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1.
Heliyon ; 10(15): e35549, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170171

RESUMEN

Background: Cancer stem cells (CSCs) are pivotal in tumor resistance to chemotherapy and gastric cancer's rapid proliferation and metastasis. We aimed to explore the CSCs-related genes in gastric cancer epithelial cells. Methods: The mRNA expression profile and single-cell sequencing data of gastric cancer were downloaded from the public database. Results: We identified WDR72 as a CSCs-related gene in gastric cancer epithelial cells. WDR72 was highly expressed in gastric cancer tissues, and high expression of WDR72 was associated with inferior prognosis of patients. WDR72 expression had a significant negative correlation with the infiltration of CD8 + T cells and activated memory CD4 + T cells. PD-L1 expression was significantly reduced in gastric cancer patients with high WDR72 expression. WDR72 was correlated with IC50 of multiple small-molecule drugs. Conclusion: We identified a novel CSCs-related gene in gastric cancer epithelial cells, WDR72, which was highly expressed in patients with high stemness scores.

2.
J Mol Biol ; : 168750, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39173734

RESUMEN

The final step in the de novo synthesis of cytidine 5'-triphosphate (CTP) is catalyzed by CTP synthase (CTPS), which can form cytoophidia in all three domains of life. Recently, we have discovered that CTPS binds to ribonucleotides (NTPs) to form filaments, and have successfully solved the structures of Drosophila melanogaster CTPS bound with NTPs. Previous biochemical studies have shown that CTPS can bind to deoxyribonucleotides (dNTPs) to produce 2'-deoxycytidine-5'-triphosphate (dCTP). However, the structural basis of CTPS binding to dNTPs is still unclear. In this study, we find that Drosophila CTPS can also form filaments with dNTPs. Using cryo-electron microscopy, we are able to solve the structure of Drosophila melanogaster CTPS bound to dNTPs with a resolution of up to 2.7 Å. By combining these structural findings with biochemical analysis, we compare the binding and reaction characteristics of NTPs and dNTPs with CTPS. Our results indicate that the same enzyme can act bifunctionally as CTP/dCTP synthase in vitro, and provide a structural basis for these activities.

3.
World J Gastrointest Endosc ; 16(8): 494-499, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39155994

RESUMEN

BACKGROUND: Heterotopic mesenteric ossification (HMO) is a clinically rare condition characterized by the formation of bone tissue in the mesentery. The worldwide reporting of such cases is limited to just over 70 instances in the medical literature. The etiology of HMO remains unclear, but the disease is possibly induced by mechanical trauma, ischemia, or intra-left lower quadrant abdominal infection, leading to the differentiation of mesenchymal stem cells into osteoblasts. Here, we present a rare case of HMO that occurred in a 34-year-old male, who presented with left lower quadrant abdominal pain. CASE SUMMARY: We report the case of a 34-year-old male patient who presented with left lower abdominal pain following trauma to the left lower abdomen. He subsequently underwent surgical treatment, and the postoperative pathological diagnosis was HMO. CONCLUSION: We believe that although there is limited literature and research on HMO, when patients with a history of trauma or surgery to the left lower abdomen present with corresponding imaging findings, clinicians should be vigilant in distinguishing this condition and promptly selecting appropriate diagnostic and therapeutic interventions.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39115479

RESUMEN

BACKGROUND: The index of microcirculatory resistance is a reliable measure for evaluating coronary microvasculature, but its prognostic value in patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. OBJECTIVES: This study aimed to evaluate the prognostic impact of post-percutaneous coronary intervention (PCI) angiography-derived index of microcirculatory resistance (angio-IMR) in patients with NSTEMI. METHODS: The culprit vessel's angio-IMR was measured after PCI in 2,212 NSTEMI patients at 3 sites. The primary endpoint was 2-year major adverse cardiac events (MACEs), defined as a composite of cardiac death, readmission for heart failure, myocardial reinfarction, and target vessel revascularization. RESULTS: The mean post-PCI angio-IMR was 20.63 ± 4.17 in NSTEMI patients. Two hundred six patients were categorized as the high post-PCI angio-IMR group according to maximally selected log-rank statistics. Patients with angio-IMR >25 showed a higher rate of MACEs than those with angio-IMR ≤25 (32.52% vs 9.37%; P < 0.001). Post-PCI angio-IMR >25 was an independent predictor of MACEs (HR: 4.230; 95% CI: 3.151-5.679; P < 0.001) and showed incremental prognostic value compared with conventional risk factors (AUC: 0.774 vs 0.716; P < 0.001; net reclassification index: 0.317; P < 0.001; integrated discrimination improvement: 0.075; P < 0.001). CONCLUSIONS: In patients undergoing PCI for NSTEMI, an increased post-PCI angio-IMR is associated with a higher risk of MACEs. The addition of post-PCI angio-IMR into conventional risk factors significantly improves the ability to reclassify patients and estimate the risk of MACEs. (Angiograph-Derived Index of Microcirculatory Resistance in Patients With Acute Myocardial Infarction; NCT05696379).

5.
Mol Biol Rep ; 51(1): 891, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110355

RESUMEN

BACKGROUND: Peptide transporter 1 (PepT1) transports bacterial oligopeptide products and induces inflammation of the bowel. Nutritional peptides compete for the binding of intestinal bacterial products to PepT1. We investigated the mechanism of short-peptide-based enteral nutrition (SPEN) on the damage to the gut caused by the bacterial oligopeptide product muramyl dipeptide (MDP), which is transported by PepT1. The gut-lung axis is a shared mucosal immune system, and immune responses and disorders can affect the gut-respiratory relationship. METHODS AND RESULTS: Sprague-Dawley rats were gavaged with solutions containing MDP, MDP + SPEN, MDP + intact-protein-based enteral nutrition (IPEN), glucose as a control, or glucose with GSK669 (a NOD2 antagonist). Inflammation, mitochondrial damage, autophagy, and apoptosis were explored to determine the role of the PepT1-nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-beclin-1 signaling pathway in the small intestinal mucosa. MDP and proinflammatory factors of lung tissue were explored to determine that MDP can migrate to lung tissue and cause inflammation. Induction of proinflammatory cell accumulation and intestinal damage in MDP gavage rats was associated with increased NOD2 and Beclin-1 mRNA expression. IL-6 and TNF-α expression and apoptosis were increased, and mitochondrial damage was severe, as indicated by increased mtDNA in the MDP group compared with controls. MDP levels and expression of proinflammatory factors in lung tissue increased in the MDP group compared with the control group. SPEN, but not IPEN, eliminated these impacts. CONCLUSIONS: Gavage of MDP to rats resulted in damage to the gut-lung axis. SPEN reverses the adverse effects of MDP. The PepT1-NOD2-beclin-1 pathway plays a role in small intestinal inflammation, mitochondrial damage, autophagy, and apoptosis.


Asunto(s)
Acetilmuramil-Alanil-Isoglutamina , Beclina-1 , Nutrición Enteral , Lesión Pulmonar , Proteína Adaptadora de Señalización NOD2 , Transportador de Péptidos 1 , Ratas Sprague-Dawley , Transducción de Señal , Animales , Transportador de Péptidos 1/metabolismo , Transportador de Péptidos 1/genética , Ratas , Beclina-1/metabolismo , Beclina-1/genética , Proteína Adaptadora de Señalización NOD2/metabolismo , Proteína Adaptadora de Señalización NOD2/genética , Transducción de Señal/efectos de los fármacos , Lesión Pulmonar/metabolismo , Masculino , Acetilmuramil-Alanil-Isoglutamina/farmacología , Nutrición Enteral/métodos , Apoptosis/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Autofagia/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Pulmón/efectos de los fármacos , Inflamación/metabolismo
6.
Eur Spine J ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39095489

RESUMEN

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

7.
BMC Pregnancy Childbirth ; 24(1): 464, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970001

RESUMEN

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.


Asunto(s)
Muerte Fetal , Ultrasonografía Prenatal , Cordón Umbilical , Humanos , Femenino , Embarazo , Cordón Umbilical/anomalías , Muerte Fetal/etiología , Adulto , Placenta/irrigación sanguínea , Placenta/patología
8.
Hum Vaccin Immunother ; 20(1): 2372883, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38977424

RESUMEN

Multiple studies have documented low human papillomavirus (HPV) vaccine uptake among Chinese girls. It remains crucial to determine the parental willingness to pay (WTP) HPV vaccine for girls. We conducted a cross-sectional study recruiting 3904 parents with girls aged 9-14 in Shanghai, China, employing an online questionnaire with a convenience sampling strategy. Parental WTP, both range of payment and estimated point value, were determined for themselves (or wives) and daughters. HPV vaccine uptake was 22.44% in mothers and 3.21% in daughters. Respondents favored WTP ≤ 1000 CNY/138 USD for themselves (or wives), whereas showed increasing WTP along with valency of HPV vaccine for daughters (2-valent: 68.62% ≤1000 CNY/138 USD; 4-valent: 56.27% 1001-2000 CNY/138-277 USD; 9-valent: 65.37% ≥2001 CNY/277 USD). Overall, respondents showed higher WTP for daughters (median 2000 CNY/277 USD; IQR 1000-3600 CNY/138-498 USD) than for themselves (2000 CNY/277 USD; 1000-3500 CNY/138-483 USD) or wives (2000 CNY/277 USD; 800-3000 CNY/110-414 USD) (each p < .05). Furthermore, parental WTP was higher for international vaccine and 9-valent vaccine (each p < 0.05). Between two assumed government subsidy scenarios, parental preference for 9-valent vaccine remained consistently high for daughters (approximately 24% in each scenario), whereas preference for themselves (or wives) was sensitive to payment change between the subsidy scenarios. Using a discrete choice experiment, we found domestic vaccine was commonly preferred; however, certain sociodemographic groups preferred multivalent HPV vaccines. In conclusion, the valency of HPV vaccine may influence parental decision-making for daughters, in addition to vaccine price. Our findings would facilitate tailoring the HPV immunization program in China.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Padres , Humanos , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/economía , Vacunas contra Papillomavirus/inmunología , Femenino , China , Estudios Transversales , Niño , Adolescente , Infecciones por Papillomavirus/prevención & control , Adulto , Padres/psicología , Encuestas y Cuestionarios , Aceptación de la Atención de Salud/estadística & datos numéricos , Vacunación/economía , Vacunación/psicología , Vacunación/estadística & datos numéricos , Masculino , Persona de Mediana Edad
9.
World J Clin Cases ; 12(18): 3505-3514, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983404

RESUMEN

BACKGROUND: Hypertrophic scar (HTS) is dermal fibroproliferative disorder, which may cause physiological and psychological problems. Currently, the potential mechanism of WuFuYin (WFY) in the treatment of HTS remained to be elucidated. AIM: To explore the potential mechanism of WFY in treating HTS. METHODS: Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. HTS-related genes were obtained from the GeneCards, DisGeNET, and National Center for Biotechnology Information. The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analysis. A protein + IBM-protein interaction (PPI) network was developed using STRING database and Cytoscape. To confirm the high affinity between compounds and targets, molecular docking was performed. RESULTS: A total of 65 core genes, which were both related to compounds and HTS, were selected from multiple databases. PPI analysis showed that CKD2, ABCC1, MMP2, MMP9, glycogen synthase kinase 3 beta (GSK3B), PRARG, MMP3, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) were the hub targets and MOL004941, MOL004935, MOL004866, MOL004993, and MOL004989 were the key compounds of WFY against HTS. The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway. Moreover, by performing molecular docking, we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity. CONCLUSION: The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941, MOL004989, and MOL004993 were the main compounds of WFY in HTS treatment.

10.
Vaccines (Basel) ; 12(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39066379

RESUMEN

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.

11.
Phytomedicine ; 132: 155792, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059090

RESUMEN

BACKGROUND: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear. PURPOSE: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides. METHODS: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI+-MS, CETSA, immunoblot and SPR assay. The RAW264.7Clec4G-RFP and RAW264.7Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects. RESULTS: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects. CONCLUSION: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis.


Asunto(s)
Pectinas , Animales , Ratones , Pectinas/farmacología , Lectinas Tipo C/metabolismo , Células RAW 264.7 , Metabolismo Energético/efectos de los fármacos , Polisacáridos/farmacología
12.
Biomedicines ; 12(7)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-39061971

RESUMEN

The aim of this systematic review is to report the normal cortical development of different fetal cerebral fissures on ultrasound, describe associated anomalies in fetuses with cortical malformations, and evaluate the quality of published charts of cortical fissures. The inclusion criteria were studies reporting development, anomalies, and reference charts of fetal cortical structures on ultrasound. The outcomes observed were the timing of the appearance of different cortical fissures according to different gestational age windows, associated central nervous system (CNS) and extra-CNS anomalies detected at ultrasound in fetuses with cortical malformation, and rate of fetuses with isolated anomaly. Furthermore, we performed a critical evaluation of the published reference charts for cortical development on ultrasound. Random-effect meta-analyses of proportions were used to combine the data. Twenty-seven studies (6875 fetuses) were included. Sylvian fissure was visualized on ultrasound in 97.69% (95% CI 92.0-100) of cases at 18-19, 98.17% (95% CI 94.8-99.8) at 20-21, 98.94% (95% CI 97.0-99.9) at 22-23, and in all cases from 24 weeks of gestation. Parieto-occipital fissure was visualized in 81.56% (95% CI 48.4-99.3) of cases at 18-19, 96.59% (95% CI 83.2-99.8) at 20-21, 96.85% (95% CI 88.8-100) at 22-23, and in all cases from 24 weeks of gestation, while the corresponding figures for calcarine fissure were 37.27% (95% CI 0.5-89.6), 80.42% (95% CI 50.2-98.2), 89.18% (95% CI 74.0-98.2), and 96.02% (95% CI 96.9-100). Malformations of cortical development were diagnosed as an isolated finding at ultrasound in 6.21% (95% CI 2.9-10.9) of cases, while they were associated with additional CNS anomalies in 93.79% (95% CI 89.1-97.2) of cases. These findings highlight the need for large studies specifically looking at the timing of the appearance of the different brain sulci. Standardized algorithms for prenatal assessment of fetuses at high risk of malformations of cortical development are also warranted.

13.
Neuroreport ; 35(13): 822-831, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-38973496

RESUMEN

The aim of this study was to explore the neuroprotective effects of the P2X7 receptor antagonist A740003 on retinal ganglion cells (RGCs) in chronic intraocular hypertension (COH) experimental glaucoma mouse model. Bioinformatics was used to analyze the glaucoma-related genes. Western blot, real-time fluorescence quantitative PCR, and immunofluorescence staining techniques were employed to explore the mechanisms underlying the neuroprotective effects of A740003 on RGCs in COH retinas. Bioinformatic analysis revealed that oxidative stress, neuroinflammation, and cell apoptosis were highly related to the pathogenesis of glaucoma. In COH retinas, intraocular pressure elevation significantly increased the levels of translocator protein, a marker of microglial activation, which could be reversed by intravitreal preinjection of A740003. A740003 also suppressed the increased mRNA levels of proinflammatory cytokines interleukin (IL) 1ß and tumor necrosis factor α in COH retinas. In addition, although the mRNA levels of anti-inflammatory cytokine IL-4 and IL-10 were kept unchanged in COH retinas, administration of A740003 could increase their levels. The mRNA and protein levels of Bax and cleaved caspase-3 were increased in COH retinas, which could be partially reversed by A740003, while the levels of Bcl-2 kept unchanged in COH retinas with or without the injections of A740003. Furthermore, A740003 partially attenuated the reduction in the numbers of Brn-3a-positive RGCs in COH mice. A740003 could provide neuroprotective roles on RGCs by inhibiting the microglia activation, attenuating the retinal inflammatory response, reducing the apoptosis of RGCs, and enhancing the survival of RGCs in COH experimental glaucoma.


Asunto(s)
Glaucoma , Ratones Endogámicos C57BL , Fármacos Neuroprotectores , Antagonistas del Receptor Purinérgico P2X , Células Ganglionares de la Retina , Animales , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , Glaucoma/tratamiento farmacológico , Glaucoma/metabolismo , Fármacos Neuroprotectores/farmacología , Ratones , Antagonistas del Receptor Purinérgico P2X/farmacología , Modelos Animales de Enfermedad , Masculino , Benzopiranos/farmacología , Neuroprotección/efectos de los fármacos , Apoptosis/efectos de los fármacos , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/efectos de los fármacos , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/metabolismo , Presión Intraocular/efectos de los fármacos , Carbazoles
14.
J Vet Med Sci ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39069486

RESUMEN

Chlorogenic acid (CGA) is a polyphenol substance contained in many plants, which has good antioxidant activity. This experiment aimed to explore the protective effects of CGA on hydrogen peroxide(H2O2)-induced inflammatory response, apoptosis, and antioxidant capacity of bovine intestinal epithelial cells (BIECs-21) under oxidative stress and its mechanism. The results showed that compared with cells treated with H2O2 alone, CGA pretreatment could improve the viability of BIECs-21. Importantly, Chlorogenic acid pretreatment significantly reduced the formation of malondialdehyde (MDA), lowered reactive oxygen species (ROS) levels, and enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) (P<0.05). In addition, CGA can also improve the intestinal barrier by increasing the abundance of tight junction proteins claudin-1 and occuludin. Meanwhile, CGA can reduce the gene expression levels of pro-inflammatory factors Interleukin-6 (IL-6) and Interleukin-8 (IL-8), increase the expression of anti-inflammatory factor Interleukin-10 (IL-10), promote the expression of the nuclear factor-related factor 2 (Nrf2) signaling pathway, enhance cell antioxidant capacity, and inhibit Nuclear Factor Kappa B (NF-κB) the activation of the signaling pathway reducing the inflammatory response, thereby alleviating inflammation and oxidative stress damage.

15.
Lancet Digit Health ; 6(7): e500-e506, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38906615

RESUMEN

BACKGROUND: Cooling towers containing Legionella spp are a high-risk source of Legionnaires' disease outbreaks. Manually locating cooling towers from aerial imagery during outbreak investigations requires expertise, is labour intensive, and can be prone to errors. We aimed to train a deep learning computer vision model to automatically detect cooling towers that are aerially visible. METHODS: Between Jan 1 and 31, 2021, we extracted satellite view images of Philadelphia (PN, USA) and New York state (NY, USA) from Google Maps and annotated cooling towers to create training datasets. We augmented training data with synthetic data and model-assisted labelling of additional cities. Using 2051 images containing 7292 cooling towers, we trained a two-stage model using YOLOv5, a model that detects objects in images, and EfficientNet-b5, a model that classifies images. We assessed the primary outcomes of sensitivity and positive predictive value (PPV) of the model against manual labelling on test datasets of 548 images, including from two cities not seen in training (Boston [MA, USA] and Athens [GA, USA]). We compared the search speed of the model with that of manual searching by four epidemiologists. FINDINGS: The model identified visible cooling towers with 95·1% sensitivity (95% CI 94·0-96·1) and a PPV of 90·1% (95% CI 90·0-90·2) in New York City and Philadelphia. In Boston, sensitivity was 91·6% (89·2-93·7) and PPV was 80·8% (80·5-81·2). In Athens, sensitivity was 86·9% (75·8-94·2) and PPV was 85·5% (84·2-86·7). For an area of New York City encompassing 45 blocks (0·26 square miles), the model searched more than 600 times faster (7·6 s; 351 potential cooling towers identified) than did human investigators (mean 83·75 min [SD 29·5]; mean 310·8 cooling towers [42·2]). INTERPRETATION: The model could be used to accelerate investigation and source control during outbreaks of Legionnaires' disease through the identification of cooling towers from aerial imagery, potentially preventing additional disease spread. The model has already been used by public health teams for outbreak investigations and to initialise cooling tower registries, which are considered best practice for preventing and responding to outbreaks of Legionnaires' disease. FUNDING: None.


Asunto(s)
Aprendizaje Profundo , Brotes de Enfermedades , Enfermedad de los Legionarios , Humanos , Brotes de Enfermedades/prevención & control , Enfermedad de los Legionarios/prevención & control , Enfermedad de los Legionarios/epidemiología , Enfermedad de los Legionarios/diagnóstico , Aire Acondicionado , Philadelphia/epidemiología , New York/epidemiología , Legionella , Imágenes Satelitales
16.
Front Physiol ; 15: 1398735, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933361

RESUMEN

Introduction: Fetal heart rate monitoring during labor can aid healthcare professionals in identifying alterations in the heart rate pattern. However, discrepancies in guidelines and obstetrician expertise present challenges in interpreting fetal heart rate, including failure to acknowledge findings or misinterpretation. Artificial intelligence has the potential to support obstetricians in diagnosing abnormal fetal heart rates. Methods: Employ preprocessing techniques to mitigate the effects of missing signals and artifacts on the model, utilize data augmentation methods to address data imbalance. Introduce a multi-scale long short-term memory neural network trained with a variety of time-scale data for automatically classifying fetal heart rate. Carried out experimental on both single and multi-scale models. Results: The results indicate that multi-scale LSTM models outperform regular LSTM models in various performance metrics. Specifically, in the single models tested, the model with a sampling rate of 10 exhibited the highest classification accuracy. The model achieves an accuracy of 85.73%, a specificity of 85.32%, and a precision of 85.53% on CTU-UHB dataset. Furthermore, the area under the receiver operating curve of 0.918 suggests that our model demonstrates a high level of credibility. Discussion: Compared to previous research, our methodology exhibits superior performance across various evaluation metrics. By incorporating alternative sampling rates into the model, we observed improvements in all performance indicators, including ACC (85.73% vs. 83.28%), SP (85.32% vs. 82.47%), PR (85.53% vs. 82.84%), recall (86.13% vs. 84.09%), F1-score (85.79% vs. 83.42%), and AUC(0.9180 vs. 0.8667). The limitations of this research include the limited consideration of pregnant women's clinical characteristics and disregard the potential impact of varying gestational weeks.

17.
Hum Vaccin Immunother ; 20(1): 2368944, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38932738

RESUMEN

This study aimed to assess the attitudes and willingness of pregnant women to receive the influenza vaccine and the factors influencing their decisions. A sample survey was conducted among pregnant women receiving prenatal care at various medical institutions in Minhang District, Shanghai, from March to June 2023. The survey included inquiries about demographic information, knowledge, and perception of influenza disease and influenza vaccine. Logistic regression models and chi-square tests were used to analyze the data. 6.9% (78/1125) of participants considered receiving the influenza vaccine during pregnancy. Participants with graduate education or above (OR = 4.632, 95%CI: 1.046-20.517), non-office workers (OR = 2.784, 95%CI: 1.560-4.970), and participants whose spouses were not office workers (OR = 0.518, 95% CI: 0.294-0.913) were significantly associated with high intent to vaccinate. Participants with superior knowledge (>30 points) exhibited greater willingness (p < .001). Participants who viewed post-influenza symptoms as mild had a significantly lower willingness to vaccinate during pregnancy (2.3%), compared to those who disagreed (p = .015). Conversely, those recognizing a heightened risk of hospitalization due to respiratory diseases in pregnant women post-influenza were significantly more inclined to vaccinate during pregnancy (8.8%) (p = .007). Participants recognizing benefits uniformly expressed willingness to receive the influenza vaccine during pregnancy (p < .001), while those perceiving barriers uniformly rejected vaccination (p < .001). Higher education, non-office worker status, and having an office worker spouse correlate with greater willingness to receive the influenza vaccine during pregnancy. Enhanced knowledge and accurate perceptions of influenza and its vaccine influenced willingness. Accumulating knowledge about influenza and its vaccine fosters accurate perceptions. Notably, overall willingness to vaccinate during pregnancy remains low, likely due to safety concerns, and lack of accurate perceptions. Targeted health education, improved communication between healthcare providers and pregnant women, and campaigns highlighting vaccine benefits for mothers and children are essential.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Vacunas contra la Influenza , Gripe Humana , Aceptación de la Atención de Salud , Mujeres Embarazadas , Vacunación , Humanos , Femenino , Embarazo , China , Adulto , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Mujeres Embarazadas/psicología , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Adulto Joven , Encuestas y Cuestionarios , Vacunación/psicología , Vacunación/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/psicología , Atención Prenatal , Estudios Transversales , Adolescente
18.
Sci Total Environ ; 946: 174295, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38936732

RESUMEN

As a terrestrial ecosystem, alpine grasslands feature diverse vegetation types and play key roles in regulating water resources and carbon storage, thus shaping global climate. The dynamics of soil nutrients in this ecosystem, responding to regional climate change, directly impact primary productivity. This review comprehensively explored the effects of climate change on soil nitrogen (N), phosphorus (P), and their balance in the alpine meadows, highlighting the significant roles these nutrients played in plant growth and species diversity. We also shed light on machine learning utilization in soil nutrient evaluation. As global warming continues, alongside shifting precipitation patterns, soil characteristics of grasslands, such as moisture and pH values vary significantly, further altering the availability and composition of soil nutrients. The rising air temperature in alpine regions substantially enhances the activity of soil organisms, accelerating nutrient mineralization and the decomposition of organic materials. Combined with varied nutrient input, such as increased N deposition, plant growth and species composition are changing. With the robust capacity to use and integrate diverse data sources, including satellite imagery, sensor-collected spectral data, camera-captured videos, and common knowledge-based text and audio, machine learning offers rapid and accurate assessments of the changes in soil nutrients and associated determinants, such as soil moisture. When combined with powerful large language models like ChatGPT, these tools provide invaluable insights and strategies for effective grassland management, aiming to foster a sustainable ecosystem that balances high productivity and advanced services with reduced environmental impacts.


Asunto(s)
Cambio Climático , Monitoreo del Ambiente , Pradera , Aprendizaje Automático , Nitrógeno , Fósforo , Suelo , Suelo/química , Nitrógeno/análisis , Fósforo/análisis , Monitoreo del Ambiente/métodos , Nutrientes/análisis , Ecosistema
19.
PLoS Comput Biol ; 20(6): e1012185, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38829926

RESUMEN

Multi-factor screenings are commonly used in diverse applications in medicine and bioengineering, including optimizing combination drug treatments and microbiome engineering. Despite the advances in high-throughput technologies, large-scale experiments typically remain prohibitively expensive. Here we introduce a machine learning platform, structure-augmented regression (SAR), that exploits the intrinsic structure of each biological system to learn a high-accuracy model with minimal data requirement. Under different environmental perturbations, each biological system exhibits a unique, structured phenotypic response. This structure can be learned based on limited data and once learned, can constrain subsequent quantitative predictions. We demonstrate that SAR requires significantly fewer data comparing to other existing machine-learning methods to achieve a high prediction accuracy, first on simulated data, then on experimental data of various systems and input dimensions. We then show how a learned structure can guide effective design of new experiments. Our approach has implications for predictive control of biological systems and an integration of machine learning prediction and experimental design.


Asunto(s)
Biología Computacional , Aprendizaje Automático , Biología Computacional/métodos , Modelos Biológicos , Simulación por Computador , Algoritmos , Humanos , Análisis de Regresión
20.
Nat Genet ; 56(7): 1468-1481, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38839885

RESUMEN

Aneuploidy is frequently detected in early human embryos as a major cause of early pregnancy failure. However, how aneuploidy affects cellular function remains elusive. Here, we profiled the transcriptomes of 14,908 single cells from 203 human euploid and aneuploid blastocysts involving autosomal and sex chromosomes. Nearly all of the blastocysts contained four lineages. In aneuploid chromosomes, 19.5% ± 1.2% of the expressed genes showed a dosage effect, and 90 dosage-sensitive domains were identified. Aneuploidy leads to prevalent genome-wide transcriptome alterations. Common effects, including apoptosis, were identified, especially in monosomies, partially explaining the lower cell numbers in autosomal monosomies. We further identified lineage-specific effects causing unstable epiblast development in aneuploidies, which was accompanied by the downregulation of TGF-ß and FGF signaling, which resulted in insufficient trophectoderm maturation. Our work provides crucial insights into the molecular basis of human aneuploid blastocysts and may shed light on the cellular interaction during blastocyst development.


Asunto(s)
Aneuploidia , Blastocisto , Análisis de la Célula Individual , Transcriptoma , Humanos , Blastocisto/metabolismo , Blastocisto/citología , Análisis de la Célula Individual/métodos , Femenino , Regulación del Desarrollo de la Expresión Génica , Desarrollo Embrionario/genética , Perfilación de la Expresión Génica/métodos , Embarazo , Transducción de Señal/genética , Apoptosis/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/genética , Linaje de la Célula/genética
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