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1.
bioRxiv ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38712081

RESUMO

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks an effective targeted therapy. To identify new therapeutic targets, we investigated the phosphohistidine phosphatase, LHPP, which has been implicated in the development of several types of cancer. However, the full significance of LHPP in cancer progression remains unclear due to our limited understanding of its molecular mechanism. We found that levels of the LHPP phosphohistidine phosphatase were significantly increased in human breast cancer patients compared to normal adjacent tissues, with the highest levels in the TNBC subtype. When LHPP was knocked out in the MDA-MB-231 human TNBC cell line, cell proliferation, wound healing capacity, and invasion were significantly reduced. However, LHPP knockout in TNBC cells did not affect the phosphohistidine protein levels. Interestingly, LHPP knockout in MDA-MB-231 cells delayed tumor growth and reduced metastasis when orthotopically transplanted into mouse mammary glands. To investigate LHPP's role in breast cancer progression, we used next-generation sequencing and proximity-labeling proteomics, and found that LHPP regulates gene expression in chemokine-mediated signaling and actin cytoskeleton organization. Depletion of LHPP reduced the presence of tumor-infiltrating macrophages in mouse xenografts. Our results uncover a new tumor promoter role for LHPP phosphohistidine phosphatase in TNBC and suggest that targeting LHPP phosphatase could be a potential therapeutic strategy for TNBC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38776207

RESUMO

In convolutional neural networks (CNNs), the convolutions are conventionally performed using a square kernel with a fixed N × N receptive field (RF). However, what matters most to the network is the effective receptive field (ERF), which indicates the extent to which input pixels contribute to an output pixel. Inspired by the property that ERFs typically exhibit a Gaussian distribution, we propose a Gaussian Mask convolutional kernel (GMConv). Specifically, GMConv utilizes the Gaussian function to generate a concentric symmetry mask that is placed over the kernel to refine the RF. We analyze the RFs of CNN kernels in different CNN layers and evaluate our approach through extensive experiments on image classification and object detection tasks. Over several tasks and standard base models, our approach compares favorably against the standard convolution. For instance, using GMConv for AlexNet and ResNet-50, the top-1 accuracy on ImageNet classification is boosted by 0.98% and 0.85% , respectively.

3.
JGH Open ; 8(4): e13055, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628386

RESUMO

Background and Aim: The microsurface structure reflects the degree of damage to the glands, which is related to the invasion depth of early gastric cancer. To evaluate the diagnostic value of quantitative microsurface structure analysis for estimating the invasion depth of early gastric cancer. Methods: White-light imaging and narrow-band imaging (NBI) endoscopy were used to visualize the lesions of the included patients. The area ratio and depth-predicting score (DPS) of each patient were calculated; meanwhile, each lesion was examined by endoscopic ultrasonography (EUS). Results: Ninety-three patients were included between 2016 and 2019. Microsurface structure is related to the histological differentiation and progression of early gastric cancer. The receiver operating characteristic curve showed that when an area ratio of 80.3% was used as a cut-off value for distinguishing mucosal (M) and submucosal (SM) type 0-II gastric cancers, the sensitivity, specificity, and accuracy were 82.9%, 80.2%, and 91.6%, respectively. The accuracies for distinguishing M/SM differentiated and undifferentiated early gastric cancers were 87.4% and 84.8%, respectively. The accuracy of EUS for distinguishing M/SM early gastric cancer was 74.9%. DPS can only distinguish M-SM1 (SM infiltration <500 µm)/SM (SM infiltration ≥500 µm) with an accuracy of 83.8%. The accuracy of using area ratio for distinguishing 0-II early gastric cancers was better than those of using DPS and EUS (P < 0.05). Conclusion: Quantitative analysis of microsurface structure can be performed to assess M/SM type 0-II gastric cancer and is expected to be effective for judging the invasion depth of gastric cancer.

4.
J Oral Microbiol ; 16(1): 2292539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405599

RESUMO

Oral microecological balance is closely associated with the development of dental caries. Oxidative stress is one of the important factors regulating the composition and structure of the oral microbial community. Streptococcus mutans is linked to the occurrence and development of dental caries. The ability of S. mutans to withstand oxidative stress affects its survival competitiveness in biofilms. The oxidative stress regulatory mechanisms of S. mutans include synthesis of reductase, regulation of metal ions uptake, regulator PerR, transcription regulator Spx, extracellular uptake of glutathione, and other related signal transduction systems. Here, we provide an overview of how S. mutans adapts to oxidative stress and its influence on oral microecology, which may offer novel options to investigate the cariogenic mechanisms of S. mutans in the oral microenvironment, and new targets for the ecological prevention and treatment of dental caries.

5.
Micromachines (Basel) ; 14(8)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37630082

RESUMO

This review focuses on the development of surface acoustic wave-enabled acoustic drop ejection (SAW-ADE) technology, which utilizes surface acoustic waves to eject droplets from liquids without touching the sample. The technology offers advantages such as high throughput, high precision, non-contact, and integration with automated systems while saving samples and reagents. The article first provides an overview of the SAW-ADE technology, including its basic theory, simulation verification, and comparison with other types of acoustic drop ejection technology. The influencing factors of SAW-ADE technology are classified into four categories: fluid properties, device configuration, presence of channels or chambers, and driving signals. The influencing factors discussed in detail from various aspects, such as the volume, viscosity, and surface tension of the liquid; the type of substrate material, interdigital transducers, and the driving waveform; sessile droplets and fluid in channels/chambers; and the power, frequency, and modulation of the input signal. The ejection performance of droplets is influenced by various factors, and their optimization can be achieved by taking into account all of the above factors and designing appropriate configurations. Additionally, the article briefly introduces the application scenarios of SAW-ADE technology in bioprinters and chemical analyses and provides prospects for future development. The article contributes to the field of microfluidics and lab-on-a-chip technology and may help researchers to design and optimize SAW-ADE systems for specific applications.

6.
Int J Ophthalmol ; 16(8): 1210-1217, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602334

RESUMO

AIM: To investigate the expression and effect of histone deacetylase 7 (HDAC7) in human retinal microvascular endothelial cells (HRMECs) under high glucose condition and related mechanism, and the expression of HDAC7 in the retinal tissue in diabetic rats. METHODS: The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot. LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities. Cell count kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, scratch test, Transwell test and tube formation assay were used to examine the ability of cell proliferation, migration, and angiogenesis. Finally, a preliminary exploration of its mechanism was performed by Western blot. RESULTS: The expression of HDAC7 was both up-regulated in retinal tissues of diabetic rats and high glucose-treated HRMECs. Down-regulation of HDAC7 expression significantly reduced the ability of proliferation, migration, and tube formation, and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs. CONCLUSION: High glucose can up-regulate the expression of HDAC7 in HRMECs. Down-regulation of HDAC7 can inhibit HRMECs activities. HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.

7.
Pharmaceutics ; 15(3)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36986755

RESUMO

Mycotoxins such as aflatoxin B1 (AFB1) are secondary fungal metabolites present in food commodities and part of one's daily exposure, especially in certain regions, e.g., sub-Saharan Africa. AFB1 is mostly metabolised by cytochrome P450 (CYP) enzymes, namely, CYP1A2 and CYP3A4. As a consequence of chronic exposure, it is interesting to check for interactions with drugs taken concomitantly. A physiologically based pharmacokinetic (PBPK) model was developed based on the literature and in-house-generated in vitro data to characterise the pharmacokinetics (PK) of AFB1. The substrate file was used in different populations (Chinese, North European Caucasian and Black South African), provided by SimCYP® software (v21), to evaluate the impact of populations on AFB1 PK. The model's performance was verified against published human in vivo PK parameters, with AUC ratios and Cmax ratios being within the 0.5-2.0-fold range. Effects on AFB1 PK were observed with commonly prescribed drugs in South Africa, leading to clearance ratios of 0.54 to 4.13. The simulations revealed that CYP3A4/CYP1A2 inducer/inhibitor drugs might have an impact on AFB1 metabolism, altering exposure to carcinogenic metabolites. AFB1 did not have effects on the PK of drugs at representative exposure concentrations. Therefore, chronic AFB1 exposure is unlikely to impact the PK of drugs taken concomitantly.

8.
Zhen Ci Yan Jiu ; 48(1): 71-6, 2023 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-36734501

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint group,with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased(P<0.05), the levels of total protein, IL-1ß and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased(P<0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed(P<0.05) in the EA group rather than in the sham-acupoint group. CONCLUSION: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.


Assuntos
Eletroacupuntura , Lesão Pulmonar Induzida por Ventilação Mecânica , Camundongos , Animais , Inflamassomos/genética , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Camundongos Endogâmicos C57BL , Pulmão/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/genética , Lesão Pulmonar Induzida por Ventilação Mecânica/terapia , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Caspase 1
9.
ACS Omega ; 8(1): 311-323, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643460

RESUMO

Microparticle separation technology is an important technology in many biomedical and chemical engineering applications from sample detection to disease diagnosis. Although a variety of microparticle separation techniques have been developed thus far, surface acoustic wave (SAW)-based microfluidic separation technology shows great potential because of its high throughput, high precision, and integration with polydimethylsiloxane (PDMS) microchannels. In this work, we demonstrate an acoustofluidic separation chip that includes a piezoelectric device that generates tilted-angle standing SAWs and a permanently bonded PDMS microchannel. We established a mathematical model of particle motion in the microchannel, simulated the particle trajectory through finite element simulation and numerical simulation, and then verified the validity of the model through acoustophoresis experiments. To improve the performance of the separation chip, the influences of particle size, flow rate, and input power on the particle deflection distance were studied. These parameters are closely related to the separation purity and separation efficiency. By optimizing the control parameters, the separation of micron and submicron particles under different throughput conditions was achieved. Moreover, the separation samples were quantitatively analyzed by digital light scattering technology and flow cytometry, and the results showed that the maximum purity of the separated particles was ∼95%, while the maximum efficiency was ∼97%.

10.
Huan Jing Ke Xue ; 44(1): 293-302, 2023 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-36635817

RESUMO

The effects of vegetable planting on soil loss and nutrient loss, runoff, soil erosion, and nitrogen (ammonium nitrogen and nitrate nitrogen) losses under individual rainfalls of fruit- and leaf-vegetable fields between April to October in 2021 were observed using in-situ observation testing. The results showed that: ① the runoff, erosion, and nitrogen loss of the fruit-vegetable pattern (eggplant-chili) were 1.27-2.00 times those under the leaf-vegetable pattern (leaf lettuce-sweet potato leaves), especially under the second season vegetable period. Those losses under the second season vegetable accounted for 50.86%-68.83% of the total losses under different vegetable patterns, which were approximately 1.03-2.04 times those under the first season vegetable. The runoff, erosion, and nutrient loss of vegetable fields under different treatments were both concentrated in June and July, and the nitrogen loss was mainly in the form of nitrate nitrogen with surface runoff. ② The runoff, erosion, and nutrient losses under individual rainfalls of vegetable fields under different treatments fluctuated among the vegetable growing season, and the losses were mainly concentrated in several typical rainfall events. On the whole, the loss and concentration of nitrate and ammonium nitrogen in runoff and erosion sediment of vegetables in the first season were lower than those in the second season. The runoff, erosion, and loss of ammonium nitrogen and nitrate nitrogen of fruit-vegetable were higher than those of leaf-vegetable. ③ Both rainfall amount and maximum 30 min rainfall intensity had significantly positive effects on runoff, soil loss, and nitrogen loss. Runoff, erosion, and nutrient losses under different vegetable patterns were mainly generated by moderate rain, heavy rain, and heavy rainstorms, which accounted for 29.58%-46.68%, 24.54%-36.79%, and 24.01%-39.13% of the total losses, respectively. The results also showed that soil erosion and nutrient losses generated by different rainfall grades were obviously different for the fruit- and leaf-vegetable treatments. The results indicated that the vegetable pattern had significant impacts on soil loss and nutrient loss, and the leaf-vegetable pattern could reduce soil erosion and nutrient loss compared with the fruit-vegetable pattern. Furthermore, for different vegetable patterns and vegetable growing seasons, the effects of rainfall on soil loss and nutrient loss were quite different. The results of this study were helpful in clarifying the soil erosion and nutrient loss characteristics of vegetable fields in South China.


Assuntos
Erosão do Solo , Verduras , Nitrogênio/análise , Nitratos , Fósforo/análise , Movimentos da Água , Solo , Chuva , China
11.
Front Microbiol ; 13: 958133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36106081

RESUMO

Cyclic di-adenosine monophosphate (c-di-AMP) is a second messenger which is widely used in signal transduction in bacteria and archaea. c-di-AMP plays an important role in the regulation of bacterial physiological activities, such as the cell cycle, cell wall stability, environmental stress response, and biofilm formation. Moreover, c-di-AMP produced by pathogens can be recognized by host cells for the activation of innate immune responses. It can induce type I interferon (IFN) response in a stimulator of interferon genes (STING)-dependent manner, activate the nuclear factor kappa B (NF-κB) pathway, inflammasome, and host autophagy, and promote the production and secretion of cytokines. In addition, c-di-AMP is capable of triggering a host mucosal immune response as a mucosal adjuvant. Therefore, c-di-AMP is now considered to be a new pathogen-associated molecular pattern in host immunity and has become a promising target in bacterial/viral vaccine and drug research. In this review, we discussed the crosstalk between bacteria and host immunity mediated by c-di-AMP and addressed the role of c-di-AMP as a mucosal adjuvant in boosting evoked immune responses of subunit vaccines. The potential application of c-di-AMP in immunomodulation and immunotherapy was also discussed in this review.

12.
Diabetes Metab Syndr Obes ; 15: 2117-2125, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903412

RESUMO

Objective: This study aimed to evaluate the effect of electroacupuncture preconditioning on regional cerebral oxygen saturation (rSO2) levels in elderly patients with diabetes. Methods: Forty patients undergoing elective diabetic foot surgery were enrolled in this study. All patients were aged 65 years and above and weighed 45-75 kg. All were characterized as class II or III according to the American Society of Anesthesiologists' physical status classification system. Patients were divided randomly into an electroacupuncture group (group E) and a control group (group C); both groups comprised 20 patients. In group E, the DU20 (Baihui), DU24 (Shenting), and EX-HN1 (Sishencong) acupoints were selected for electroacupuncture 30 min prior to administering anesthesia, while in group C, patients underwent routine anesthesia without electroacupuncture. The patients in both groups were anesthetized using a sciatic nerve block. The number of cases with increased or decreased regional oxygen saturation (rSO2) compared with the baseline as well as rSO2 variability in the two groups were recorded and compared. Results: There was no significant difference in the preoperative rSO2 values between the two groups (54.4 ± 4.8 (L), 53.9 ± 5.2 (R) [group C] vs 54.1 ± 5.2 (L), 54.5 ± 4.6 (R)[group E]). Compared with group C, the rSO2 in group E increased (50.3 ± 3.9 [group C] vs 58.4 ± 3.2[group E]), and this difference was statistically significant (P < 0.001). Conclusion: Electroacupuncture stimulation can increase rSO2 levels in patients with diabetes. Clinical Registration Number: ChiCTR2100048783 (http://www.chictr.org.cn).

13.
Neurochem Res ; 47(8): 2158-2172, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35661963

RESUMO

Type 2 diabetes (T2DM) is a well known risk factor for Alzheimer's disease. Mitochondria are the center of intracellular energy metabolism and the main source of reactive oxygen species. Mitochondrial dysfunction has been identified as a key factor in diabetes-associated brain alterations contributing to neurodegenerative events. Defective insulin signaling may act in concert with neurodegenerative mechanisms leading to abnormalities in mitochondrial structure and function. Mitochondrial dysfunction triggers neuronal energy exhaustion and oxidative stress, leading to brain neuronal damage and cognitive impairment. The normality of mitochondrial function is basically maintained by mitochondrial quality control mechanisms. In T2DM, defects in the mitochondrial quality control pathway in the brain have been found to lead to mitochondrial dysfunction and cognitive impairment. Here, we discuss the association of mitochondrial dysfunction with T2DM and cognitive impairment. We also review the molecular mechanisms of mitochondrial quality control and impacts of mitochondrial quality control on the progression of cognitive impairment in T2DM.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
14.
Sci Rep ; 12(1): 7930, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562384

RESUMO

This paper demonstrates that surface acoustic wave (SAW) atomization can produce suitable aerosol concentration and size distribution for efficient inhaled lung drug delivery and is a potential atomization device for asthma treatment. Using the SAW device, we present comprehensive experimental results exploring the complexity of the acoustic atomization process and the influence of input power, device frequency, and liquid flow rate on aerosol size distribution. It is hoped that these studies will explain the mechanism of SAW atomization aerosol generation and how they can be controlled. The insights from the high-speed flow visualization studies reveal that it is possible by setting the input power above 4.17 W, thus allowing atomization to occur from a relatively thin film, forming dense, monodisperse aerosols. Moreover, we found that the aerosol droplet size can be effectively changed by adjusting the input power and liquid flow rate to change the film conditions. In this work, we proposed a method to realize drug atomization by a microfluidic channel. A SU-8 flow channel was prepared on the surface of a piezoelectric substrate by photolithography technology. Combined with the silicon dioxide coating process and PDMS process closed microfluidic channel was prepared, and continuous drug atomization was provided to improve the deposition efficiency of drug atomization by microfluidic.


Assuntos
Microfluídica , Som , Acústica , Aerossóis , Sistemas de Liberação de Medicamentos
16.
Drug Metab Dispos ; 50(4): 386-400, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35046066

RESUMO

Concerns over maternal and fetal drug exposures highlight the need for a better understanding of drug distribution into the fetus through the placental barrier. This study aimed to predict maternal and fetal drug disposition using physiologically based pharmacokinetic (PBPK) modeling. The detailed maternal-placental-fetal PBPK model within the Simcyp Simulator V20 was used to predict the maternal and fetoplacental exposure of cefazolin, cefuroxime, and amoxicillin during pregnancy and at delivery. The mechanistic dynamic model includes physiologic changes of the maternal, fetal, and placental parameters over the course of pregnancy. Placental kinetics were parametrized using permeability parameters determined from the physicochemical properties of these compounds. Then, the PBPK predictions were compared with the observed data. Fully bottom-up fetoplacental PBPK models were developed for cefuroxime, cefazolin, and amoxicillin without any parameter fitting. Predictions in nonpregnant subjects and in pregnant subjects fall within 2-fold of the observed values. Predictions matched observed pharmacokinetic data reported in nine maternal (five fetoplacental) studies for cefuroxime, 10 maternal (five fetoplacental) studies for cefazolin, and six maternal (two fetoplacental) studies for amoxicillin. Integration of the fetal and maternal system parameters within PBPK models, together with compound-related parameters used to calculate placental permeability, facilitates and extends the applications of the maternal-placental-fetal PBPK model. The developed model can also be used for designing clinical trials and prospectively used for maternal-fetal risk assessment after maternally administered drugs or unintended exposure to environmental toxicants. SIGNIFICANCE STATEMENT: This study investigates the performance of an integrated maternal-placental-fetal PBPK model to predict maternal and fetal tissue exposure of renally eliminated antibiotics that cross the placenta through a passive diffusion mechanism. The transplacental permeability clearance was predicted from the drug physicochemical properties. Results demonstrate that the PBPK approach can facilitate the prediction of maternal and fetal drug exposure simultaneously at any gestational age to support its use in the maternal-fetal exposure assessments.


Assuntos
Cefazolina , Cefuroxima , Amoxicilina , Cefazolina/farmacocinética , Cefuroxima/farmacocinética , Feminino , Humanos , Troca Materno-Fetal/fisiologia , Modelos Biológicos , Placenta , Gravidez
17.
Clin Pharmacokinet ; 61(5): 725-748, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35067869

RESUMO

BACKGROUND: Concerns over maternal and fetal drug exposure during pregnancy highlight the need for improved understanding of drug distribution to the fetus through the placental barrier. OBJECTIVE: Our objective was to predict maternal and fetal drug disposition using a physiologically based pharmacokinetic (PBPK) modeling approach. METHODS: We used the detailed maternal-placental-fetal PBPK model within the Simcyp Simulator V20 to predict the maternal and fetal drug exposure of acyclovir, emtricitabine, lamivudine, and metformin during pregnancy and at delivery. The dynamic model includes gestational changes to the maternal, fetal, and placental physiological parameters. Placental kinetics were parameterized using published ex vivo data for these four compounds. Amniotic data were included where available. PBPK predictions were compared with the observed data using twofold criteria. RESULTS: Maternal-fetal PBPK models were developed completely from the bottom up without any parameter adjustments. The PBPK model-predicted exposures matched the observed maternal and umbilical exposure for acyclovir (six maternal studies, all of which all reported umbilical exposure), emtricitabine (six maternal studies, of which four reported umbilical exposure), lamivudine, (five maternal studies, of which four reported umbilical exposure), and metformin (seven studies, of which six reported umbilical exposure). Predicted pharmacokinetic parameters were within twofold of the observed values. CONCLUSION: Integration of fetal and maternal system parameters within PBPK models, together with experimental data from ex vivo placental perfusion studies, facilitated and extended the application of the pregnancy PBPK model. Such models can also be used inform clinical trials and maternal/fetal risk assessment following maternally administered drugs or unintended exposure to environmental toxicants.


Assuntos
Troca Materno-Fetal , Metformina , Aciclovir , Emtricitabina/farmacocinética , Feminino , Feto , Humanos , Lamivudina , Troca Materno-Fetal/fisiologia , Modelos Biológicos , Preparações Farmacêuticas , Placenta , Gravidez
18.
Environ Geochem Health ; 44(3): 1081-1098, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34170458

RESUMO

A machine learning method was used to process a multiagent information database to study the spatial distribution characteristics of agglomerations of metal-related enterprises and to analyze the spatial and temporal differentiation characteristics of pollution reduction in metal-related enterprises. Based on the spatial distribution of enterprises and a simulation of their pollution reduction behaviors, the layout of 380 enterprises sample is optimized, and the direction of industrial transfer is planned to give full play to the pollution reduction effect of enterprise agglomeration. The results showed that (1) the metal-related enterprises in the Chang-Zhu-Tan urban agglomeration have obvious spatial heterogeneity and are mainly distributed in the district of Changsha, the Qingshuitang Industrial Zone, Liling city and the Qibaoshan Industrial Zone of Liuyang city, while the metal-related enterprises in Shaoshan city, Zhuzhou County and Liling city are scattered. (2) The pollution emission behaviors of enterprises differ in time and space, and the pollution concentrations are highest in industrial parks such as Qingshuitang and Zhubu Port. (3) There is an interactive relationship between the degree of enterprise agglomeration and the pollution reduction effect. The spatial positive coupling degree between the concentration of metal-related enterprises and the degree of metal-related pollution is significant, accounting for 94.96% of the study area. Low pollution-high agglomeration areas, high pollution-low agglomeration areas, high pollution-high agglomeration areas, and low pollution-low agglomeration area account for 1.01%, 4.03%, 2.87%, and 92.09% of the study area, respectively. Finally, based on the new development concept of dual circulation and the theory of a two-oriented society in the new era, the paper puts forward suggestions and policies for the sustainable development of industrial transfer.


Assuntos
Poluição Ambiental , Indústrias , China , Cidades , Metais , Desenvolvimento Sustentável
19.
Turk J Gastroenterol ; 32(10): 859-869, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34787091

RESUMO

BACKGROUND: For patients undergoing gastroscopy, it is necessary to judge whether there is Helicobacter pylori infection, atrophy/intestinal metaplasia. This study aimed to evaluate and compare the light color imaging (LCI) and white light imaging (WLI) combined score during gastroscopy. METHODS: Each included patient underwent normalized gastroscopy with WLI and LCI, and all notable findings were photographed. Four endoscopists reviewed the endoscopic images of each patient. The clinical information, results of the H. pylori tests were unavailable at review. The total LCI and WLI scores of each patient were calculated and their detection in high-risk populations of gastric cancer were evaluated. The diagnostic values of LCI and WLI for intestinal metaplasia were also calculated. RESULTS: In total, 392 patients were included in the study. The degree of inflammation and proportion of active inflammation cases were significantly higher in the H. pylori gastritis group than in the non-H. pylori gastritis group; their endoscopic manifestations were also different. The LCI combined score improved the diagnostic value of each individual observation index in the diagnosis of H. pylori infection compared with the WLI combined score. The sensitivity, specificity, and accuracy were 91.9% (91.9% vs 81.5%), 91.1% (91.1% vs 80.2%), and 95.8% (95.8% vs 93.2%), respectively. The accuracy of LCI in the diagnosis of intestinal metaplasia was higher than that of WLI (83.4% vs 69.6%). CONCLUSION: The LCI and LCI combined score improved the diagnosis of H. pylori gastritis and intestinal metaplasia, and it is considered valuable in identifying the high-risk population of gastric cancer.


Assuntos
Gastroscopia , Aumento da Imagem , Neoplasias Gástricas , Cor , Gastroscopia/métodos , Humanos , Aumento da Imagem/métodos , Luz , Medição de Risco , Neoplasias Gástricas/diagnóstico por imagem
20.
BMC Geriatr ; 21(1): 525, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600489

RESUMO

BACKGROUND: The relationship between dietary and drinking water habits and oral health are still unclear. We aimed at evaluating the association of dietary and drinking water habits with number of teeth in the elderly adults. METHODS: We conducted a longitudinal study based on the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2018. The data of dietary and drinking water habits at baseline were collected using a questionnaire. The number of teeth at baseline and follow-up was collected for each subject. We used the linear mixed-effect model to analyze the associations of dietary habits and drinking water sources with tooth number. RESULTS: Among 19,896 participants at baseline, the mean age of the participants was 83.87 years, with the average number of natural teeth of 9.37, 8.26, 8.38, 8.68, 4.05, 1.92, 1.12, 2.20 for the first to eighth waves of survey. Compared with subjects drinking tap water, 1.036 (95 % CI: -1.206, -0.865), 0.880 (95 % CI: -1.122, -0.637) and 1.331 (95 % CI: -1.715, -0.947) fewer natural teeth were reported for those drinking well, surface water and spring at baseline survey. Compared with participants with rice intake as the staple food, those with wheat intake (ß = -0.684; 95 % CI: -0.865, -0.503) tended to have fewer natural teeth. Compared with participants with fresh fruit intake almost every day, those with quite often intake of fresh fruit tended to have fewer teeth with a significant dose-response trend (Ptrend <0.001). Similar decreased trend for number of teeth was also indicated for increased frequency of vegetable intake (Ptrend <0.001). Fewer number of teeth was found for subjects with less frequency of meat and fish intakes. CONCLUSIONS: The study suggested that drinking well, surface water, and spring, intakes of wheat as staple food, as well as less frequency of fresh fruit, vegetable, meat and fish intakes were associated with significantly fewer number of teeth in the Chinese elderly population.


Assuntos
Água Potável , Idoso , Idoso de 80 Anos ou mais , Animais , China/epidemiologia , Dieta , Hábitos , Humanos , Estudos Longitudinais
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