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This study examines the economic impact of soaring international energy prices during the Russia-Ukraine conflict from February 23, 2022, to May 31, 2022. Notably, by applying a CGE model, this study offers insights into energy policies at both macroeconomic and industrial levels, emphasizing the model's utility in analyzing complex economic interactions under geopolitical stress. Findings indicate that: (1) Russia, a critical energy-producing country, faced severe economic setbacks due to sanctions, with its GDP contracting by 5.5 %, household income decreasing by 4 %, and consumer spending dropping by 3.5 %. This was accompanied by a significant reduction in domestic investment by 6 %, a decline in output by 5 %, and a decrease in societal welfare indicators. (2) Other energy-producing countries or regions, such as the Middle Eastern oil-producing countries, Australia, Canada, Mexico, and Southeast Asia, experienced economic benefits from the global energy market's "crowding-out effect." These regions saw an increase in GDP ranging from 2 % to 4.5 %, output growth by 3 %-6 %, and household income and consumption improvements by approximately 3 %-5 %. However, these benefits were tempered by a 1 %-2.5 % decline in domestic investment due to rising local energy costs. (3) Developed and developing regions, suffered adverse impacts, including the US, UK, EU, Japan, China, South Asia, Middle Eastern non-oil-producing countries, and Africa. These regions reported a decrease in GDP by 0.5 %-3 %, a decline in household income by 2 %-4 %, and lower consumption rates by 1.5 %-3.5 %. The economic strain was further exacerbated by an inflation increase of up to 2 % across these economies. This research offers valuable insights for governments and policymakers globally to address the challenges posed by the Ukraine crisis-induced energy crisis, underscoring the need for strategic energy policy adjustments and economic resilience planning.
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Importance: Diagnosing solid lesions in the pancreas via endoscopic ultrasonographic (EUS) images is challenging. Artificial intelligence (AI) has the potential to help with such diagnosis, but existing AI models focus solely on a single modality. Objective: To advance the clinical diagnosis of solid lesions in the pancreas through developing a multimodal AI model integrating both clinical information and EUS images. Design, Setting, and Participants: In this randomized crossover trial conducted from January 1 to June 30, 2023, from 4 centers across China, 12 endoscopists of varying levels of expertise were randomly assigned to diagnose solid lesions in the pancreas with or without AI assistance. Endoscopic ultrasonographic images and clinical information of 439 patients from 1 institution who had solid lesions in the pancreas between January 1, 2014, and December 31, 2022, were collected to train and validate the joint-AI model, while 189 patients from 3 external institutions were used to evaluate the robustness and generalizability of the model. Intervention: Conventional or AI-assisted diagnosis of solid lesions in the pancreas. Main Outcomes and Measures: In the retrospective dataset, the performance of the joint-AI model was evaluated internally and externally. In the prospective dataset, diagnostic performance of the endoscopists with or without the AI assistance was compared. Results: The retrospective dataset included 628 patients (400 men [63.7%]; mean [SD] age, 57.7 [27.4] years) who underwent EUS procedures. A total of 130 patients (81 men [62.3%]; mean [SD] age, 58.4 [11.7] years) were prospectively recruited for the crossover trial. The area under the curve of the joint-AI model ranged from 0.996 (95% CI, 0.993-0.998) in the internal test dataset to 0.955 (95% CI, 0.940-0.968), 0.924 (95% CI, 0.888-0.955), and 0.976 (95% CI, 0.942-0.995) in the 3 external test datasets, respectively. The diagnostic accuracy of novice endoscopists was significantly enhanced with AI assistance (0.69 [95% CI, 0.61-0.76] vs 0.90 [95% CI, 0.83-0.94]; P < .001), and the supplementary interpretability information alleviated the skepticism of the experienced endoscopists. Conclusions and Relevance: In this randomized crossover trial of diagnosing solid lesions in the pancreas with or without AI assistance, the joint-AI model demonstrated positive human-AI interaction, which suggested its potential to facilitate a clinical diagnosis. Nevertheless, future randomized clinical trials are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT05476978.
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Intelligence artificielle , Études croisées , Humains , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Endosonographie/méthodes , Tumeurs du pancréas/diagnostic , Tumeurs du pancréas/imagerie diagnostique , Adulte , Pancréas/imagerie diagnostique , Chine , Études rétrospectivesRÉSUMÉ
In recent years, there has been increasing interest in studying gut microbiome-derived hydrolases in relation to oral drug metabolism, particularly focusing on natural product drugs. Despite the significance of natural product drugs in the field of oral medications, there is a lack of research on the regulatory interplay between gut microbiome-derived hydrolases and these drugs. This review delves into the interaction between intestinal microbiome-derived hydrolases and natural product drugs metabolism from three key perspectives. Firstly, it examines the impact of glycoside hydrolases, amide hydrolases, carboxylesterase, bile salt hydrolases, and epoxide hydrolase on the structure of natural products. Secondly, it explores how natural product drugs influence microbiome-derived hydrolases. Lastly, it analyzes the impact of interactions between hydrolases and natural products on disease development and the challenges in developing microbial-derived enzymes. The overarching goal of this review is to lay a solid theoretical foundation for the advancement of research and development in new natural product drugs and personalized treatment.
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Produits biologiques , Microbiome gastro-intestinal , Hydrolases , Produits biologiques/métabolisme , Produits biologiques/pharmacologie , Humains , Hydrolases/métabolisme , Animaux , Glycosidases/métabolisme , Bactéries/métabolisme , Bactéries/enzymologieRÉSUMÉ
The development of highly efficient catalysts for formaldehyde (HCHO) oxidation is of significant interest for the improvement of indoor air quality. Up to 400 works relating to the catalytic oxidation of HCHO have been published to date; however, their analysis for collective inference through conventional literature search is still a challenging task. A machine learning (ML) framework was presented to predict catalyst performance from experimental descriptors based on an HCHO oxidation catalysts database. MnOx, CeO2, Co3O4, TiO2, FeOx, ZrO2, Al2O3, SiO2, and carbon-based catalysts with different promoters were compiled from the literature. Notably, 20 descriptors including reaction catalyst composition, reaction conditions, and catalyst physical properties were collected for data mining (2263 data points). Furthermore, the eXtreme Gradient Boosting algorithm was employed, which successfully predicted the conversion efficiency of HCHO with an R-square value of 0.81. Shapley additive analysis suggested Pt/MnO2 and Ag/Ce-Co3O4 exhibited excellent catalytic performance of HCHO oxidation based on the analysis of the entire database. Validated by experimental tests and theoretical simulations, the key descriptor identified by ML, i.e., the first promoter, was further described as metal-support interactions. This study highlights ML as a useful tool for database establishment and the catalyst rational design strategy based on the importance of analysis between experimental descriptors and the performance of complex catalytic systems.
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Pollution de l'air intérieur , Formaldéhyde , Apprentissage machine , Oxydoréduction , Formaldéhyde/composition chimique , CatalyseRÉSUMÉ
BACKGROUND: Rhubarb is widely distributed and cultivated worldwide, and its leaves presented antioxidant activity and could be used as food additive. However, the chemical ingredients, and protective effect of Rheum officinale leaf juice (JROL) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) are still unclear. PURPOSE: This paper sought to the characterization and functional properties of JROL, and explore the underlying mechanism on UC mice. METHODS: UPLC-ESI-Q-TOF/MS and other analytical instruments were employed to determine the chemical ingredients of JROL. After inducing UC model using 3% DSS, multiple biological methods were used to evaluate its protective effect and the potential mechanism. RESULTS: JROL is rich in proximate compositions and minerals and has high nutritional value, and contains reducing sugars, polysaccharides and pectin. Fifteen compounds were identified using UPLC-ESI-Q-TOF/MS. Among them, rutin has the highest content (2.22 %) in UPLC analysis. JROL presented protective effect on DSS-induced UC, and alleviated morphological alterations and ultra-structural feature of tissue, and the polysaccharides and flavonoids may contribute to its protective effect. JROL inhibited NF-κB/NLRP3 signaling pathway to alleviate inflammatory response, oxidative stress and intestinal injury by decreasing the expression of p-p65, p-IκBα, NLRP3, ASC, etc.. Moreover, it up-regulated the expression of tight junction proteins, and re-balanced the disturbance of gut microbiota to regulate the inflammatory response. Finally, a correlation among the inflammatory response, NF-κB/NLRP3 pathway and gut microbiota was established. Moreover, JROL presented the safety in the acute toxicity test. CONCLUSION: JROL could be used as a potential new source for treating UC.
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Rectocolite hémorragique , Sulfate dextran , Feuilles de plante , Rheum , Rectocolite hémorragique/induit chimiquement , Rectocolite hémorragique/traitement médicamenteux , Animaux , Rheum/composition chimique , Feuilles de plante/composition chimique , Souris , Mâle , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Modèles animaux de maladie humaine , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Souris de lignée C57BLRÉSUMÉ
Fringe projection profilometry is a non-contact and highly efficient 3D measurement technique widely used in various applications. However, the nonlinear intensity response of digital projectors affects measurement accuracy. While increasing the number of fringe projections can reduce the errors caused by nonlinear problems, it significantly prolongs the measurement time. In order to improve both accuracy and speed simultaneously, a nonlinear phase error correction method based on multi-grayscale coding is proposed. The intensity response curve of the system is fitted by the grayscale images, and then the grayscale values of the phase-shifting fringe images are corrected to reduce the nonlinear error. In order to reduce the number of fringe projections and speed up the measurement, the multi-grayscale coding method is used to divide the phase interval by the order of the gray values of the same pixel in multiple grayscale images. The experimental results validate the efficacy of the proposed multi-grayscale coding method. An accurate phase calculation is achieved, and a single reconstruction can be achieved with only seven photos. After the nonlinear correction, the phase accuracy of the three-step phase-shifting algorithm is increased by 50.77%, and the reconstruction accuracy of the standard ball is increased by 46.38%.
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The common marmoset (Callithrix jacchus) is a small and highly social New World monkey with high reproduction rates, which has been proven to be a compelling non-human primate model for biomedical and neuroscience research. Some females give birth to triplets; however, the parents cannot raise all of them. To save these infants, we have developed a hand-rearing method for raising newborn marmosets. In this protocol, we describe the formula of the food, the time for feeding, the configuration of the temperature and humidity, as well as the adaptation of the hand-reared infants to the colony environment. This hand-rearing method significantly increases the survival rate of marmoset infants (without hand-rearing: 45%; with hand-rearing: 86%) and provides the opportunity to study the development of marmoset infants with similar genetic backgrounds raised in different postnatal environments. As the method is practical and easy to use, we anticipate that it could also be applied to other labs working with common marmosets.
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Callithrix , Aliments , Animaux , FemelleRÉSUMÉ
INTRODUCTION: Chronic gastritis is a common disease worldwide. Studies have consistently shown that chronic gastritis is usually associated with gastric microbial dysbiosis, especially the infection of Helicobacter pylori. However, the interaction between H. pylori and non-H. pylori bacteria in patients with chronic gastritis has not been clearly identified yet. Consequently, we designed a protocol for a systematic review and meta-analysis, which focused on identifying the changes in gastrointestinal microbiota composition between patients with H. pylori-infective and non-infective chronic gastritis. METHOD AND ANALYSIS: We will search PubMed, EMBASE and Cochrane Library databases to retrieve observational studies on humans. The eligible studies must include data about the relative abundance of the gastrointestinal microbiome in patients with H. pylori-infective or non-infective chronic gastritis. Only the data of adults aged over 18 years will be analysed. Two researchers will extract the data independently, and Newcastle-Ottawa Scale will be used to assess the risk of bias. Random-effects model will be performed in quantitative analyses. Correlation analysis, bioinformatics analysis and function analysis will be performed. DISCUSSION: Currently, numerous studies have revealed the role of H. pylori in chronic gastritis. However, the alterations of non-H. pylori bacteria in patients with chronic gastritis remain an open question. The results of our study might provide new insights into future diagnosis and treatments. ETHICS AND DISSEMINATION: This study is based on published documents, unrelated to personal data, so ethical approval is not in need. The results of this study are expected to be published in journals or conference proceedings. PROSPERO REGISTRATION NUMBER: CRD42020205260; Pre-results.
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Gastrite atrophique , Gastrite , Microbiome gastro-intestinal , Helicobacter pylori , Adulte , Humains , Adulte d'âge moyen , Gastrite/microbiologie , Revues systématiques comme sujet , Méta-analyse comme sujetRÉSUMÉ
Background: The ciliary muscle plays a role in changing the shape of the crystalline lens to maintain the clear retinal image during near work. Studying the dynamic changes of the ciliary muscle during accommodation is necessary for understanding the mechanism of presbyopia. Optical coherence tomography (OCT) has been frequently used to image the ciliary muscle and its changes during accommodation in vivo. However, the segmentation process is cumbersome and time-consuming due to the large image data sets and the impact of low imaging quality. Objectives: This study aimed to establish a fully automatic method for segmenting and quantifying the ciliary muscle on the basis of optical coherence tomography (OCT) images. Design: A perspective cross-sectional study. Methods: In this study, 3500 signed images were used to develop a deep learning system. A novel deep learning algorithm was created from the widely used U-net and a full-resolution residual network to realize automatic segmentation and quantification of the ciliary muscle. Finally, the algorithm-predicted results and manual annotation were compared. Results: For segmentation performed by the system, the total mean pixel value difference (PVD) was 1.12, and the Dice coefficient, intersection over union (IoU), and sensitivity values were 93.8%, 88.7%, and 93.9%, respectively. The performance of the system was comparable with that of experienced specialists. The system could also successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation. Conclusion: We developed an automatic segmentation framework for the ciliary muscle that can be used to analyze the morphological parameters of the ciliary muscle and its dynamic changes during accommodation.
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Cortical feedback has long been considered crucial for the modulation of sensory perception and recognition. However, previous studies have shown varying modulatory effects of the primary auditory cortex (A1) on the auditory response of subcortical neurons, which complicate interpretations regarding the function of A1 in sound perception and recognition. This has been further complicated by studies conducted under different brain states. In the current study, we used cryo-inactivation in A1 to examine the role of corticothalamic feedback on medial geniculate body (MGB) neurons in awake marmosets. The primary effects of A1 inactivation were a frequency-specific decrease in the auditory response of most MGB neurons coupled with an increased spontaneous firing rate, which together resulted in a decrease in the signal-to-noise ratio. In addition, we report for the first time that A1 robustly modulated the long-lasting sustained response of MGB neurons, which changed the frequency tuning after A1 inactivation, e.g. some neurons are sharper with corticofugal feedback and some get broader. Taken together, our results demonstrate that corticothalamic modulation in awake marmosets serves to enhance sensory processing in a manner similar to center-surround models proposed in visual and somatosensory systems, a finding which supports common principles of corticothalamic processing across sensory systems.
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Cortex auditif , Callithrix , Animaux , Vigilance , Cortex auditif/physiologie , Stimulation acoustique , Thalamus/physiologie , Corps géniculés/physiologie , Perception auditive/physiologie , Voies auditives/physiologieRÉSUMÉ
Purpose: Photoreceptor loss plays a role in visual impairment in pathological myopia. As the nutrition and oxygen demands of photoreceptors are mainly supported by the choroidal vessels, we aimed to investigate changes in the choroidal vasculature and their correlations with visual acuity in pathological myopia. Methods: The cohort was composed of 136 eyes from 80 participants, including 42 eyes from 21 participants with emmetropia/low myopia, 48 eyes from 26 participants with simple high myopia, and 46 eyes from 33 participants with pathological myopia. Swept-source optical coherence tomography (OCT) was used to image the eyes with a 12-mm radial line scan protocol. The parameters for 6-mm diameters of macula area centered on the fovea were analyzed. A custom deep learning algorithm based on a modified residual U-Net architecture was used to segment the choroidal boundaries. Then, the distance between the two boundaries was determined and choroidal thickness (CT), luminal area (LA), and stromal area (SA) were demarcated based on Niblack's auto-local threshold algorithm after binarization of the OCT images. Finally, the ratio of LA and total choroidal area was defined as the choroidal vascularity index (CVI). The choroidal parameters in three groups were compared, and correlations of the choroidal parameters with age, gender, axial length, and best-corrected visual acuity (BCVA) were analyzed. Results: The CVI, CT, LA, and SA values were lower in pathological myopia than in emmetropia/low myopia and simple high myopia (P < 0.05). The CT, LA, and SA values were lower in simple high myopia than in emmetropia/low myopia (P < 0.05), whereas there was no difference between the CVIs in the emmetropia/low myopia and high myopia groups (P > 0.05). The CVI was nonlinear with increases in axial length (AL), and there was a critical AL flexion point, approximately 27.26 mm; however, the CT, LA, and SA were negatively correlated with AL. Further analysis showed that only younger subjects (40 years old or less) showed significant AL flexion points. Simple and multiple regression models showed that the CVI was correlated with BCVA (P < 0.05). Conclusions: Choroidal vascular alterations, especially decreased CVI, occurred in patients with pathological myopia. The CVI decreased with axial elongation beyond the flexion point and was correlated with visual impairment, indicating that the CVI might be a reliable imaging biomarker to monitor the progression of pathological myopia.
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Myopie dégénérative , Humains , Adulte , Myopie dégénérative/anatomopathologie , Études transversales , Choroïde/vascularisation , Acuité visuelle , Tomographie par cohérence optique/méthodes , Études rétrospectivesRÉSUMÉ
The use of assisted reproductive technology (ART) has risen steadily worldwide over the past 3 decades and helps many infertile families. However, ART treatments lead to an abnormal internal environment in the uterus, which may increase the risks of health problems for the offspring. Higher maternal estradiol (E2) is a notable feature in women who use ART treatments, and this has been suggested as a key factor for the risk of diseases in the offspring. In the current study, we have established a marmoset model with a high E2 level in early pregnancy to examine its potential risk to the development and behavior of the offspring. In comparison with the normal group, babies of the high E2 group exhibited lower average survival rates and birth weights. However, those who survived in the high E2 group demonstrated normal vocal production with rich call repertoires, normal speed during locomotion, and normal behaviors in the home cage. In contrast to the normal group, surviving babies of the high E2 group spent more time sleeping during development without signs of sleep disorders. In summary, our study revealed that high estrogen in early pregnancy may cause low survival rates and birth weights of the offspring, though the surviving infants did not show obvious behavioral deficiencies during development. The current study is a valuable and highly important non-human primate study for evaluating the safety of ART treatments. However, it is worth noting that some results did not reach the significant level, which may be due to the small sample size caused by animal shortage stemming from the COVID-19 epidemic.
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Temporal processing is crucial for auditory perception and cognition, especially for communication sounds. Previous studies have shown that the auditory cortex and the thalamus use temporal and rate representations to encode slowly and rapidly changing time-varying sounds. However, how the primate inferior colliculus (IC) encodes time-varying sounds at the millisecond scale remains unclear. In this study, we investigated the temporal processing by IC neurons in awake marmosets to Gaussian click trains with varying interclick intervals (2-100 ms). Strikingly, we found that 28% of IC neurons exhibited rate representation with nonsynchronized responses, which is in sharp contrast to the current view that the IC only uses a temporal representation to encode time-varying signals. Moreover, IC neurons with rate representation exhibited response properties distinct from those with temporal representation. We further demonstrated that reversible inactivation of the primary auditory cortex modulated 17% of the stimulus-synchronized responses and 21% of the nonsynchronized responses of IC neurons, revealing that cortico-colliculus projections play a role, but not a crucial one, in temporal processing in the IC. This study has significantly advanced our understanding of temporal processing in the IC of awake animals and provides new insights into temporal processing from the midbrain to the cortex.
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Cortex auditif , Colliculus inférieurs , Stimulation acoustique , Animaux , Cortex auditif/physiologie , Voies auditives/physiologie , Perception auditive/physiologie , Callithrix , Colliculus inférieurs/physiologie , Vigilance/physiologieRÉSUMÉ
TANK-binding kinase 1 (TBK1) plays a pivotal role in antiviral innate immunity. TBK1 mediates the activation of interferon regulatory factor (IRF) 3, leading to the induction of type I IFNs (IFN-α/ß) and of NF-κB signal transduction following viral infections. TBK1 must be tightly regulated to effectively control viral infections and maintain immune homeostasis. Here, we found that E3 ubiquitin ligase RNF19a mediated K48-linked ubiquitination and proteasomal degradation of TBK1. Specifically, the silence of RNF19a enhanced the production of type I interferons and suppressed RNA viral replication. Our results uncover that RNF19a acts as a negative mediator in the RIG-I signaling pathway to attenuate antiviral immune responses and suggest RNF19a as a potential therapy target in clinical infectious and inflammatory diseases.
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Antiviraux/immunologie , Immunité , Protein-Serine-Threonine Kinases/métabolisme , Protéolyse , Virus à ARN/immunologie , Ubiquitin-protein ligases/métabolisme , Animaux , Herpèsvirus humain de type 1/physiologie , Interféron de type I/métabolisme , Lysine/métabolisme , Macrophages péritonéaux/métabolisme , Macrophages péritonéaux/virologie , Mâle , Souris de lignée C57BL , Ubiquitination , Vesiculovirus/physiologieRÉSUMÉ
Professor GAO Wei-bin's clinical experience of electroacupuncture (EA) with dense wave at periotic points for neurotic tinnitus is introduced. Based on the basic theory of TCM and the perspective of neuroanatomy, EA with dense wave at new periotic points (four points at mastoid process) and Ermen (TE 21), Tinggong (SI 19) could have the effects of qi reaching affected area, and play the treatment role of "where the acupoint is, where the efficacy is".
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Électroacupuncture , Acouphène , Humains , Acouphène/thérapie , Points d'acupuncture , Médecine traditionnelle chinoiseRÉSUMÉ
Background: The gastric microbiota profile alters during gastric carcinogenesis. We aimed to identify the alterations in the alpha diversity and relative abundance of bacterial phyla and genera of gastric microbiota in the development of gastric cancer (GC). Methods: The systematic review was performed based on a published protocol with the registration number CRD42020206973. We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2021) for observational studies reporting either the relative abundance of bacterial phyla or genera, or alpha diversity indexes in both GC and non-cancer groups. Selection of studies and data extraction were performed independently by two researchers, with disagreements resolved through discussion. Risk of bias was assessed using the self-modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD). Results: Our systematic review included 751 GC patients and 792 non-cancer patients from 14 case-control studies. Gastric cancer group had fewer operational taxonomic units (OTUs) (MD = -68.52, 95%CI: -126.65 to -10.39) and a lower Simpson index (MD = -0.13, 95%CI: -0.20 to -0.07) compared with non-cancer group. At the phylum level, gastric cancer group had a higher abundance of Firmicutes (MD = 7.11, 95%CI: 1.76 to 12.46). At the genus level, Streptococcus (MD = 3.03, 95%CI: 0.07 to 6.00) and Lactobacillus (MD = 5.15, 95%CI: 1.27 to 9.04) were found to be enriched in GCgroup. The relative abundance of the rest bacterial phyla or genera analyzed in our study did not significantly differ between two groups. Subgroup analyses indicated that the source of samples was the major source of interstudy heterogeneity. Conclusion: This systematic review suggested that gastric microbiota dysbiosis occurred in gastric carcinogenesis, with alpha diversity declined and microbiota composition altered.
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BACKGROUND: Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid found as an environmental contaminant. This study aims to investigate the effects of PFHxS exposure on female reproduction and the underlying mechanism in mice. METHODS: Eight-week-old ICR mice were divided randomly into four groups administered corn oil (vehicle) and PFHxS at doses of 0.5, 5, and 50 mg/kg/day for 42 days by intragastric administration. Body weight, ovarian weight, estrous cycle, follicle counts, and serum sex hormone levels were evaluated. The expression of kisspeptin and gonadotropin releasing hormone (GnRH) in the hypothalamus was also detected. RESULTS: Compared to vehicle exposure, 5 mg/kg/day PFHxS treatment prolonged the estrous cycle, especially the duration of diestrus, after 42 days of treatment. The numbers of secondary follicles, antral follicles and corpus lutea were significantly reduced in the PFHxS-treated mice. Moreover, compared with the control mice, the PFHxS-treated mice showed decreases in the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2), and reduced GnRH mRNA levels, along with the lack of an LH surge. Furthermore, the PFHxS-treated mice had lower levels of kisspeptin immunoreactivity and kiss-1 mRNA in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) than the control mice. After intraventricular administration of kisspeptin-10, the numbers of secondary follicles, antral follicles and corpus lutea recovered, along with the levels of GnRH mRNA, FSH, and LH in the mice treated with 5 mg/kg/day PFHxS. CONCLUSION: These results indicate that chronic exposure of mice to 5 mg/kg/day PFHxS affects reproductive functions by inhibiting kisspeptin expression in the ARC and AVPV regions, leading to deficits in follicular development and ovulation.
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Fluorocarbones/effets indésirables , Kisspeptines/effets des médicaments et des substances chimiques , Reproduction/effets des médicaments et des substances chimiques , Animaux , SourisRÉSUMÉ
INTRODUCTION: The human stomach is a complex and diverse microbial ecosystem. Consecutive alternations of gastric microbiota occur in gastric carcinogenesis, while the changing pattern during this process remains controversial across studies. We aim to identify the changes in the diversity and composition of gastric mucosal microbiota in gastric tumorigenesis. METHODS AND ANALYSIS: We will search through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles for observational articles reporting either the relative abundance of bacteria at the phylum or genus level or at least one of the alpha diversity indexes respectively and clearly in both gastric cancer and non-cancer groups. Selection of studies and data extraction will be performed independently by two researchers. Disagreements will be resolved through discussion. Risk of bias will be assessed using the modified Newcastle-Ottawa Scale. Quantitative analyses will be performed using a random effects model, where the effect measurement will be expressed as the MD. ETHICS AND DISSEMINATION: Ethical approval for this systematic review is not required, as the study is based exclusively on published documents and will not include any individual data. Findings of this study are expected to be disseminated through peer-reviewed journals or conference proceedings. PROSPERO REGISTRATION NUMBER: CRD42020206973.
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Microbiote , Tumeurs de l'estomac , Carcinogenèse , Humains , Plan de recherche , Revues systématiques comme sujetRÉSUMÉ
Age-associated decline of the immune system is referred to as immunosenescence. The E3 ligase RING finger 10 (RNF10) has long been associated with the innate immune response, although a potential role in immunosenescence has not previously been reported. In the present study, we identified that RNF10 expression is lower in aged mouse macrophages than in young cells. After lipopolysaccharide stimulation, RNF10 expression remained at a basal low level in aged mouse cells, but declined sharply in young mouse cells. Knockdown of RNF10 enhanced both the nuclear factor-κB and interferon regulatory factor 3 signaling pathways and thus enhanced proinflammatory cytokines and type I interferons in macrophages, promoting clearance of Listeria monocytogenes. These findings indicate that dysregulated expression of RNF10 is associated with age-associated immune dysfunction, and RNF10 may thus be a potential target for the treatment of age-related inflammatory diseases.
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Vieillissement/immunologie , Protéines de transport/métabolisme , Infections à Listeria/immunologie , Macrophages/immunologie , Vieillissement/sang , Animaux , Protéines de transport/génétique , Modèles animaux de maladie humaine , Techniques de knock-down de gènes , Humains , Inflammation/immunologie , Interféron de type I/métabolisme , Lipopolysaccharides/immunologie , Listeria monocytogenes/immunologie , Infections à Listeria/microbiologie , Macrophages/métabolisme , Mâle , SourisRÉSUMÉ
Perfluorooctanoic acid (PFOA) is widely used in household applications. High-dose exposure to PFOA has been associated with increased risks of infertility and premature ovarian insufficiency in woman. PFOA can alter hepatic gene expression by activating peroxisome proliferator-activated receptor α (PPARα). The present study investigated whether exposure to PFOA via PPARα activation alters the synthesis of hepatic fibroblast growth factor 21 (FGF21) to disturb female neuroendocrine and reproductive function. In the present study, we show that the oral administration of PFOA (2 or 5 mg kg-1 ) in adult female mice (PFOA mice) caused prolonged dioestrous, a reduction in the number of corpora lutea and decreased levels of hypothalamic gonadotrophin-releasing hormone, serum progesterone and luteinising hormone (LH). Exposure to PFOA decreased the expression of vasopressin in the suprachiasmatic nucleus (SCN) and kisspeptin in the anteroventral periventricular nucleus (AVPV) with deficits in preovulation or oestrogen-induced LH surge. PFOA via activation of PPARα increased dose-dependently hepatic FGF21 expression, leading to elevated serum and hypothalamic FGF21 concentrations. Treatment of PFOA mice with the PPARα antagonist GW6471 or the FGF21 inhibitor PD173074 rescued SCN vasopressin and AVPV-kisspeptin expression. Either administration of GW6471 and PD173074 or treatment with vasopressin and the G protein coupled receptor 54 agonist kisspeptin-10 in PFOA-mice was able to recover the regular oestrous cycle, ovulation ability, LH surge production and reproductive hormone levels. The present study provides in vivo evidence that exposure to PFOA (≥2 mg kg-1 ) in mice causes down-regulation of the kisspeptin-reproductive endocrine system by enhancing PPARα-mediated hepatic FGF21 expression. The liver-brain reproductive endocrine disorder caused by PFOA exposure may lead to prolonged dioestrous and ovulation failure.