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It is important to study the impact of land use change on terrestrial ecosystem carbon stocks in urban agglomerations for the optimization of land use structure and sustainable development in urban agglomerations. Based on the patch-generating land use simulation (PLUS) model and integrated valuation of ecosystem services and trade-offs (InVEST) model, a simulation was developed that predicted the land use change and carbon stock of the Guanzhong Plain urban agglomeration in 2040 under different scenarios and further analyzed the impact of land use change on carbon stock. The results showed that:â The land use types of the Guanzhong Plain urban agglomeration were mainly cultivated land, forest land, and grassland, which accounted for more than 90 % of the total study area. â¡ From 2000 to 2020, the carbon stock in the Guanzhong Plain showed a continuous downward trend, with cropland, woodland, and grassland being the main sources of carbon stock in the Guanzhong Plain, and the overall carbon stock declined by 15.12×106 t, with the spatial distribution presenting the distribution characteristics of "high in the north and south and low in the middle." ⢠By 2040, the carbon stock would decrease the most under the urban development scenario, with a total reduction of 27.08×106 t, and the least under the ecological development scenario, with a total reduction of 4.14×106t. The research results can provide data support for the high-quality development and rational land use planning of the Guanzhong Plain urban agglomeration.
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To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , China/epidemiología , Prevalencia , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Papillomaviridae/genética , Papillomaviridae/clasificación , Genotipo , Neoplasias Vaginales/virología , Neoplasias Vaginales/epidemiología , Condiloma Acuminado/virología , Condiloma Acuminado/epidemiologíaRESUMEN
In this paper, complex-variable sine-Gaussian cross-phase (CVSGCP) beams are proposed, and the transmission dynamics properties of the CVSGCP beams in strongly nonlocal nonlinear media are investigated. CVSGCP beams can produce a variety of mode transformation characteristics during transmission. The roles of parameters in the sine and cross-phase terms of the initial light field expression in the evolution of light intensity modes, phase, and beam width are analyzed in detail, and it is proved that the effect of cross phase is to cause the beams to rotate. The control of different modes can be achieved by selecting suitable parameters, which have certain advantages in the practical application of CVSGCP beams. CVSGCP beams can be regarded as generalized high-order breathers because light intensity modes and beam width show periodic oscillation distribution during transmission. The typical evolution characteristics of the CVSGCP beams are verified by numerical simulation. Strongly nonlocal nonlinear optical media can be mathematically equivalent to a variety of optical systems, such as gradient index potential wells and resonant potential wells, so the conclusions in this paper can also be extended to these equivalent optical systems.
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The ANLN gene encodes anillin, a protein that binds to actin. Recent research has identified ANLN's function in the initiation and advancement of different cancers. However, its impact on gallbladder cancer (GBC) remains unexplored. This study aimed to elucidate its possible molecular mechanisms in GBC. ANLN expression was assessed using quantitative real-time polymerase chain reaction (QRT-PCR), Western blotting (WB), and immunohistochemistry (IHC), revealing elevated levels in GBC tissues. ANLN knockdown resulted in the inhibition of cell proliferation and migration, leading to apoptosis and cell cycle arrest. Conversely, ANLN overexpression had the opposite effects on GBC cells. In vivo experiments confirmed that ANLN knockdown inhibited GBC cell growth. RNA-seq and bioinformatics analysis revealed ANLN's function in activating the PI3K/AKT signaling pathway. We further confirmed that ANLN could upregulate STRA6 expression, which activated PI3K/AKT signaling to enhance the growth and movement of GBC cells. These findings demonstrate ANLN's involvement in GBC initiation and progression, suggesting its potential as a novel target for GBC.
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DESIGN: Clinimetric evaluation study. INTRODUCTION: The Chinese Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire has necessitated the development of a revised version to the specific needs of individuals with upper extremity injuries with the progress of times and lifestyle changes. PURPOSE OF THE STUDY: This research aimed to evaluate the reliability and validity of Modified Chinese Disability of Arm, Shoulder and Hand (MC-DASH) questionnaire in individuals with upper extremity injuries. METHODS: One hundred and one individuals with upper extremity injuries (UEI) were recruited. The function of upper extremity was measured using the electronic version of MC-DASH, and compared against the Chinese Disability of Arm, Shoulder and Hand. The MC-DASH was reassessed within three days in all individuals. We investigated the internal consistency, test-retest reliability, content validity, criterion validity, and construct validity of MC-DASH. RESULTS: The internal consistency was deemed sufficient, as indicated by a Cronbach's alpha of 0.986 and an intraclass correlation coefficient of 0.957. Moreover, the mean total scores of MC-DASH on the first-test and retest were 37.86 and 38.19, respectively (ICC: 0.957, 95 %CI: 0.937-0.971, p < 0.001). Furthermore, the MC-DASH version exhibited satisfactory content validity evidenced by its strong correlation (R= 0.903, p < 0.001) with the Chinese DASH. Three major influencing factors were identified from 37 items. The cumulative variance contribution rate of the MC-DASH questionnaire was 75.76 %, confirming its construct validity. CONCLUSION: The Modified Chinese Disability of Arm, Shoulder and Hand questionnaire has been shown to be a valid, reliable, and practical tool for use in patients with upper extremity injuries.
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Traumatismos del Brazo , Hombro , Humanos , Brazo , Reproducibilidad de los Resultados , Evaluación de la Discapacidad , Extremidad Superior , Mano , Traumatismos del Brazo/diagnóstico , Encuestas y Cuestionarios , Ceguera , China/epidemiologíaRESUMEN
Hydrometallurgy recycling of heavy metals from electroplating sludge is of hot spot in recent decades. Such recycling was tedious in the separation of impure Fe/Al prior to heavy metals from acid leachate after sludge dissolution. Herein, a facile hydrothermal route was developed to separate Fe/Al from Cu-bearing leachate. The results showed that when the leachate was directly hydrothermally treated at 160 °C in the presence of nitrate and ethanol, Al/Cu were stable in the leachate, but nearly 100% Fe was removed as hematite nanoparticles. With the addition of chloridion, the removal efficiencies of Fe/Al/Cu did not change apparently, but the corresponding precipitate was akageneite, not hematite. By replacing chloridion with sulfate, nearly 100% Fe and 98.6% Al were separated as natrojarosite/natroalunite block, while the Cu loss was only 1.7%. However, with the supplementary of phosphate, the Fe/Al removal achieved nearly 100%, but the Cu removal also achieved by 92.6%. The thermodynamic analysis showed that Cu was precipitated rapidly via the phosphate/Cu oxyhydroxide route by adding phosphate but removed slightly via the coordination route on the Fe/Al precipitates with the addition of nitrate, chloridion, and sulfate. In summary, Fe was effectively separated as hematite, akageneite, natrojarosite, and phosphate halite, in the presence of nitrate, chloridion, sulfate, and phosphate, separately. But the removal of Al as natroalunite and AlPO4 only started by adding sulfate and phosphate, respectively. Such results enabled a short hydrometallurgy process to effectively recycle heavy metals from electroplating sludge.
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Compuestos Férricos , Metales Pesados , Aguas del Alcantarillado , Nitratos , Fosfatos , SulfatosRESUMEN
Spent lithium battery is a polymetallic waste, and valuable to be recovered as Li-bearing chemical with the barriers of impurities separation, especially Fe and Al. Here in, Li-rich cathode powder was manually disassembled from spent battery, and then recovered as lithiophosphate plate in consideration of effective separation of impure Fe/Al. The powder comprised of 23.2% Fe, 3.2% Al, 5.5% Li and 19.6% P, and then dissolved by azotic acid as Li-rich solution. When the solution was heated to 190°C for 10â h with the supplementary of saccharose, more than 99.9% Fe and 98.9% Al were removed as spherical giniite particles, in accordance with the rest of Fe/Al at the concentrations of 2.1 and 14â mg/L, whilst the loss of Li was less than 1.5%. But without saccharose, the Fe/Al removals only achieved by 99.2% and 52.1%. It is also found that the Fe/Al/Li removal achieved by 99.6%, 96% and 25.3% after adjusting the solution to pH 2.7 by NaOH. After hydrothermal treatment, the rest Li can be recycled as lithiophosphate plate by pH adjustment, in contrast to the recovery efficiency of 98.5% Li. Such method raised a facile route to effectively separate impure Fe/Al from Li-rich cathode powder, and showed promising application in the industrial recovery of spent battery.
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Small-scale water sources serving villages and towns are the main source of drinking water in rural areas. Compared to centralized water sources, rural water sources are less frequently monitored for water quality and have poor post-treatment facilities, making them vulnerable to drinking health risks. To reveal the hydrochemical characteristics, contaminant sources, and health risks in rural water sources, 189 water samples were collected from lakes and reservoirs, rivers, and groundwater in North and East China for major ions, nutrient salts, microelements, and stable isotope analysis. Statistical analysis and isotopic tracing were performed, as well as human health risk assessment. The exceeding threshold rates for fluoride (F-) and nitrate (NO3-) in surface water were 1.8 % and 9.1 %, respectively. For groundwater, the exceeding threshold rates were 20.9 % for F-, 15.7 % for total iodine (TI), and 4.5 % for NO3-. F- and TI were mainly derived from the leaching of fluoride- and iodine-containing minerals by cationic exchange, and NO3- is mainly derived from nitrogen in the soil (31.7-43.9 %), the use of ammonia fertilizers (24.3-36.1 %), and the discharge of manure and sewage (19.4-31.9 %). Nitrogen in the soil can be an important source of nitrate in the aquatic environment, and soils with higher clay content have a greater retention effect on the migration of nitrogen pollutants from the surface to the groundwater. F- in water sources contributes most to human health risks for drinking, followed by NO3- and TI, and a higher proportion of groundwater (37 %) present health risks for drinking than surface water (14 %) for children. Authorities should give high priority to optimizing the choice of water sources and technology for water treatment, and rational measures should be taken to protect water sources from the threats of anthropogenic pollution.
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Agua Potable , Agua Subterránea , Yodo , Contaminantes Químicos del Agua , Niño , Humanos , Nitratos/análisis , Fluoruros/análisis , Agua Potable/análisis , Isótopos de Nitrógeno/análisis , Yodo/análisis , Monitoreo del Ambiente , Compuestos Orgánicos/análisis , Nitrógeno/análisis , Calidad del Agua , Agua Subterránea/química , Suelo/química , China , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Ferroptosis is characterized by accumulation of lipid peroxides that leads to oxidative stress. In progressive rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) suffered from oxidative stress induced by generation of excess reactive oxygen species (ROS) and survived from elevated lipid oxidation. However the phenomenon of abnormal synovial fibroblasts proliferation under ferroptotic stress remain to be explained and the effects of this event on disease progression of RA need to be investigated. METHODS: FLS from RA patients (RA-FLS) were stimulated with LPS as an inflammatory model in vitro, and simultaneously treated with ferroptosis inducer Erastin/RSL3 or inhibitor ferrostatin-1. Besides, small extracellular vesicles (sEV) from the supernatant of RA-FLS culture under Erastin/RSL3 management were isolated. The degree of ferroptosis in cells were evaluated by Lipid-ROS detection via flowcytometry and ferroptosis marker protein expression determined by western bloting. The expression of core component of ESCRT-III CHMP4A and CHMP5 was determined by western bloting, and knockdown of CHMP4A was further performed to detect the influence of ESCRT-III complex on ferroptosis as well as LPS/Erastin induced sEV (LPS/Erastin-sEV) releasing. Moreover, miR-433-3p level in the isolated sEV was evaluated by RT-qPCR and interaction of miR-433-3p with FOXO1/VEGF axis were evaluated. MiR-433-3p was overexpressed in synovial mesenchymal stem cells (SMSCs) via miR-433-3p mimics transfection. RA-FLS was co-cultured with human dermal microvascular endothelial cells (HDMECs). LPS/Erastin-sEV or sEV derived from miR-433-3p-overexpressing SMSCs (miR-433-3p-SMSCs-sEV) were added to the co-culture system, and supernatants from co-culture without sEV were given to HDMECs. Angiogenic activity of HDMECs were identified by transwell test and endothelial tube formation analysis. Erastin-sEV and miR-433-3p-SMSCs-sEV were also administrated in collagen-induced arthritis (CIA) mouse model respectively, and progression of arthritis were evaluated. RESULTS: Ferroptosis of RA-FLS was triggered by LPS/Erastin and accompanied with increased expression of ESCRT-III core components as well as elevated release of sEV from RA-FLS. HDMECs' migration and tube formation in vitro was significantly induced/suppressed by supernatants from co-culture under management of Erastin-sEV/miR-433-3p-SMSCs-sEV due to varied VEGF expression regulated by miR-433-3p targeting FOXO1. MiR-433-3p-SMSCs-sEV could inhibit the Erastin-sEV promoted VEGF expression and mitigated arthritis severity. CONCLUSION: Erastin-sEV could aggravate synovial angiogenesis and promote arthritis progression. Administration of miR-433-3p-SMSCs-sEV may be a potential novel therapeutic method as significant antagonism to Erastin-sEV for RA treatment.
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Artritis Reumatoide , Vesículas Extracelulares , Ferroptosis , MicroARNs , Sinoviocitos , Animales , Ratones , Humanos , Células Endoteliales/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Lipopolisacáridos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular , Artritis Reumatoide/tratamiento farmacológico , MicroARNs/metabolismo , Vesículas Extracelulares/metabolismo , Fibroblastos/metabolismo , Células CultivadasRESUMEN
Steady-state visual evoked potential (SSVEP) is one of the most popular brain-computer interface (BCI) paradigms, with high information transmission rate and signal-to-noise ratio. Many calibration-free and calibration-based approaches have been proposed to improve the performance of SSVEP-based BCIs. This paper considers a quick calibration scenario, where there are plenty of data from multiple source subjects, but only a small number of calibration trials from a subset of stimulus frequencies for the new subject. We propose small data least-squares transformation (sd-LST) to solve this problem. Experiments on three publicly available SSVEP datasets demonstrated that sd-LST outperformed several classical or state-of-the-art approaches, with only about 10 calibration trials for 40-target SSVEP-based BCI spellers.
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Interfaces Cerebro-Computador , Potenciales Evocados Visuales , Humanos , Electroencefalografía , Estimulación Luminosa , AlgoritmosRESUMEN
BACKGROUND: Gait disability affects the daily lives of patients with stroke in both home and community settings. An abnormal foot-ankle position can cause instability on the supporting surface and negatively affect gait. Our research team explored the ability of a portable peroneal nerve-targeting electrical stimulator to improve gait ability by adjusting the foot-ankle position during walking in patients with chronic stroke undergoing home-based rehabilitation. METHODS: This was a double-blinded, parallel-group randomized controlled trial. Thirty-one patients with chronic stroke and ankle-foot motor impairment were randomized to receive 3 weeks of gait training, which involved using the transcutaneous peroneal nerve stimulator while walking (tPNS group; n = 16, mean age: 52.25 years), or conventional home and/or community gait training therapy (CT group; n = 15, mean age: 54.8 years). Functional assessments were performed before and after the 3-week intervention. The outcome measures included spatiotemporal gait parameters, three-dimensional kinematic and kinetic data on the ankle-foot joint, and a clinical motor and balance function assessment based on the Fugl-Meyer Assessment of Lower Extremity (FMA-LE) and Berg Balance scales (BBS). Additionally, 16 age-matched healthy adults served as a baseline control of three-dimensional gait data for both trial groups. RESULTS: The FMA-LE and BBS scores improved in both the tPNS groups (p = 0.004 and 0.001, respectively) and CT groups (p = 0.034 and 0.028, respectively) from before to after training. Participants in the tPNS group exhibited significant differences in spatiotemporal gait parameters, including double feet support, stride length, and walking speed of affected side, and the unaffected foot off within a gait cycle after training (p = 0.043, 0.017, 0.001 and 0.010, respectively). Additionally, the tPNS group exhibited significant differences in kinematic parameters, such as the ankle angle at the transverse plane (p = 0.021) and foot progression angle at the frontal plane (p = 0.009) upon initial contact, and the peak ankle joint angle at the transverse plane (p = 0.023) and foot progression angle (FPA) at the frontal and transverse planes (p = 0.032 and 0.046, respectively) during gait cycles after 3 weeks of training. CONCLUSIONS: Use of a portable tPNS device during walking tasks appeared to improve spatiotemporal gait parameters and ankle and foot angles more effectively than conventional home rehabilitation in patients with chronic stroke. Although guidelines for home-based rehabilitation training services and an increasing variety of market devices are available, no evidence for improvement of motor function and balance was superior to conventional rehabilitation. Trial registration Chictr, ChiCTR2000040137. Registered 22 November 2020, https://www.chictr.org.cn/showproj.aspx?proj=64424.
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Trastornos Neurológicos de la Marcha , Neuropatías Peroneas , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Adulto , Fenómenos Biomecánicos , Marcha , Trastornos Neurológicos de la Marcha/rehabilitación , Humanos , Persona de Mediana Edad , Neuropatías Peroneas/complicaciones , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/efectos adversos , Resultado del TratamientoRESUMEN
Photon counting detectors such as single-photon avalanche diode (SPAD) arrays can be used to improve the sensitivity of optical wireless communication (OWC) systems. However, the achievable data rate of SPAD-based OWC systems is strongly limited by the nonlinearity induced by the SPAD dead time. In this work, the performance of a SPAD-based OWC system with orthogonal frequency division multiplexing (OFDM) is investigated and compared with that of on-off keying (OOK). We employ nonlinear equalization, peak-to-average power ratio optimization by adjusting the OFDM clipping level, and adaptive bit and energy loading to achieve a record experimental data rate of 5 Gbps. The contrasting optimal regimes of operation of the two modulation schemes are also demonstrated.
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BACKGROUND: Dyslipidemia International Study II (DYSIS II)-China was conducted to determine the low-density lipoprotein cholesterol (LDL-C) goal (<1.8 mmol/L) attainment rate in patients with post-acute coronary syndrome (ACS). HYPOTHESIS: Compliance with treatment guideline recommendations improves the LDL-C goal attainment rate in post-ACS patients. METHODS: This multicenter prospective observational study conducted at 28 tertiary hospitals determined the LDL-C goal attainment rates at admission and 6-month follow-up in patients on lipid-lowering treatment (LLT) for ≥3 months and those not on LLT (LLT-naive or off LLT for ≥3 months) at admission. Predictors of goal attainment at 6 months were identified using multivariate logistic regression. RESULTS: The LDL-C goal attainment rate at admission in 1102/1103 enrolled patients was 17.1%; it was 41.2% among 752 patients with available lipid results at 6 months. The distance to goal was 0.7 mmol/L at 6 months. Statin monotherapy was the most prescribed LLT. Only 7.7% of patients were receiving statin + ezetimibe and 8.4% of patients were receiving an atorvastatin-equivalent dose of ≥40 mg/day at 6 months. Being male (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.6) and undergoing percutaneous coronary intervention during index hospitalization (OR 1.5, 95% CI 1.1 to 2.1) were the independent predictors for LDL-C goal attainment. CONCLUSIONS: This real-world DYSIS II study in China reports a low LDL-C goal attainment rate in post-ACS patients even after 6 months of LLT. Lack of intensification of statin therapy and underutilization of combinations suggest gaps between real-world treatment practices and guideline recommendations.
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Síndrome Coronario Agudo , Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , China/epidemiología , Dislipidemias/diagnóstico , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Objetivos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lípidos , Masculino , Resultado del TratamientoRESUMEN
Rac GTPase activating protein 1 (RACGAP1) has been characterized in the pathogenesis and progression of several malignancies, however, little is known regarding its role in the development of gallbladder cancer (GBC). This investigation seeks to describe the role of RACGAP1 and its associated molecular mechanisms in GBC. It was found that RACGAP1 was highly expressed in human GBC tissues, which was associated to poorer overall survival (OS). Gene knockdown of RACGAP1 hindered tumor cell proliferation and survival both in vitro and in vivo. We further identified that RACGAP1 was involved in DNA repair through its binding with DNA ligase 3 (LIG3), a crucial component of the alternative-non-homologous end joining (Alt-NHEJ) pathway. RACGAP1 regulated LIG3 expression independent of RhoA activity. RACGAP1 knockdown resulted in LIG3-dependent repair dysfunction, accumulated DNA damage and Poly(ADP-ribosyl) modification (PARylation) enhancement, leading to increased apoptosis and suppressed cell growth. We conclude that RACGAP1 exerts a tumor-promoting role via binding LIG3 to reduce apoptosis and facilitate cell growth in GBC, pointing to RACGAP1 as a potential therapeutic target for GBC.
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Apoptosis/genética , ADN Ligasa (ATP)/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Neoplasias de la Vesícula Biliar/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Animales , Proliferación Celular/genética , ADN Ligasa (ATP)/genética , Femenino , Proteínas Activadoras de GTPasa/genética , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Proteínas de Unión a Poli-ADP-Ribosa/genética , Tasa de Supervivencia , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
BACKGROUND & AIMS: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression. METHODS: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations. RESULTS: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC. CONCLUSIONS: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy. LAY SUMMARY: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations.
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Receptores ErbB/inmunología , Neoplasias de la Vesícula Biliar/inmunología , Huésped Inmunocomprometido/fisiología , Midkina/efectos adversos , Proliferación Celular/genética , China/epidemiología , Receptores ErbB/antagonistas & inhibidores , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/fisiopatología , Humanos , Midkina/genética , Análisis de Secuencia de ARN/métodos , Análisis de Secuencia de ARN/estadística & datos numéricos , Transducción de Señal/genética , Análisis de la Célula Individual/métodos , Análisis de la Célula Individual/estadística & datos numéricos , Secuenciación del Exoma/métodos , Secuenciación del Exoma/estadística & datos numéricosRESUMEN
Dysfunction of Sirtuin 3 (SIRT3), an NAD+-dependent histone deacetylase, impairs varied mitochondrial metabolic pathways in human cancer. Here, we explored suppressive activity of SIRT3 in the progression of gallbladder cancer (GBC). Expression levels of SIRT3 in patients with GBC were lower than those in the adjacent normal tissue. In addition, decreased expression of SIRT3 in these patients was correlated with poor overall survival. Knockdown of SIRT3 gene in GBC cell lines induced mitochondrial respiration and energy metabolism, but inhibited oxidative ROS. Silence of SIRT3 gene also suppressed AKT-dependent ferroptosis, an iron-dependent and lipid peroxide-mediated cell death. Blockade of AKT activity in sh-SIRT3 cells induced ACSL4 expression that drives ferroptosis, and inhibited epithelial-mesenchymal (EMT) markers and invasive activity. In contrast, overexpression of SIRT3 led to the opposite effects on mitochondrial metabolism and EMT. Finally, transplantation of sh-SIRT3 cells in nude mice resulted in rapid tumor growth and larger tumors that expressed lower E-cadherin and lipid peroxide 4-hydroxynonenal (4-HNE) than those observed in control tumors. Collectively, our studies indicate that SIRT3 functions to inhibit AKT-dependent mitochondrial metabolism and EMT, leading to ferroptosis and tumor suppression.
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Neoplasias de la Vesícula Biliar/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sirtuina 3/metabolismo , Animales , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Femenino , Ferroptosis/fisiología , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , Xenoinjertos , Humanos , Masculino , Ratones , Persona de Mediana EdadRESUMEN
Since licensure of human papillomavirus (HPV) vaccine in mainland China, little research has been conducted about healthcare providers' (HCPs) understanding and recommendation of HPV vaccine. A multi-stage convenience sample of Chinese HCPs (N = 5270) were surveyed, involving obstetrician-gynecologists, HCPs from Division of Expanded Program on Immunization (DEPI), Community Health Center (CHC) and other non-HPV closely related professions. Binary logistic regression was conducted to explore factors associated with knowledge and recommendation behaviors. Overall, HCPs showed basic HPV/HPV vaccine knowledge with median (interquartile range) score at 9.5 (7.5-11.6) out of 16 and relatively high recommendation behavior (74.8%). Identified knowledge gaps among HCPs included risk factors of HPV infection, best time to vaccinate, prophylactic functions of HPV vaccine and especially classification of low-risk and high-risk types. Profession-specific analysis in individual knowledge item showed HCPs from CHC were suboptimal on HPV while obstetrician-gynecologists were less competent on HPV vaccine knowledge. Obstetrician-gynecologists also recommended vaccination less frequently than HCPs from DEPI and CHC. Besides being key predictors of recommendation practice (2.74, 95% CI: 2.34-3.21), knowledge shared independent determinants with recommendation behavior on age and ethnicity and additionally associated with education and title by itself. Findings highlight overall and profession-specific gaps on HPV and HPV vaccine knowledge and recommendation practice. Future education and training efforts should be profession-niche-targeting and focus much on HCPs with lower title or education background and from minorities.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , China , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Mercadotecnía , Infecciones por Papillomavirus/prevención & control , Encuestas y Cuestionarios , VacunaciónRESUMEN
We show that organic photovoltaics (OPVs) are suitable for high-speed optical wireless data receivers that can also harvest power. In addition, these OPVs are of particular interest for indoor applications, as their bandgap is larger than that of silicon, leading to better matching to the spectrum of artificial light. By selecting a suitable combination of a narrow bandgap donor polymer and a nonfullerene acceptor, stable OPVs are fabricated with a power conversion efficiency of 8.8% under 1 Sun and 14% under indoor lighting conditions. In an optical wireless communication experiment, a data rate of 363 Mb/s and a simultaneous harvested power of 10.9 mW are achieved in a 4-by-4 multiple-input multiple-output (MIMO) setup that consists of four laser diodes, each transmitting 56 mW optical power and four OPV cells on a single panel as receivers at a distance of 40 cm. This result is the highest reported data rate using OPVs as data receivers and energy harvesters. This finding may be relevant to future mobile communication applications because it enables enhanced wireless data communication performance while prolonging the battery life in a mobile device.
RESUMEN
BACKGROUND: Human papillomavirus (HPV) vaccine has been increasingly discussed in mainland China since its first approval in 2016. To date, nearly all studies assessing HPV vaccine perceptions and attitudes were implemented during pre-licensure period. Therefore, the nationwide post-marketing survey was conducted to update knowledge, attitudes and practice on HPV vaccine among general population in mainland China. METHODS: Participants aged 18-45 years living in mainland China were recruited in April 2019 by multi-stage non-randomized sampling. Sociodemographic factors, HPV and HPV vaccine related awareness, knowledge, attitudes, vaccine uptake and potential obstacles were assessed in questionnaires. Bivariate analysis and multivariate regression were used to identify disparity among subgroups with different sociodemographic characteristics. RESULTS: 4,000 women (32.1 ± 7.81y) and 1,000 men (31.8 ± 7.96y) were included in final analysis. Less than one third of participants had heard of HPV (female: 31%; male: 22%) and HPV vaccine (female: 34%; male: 23%). Knowledge score was also unfavorable on HPV (female: 3 out of 13; male: 1.8 out of 13) and HPV vaccine (female: 3 out of 6; male: 2 out of 5). Only 3% females had been vaccinated three years after HPV licensure in China, although willingness to get vaccinated among those unvaccinated were high (mean willingness score ± SD: female: 3.3 ± 0.97; male: 3.0 ± 0.98). Industry of employment and household income were the major factors related to awareness and knowledge of vaccine, whereas HPV and HPV vaccine awareness were key influential factors for willingness. The main obstacles of vaccination were safety concerns, lack of knowledge, and high price of HPV vaccines. CONCLUSIONS: Findings highlight a lack of vaccine awareness, knowledge, and poor uptake in mainland China and underscore the necessity of health education campaigns. The identified priority groups, contents to be delivered and practical obstacles could furthermore provide insight into health education to reduce disparities and accelerate HPV vaccine roll-out in China.