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To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.
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Diabetes Mellitus Tipo 2 , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Estudos de Casos e Controles , Inseticidas , Glicemia/análise , Malation/análogos & derivados , Compostos Organotiofosforados , China , Adulto , InflamaçãoRESUMO
There is no evidence on the associations between persistent organic pollutants (POPs) and the incidence of chronic kidney disease (CKD) in the Chinese rural population. We aimed to investigate the individual and mixed effects of 22 POPs on the prevalence and incidence of CKD, and the joint effects of POPs and abnormal glucose metabolism as well as the modification effects of healthy lifestyle on these associations. A total of 2775 subjects, including 925 subjects with normal plasma glucose (NPG) and 925 subjects with prediabetes (PDM) and type 2 diabetes mellitus (T2DM), were enrolled from the Henan Rural Cohort Study. Logistic regression and quantile g-computation were performed to assess the individual and mixed effects of POPs on the risk of CKD. Joint effects of POPs and abnormal glucose metabolism status, as well as the modification effects of lifestyle on CKD were assessed. After 3-year follow-up, an increment of ln-o,p'-DDT was related to an elevated risk of CKD prevalence. Positive associations of p,p'-DDE and ß-BHC with CKD incidence were observed (Pâ¯<â¯0.05). In addition, participants with high levels of ∑POPs were associated elevated incidence risk of CKD (OR: 1.217, 95%CI: 1.008-1.469). One quartile increase in POPs mixture was associated with the increased incidence of CKD among T2DM patients (Pâ¯<â¯0.05). Further, a higher risk of CKD was observed among PDM and T2DM patients with high levels of o,p'-DDT, p,p'-DDE, ß-BHC, and ∑POPs than NPG subjects with low levels of pollutants. In addition, interactive effects of ∑POPs and lifestyle score on CKD incidence were found. Individual and mixed exposure to POPs increased the prevalence and incidence of CKD, and glucose metabolic status exacerbated the risk of CKD resulting from such exposures. Further, the modifying effects of lifestyle were observed, highlighting the importance of precision prevention for high-risk CKD population and healthy lifestyle intervention measures.
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OBJECTIVE: To investigate the safety and clinical effect of testis-sparing microsurgery (TSMS) in the treatment of benign testis tumor (BTT). METHODS: We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023. The median age of the patients was 23 years. All the tumors were unilateral, 7 in the left and 9 in the right side, with a median diameter of 1.85 cm (1.0ï¼3.5 cm). The patients all underwent color Doppler flow imaging (CDFI), MRI, semen analysis and examination of serum T, alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH), followed by TSMS. The boundaries between the tumors and normal testis tissue were accurately identified under the microscope, and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely. Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue. The resected specimens were subjected to fast frozen pathology intraoperatively, and the patients were followed up for 14ï¼40 months by regular scrotal CDFI, MRI and examinations of serum T and semen parameters. RESULTS: The levels of serum T, AFP, HCG and LDH and semen parameters were all within the normal range preoperatively. TSMS were successfully completed in all the cases, and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors: Urinary and Male Genital Tumors. CDFI showed normal blood supply within the testis tissue at 1 month after surgery. No signs of intra-testicular tumor residue, recurrence or metastasis, nor significant changes in the levels of serum T, AFP, HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline. Natural conception was achieved in 2 cases at 16 and 18 months respectively after surgery. CONCLUSION: BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histopathology. TSMS can achieve complete excision of the tumor, maximal sparing of the normal testis tissue and thereby effective preservation of male fertility.
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Microcirurgia , Neoplasias Testiculares , Testículo , Humanos , Masculino , Microcirurgia/métodos , Neoplasias Testiculares/cirurgia , Estudos Retrospectivos , Adulto Jovem , Testículo/cirurgia , Adulto , alfa-Fetoproteínas/análise , Tratamentos com Preservação do Órgão/métodosRESUMO
Background: Wound healing has always been a serious issue for doctors and primary health care systems. In addition, adipose stem cell-derived exosomes have been proven to play a positive and effective role in tissue repair and regeneration. A systematic review of these preclinical studies was performed to assess the efficacy of adipose stem cell-derived exosomes (ADSC-Exos) in treating wounds. This article aimed to study the effectiveness of ADSC-Exos for the treatment of animal skin wounds and includes a meta-analysis of exosomes from general wounds and diabetic ulcer wounds in in vitro models of animals to provide a theoretical basis for clinical translation. Methods: A total of 19 studies with 356 animals were identified by searching the PubMed, Cochrane, MEDLINE Complete, Web of Science, CNKI and Wanfang databases from inception to 15 November 2022. No language or time restrictions were applied. Stata17 was used for all the data analyses. Results: The meta-analysis showed that ADSC-Exo therapy significantly improved the wound healing rate in the control group, except in the diabetes group on day 7. Day 7 of general wounds [standard mean difference (SMD) 2.87, 95% confidence interval (CI) 1.91-3.83)] and day 14 (SMD 2.89, 95%CI 1.47-4.30). Day 14 (SMD 3.43, 95%CI 1.28-5.58) of diabetic wounds. Other outcomes, such as blood vessel density, collagen deposition and wound re-epithelization, improved with the administration of ADSC-Exos. Conclusions: A meta-analysis showed that ADSC-Exo therapy applied to general and diabetic wounds can promote neovascularization, improve epithelization and collagen fiber deposition, promote healing, and reduce scar formation. ADSC-Exos have broad potential in preclinical research and clinical fields.
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Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.
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Sequenciamento de Nucleotídeos em Larga Escala , Pulmão , Musaranhos , Viroma , Animais , Musaranhos/virologia , China , Pulmão/virologia , Viroma/genética , Filogenia , Vírus de RNA/genética , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , RNA Viral/genética , Vírus da Influenza A/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Vírus da Raiva/genética , Vírus da Raiva/classificação , Vírus da Raiva/isolamento & purificação , Reservatórios de Doenças/virologiaRESUMO
Herein, high-efficiency green fluorescence nitrogen doped CDs (G-CDs) were prepared using acetaminophen and ethylenediamine as precursors. The G-CDs exhibited good anti-photobleaching, salttolerance and low cytotoxicity. Interestingly, the G-CDs revealed excellent fluorescence stability in the pH range of 6-12, however, the intensity of the G-CDs was almost completely quenched in other pH values. The MnO4- demonstrated strong fluorescence quenching capability on our G-CDs with the mechanism involving dynamic quenching caused by energy transfer. G-CDs exhibited a strong linear relationship with MnO4- concentration in the range of 0-75 µmol/L, with a low limit detection of 7.6 nmol/L. What was even more interesting was that the G-CDs displayed bright green solid-state fluorescence, and exhibited potential application in anti-counterfeiting.
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BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.
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Antibacterianos , Bismuto , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/terapia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Transplante de Microbiota Fecal/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Estudos Prospectivos , Bismuto/uso terapêutico , Quimioterapia Combinada , China , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Resultado do Tratamento , Idoso , Fezes/microbiologiaRESUMO
Electrons are the carriers of heat and electricity in materials and exhibit abundant transport phenomena such as ballistic, diffusive, and hydrodynamic behaviors in systems with different sizes. The electron Boltzmann transport equation (eBTE) is a reliable model for describing electron transport, but it is a challenging problem to efficiently obtain the numerical solutions of the eBTE within one unified scheme involving ballistic, hydrodynamics, and/or diffusive regimes. In this work, a discrete unified gas kinetic scheme (DUGKS) in the finite-volume framework is developed based on the eBTE with the Callaway relaxation model for electron transport. By reconstructing the distribution function at the cell interface, the processes of electron drift and scattering are coupled together within a single time step. Numerical tests demonstrate that the DUGKS can be adaptively applied to multiscale electron transport, across different regimes.
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BACKGROUND AND AIMS: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. METHODS: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. RESULTS: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. CONCLUSIONS: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.
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Chirality is an important aspect of nature, and numerous macroscopic methods have been developed to understand and control chirality. For the chiral tertiary amines, their flexible flipping process makes it possible to achieve high chiral controllability without bond formation and breaking. Here, we present a type of stable chiral single-molecule devices formed by tertiary amines, using graphene-molecule-graphene single-molecule junctions. These single-molecule devices allow real-time, in situ, and long-time measurements of the flipping process of an individual chiral nitrogen center with high temporal resolution. Temperature- and bias voltage-dependent experiments, along with theoretical investigations, revealed diverse chiral intermediates, indicating the regulation of the flipping dynamics by energy-related factors. Angle-dependent measurements further demonstrated efficient enrichment of chiral states using linearly polarized light by a symmetry-related factor. This approach offers a reliable means for understanding the chirality's origin, elucidating microscopic chirality regulation mechanisms, and aiding in the design of effective drugs.
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A highly sensitive ultra-small ratiometric fluorescence nanosphere probe was successfully manufactured to detect Sunset Yellow (SY). The probe, CMCS@N, S-CDs/Rh6G, was formed through the encapsulation of N, S-CDs and Rh6G within carboxymethyl chitosan (CMCS) through in situ cross-linking. Remarkably, our nanosphere probe had an average grain diameter of 6.80 nm and exhibited excellent dispersibility without the need for additional solvents. The probe exhibited a strong linear relationship with SY concentration in the range of 0.26-100 µM, with a low detection limit of 0.078 µM. Furthermore, SY demonstrated strong fluorescence quenching capability on our nanosphere probe, with the fluorescence quenching mechanism involving a combined effects of inner filter effect (IFE) and static quenching. Notably, our nanosphere probe retained the bacteriostatic properties of CMCS, with a substantial bacteriostasis rate of 77.58 %, introducing novel potential applications.
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Compostos Azo , Quitosana , Corantes Fluorescentes , Nanosferas , Nanosferas/química , Corantes Fluorescentes/química , Quitosana/química , Quitosana/análogos & derivados , Compostos Azo/química , Espectrometria de Fluorescência/métodos , Limite de Detecção , Fluorescência , Tamanho da PartículaRESUMO
OBJECTIVE: To summarize the application experience of the pneumatic arm in transnasal sphenoidal pituitary adenoma resection under neuroendoscope. METHODS: A retrospective analysis was conducted on the clinical data of 52 patients with pituitary adenoma who underwent endoscopic transsphenoidal surgery with pneumatic arm fixation in the Neurosurgery Department of the First Affiliated Hospital of Anhui Medical University from July 2021 to March 2024. Among them, there were 5 cases of pituitary microadenoma, 35 cases of macroadenoma, and 12 cases of giant adenoma. Head CT and a full set of hormones were re-examined within 24 hours after surgery to evaluate the surgical effect. Follow-up was conducted by the outpatient department after surgery to assess the clinical symptoms, hormone level, and imaging of all patients. RESULTS: Among 52 patients, gross total resection was achieved in 48 cases (92.3%), subtotal resection in 3 cases (5.8%), and partial resection in 1 case (1.9%). Preoperatively, 43 patients had diminished vision, with 40 showing improvement postoperatively, 1 worsening, and 2 having no significant improvement. Thirty-eight patients had headaches preoperatively, and all showed varying degrees of improvement postoperatively. Routine hormone examination within 24 hours after surgery showed that all 20 prolactinoma patients had restored normal hormone levels, 10 of 12 growth hormone-secreting adenoma patients normalized, and 4 of 6 cases of adrenocorticotropic hormone-secreting adenoma immediately relieved after surgery. Postoperative complications included intracranial hematoma in 1 case, cerebrospinal fluid leakage in 2 cases, transient diabetes insipidus in 6 cases, intracranial infection in 1 case, and no death cases. The median follow-up time of 52 patients was 18.6 months (range: 1-32 mo). During the follow-up period, the initial clinical symptoms of all patients improved to varying degrees, and they were able to work and live normally. At the last follow-up, 1 patient had recurrent tumor and 1 patient had progression. CONCLUSION: Transnasal sphenoidal resection of pituitary adenoma using a pneumatic arm-fixed neuroendoscope allows the operator to perform the surgery with both hands, resulting in satisfactory overall tumor resection and fewer surgical complications. This technique has good clinical value for promotion.
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OBJECTIVE: To explore the effect and mechanism of Dahuang Zhechong Pill (DHZCP) on liver fibrosis. METHODS: Liver fibrosis cell model was induced by transforming growth factor-ß (TGF-ß) in hepatic stellate cells (HSC-T6). DHZCP medicated serum (DMS) was prepared in rats. HSC-T6 cells were divided into the control (15% normal blank serum culture), TGF-ß (15% normal blank serum + 5 ng/mL TGF-ß), DHZCP (15% DMS + 5 ng/mL TGF-ß), DHZCP+PDTC [15% DMS + 4 mmol/L ammonium pyrrolidine dithiocarbamate (PDTC)+ 5 ng/mL TGF-ß], and PDTC groups (4 mmol/L PDTC + 5 ng/mL TGF-ß). Cell activity was detected by cell counting kit 8 and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cell supernatant were determined by enzyme-linked immunosorbnent assay. Western blot was used to measure the expressions of p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-ß1 (p38 MAPK/NF-κ B/TGF-ß1) pathway related proteins, and the localization and expressions of these proteins were observed by immunofluorescence staining. RESULTS: DHZCP improves the viability of cells damaged by TGF-ß and reduces inflammatory cytokines and ALT and AST levels in the supernatant of HSC-T6 cells induced with TGF-ß (P<0.05 or P<0.01). Compared with the TGF-ß group, NF-κ B p65 levels in the DHZCP group were decreased (P<0.05). p38 MAPK and NF-κ B p65 levels in the DHZCP+PDTC were also reduced (P<0.01). Compared with the TGF-ß group, the protein expression of Smad2 showed a downward trend in the DHZCP, DHZCP+PDTC, and PDTC groups (all P<0.01), and the decreasing trend of Samd3 was statistically significant only in DHZCP+PDTC group (P<0.01), whereas Smad7 was increased (P<0.05 or P<0.01). CONCLUSION: DHZCP can inhibit the process of HSC-T6 cell fibrosis by down-regulating the expression of p38 MAPK/NF-κ B/TGF-ß1 pathway.
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Chirality, a fundamental attribute of nature, significantly influences a wide range of phenomena related to physical properties, chemical reactions, biological pharmacology, and so on. As a pivotal aspect of chirality research, chirality recognition contributes to the synthesis of complex chiral products from simple chiral compounds and exhibits intricate interplay between chiral materials. However, macroscopic detection technologies cannot unveil the dynamic process and intrinsic mechanisms of single-molecule chirality recognition. Herein, we present a single-molecule detection platform based on graphene-molecule-graphene single-molecule junctions to measure the chirality recognition involving interactions between amines and chiral alcohols. This approach leads to the realization of in situ and real-time direct observation of chirality recognition at the single-molecule level, demonstrating that chiral alcohols exhibit compelling potential to induce the formation of the corresponding chiral configuration of molecules. The amalgamation of theoretical analyses with experimental findings reveals a synergistic action between electrostatic interactions and steric hindrance effects in the chirality recognition process, thus substantiating the microscopic mechanism governing the chiral structure-activity relationship. These studies open up a pathway for exploring novel chiral phenomena from the fundamental limits of chemistry, such as chiral origin and chiral amplification, and offer important insights into the precise synthesis of chiral materials.
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Thermal conductivity is a critical material property in numerous applications, such as those related to thermoelectric devices and heat dissipation. Effectively modulating thermal conductivity has become a great concern in the field of heat conduction. Here, a quantum modulation strategy is proposed to modulate the thermal conductivity/heat flux by exciting targeted phonons. It shows that the thermal conductivity of graphene can be tailored in the range of 1559 W m-1 K-1 (decreased to 49%) to 4093 W m-1 K-1 (increased to 128%), compared with the intrinsic value of 3189 W m-1 K-1. The effects are also observed for graphene nanoribbons and bulk silicon. The results are obtained through both density functional theory calculations and molecular dynamics simulations. This novel modulation strategy may pave the way for quantum heat conduction.
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The application of disposable tableware has increased substantially in recent times due to the rapidly growing food delivery business in China. Synthetic phenolic antioxidants (SPAs) are widely used in food contact materials (FCMs) to delay the process of oxidation; however, their compositions, concentrations, and potential health hazards remain unclear. Therefore, FCMs comprised of five materials obtained from 19 categories (n = 118) in China were analyzed for SPAs concentrations. FCMs have been found to contain a variety of SPAs, with ∑SPAs concentrations ranging from 44.18 to 69,485.12 µg/kg (median: 2615.63 µg/kg). The predominant congeners identified in the sample include 2,4-di-tert-butylphenol (2,4-DTBP), 2,6-di-tert-butylphenol (2,6-DTBP), and 2,6-di-tert-butyl-p-benzoquinone (BHT-Q) with a median concentration of 885.75, 555.45 and of 217.44 µg/kg, respectively. Milky tea paper cups, instant noodle buckets, milky teacups, and disposable cups showed high levels of SPAs. 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (AO 2246) was predominantly detected in polyethylene and polyethylene terephthalate-based products. The migration test identified disposable plastic cups and bowls as the predominant FCMs and 2,4-DTBP as the dominant SPA. The exposure risk of SPAs decreased with age. In children, the estimated daily intake of ∑SPAs from FCMs was determined to be 17.56 ng/kg body weight/day, which was 8.3 times higher than that of phthalic acid esters. The current findings indicate the potential ingestion risk of SPAs during the daily life application of multiple FCM categories.
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Antioxidantes , Exposição Dietética , Fenóis , Fenóis/análise , China , Exposição Dietética/análise , Humanos , Antioxidantes/análise , Antioxidantes/química , Contaminação de Alimentos/análise , Embalagem de AlimentosRESUMO
Oral delivery is the most widely used and convenient route of administration of medicine. However, oral administration of hydrophilic macromolecules is commonly limited by low intestinal permeability and pre-systemic degradation in the gastrointestinal (GI) tract. Overcoming some of these challenges allowed emergence of oral dosage forms of peptide-based drugs in clinical settings. Antisense oligonucleotides (ASOs) have also been investigated for oral administration but despite the recent progress, the bioavailability remains low. Given the advancement with highly potent and durable trivalent N-acetylgalactosamine (GalNAc)-conjugated small interfering RNAs (siRNAs) via subcutaneous (s.c.) injection, we explored their activities after oral administration. We report robust RNA interference (RNAi) activity of orally administrated GalNAc-siRNAs co-formulated with permeation enhancers (PEs) in rodents and non-human primates (NHPs). The relative bioavailability calculated from NHP liver exposure was <2.0% despite minimal enzymatic degradation in the GI. To investigate the impact of oligonucleotide size on oral delivery, highly specific GalNAc-conjugated single-stranded oligonucleotides known as REVERSIRs with different lengths were employed and their activities for reversal of RNAi effect were monitored. Our data suggests that intestinal permeability is highly influenced by the size of oligonucleotides. Further improvements in the potency of siRNA and PE could make oral delivery of GalNAc-siRNAs as a practical solution.
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Acetilgalactosamina , RNA Interferente Pequeno , Animais , Acetilgalactosamina/química , Acetilgalactosamina/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Administração Oral , Camundongos , Ratos , Interferência de RNA , Masculino , Disponibilidade Biológica , Humanos , Ratos Sprague-Dawley , Macaca fascicularis , Fígado/metabolismo , Macaca mulattaRESUMO
Efficiently generating 3D holograms is one of the most challenging research topics in the field of holography. This work introduces a method for generating multi-depth phase-only holograms using a fully convolutional neural network (FCN). The method primarily involves a forward-backward-diffraction framework to compute multi-depth diffraction fields, along with a layer-by-layer replacement method (L2RM) to handle occlusion relationships. The diffraction fields computed by the former are fed into the carefully designed FCN, which leverages its powerful non-linear fitting capability to generate multi-depth holograms of 3D scenes. The latter can smooth the boundaries of different layers in scene reconstruction by complementing information of occluded objects, thus enhancing the reconstruction quality of holograms. The proposed method can generate a multi-depth 3D hologram with a PSNR of 31.8 dB in just 90 ms for a resolution of 2160 × 3840 on the NVIDIA Tesla A100 40G tensor core GPU. Additionally, numerical and experimental results indicate that the generated holograms accurately reconstruct clear 3D scenes with correct occlusion relationships and provide excellent depth focusing.
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In line with the "healthy aging" principle, we aim to assess the exposure map and health risks of environmental chemicals in the elderly. Blood samples from 918 elderly individuals in Wuhan, China, were analyzed using the combined gas/liquid-mass spectrometry technology to detect levels of 118 environmental chemicals. Cluster analysis identified exposure profiles, while risk indexes and bioanalytical equivalence percentages were calculated using EPA's ToxCast database. The detection rates for 87 compounds exceeded 70%. DEHP, DiBP, naphthalene, phenanthrene, DnBP, pyrene, anthracene, permethrin, fluoranthene, and PFOS showed the highest concentrations. Fat-soluble pollutants varied across lifestyles. In cluster 2, which was characterized by higher concentrations of fat-soluble substances, the proportion of smokers or drinkers was higher than that of nonsmokers or nondrinkers. Pesticides emerged as the most active environmental chemicals in peroxisome proliferator-activated receptor gamma antagonist, thyroid hormone receptor (TR) antagonist, TR agonist, and androgen receptor (AR) agonist activity assays. Additionally, PAEs and polycyclic aromatic hydrocarbons played significant roles as active contaminants for the corresponding targets of AR antagonists and estrogen receptor alpha. We proposed a list of priority pollutants linked to endocrine-disrupting toxic effects in the elderly, which may provide the groundwork for further research into environmental etiology.