback loop to enhance the effect of ID3 on the radiosensitivity of colorectal cancer. Irradiation tests in nude mice also confirmed that HCT116 cells with ID3 knockdown were more affected by irradiation. Immunohistochemical study showed that rectal cancer patients with low expression of ID3 had better radiotherapy efficacy. CONCLUSIONS: ID3 and PPARγ influence the radiosensitivity of colorectal cancer cells by interacting with MDC1 to form a positive feedback loop that promotes DNA damage repair. Patients with low expression of ID3 who received neoadjuvant chemoradiotherapy can obtain a better curative effect.
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Reparación del ADN , PPAR gamma , Neoplasias del Recto , Animales , Humanos , Ratones , Línea Celular Tumoral , Daño del ADN , Reparación del ADN/genética , Retroalimentación , Proteínas Inhibidoras de la Diferenciación/genética , Ratones Desnudos , Proteínas de Neoplasias/genética , PPAR gamma/genética , Tolerancia a Radiación/genética , Neoplasias del Recto/genética , Neoplasias del Recto/radioterapiaRESUMEN
There is a burgeoning demand for modified plant-based proteins with desirable physicochemical and functional properties. The cereal Qingke is a promising alternative protein source, but its use has been limited by its imperfect functional characteristics. To investigate the effect of ultrasound treatment on Qingke protein, we applied single- (40 kHz), dual- (28/40 kHz), and tri- (28/40/50 kHz) frequency ultrasound on the isolated protein and measured subsequent physicochemical and structural changes. The results showed that the physicochemical properties of proteins were modified following ultrasound treatment, and many of these changes significantly increased with increasing frequency. Compared with the native Qingke protein (control), the solubility, foaming activity, stability, and water or oil holding capacity of tri-frequency ultrasound modified Qingke protein increased by 43.54%, 20.83%, 20.51%, 28.9%, and 45.2%, respectively. Furthermore, ultrasound treatment altered the secondary and tertiary structures of the protein resulting in more exposed chromophoric groups and inner hydrophobic groups, as well as reduced ß-sheets and increasedrandom coils, relative to the control. Rheological and texture characterization indicated that the values of G' and G'', hardness, gumminess, and chewiness decreased after ultrasound treatment. This study could provide a theoretical basis for the application of multi-frequency ultrasonic technology for modification of Qingke protein to expand its potential use as an alternative protein source.
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Proteínas de Plantas , Agua , Interacciones Hidrofóbicas e Hidrofílicas , Solubilidad , Proteínas de Plantas/química , Agua/química , ReologíaRESUMEN
Background: Increasing studies have found that PM2.5 has large adverse effects on stroke mortality. We want to investigate the long-term trends in the mortality of stroke attributable to ambient particulate matter pollution and household air pollution to provide evidence facilitating the design of policy. Methods: The deaths data of stroke and its subtypes attributable to PM2.5 were obtained from the Global Burden of Disease (GBD) 2019, analyzed by Joinpoint regression software and the age-period-cohort (APC) method to assess the magnitude of the trends in mortality and the temporal trends in the mortality rate by age, period, and cohort. Results: From 1990 to 2019, the age-standardized mortality rate (ASMR) attributable to PM2.5 exposure trended downwards, but the trends of ambient particulate matter pollution and household air pollution were opposite. The trends varied among subtypes, the AAPC of intracerebral hemorrhage, ischemic stroke, and subarachnoid hemorrhage attributable to PM2.5 were 0.7, 2.5, and-3.3%, respectively. The longitudinal age curve of the APC model showed that the mortality rates due to PM2.5 exposure increased with age. The period RRs of ischemic stroke due to ambient particulate matter pollution increased significantly. The cohort RRs of ambient particulate matter pollution increased among those born from 1905 to 1990. The net drifts of all subtypes attributable to PM2.5 were below 0, but owing to the increase of ambient particulate matter pollution, the range of the decline was small. Males had higher net drift values, compared with females. Conclusions: Ambient particulate matter pollution has become the main type of PM2.5 leading to stroke in China. PM2.5 exposure is more harmful to ischemic stroke, males, and elderly. Chinese government should pay attention to the long-term impact of ambient air pollution on stroke and take effective public health policies and interventions.