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Histones methyltransferase NSD3 targeting H3K36 is frequently disordered and mutant in various cancers, while the function of NSD3 during cancer initiation and progression remains unclear. In this study, it is proved that downregulated level of NSD3 is linked to clinical features and poor survival in lung adenocarcinoma. In vivo, NSD3 inhibited the proliferation, immigration, and invasion ability of lung adenocarcinoma. Meanwhile, NSD3 suppressed glycolysis by inhibiting HK2 translation, transcription, glucose uptake, and lactate production in lung adenocarcinoma. Mechanistically, as an intermediary, NSD3 binds to PPP1CB and p-STAT3 in protein levels, thus forming a trimer to dephosphorylate the level of p-STAT3 by PPP1CB, leading to the suppression of HK2 transcription. Interestingly, the phosphorylation function of PPP1CB is related to the concentration of carbon dioxide and pH value in the culture environment. Together, this study revealed the critical non-epigenetic role of NSD3 in the regulation of STAT3-dependent glycolysis, providing a piece of compelling evidence for targeting the NSD3/PPP1CB/p-STAT3 in lung adenocarcinoma.
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Adenocarcinoma del Pulmón , Glucólisis , N-Metiltransferasa de Histona-Lisina , Neoplasias Pulmonares , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Proliferación Celular/genética , Modelos Animales de Enfermedad , Glucólisis/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones Desnudos , Proteína Fosfatasa 1/metabolismo , Proteína Fosfatasa 1/genética , Transducción de Señal/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genéticaRESUMEN
The ability to freeze and stabilize reaction intermediates in their metastable states and obtain their structural and chemical information with high spatial resolution is critical to advance materials technologies such as catalysis and batteries. Here, we develop an electrified operando-freezing methodology to preserve these metastable states under electrochemical reaction conditions for cryogenic electron microscopy (cryo-EM) imaging and spectroscopy. Using Cu catalysts for CO2 reduction as a model system, we observe restructuring of the Cu catalyst in a CO2 atmosphere while the same catalyst remains intact in air at the nanometer scale. Furthermore, we discover the existence of a single valence Cu (1+) state and C-O bonding at the electrified liquid-solid interface of the operando-frozen samples, which are key reaction intermediates that traditional ex situ measurements fail to detect. This work highlights our novel technique to study the local structure and chemistry of electrified liquid-solid interfaces, with broad impact beyond catalysis.
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Bone morphogenetic protein 6 (BMP-6) is a constituent of the TGF-ß superfamily, known for its ability to stimulate bone and cartilage formation. The investigation of bmp6's involvement in the formation of intermuscular bones in fish has garnered significant attention in recent years. The rib cage is an important skeletal structure that plays a protective function for internal organs in fish. However, there has been limited research conducted on the effects of the bmp6 gene on rib development. Silver carp is one of four major fish in China, favoured for its affordability and tender muscle. Nevertheless, the presence of numerous intermuscular bones in silver carp significantly hinders the advancement of its palatability and suitability for processing. This study showcases the effective utilisation of CRISPR/Cas9 technology for the purpose of disrupting the bmp6 gene in silver carp, leading to the creation of chimeras in the P0 generation, marking the first instance of such an achievement. The chimeras exhibited complete viability, normal appearance, and partial intermuscular bones loss, with approximately 30% of them displaying rib bifurcation or bending. Subsequently, a transcriptome analysis on ribs of P0 chimeras and wild-type silver carp was conducted, leading to the identification of 934 genes exhibiting differential expression, of which 483 were found to be up-regulated and 451 were found to be down-regulated. The results of the KEGG analysis revealed that the "NF-kappa B signalling pathway", "Hippo signalling pathway", "osteoclast differentiation", and "haematopoietic cell lineage" exhibited enrichment and displayed a significant correlation with bone development. The up-regulated genes such as tnfα, fos, and ctgf in pathways may facilitate the proliferation and differentiation of osteoclasts, whereas the down-regulation of genes such as tgfb2 and tgfbr1 in pathways may hinder the formation and specialisation of osteoblasts, ultimately resulting in rib abnormalities. This study presents novel findings on the impact of bmp6 gene deletion on the rib development of silver carp, while simultaneously investigating the previously unexplored molecular mechanisms underlying rib defects in fish.
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BACKGROUND: Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms. METHODS: The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway. RESULTS: Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and transforming growth factor-ß1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions. CONCLUSIONS: Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.
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Proteínas Quinasas Activadas por AMP , Fibrosis Pulmonar , Dióxido de Silicio , Simvastatina , Animales , Masculino , Ratas , Acetofenonas/farmacología , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , NADPH Oxidasa 4/metabolismo , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/prevención & control , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Neumonía/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Ribonucleótidos/farmacología , Transducción de Señal/efectos de los fármacos , Silicosis/tratamiento farmacológico , Silicosis/patología , Silicosis/metabolismo , Simvastatina/farmacología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND AND STUDY AIMS: Endoscopic submucosal excavation (ESE) and endoscopic full-thickness resection (EFTR) are common endoscopic minimally invasive methods for treatment of gastric submucosal tumors (SMTs). However, it is sometimes difficult to expose the tumor optimally. This study aimed to explore the safety and effectiveness of tumor traction using orthodontic rubber band (ORB) combined with clips to assist ESE and EFTR of gastric SMTs. PATIENTS AND METHODS: The data of patients with gastric SMTs who underwent ESE or EFR at the Endoscopy Center of the 900th Hospital of PLA from January 2021 to May 2022 were retrospectively analyzed. Baseline characteristics and clinical outcomes, including operation time and postoperative adverse events, were compared between patients receiving ORB-ESE/EFTR and conventional ESE/EFTR. RESULTS: A total of 52 patients were enrolled: 16 patients who underwent ORB-ESE /EFTR and 36 patients who underwent conventional ESE/EFTR. Median procedure time was significantly shorter in the ORB-ESE/EFTR group than in the conventional ESE/EFTR group (32 [IQR, 23.8, 38.0] minutes vs. 39.0 [IQR, 34.6-67.3] minutes, P = 0.002). Baseline characteristics, en bloc resection rate, incidence of postoperative adverse events, and postoperative pathology results were comparable between the two groups (P > 0.05). CONCLUSION: Use of ORB with clips-assisted traction during ESE/EFTR of gastric SMT can shorten the surgical time. Further large prospective studies are needed to confirm the findings of this study.
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Resección Endoscópica de la Mucosa , Tempo Operativo , Neoplasias Gástricas , Tracción , Humanos , Femenino , Masculino , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Persona de Mediana Edad , Estudios Retrospectivos , Tracción/métodos , Tracción/instrumentación , Resección Endoscópica de la Mucosa/métodos , Resección Endoscópica de la Mucosa/instrumentación , Gastroscopía/métodos , Anciano , Adulto , Mucosa Gástrica/cirugía , Mucosa Gástrica/patología , Complicaciones Posoperatorias , Resultado del Tratamiento , GomaRESUMEN
Background: Clinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia. Methods: Data were collected on 271 BRCA1 and 301 BRCA2 families from Malaysia and Singapore, ascertained through population/hospital-based case-series (88%) and genetic clinics (12%). Age-specific cancer risks were estimated using a modified segregation analysis method, adjusted for ascertainment. Findings: BC and OC relative risks (RRs) varied across age groups for both BRCA1 and BRCA2. The age-specific RR estimates were similar across ethnicities and country of residence. For BRCA1 carriers of Malay, Indian and Chinese ancestry born between 1950 and 1959 in Malaysia, the cumulative risk (95% CI) of BC by age 80 was 40% (36%-44%), 49% (44%-53%) and 55% (51%-60%), respectively. The corresponding estimates for BRCA2 were 29% (26-32%), 36% (33%-40%) and 42% (38%-45%). The corresponding cumulative BC risks for Singapore residents from the same birth cohort, where the underlying population cancer incidences are higher compared to Malaysia, were higher, varying by ancestry group between 57 and 61% for BRCA1, and between 43 and 47% for BRCA2 carriers. The cumulative risk of OC by age 80 was 31% (27-36%) for BRCA1 and 12% (10%-15%) for BRCA2 carriers in Malaysia born between 1950 and 1959; and 42% (34-50%) for BRCA1 and 20% (14-27%) for BRCA2 carriers of the same birth cohort in Singapore. There was evidence of increased BC and OC risks for women from >1960 birth cohorts (p-value = 3.6 × 10-5 for BRCA1 and 0.018 for BRCA2). Interpretation: The absolute age-specific cancer risks of Asian carriers vary depending on the underlying population-specific cancer incidences, and hence should be customised to allow for more accurate cancer risk management. Funding: Wellcome Trust [grant no: v203477/Z/16/Z]; CRUK (PPRPGM-Nov20∖100002).
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We expand the concept of epitaxy to a regime of "twisted epitaxy" with the epilayer crystal orientation between two substrates influenced by their relative orientation. We annealed nanometer-thick gold (Au) nanoparticles between two substrates of exfoliated hexagonal molybdenum disulfide (MoS2) with varying orientation of their basal planes with a mutual twist angle ranging from 0° to 60°. Transmission electron microscopy studies show that Au aligns midway between the top and bottom MoS2 when the twist angle of the bilayer is small (<~7°). For larger twist angles, Au has only a small misorientation with the bottom MoS2 that varies approximately sinusoidally with twist angle of the bilayer MoS2. Four-dimensional scanning transmission electron microscopy analysis further reveals a periodic strain variation (<|±0.5%|) in the Au nanodisks associated with the twisted epitaxy, consistent with the Moiré registry of the two MoS2 twisted layers.
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Due to a lack of ancestry-matched, functional, and segregation data, Asians have a higher rate of receiving a variant of uncertain significance (VUS) result following panel testing. Managing VUS results presents challenges, as it often leads to increased anxiety and distress among cancer patients undergoing genetic testing. This exploratory study aims to investigate the experience of Asian cancer patients upon receiving a VUS result. A qualitative, semi-structured interview study was conducted, involving cancer patients who had received a VUS result through the Cancer Genetics Service of the National Cancer Centre Singapore. Twenty participants were interviewed, and their responses were transcribed and analyzed using thematic analysis to identify key themes. Thematic analysis revealed five major themes: (1) VUS results are interpreted as uncertain outcomes; (2) a VUS result provides relief and prompts positive behavioral adjustments; (3) patients employ fatalism and religion as coping mechanisms to navigate uncertainty; (4) genetic counselors, family, and the community offer reassurance and support; (5) patients value updates on variant classifications for future management. While this novel study provides unique insights into the perspectives of Asian patients who receive VUS results, it also highlights patients' effective management of VUS results and uncertainty, which has implications for improving counseling practices in Asia. Emphasis must be placed on accurate interpretation and clear communication of VUS results to dispel the possibility of misconceptions, misdiagnosis, and mismanagement in cancer care.
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The association between HIV pre-exposure prophylaxis (PrEP) and the natural history of human papillomavirus (HPV) has not been well documented. Our objective was to evaluate the impact of PrEP on the prevalence, incidence, and clearance of anal HPV among men who have sex with men (MSM). Sexually active, HIV-negative MSM aged 18 years and older in Xinjiang, China since September 1, 2016, were enrolled in an ongoing observational cohort study of HPV. At baseline and every 6 months, an anal swab was taken to test for HPV and a questionnaire on sociodemographic characteristics and sexual behaviors was collected. Those who consented to receive PrEP were enrolled in an open-label PrEP intervention study from November 1, 2019, to June 30, 2021. This study analyzed data from participants present in the HPV cohort between November 1, 2019, and June 30, 2021. We compared the prevalence, incidence, and clearance of anal HPV between men who received PrEP (PrEP users) and those who did not (non-PrEP users), and compared men before and after initiating PrEP. We calculated prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for both comparisons. Of the 870 participants present in the HPV cohort during the period between November 1, 2019, and June 30, 2021, 859 had adequate ß-globin for HPV genotype testing and were included in our study. Among them, 429 were PrEP users, while 430 were non-PrEP users. Median age was 32 years (interquartile range [IQR]: 26-38). Among PrEP users, 217 were tested for anal HPV before PrEP initiation. PrEP users had lower prevalence of HPV 45, 51, and 54 (PRs: 0.27 [95% CI: 0.09-0.80], 0.42 [0.21-0.85], and 0.41 [0.17-0.99], respectively) and lower clearance of HPV 16 (CRR: 0.31 [0.10-0.91]) compared with non-PrEP users. PrEP users exhibited lower prevalence of HPV 51 (PR: 0.31 [0.12-0.84]), lower incidence of HPV 6, 11, 16, 39 and 61 (IRRs: 0.34 [0.13-0.90], 0.26 [0.08-0.87], 0.44 [0.21-0.91], 0.21 [0.05-0.93], and 0.19 [0.04-0.82], respectively), as well as higher clearance of HPV 52 (CRR: 2.17 [1.08-4.35]) after PrEP initiation. PrEP use may lower the risk of HPV infection among MSM in Xinjiang, China. Our findings further extend the knowledge of the impact of PrEP on sexually transmitted infections.
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Infecciones por VIH , Infecciones por Papillomavirus , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Adulto , Virus del Papiloma Humano , Incidencia , Homosexualidad Masculina , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Prevalencia , Estudios de Cohortes , Papillomaviridae/genética , China/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & controlRESUMEN
ABSTRACT: Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.
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Neoplasias Pulmonares , Neoplasias , Humanos , Neoplasias/radioterapia , Neoplasias/patología , Neoplasias Pulmonares/complicaciones , Fibroblastos/patología , Biomarcadores , Macrófagos/patología , Hipoxia , Microambiente TumoralRESUMEN
OBJECTIVES: This study aimed to assess the effects of COVID-19 nonpharmaceutical interventions (NPIs) on the human papillomavirus (HPV) epidemic among men who have sex with men (MSM) in Xinjiang, China. METHODS: In our cohort study, we enrolled and followed HIV-negative MSM in Xinjiang, China, between 2016 and 2022. Anal swab samples were collected to test for HPV DNA. We used interrupted time series analysis to characterize the temporal trends in HPV prevalence, incidence, and clearance before (September 01, 2016, to July 16, 2020) and during the implementation of COVID-19 NPIs in Xinjiang (July 17, 2020, to March 31, 2022). We used binomial segmented regression models to estimate the impact of COVID-19 NPIs on HPV prevalence, incidence, and clearance. RESULTS: We recruited 1296 MSM who contributed to a total of 5374 HPV tests in our study. COVID-19 NPIs were associated with a 37.9% decrease in the prevalence (prevalence ratio, 0.621; 95% confidence interval, 0.465-0.830), 52.2% decrease in the incidence (risk ratio, 0.478; 0.377-0.606), and 40.4% increase in the clearance (risk ratio, 1.404; 1.212-1.627) of HPV of any genotype after the implementation of COVID-19 NPIs in Xinjiang. CONCLUSION: COVID-19 NPIs may lead to lower transmission and higher clearance of HPV among MSM. Future studies are needed to clarify the longer-term impact of COVID-19 on the transmission and natural history of HPV among MSM.
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COVID-19 , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/complicaciones , Virus del Papiloma Humano , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/complicaciones , Factores de Riesgo , Estudios de Cohortes , Prevalencia , Incidencia , Análisis de Series de Tiempo Interrumpido , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/complicaciones , Papillomaviridae/genéticaRESUMEN
Pancreatic cancer remains a leading cause of cancer-related mortality worldwide. Treatment outcomes remain largely dismal despite significant medical advancements. This lends urgency to the need to understand its risk factors in order to guide early detection and improve outcomes. There are both modifiable and non-modifiable risk factors, the more established of such being that of age, smoking, obesity, diabetes mellitus (DM), alcohol and certain genetic predisposition syndromes with underlying germline mutations. Some genetic predisposition syndromes such as BRCA1/2, PALB2, ATM, and CDKN2A are well-established, arising from germline mutations that result in carcinogenesis through mechanisms such as cell injury, dysregulation of cell growth, dysfunctional DNA repair, and disruption of cell mobility and adhesion. There is also a significant proportion of familial pancreatic cancer (FPC) for which the underlying predisposing genetic mechanism is not yet understood. Nuances have emerged in the ethnic and geographical differences of pancreatic cancer predisposition, and these may be attributed to differences in lifestyle, standard of living, socioeconomic factors, and genetics. This review describes in detail the factors contributing to pancreatic cancer with focus on ethnic and geographical differences and hereditary genetic syndromes. Greater insight into the interplay of these factors can guide clinicians and healthcare authorities in addressing modifiable risk factors, implementing measures for early detection in high-risk individuals, initiating early treatment of pancreatic cancer, and directing future research towards existing knowledge deficits, in order to improve survival outcomes.
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Predisposición Genética a la Enfermedad , Neoplasias Pancreáticas , Humanos , Proteína BRCA1 , Síndrome , Proteína BRCA2 , Neoplasias Pancreáticas/terapia , Neoplasias PancreáticasRESUMEN
Manganese-based aqueous batteries utilizing Mn2+ /MnO2 redox reactions are promising choices for grid-scale energy storage due to their high theoretical specific capacity, high power capability, low-cost, and intrinsic safety with water-based electrolytes. However, the application of such systems is hindered by the insulating nature of deposited MnO2 , resulting in low normalized areal loading (0.005-0.05 mAh cm-2 ) during the charge/discharge cycle. In this work, the electrochemical performance of various MnO2 polymorphs in Mn2+ /MnO2 redox reactions is investigated, and É-MnO2 with low conductivity is determined to be the primary electrochemically deposited phase in normal acidic aqueous electrolyte. It is found that increasing the temperature can change the deposited phase from É-MnO2 with low conductivity to γ-MnO2 with two order of magnitude increase in conductivity. It is demonstrated that the highly conductive γ-MnO2 can be effectively exploited for ultrahigh areal loading electrode, and a normalized areal loading of 33 mAh cm-2 is achieved. At a mild temperature of 50 °C, cells are cycled with an ultrahigh areal loading of 20 mAh cm-2 (1-2 orders of magnitude higher than previous studies) for over 200 cycles with only 13% capacity loss.
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BACKGROUND: Although Singapore is one of the highest vaccinated countries in the world, vaccine hesitancy remains in a subpopulation, including individuals with cancer predisposition syndromes. At the Cancer Genetics Service National Cancer Centre Singapore, we see patients with germline genetic alterations, most being BRCA1/2 pathogenic/likely pathogenic variant (PV/LPV) carriers. While reported safe for cancer patients, there are limited studies addressing the safety profile and outcomes of COVID-19 vaccination among individuals with germline PV/LPV in cancer predisposition genes such as BRCA1/2. This study aims to evaluate the outcomes of COVID-19 vaccination among germline PV/LPV carriers in BRCA1/2. METHODS: We conducted a phone call survey of COVID-19 vaccination uptake and toxicity in a prospective cohort of 189 participants with germline BRCA1/2 PV/LPV between 1st Sept 2021 and 30th Sept 2021. We collected demographics data including gender, race, age, history of cancer, types of cancer, and number of cancers. Statistical difference in baseline demographics between responders with history of cancer and those without were assessed using Chi-square, Fisher's exact and independent t-test analysis. Logistic regression was used to evaluate effect of demographics on the occurrence of post-vaccination side effects. RESULTS: Among 189 BRCA1/2 PV/LPV carriers responded, 97 carried PV/LPV in BRCA1 and 92 in BRCA2. Majority were vaccinated (89.5%) and had completed the two-dose vaccine schedule, with 7 (4.1%) received only one dose. The most common post-vaccination side effects was myalgia (56.5%) followed by fever (40.2%), headache (16.3%) and fatigue (11.2%). There were no major severe side events. Evaluation by logistic regression showed that the occurrence of side effects was not affected by PV/LPV gene (BRCA1 or BRCA2), gender, race, age or history of cancer. CONCLUSION: The post-vaccination side effects profile among individuals with germline PV/LPV in BRCA1/2 is consistent with the Singaporean general population, hence recommendations for COVID-19 vaccination for these individuals should not differ from non-carriers and should be encouraged by their healthcare providers.
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Objective: Aryl hydrocarbon receptor (AhR) is a transcription factor. It is reported that AhR is associated with non-small cell lung cancer (NSCLC), but the mechanisms underlying this relationship remain unclear. Therefore, we investigated the role of AhR in NSCLC to elucidate the underlying mechanisms. Methods: We collected clinical lung cancer samples and constructed AhR overexpression and knockdown cell lines to investigate the tumorigenicity of AhR in vivo and in vitro. Furthermore, we performed a ferroptosis induction experiment and chromatin immunoprecipitation experiment. Results: AhR was highly expressed in NSCLC tissue. AhR knockdown cells showed ferroptosis related phenomenon. Furthermore, Chromatin immunoprecipitation confirmed the correlation between AhR and solute carrier family 7 member 11 (SLC7A11) and ferroptosis induction experiment confirmed that AhR affects ferroptosis via SLC7A11. Specifically, AhR regulates ferroptosis-related SLC7A11, which affects ferroptosis and promotes NSCLC progression. Conclusions: AhR promoted NSCLC development and positively correlated with SLC7A11, affecting its actions. AhR bound to the promoter region of SLC7A11 promotes NSCLC by activating SLC7A11 expression, improving the oxidative sensitivity of cells, and inhibiting ferroptosis. Thus, AhR affects ferroptosis in NSCLC by regulating SLC7A11, providing foundational evidence for novel ferroptosis-related treatments.
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Ginger, an important cash crop, has been cultivated for thousands of years in China. However, comparative studies on soil bacterial communities of Chinese ginger varieties, especially after flooding, are lacking. Here, we comprehensively compared the bacterial communities of two types of ginger soils from four different locations. Surprisingly, the 100-year flood (20 July 2021, in Henan, China) did not significantly affect the soil bacterial composition compared with previous reports. In contrast, flooding may have brought in nutrients and promoted the propagation of eutrophic bacteria, and Alphaproteobacteria were the most abundant in the Zhangliang region (~25%). However, due to the most severe flooding and inundation, the Zhangliang region, also probably contaminated with polycyclic aromatic hydrocarbons and heavy metals, showed the lowest microbial diversity. Moreover, the geographical location influenced the microbial communities more than did the soil type or ginger variety. These findings help us understand the species and composition of bacteria and infection of ginger after flooding and soaking. Further, the interaction mechanisms underlying these emerging phenomena need to be further investigated. IMPORTANCE There are few comparative studies on the soil bacterial communities of Chinese ginger varieties after flooding. After a 100-year flood (20 July 2021, in Henan, China), we comprehensively compared the bacterial communities of two types of ginger soils from four different locations. Surprisingly, this flood did not significantly affect the soil bacterial composition compared with previous reports. In contrast, it was found that the flooding may have brought in nutrients and promoted the propagation of eutrophic bacteria for the Zhangliang region. However, the flooding had also brought in polycyclic aromatic hydrocarbon and heavy metal contamination. Moreover, we also verified that geographical location influenced the microbial communities more than did the soil type or ginger variety. These findings help us understand the species and composition of bacteria and infection of ginger after flooding and soaking.
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Objective: To explore the key sites in which L-arginine affects the expression of human coagulation factor VIII gene, and to create new drug targets for the treatment of hemophilia. Methods: A total of 5 human FVIII genes (A1, A2, A3, C1 and C2) with B domain deletion were transfected into human umbilical vein endothelial cells (HUVECs) as promoters. Run-on assay and ELISA analysis were performed to observe the driving effect of each domain gene on chloramphenicol acetyl transferase (CAT) gene transcription and expression, and the effect of L-arginine on each promoter. Results: In co-culture with L-arginine, transcriptional expression of the CAT gene was not detected in the PCAT3-Basic group (negative control without promoters), PA3-CAT3-Enhancer group or PC1-CAT3-Enhancer group. The transcriptional expression of CAT gene in the PCAT3-Control group (positive control with promoters) and PA1-CAT3-Enhancer group was unchanged compared with the non-L-arginine intervention, while the transcriptional expression of CAT gene in the PA2-CAT3-Enhancer group was significantly enhanced. Conclusions: A1 and A2 domain genes had promoter function and could initiate the transcription and expression of CAT gene, but A3, C1 and C2 domain genes could not. Moreover, L-arginine can significantly enhance transcription and expression of human coagulation factor VIII via A2 domain.
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Células Endoteliales , Factor VIII , Humanos , Factor VIII/genética , Factor VIII/metabolismo , Células Endoteliales/metabolismo , Arginina/farmacologíaRESUMEN
In this paper, a random forest regression (RFR) rain size characterization method based on a laser ultrasound technique is investigated to predict the grain size of titanium alloy (Ti-6Al-4V). The longitudinal wave velocity of the ultrasound signal and the attenuation coefficient at different frequencies are used as the input and the grain size is used as the output. An RFR algorithm was used to develop a grain size prediction model. Meanwhile, the grain size calculation model based on conventional scattering attenuation was established by calibrating the n value in the classical scattering theory using the attenuation coefficients at different frequencies of ultrasonic signals. The results show that the RFR algorithm is feasible for the grain size characterization of titanium alloys.
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Improving Coulombic efficiency (CE) is key to the adoption of high energy density lithium metal batteries. Liquid electrolyte engineering has emerged as a promising strategy for improving the CE of lithium metal batteries, but its complexity renders the performance prediction and design of electrolytes challenging. Here, we develop machine learning (ML) models that assist and accelerate the design of high-performance electrolytes. Using the elemental composition of electrolytes as the features of our models, we apply linear regression, random forest, and bagging models to identify the critical features for predicting CE. Our models reveal that a reduction in the solvent oxygen content is critical for superior CE. We use the ML models to design electrolyte formulations with fluorine-free solvents that achieve a high CE of 99.70%. This work highlights the promise of data-driven approaches that can accelerate the design of high-performance electrolytes for lithium metal batteries.
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Inorganic-rich solid-electrolyte interphases (SEIs) on Li metal anodes improve the electrochemical performance of Li metal batteries (LMBs). Therefore, a fundamental understanding of the roles played by essential inorganic compounds in SEIs is critical to realizing and developing high-performance LMBs. Among the prevalent SEI inorganic compounds observed for Li metal anodes, Li3N is often found in the SEIs of high-performance LMBs. Herein, we elucidate new features of Li3N by utilizing a suspension electrolyte design that contributes to the improved electrochemical performance of the Li metal anode. Through empirical and computational studies, we show that Li3N guides Li electrodeposition along its surface, creates a weakly solvating environment by decreasing Li+-solvent coordination, induces organic-poor SEI on the Li metal anode, and facilitates Li+ transport in the electrolyte. Importantly, recognizing specific roles of SEI inorganics for Li metal anodes can serve as one of the rational guidelines to design and optimize SEIs through electrolyte engineering for LMBs.