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Hyperglycaemia-induced ferroptosis is a significant contributor to kidney dysfunction in diabetic nephropathy (DN) patients. In addition, targeting ferroptosis has clinical implications for the treatment of DN. However, effective therapeutic targets for ferroptosis have not been identified. In this study, we aimed to explore the precise role of protein arginine methyltransferase 6 (PRMT6) in regulating ferroptosis in DN. In the present study, we utilized a mouse DN model consisting of both wild-type and PRMT6-knockout (PRMT6-/-) mice. Transcriptomic and lipidomic analyses, along with various molecular biological methodologies, were used to determine the potential mechanism by which PRMT6 regulates ferroptosis in DN. Our results indicate that PRMT6 downregulation participates in kidney dysfunction and renal cell death via the modulation of ferroptosis in DN. Moreover, PRMT6 reduction induced lipid peroxidation by upregulating acyl-CoA synthetase long-chain family member 1 (ACSL1) expression, ultimately contributing to ferroptosis. Furthermore, we investigated the molecular mechanism by which PRMT6 interacts with signal transducer and activator of transcription 1 (STAT1) to jointly regulate ACSL1 transcription. Additionally, treatment with the STAT1-specific inhibitor fludarabine delayed DN progression. Furthermore, we observed that PRMT6 and STAT1 synergistically regulate ACSL1 transcription to mediate ferroptosis in hyperglycaemic cells. Our study demonstrated that PRMT6 and STAT1 comodulate ACSL1 transcription to induce the production of phospholipid-polyunsaturated fatty acids (PL-PUFAs), thus participating in ferroptosis in DN. These findings suggest that the PRMT6/STAT1/ACSL1 axis is a new therapeutic target for the prevention and treatment of DN.
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OBJECTIVE: To explore the correlation between structural chromosomal abnormality and clinical characteristics of a child featuring gonadal dysplasia. METHODS: A 13-year-old child who was admitted to Lianyungang Maternal and Child Health Care Hospital on February 7, 2023 for primary amenorrhoea and occasional abdominal pain was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected. G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. "Pseudodual centromere isochromosome X" and "psu idic(X)" were used as keywords to search the CNKI, Wanfang and PubMed databases, and the search period was set as from January 1, 2002 to June 1, 2023. Relevant literature on the structural abnormality of X chromosome was searched and analyzed retrospectively. RESULTS: The child has a height of 153 cm and weighed 45 kg. She has no obvious facial dysmorphism. Laboratory tests showed that she had higher FSH and luteinizing hormone, and lower E2. Ultrasonography showed that she had small ovaries and rudimentary uterus. She was found to have a karyotype of 46,X,psu idic(X)(q21.3)[40]/mos 45,X[3], whilst both of her parents had a normal karyotype. CNV-seq showed that she had a 63.27 Mb deletion in Xq21.32q28 and a 91.59 Mb duplication in Xp22.33q21.32 (mosaicism rate = 74%). A total of 11 relevant literature were retrieved. Clinical phenotypes of patients with similar structural chromosomal abnormalities were diverse, which was closely related to the mosaicism rate of the 45,X karyotype and the location of the breaking point. CONCLUSION: 46,X,psu idic(X)(q21.3)/45,X probably underlay the dysplasia of uterus and ovary and sex hormone abnormalities in this child, while her height was spared. Deletion of Xq21.32q28 is a key factor leading to Turner syndrome-like phenotype such as rudimentary uterus and ovarian dysplasia.
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Cariotipificación , Humanos , Femenino , Adolescente , Cromosomas Humanos X/genética , Aberraciones Cromosómicas Sexuales , Variaciones en el Número de Copia de ADN , Bandeo Cromosómico , Pruebas GenéticasRESUMEN
AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.
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Enfermedades Pulmonares , Neostigmina , Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes , Complicaciones Posoperatorias , Rocuronio , Sugammadex , Humanos , Neostigmina/efectos adversos , Neostigmina/administración & dosificación , Sugammadex/efectos adversos , Sugammadex/administración & dosificación , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Bloqueo Neuromuscular/efectos adversos , Bloqueo Neuromuscular/métodos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano , Rocuronio/administración & dosificación , Rocuronio/efectos adversos , Fármacos Neuromusculares no Despolarizantes/efectos adversos , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Enfermedades Pulmonares/prevención & control , Adulto , Respiración Artificial/efectos adversos , Anestesia General/efectos adversosRESUMEN
Diabetic kidney disease (DKD), a primary microvascular complication arising from diabetes, may result in end-stage renal disease. Epigenetic regulation of endothelial mesenchymal transition (EndMT) has been recently reported to exert function in metabolic memory and DKD. Here, we investigated the mechanism which Sirt7 modulated EndMT in human glomerular endothelial cells (HGECs) in the occurrence of metabolic memory in DKD. Lower levels of SDC1 and Sirt7 were noted in the glomeruli of both DKD patients and diabetes-induced renal injury rats, as well as in human glomerular endothelial cells (HGECs) with high blood sugar. Endothelial-to-mesenchymal transition (EndMT) was sustained despite the normalization of glycaemic control. We also found that Sirt7 overexpression associated with glucose normalization promoted the SDC1 expression and reversed EndMT in HGECs. Furthermore, the sh-Sirt7-mediated EndMT could be reversed by SDC1 overexpression. The ChIP assay revealed enrichment of Sirt7 and H3K18ac in the SDC1 promoter region. Furthermore, hypermethylated in cancer 1 (HIC1) was found to be associated with Sirt7. Overexpression of HIC1 with normoglycaemia reversed high glucose-mediated EndMT in HGECs. The knockdown of HIC1-mediated EndMT was reversed by SDC1 upregulation. In addition, the enrichment of HIC1 and Sirt7 was observed in the same promoter region of SDC1. The overexpressed Sirt7 reversed EndMT and improved renal function in insulin-treated diabetic models. This study demonstrated that the hyperglycaemia-mediated interaction between Sirt7 and HIC1 exerts a role in the metabolic memory in DKD by inactivating SDC1 transcription and mediating EndMT despite glucose normalization in HGECs.
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Nefropatías Diabéticas , Células Endoteliales , Hiperglucemia , Factores de Transcripción de Tipo Kruppel , Sirtuinas , Sindecano-1 , Sindecano-1/metabolismo , Sindecano-1/genética , Humanos , Animales , Hiperglucemia/metabolismo , Hiperglucemia/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Ratas , Masculino , Células Endoteliales/metabolismo , Sirtuinas/metabolismo , Sirtuinas/genética , Transición Epitelial-Mesenquimal/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/complicaciones , Ratas Sprague-Dawley , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Epigénesis Genética , Regulación de la Expresión Génica , Regiones Promotoras Genéticas , Transición Endotelial-MesenquimatosaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a global health issue with noticeably high incidence and mortality. Microsimulation models offer a time-efficient method to dynamically analyze multiple screening strategies. The study aimed to identify the efficient organized CRC screening strategies for Shenzhen City. METHODS: A microsimulation model named CMOST was employed to simulate CRC screening among 1 million people without migration in Shenzhen, with two CRC developing pathways and real-world participation rates. Initial screening included the National Colorectal Polyp Care score (NCPCS), fecal immunochemical test (FIT), and risk-stratification model (RS model), followed by diagnostic colonoscopy for positive results. Several start-ages (40, 45, 50 years), stop-ages (70, 75, 80 years), and screening intervals (annual, biennial, triennial) were assessed for each strategy. The efficiency of CRC screening was assessed by number of colonoscopies versus life-years gained (LYG). RESULTS: The screening strategies reduced CRC lifetime incidence by 14-27 cases (30.9-59.0%) and mortality by 7-12 deaths (41.5-71.3%), yielded 83-155 LYG, while requiring 920 to 5901 colonoscopies per 1000 individuals. Out of 81 screening, 23 strategies were estimated efficient. Most of the efficient screening strategies started at age 40 (17 out of 23 strategies) and stopped at age 70 (13 out of 23 strategies). Predominant screening intervals identified were annual for NCPCS, biennial for FIT, and triennial for RS models. The incremental colonoscopies to LYG ratios of efficient screening increased with shorter intervals within the same test category. Compared with no screening, when screening at the same start-to-stop age and interval, the additional colonoscopies per LYG increased progressively for FIT, NCPCS and RS model. CONCLUSION: This study identifies efficient CRC screening strategies for the average-risk population in Shenzhen. Most efficient screening strategies indeed start at age 40, but the optimal starting age depends on the chosen willingness-to-pay threshold. Within insufficient colonoscopy resources, efficient FIT and NCPCS screening strategies might be CRC initial screening strategies. We acknowledged the age-dependency bias of the results with NCPCS and RS.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Humanos , Adulto , Anciano , Detección Precoz del Cáncer/métodos , Colonoscopía , Factores de Riesgo , Neoplasias Colorrectales/prevención & control , Sangre Oculta , Análisis Costo-Beneficio , Tamizaje Masivo/métodosRESUMEN
Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide. It is reported that the endothelial-to-mesenchymal transition (EndMT) in glomerular endothelial cells plays an important role in DN. As a specific form of epithelial-to-mesenchymal transition, EndMT may involve common regulators of epithelial-to-mesenchymal transition. Fascin has been shown to mediate epithelial-to-mesenchymal transition. In addition, SirT7 has been confir med to contribute to inflammation in hyperglycemic endothelial cells via the modulation of gene transcription. In this study, we speculate that SirT7 modulates fascin transcription and is thus involved in EndMT in hyperglycemic glomerular endothelial cells. Our data indicate that α-smooth muscle actin (α-SMA) and fascin levels are increased, while CD31 levels are decreased in the kidneys of DN rats. Consistently, our cellular experiments reveal that high glucose treatment elevates fascin levels and induces EndMT in human glomerular endothelial cells (HGECs). Moreover, silencing of fascin inhibits EndMT in hyperglycaemic HGECs. In addition, SirT7 is found to be decreased in hyperglycemic cells and in the kidneys of DN mice. Moreover, the inhibition of SirT7 increases fascin level and mediates EndMT. An increase in SirtT7 expression decreases fascin expression, inhibits EndMT, and improves renal function in hyperglycemic cells and DN mice. SirT7 is found to bind to the promoter region of fascin. In summary, the present study indicates that SirT7 transcribes fascin to contribute to hyperglycemia-induced EndMT in DN patients.
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Proteínas Portadoras , Nefropatías Diabéticas , Proteínas de Microfilamentos , Animales , Humanos , Ratones , Ratas , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Células Endoteliales/metabolismo , Transición Endotelial-Mesenquimatosa , Transición Epitelial-Mesenquimal , Riñón/metabolismoRESUMEN
With the evolution of artificial intelligence, the explosive growth of data from sensory terminals gives rise to severe energy-efficiency bottleneck issues due to cumbersome data interactions among sensory, memory, and computing modules. Heterogeneous integration methods such as chiplet technology can significantly reduce unnecessary data movement; however, they fail to address the fundamental issue of the substantial time and energy overheads resulting from the physical separation of computing and sensory components. Brain-inspired in-sensor neuromorphic computing (ISNC) has plenty of room for such data-intensive applications. However, one key obstacle in developing ISNC systems is the lack of compatibility between material systems and manufacturing processes deployed in sensors and computing units. This study successfully addresses this challenge by implementing fully CMOS-compatible TiN/HfOx-based neuristor array. The developed ISNC system demonstrates several advantageous features, including multilevel analogue modulation, minimal dispersion, and no significant degradation in conductance (@125 °C). These characteristics enable stable and reproducible neuromorphic computing. Additionally, the device exhibits modulatable sensory and multi-store memory processes. Furthermore, the system achieves information recognition with a high accuracy rate of 93%, along with frequency selectivity and notable activity-dependent plasticity. This work provides a promising route to affordable and highly efficient sensory neuromorphic systems.
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Inteligencia Artificial , Sustancias Explosivas , Encéfalo , Comercio , MovimientoRESUMEN
BACKGROUND: Emergence delirium (ED) is generally occurred after anesthesia associated with increased risks of long-term adverse outcomes. Therefore, this study aimed to evaluate the efficacy of preconditioning with nasal splint and mouth-breathing training on prevention of ED after general anesthesia. METHODS: This randomized controlled trial enrolled 200 adult patients undergoing ESS. Patients were randomized to receive either nasal splinting and mouth breathing training (n = 100) or standard care (n = 100) before surgery. The primary outcome was the occurrence of ED within 30 min of extubation, assessed using the Riker Sedation-Agitation Scale. Logistic regression identified risk factors for ED. RESULTS: Totally 200 patients were randomized and 182 aged from 18 to 82 years with 59.9% of males were included in the final analysis (90 in C-group and 92 in P-group). ED occurred in 16.3% of the intervention group vs. 35.6% of controls (P = 0.004). Male sex, smoking and function endoscopic sinus surgery (FESS) were independent risk factors for ED. CONCLUSIONS: Preoperative nasal splinting and mouth breathing training significantly reduced the incidence of emergence delirium in patients undergoing endoscopic sinus surgery. TRIAL REGISTRATION: ChiCTR1900024925 ( https://www.chictr.org.cn/index.aspx ) registered on 3/8/2019.
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Anestesiología , Delirio del Despertar , Adulto , Humanos , Masculino , Delirio del Despertar/prevención & control , Respiración por la Boca , Extubación Traqueal , Anestesia GeneralRESUMEN
PURPOSE: Type 2 diabetes mellitus (T2DM) is a persistent metabolic condition with an unknown pathophysiology. Moreover, T2DM remains a serious health risk despite advances in medication and preventive care. Randomised controlled trials (RCTs) have provided evidence that probiotics may have positive effects on glucolipid metabolism. Therefore, we performed a meta-analysis of RCTs to measure the effect of probiotic therapy on glucolipid metabolism in patients with T2DM. METHODS: With no constraints on the language used in the literature, Excerpta Medica Database, PubMed, the Cochrane Library, and the Web of Science were searched for pertinent RCTs published between the date of creation and 18 August 2022. Stringent inclusion and exclusion criteria were applied by two reviewers to independently examine the literature. The risk of bias associated with the inclusion of the original studies was assessed using the Cochrane risk-of-bias tool, and Stata 15.0 was used to perform the meta-analysis. RESULTS: Thirty-seven publications containing a total of 2502 research participants were included in the meta-analysis. The results showed that after a probiotic intervention, the experimental group showed a significant decrease in body mass index (standardised mean difference (SMD) = -0.42, 95% confidence interval (CI) [-0.76, -0.08]), fasting glucose concentration (SMD = -0.73, 95% CI [-0.97, -0.48]), fasting insulin concentration (SMD = -0.67, 95% CI [-0.99, -0.36]), glycated haemoglobin concentration (SMD = -0.55, 95% CI [-0.75, -0.35]), Homeostatic Model Assessment for Insulin Resistance score (SMD = -0.88, 95% CI [-1.17, -0.59]), triglyceride concentration (SMD = -0.30, 95% CI [-0.43, -0.17]), total cholesterol concentration (SMD = -0.27, 95% CI [-0.43, -0.11]), and low-density lipoprotein concentration (SMD = -0.20, 95% CI [-0.37, -0.04]), and an increase in high-density lipoprotein concentration (SMD = 0.31, 95% CI [0.08, 0.54]). Moreover, subgroup analyses showed that patients with a longer intervention time, or those who were treated with multiple strains of probiotics, may benefit more than those with a shorter intervention time or those who were treated with a single probiotic strain, respectively. CONCLUSION: Probiotic supplementation improves glucolipid metabolism in patients with T2DM, offering an alternative approach for the treatment of these patients.
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Diabetes Mellitus Tipo 2 , Probióticos , Humanos , Diabetes Mellitus Tipo 2/prevención & control , Probióticos/uso terapéutico , Hemoglobina Glucada , Insulina , AyunoRESUMEN
A broadband and CMOS-compatible polarization beam splitter and rotator (PSR) built on the silicon nitride-on-silicon multilayer platform is presented. The PSR is realized by cascading a polarization beam splitter and a polarization rotator, which are both subtly constructed with an asymmetrical directional coupler waveguide structure. The advantage of this device is that the function of PSR can be directly realized in the SiN layer, providing a promising solution to the polarization diversity schemes in SiN photonic circuits. The chip is expected to have high power handling capability as the light is input from the SiN waveguide. The use of silicon dioxide as the upper cladding of the device ensures its compatibility with the metal back-end-of-line process. By optimizing the structure parameters, a polarization conversion loss lower than 1 dB and cross talk larger than 27.6 dB can be obtained for TM-TE mode conversion over a wavelength range of 1450 to 1600 nm. For TE mode, the insertion loss is lower than 0.26 dB and cross talk is larger than 25.3 dB over the same wavelength range. The proposed device has good potential in diversifying the functionalities of the multilayer photonic chip with high integration density.
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Objective: This work studied the molecular mechanism of the Saposhnikovia divaricata-Angelica dahurica herb pair (SAHP) in migraine treatment. Methods: The active ingredients of drugs were screened, and potential targets were predicted by the Traditional Chinese Medicine Systems Pharmacology (TCMSP), TCMID, ETCM, and other databases. Migraine-related targets were obtained by harnessing the GeneCards, DrugBank, OMIM, TTD, and other databases. The protein-protein interaction (PPI) network was constructed with STRING software by performing a Venn analysis with bioinformatics. Gene Ontology (GO) functional enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with the Metascape platform. The component-target-pathway (C-T-P) network was constructed with Cytoscape 3.7.2 software, and molecular docking was assessed with AutoDockVina software. Results: A total of 183 relevant targets and 39 active ingredients in migraine therapy were obtained from SAHP. The active ingredients and targets were screened according to topological parameters: wogonin, anomalin, imperatorin, prangenin, 2-linoleoylglycerol, and methylenetanshinquinone were identified as key active ingredients. PTGS2, PIK3CA, PIK3CB, PIK3CD, F2, and AR were identified as key targets. The molecular docking results demonstrated high binding activity between the key active ingredients and key targets. A total of 20 important signaling pathways, including neural signaling pathways, calcium signaling pathways, pathways in cancer, cAMP signaling pathways, and PI3K-Akt signaling pathways, were obtained through enrichment analysis. Conclusion: Migraine with SAHP is mainly treated through anti-inflammatory and analgesic effects. The herb pair can be used for migraine using "multicomponent, multitarget, and multipathway" approaches.
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ABSTRACT: This study aimed to assess the association of subchorionic hematoma (SCH) size measured by virtual organ computer-aided analysis (VOCAL) with the first-trimester pregnancy outcome. A total of 139 first-trimester pregnancies from 6 to 12 weeks of gestational age with SCH were included. The circumference, area, and volume of the SCH (Cs, As, and 3DVs) and gestational sac (Cg, Ag, and 3DVg) were automatically calculated by VOCAL. Interobserver agreement was assessed with the intraclass correlation coefficient and Bland-Altman plot. Odds ratios for the clinical and ultrasound characteristics of adverse pregnancy outcomes were estimated by univariate or multivariable logistic regression. There was high interobserver agreement in VOCAL measurements of the SCH and gestational sac (intraclass correlation coefficients, >0.900). By univariate regression analysis, women with adverse pregnancy outcomes were more likely to have vaginal bleeding, a larger As and 3DVs, and higher Cs/Cg, As/Ag, and 3DVs/3DVg ratios (all P < 0.05). In the multivariable regression analysis, a higher 3DVs/3DVg ratio of SCH (odds ratio, 1.034; 95% confidence interval [CI], 1.015-1.053; P = 0.000) and vaginal heavy bleeding had a significant positive relationship with the risk of adverse pregnancy outcomes (odds ratio, 7.846; 95% CI, 1.104-55.737; P = 0.039) remained associated with an increased risk of adverse pregnancy outcomes. With 11.87% as the cutoff, the receiver operating characteristic curve yielded a good predictive performance (area under the curve, 0.713) and high sensitivity (91.18%). The measurements of SCH by VOCAL provide high reliability for estimating the total hematoma burden in first-trimester pregnant patients. A greater volume proportion (3DVs/3DVg) of SCH worsens the pregnancy outcome, and a greater risk of adverse pregnancy outcome also associated with the severity of vaginal bleeding.
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Complicaciones del Embarazo , Resultado del Embarazo , Embarazo , Humanos , Femenino , Primer Trimestre del Embarazo , Reproducibilidad de los Resultados , Ultrasonografía Prenatal , Complicaciones del Embarazo/diagnóstico por imagen , Hemorragia Uterina/diagnóstico por imagen , Hemorragia Uterina/complicaciones , Hematoma/diagnóstico por imagen , Hematoma/complicaciones , ComputadoresRESUMEN
Sensors that have low power consumption, high scalability and the ability of rapidly detecting multitudinous external stimulus are of great value in cyber-physical interactive applications. Herein, we reported the fabrication of ferroelectric barium strontium titanate ((Ba70Sr30)TiO3, BST) thin films on silicon substrates by magnetron sputtering. The as-grown BST films have a pure perovskite structure and exhibit excellent ferroelectric characteristics, such as a remnant polarization of 2.4 µC/cm2, a ferro-to-paraelectric (tetragonal-to-cubic) phase transition temperature of 31.2 °C, and a broad optical bandgap of 3.58 eV. Capacitor-based sensors made from the BST films have shown an outstanding average sensitivity of 0.10 mV·Pa-1 in the 10-80 kPa regime and work extremely steadily over 1000 cycles. More importantly, utilizing the Pockels effect, optical manipulation in BST can be also realized by a smaller bias and its electro-optic coefficient reff is estimated to be 83.5 pmV-1, which is 2.6 times larger than in the current standard material (LiNbO3) for electro-optical devices. Our work established BST thin film as a powerful design paradigm toward on-chip integrations with diverse electronics into sensors via CMOS-comparable technique.
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A CMOS-compatible, broadband, and polarization-independent edge coupler for efficient chip coupling with standard single-mode fiber is proposed. Three layers of a silicon nitride waveguide array with the same structures are used in the top oxide cladding of the chip to achieve high coupling efficiency and to simplify the mode transformation structure. Optimal total coupling loss at the wavelength of 1550 nm, -0.49dB for TE mode polarization and -0.92dB for TM mode polarization is obtained. The -1dB bandwidth is beyond 160 nm for TE mode polarization and â¼130nm for TM mode polarization, respectively. A significant reduction in the packaging cost of silicon photonic chips is anticipated. Meanwhile, the structure holds vast potential for on-chip three-dimensional photonic integrations or fiber-to-chip, chip-to-chip optical interconnections.
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Aim: This study used machine learning methods to develop a prediction model for knee pain in middle-aged and elderly individuals. Methods: A total of 5386 individuals above 45 years old were obtained from the National Health and Nutrition Examination Survey. Participants were randomly divided into a training set and a test set at a 7 : 3 ratio. The training set was used to create a prediction model, whereas the test set was used to validate the proposed model. We constructed multiple predictive models based on three machine learning methods: logistic regression, random forest, and Extreme Gradient Boosting. The model performance was evaluated by areas under the receiver (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. Additionally, we created a simplified nomogram based on logistic regression for better clinical application. Results: About 31.4% (1690) individuals were with self-reported knee pain. The logistic regression showed that female gender (odds ratio [OR] = 1.28), pain elsewhere (OR = 4.64), and body mass index (OR = 1.05) were significantly associated with increased risk of knee pain. In the test set, the logistic regression (AUC = 0.71) showed similar but slightly higher accuracy than the random forest (AUC = 0.70), while the performance of the Extreme Gradient Boosting model was less reliable (AUC = 0.59). Based on mean decrease accuracy, the most important first five predictions were pain elsewhere, waist circumference, body mass index, age, and gender. Additionally, the most important first five predictions with the highest mean decrease Gini index were pain elsewhere, body mass index, waist circumference, triglycerides, and age. The nomogram model showed good discrimination ability with an AUC of 0.75 (0.73-0.77), a sensitivity of 0.72, specificity of 0.71, a positive predictive value of 0.45, and a negative predictive value of 0.88. Conclusion: This study proposed a convenient nomogram tool to evaluate the risk of knee pain for the middle-aged and elderly US population in primary care. All the input variables can be easily obtained in a clinical setting, and no additional radiologic assessments were required.
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Aprendizaje Automático , Dolor , Anciano , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Encuestas Nutricionales , Dolor/diagnóstico , Dolor/etiología , TriglicéridosRESUMEN
Hepatitis B virus (HBV) infection is a public health threat worldwide, and there is no direct treatment yet available. In the event of infection, patients may present liver cirrhosis and cancer, which threaten the patients' health globally, especially in the Asia-Pacific region and China. In 2019, Chinese hepatopathologists updated the 2015 Guidelines for the Prevention and Treatment of Chronic Hepatitis B as the clinical reference. The other versions formulated by the American Association for the Study of Liver Diseases (2018 AASLD guidelines) (AASLD, 2018), European Association for the Study of the Liver (2017 EASL guidelines) (EASL, 2017), and Asian-Pacific Association for the Study of the Liver (2015 APASL guidelines) (APASL, 2015) also provide clinical guidance. However, there are still some issues that need to be addressed. In the present study, the following aspects will be introduced successively: (1) Who should be treated in the general population according to the guidelines; (2) Treatment of specific populations infected with HBV; (3) Controversial issues in clinical practice; (4) Perspective.
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Exploiting multifunctional thin film transistors (TFTs) by low-temperature manufacturing strategy is a crucial step toward flexible electronics. Herein, a multifunctional indium-tungsten-oxide (IWO)-based TFT, gated by solid-state chitosan electrolyte membrane, is fabricated on paper substrate at room temperature. The chitosan exhibits a high specific electric-double-layer capacitance of 2.0 µF cm-2 due to the existence of mobile protons. The IWO-based TFT possesses excellent electrical properties, including a low threshold voltage of 0.2 V, larger current switching ratio of 1.3 × 106, high field effect mobility of 15.0 cm2 V-1s-1, and small subthreshold swing of 117 mV/decade, respectively. Multifunctional operations including inverter, Schmitt triggers, and NAND gate are successfully demonstrated. As an example of information processing, the essential signal transmission functions of biological synapses also be emulated in the fabricated IWO-based TFTs. The experimental results indicate that such flexible IWO-based TFTs on low-cost and biodegradable paper provide the new-concept building blocks for flexible electronics.
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The prevalence of diabetes mellitus is increasing globally. Probiotics have been shown to be an effective intervention for diabetes. This study focused on the relieving effects and possible mechanisms of 16 strains of two dominant Bifidobacterium species (B. bifidum and B. adolescentis, which exist in the human gut at different life stages) on type 2 diabetes (T2D). The results indicated that more B. adolescentis strains appeared to be superior in alleviating T2D symptoms than B. bifidum strains. This effect was closely related to the ability of B. adolescentis to restore the homeostasis of the gut microbiota, increase the abundance of short-chain fatty acid-producing flora, and alleviate inflammation in mice with T2D. In addition, compared with B. bifidum, B. adolescentis had a higher number of core genes, and these genes were more evolutionarily stable, including unique environmental tolerance, carbon and nitrogen utilization genes, and a blood sugar regulation gene, glgP. This may be one of the reasons why B. adolescentis is more likely to colonize in the adult gut and show a superior ability to relieve T2D. This study provides insights into future studies aimed at investigating probiotics for the treatment of metabolic diseases.
Asunto(s)
Bifidobacterium adolescentis , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Probióticos , Animales , Bifidobacterium/metabolismo , Bifidobacterium adolescentis/genética , Bifidobacterium adolescentis/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Heces/microbiología , Microbioma Gastrointestinal/fisiología , Ratones , Probióticos/uso terapéuticoRESUMEN
Diabetic nephropathy (DN) is one of the most serious complications of advanced diabetes, and increases patient mortality. Recently, epigenetics-mediated hyperglycemic memory in pathological process of DN has received attention. The purpose of this study was to determine the underlying mechanism by which sirt7 modulates hyperglycemic memory in DN. In glomerular endothelial cells (GECs) cultured in high glucose and glomeruli of DN patients and rats, an increase in p65 phosphorylation and endothelial adhesion molecule levels persisted after glucose normalization but was reversed by glucose normalization associated with death-associated protein kinase-3 (DAPK3) knockout or DAPK3 inhibitor. High glucose-mediated decrease in sirt7, the deacetylase modulating H3K18-acetylation (H3K18ac), was sustained after normoglycemia. Sirt7 overexpression accompanied by glucose normalization suppressed DAPK3 expression and inflammation in GECs. Moreover, sh-sirt7-induced inflammation was inhibited by si-DAPK3. Furthermore, sirt7 and H3K18ac were located at the DAPK3 promoter region. ELK1 was found to combine with sirt7. si-ELK1 supplemented with normoglycemia inhibited high glucose-induced DAPK3 expression and inflammation in GECs. ELK1 overexpression-mediated inflammation was inhibited by si-DAPK3. In addition, ELK1 and sirt7 were located at the same promoter region of DAPK3. ELK1 overexpression enhanced DAPK3 promoter activity, which disappeared after specific binding site mutation. In vivo, sirt7 overexpression decreased inflammation and improved renal function during insulin treatment of DN rats, whereas insulin alone did not work. Our data demonstrated high glucose-mediated mutual inhibition between sirt7 and ELK1 induced DAPK3 transcription and inflammation despite normoglycemia in GECs, thus forming a vicious cycle and participating in the occurrence of hyperglycemic memory in DN.