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"Gao, Jing"
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سفر رجل : رواية
يتناهى إليك الآن صوت قداس بصوت كودالي، وهي امرأة تغني بصحبة الأرغن. فالناس يحتاجون إلى الصلاة كحاجتهم إلى تناول الطعام وممارسة الجنس، ولديك أنت أيضا مشاعر دينية. ليلة أمس، كانت المرأة التي تقطن في الغرفة فوقي تصرخ طوال الوقت. كان شيئا معذبا، مما منع عن جفنيك النوم الليلة بطولها. ومنذ منتصف الليل وحتى الساعة الثالثة، لم تتوقف عن الصراخ واللهاث والتأوه، ثم أطلقت ضحكة عالية. لم تستطع أن تعرف إن كان ما يحدث نشوة أم اغتصاب. في بادئ الأمر، ظننت أن الصوت ينبعث من الغرفة المجاورة، لكنك سمعت أصواتا على الأرضية فوقك، وبدا أنهما كانا يلعبان ألعابا جنسية على أرضية الغرفة، ربما كان نوعا من الاغتصاب الذي حدثتك عنه مارغريث. لكن ماذا يعني لو كان هذا ما يحدث، كان يحدث في غرفة الفندق، ولم يسأل أحد أسئلة. بعدها، سمعت ضحكة، ضحكة شبقة صاخبة أثارت شهوتك. إلا أن قلبك يعيش في سلام الآن، وهناك الأرغن والجوقة الرائعة ذات الأصوات الصادحة.
BOOK
Shaping Polarization Of Tumor-Associated Macrophages In Cancer Immunotherapy
Different stimuli can polarize macrophages into two basic types, M1 and M2. Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) are composed of heterogeneous subpopulations, which include the M1 anti-tumor and M2 pro-tumor phenotypes. TAMs predominantly play a M2-like tumor-promoting role in the TME and regulate various malignant effects, such as angiogenesis, immune suppression, and tumor metastasis; hence, TAMs have emerged as a hot topic of research in cancer therapy. This review focuses on three main aspects of TAMs. First, we summarize macrophage polarization along with the effects on the TME. Second, recent advances and challenges in cancer treatment and the role of M2-like TAMs in immune checkpoint blockade and CAR-T cell therapy are emphasized. Finally, factors, such as signaling pathways, associated with TAM polarization and potential strategies for targeting TAM repolarization to the M1 pro-inflammatory phenotype for cancer therapy are discussed.
Journal Article
سفر رجل : رواية
يتناهى إليك الآن صوت قداس بصوت كودالي، وهي امرأة تغني بصحبة الأرغن. فالناس يحتاجون إلى الصلاة كحاجتهم إلى تناول الطعام وممارسة الجنس، ولديك أنت أيضا مشاعر دينية. ليلة أمس، كانت المرأة التي تقطن في الغرفة فوقي تصرخ طوال الوقت. كان شيئا معذبا، مما منع عن جفنيك النوم الليلة بطولها. ومنذ منتصف الليل وحتى الساعة الثالثة، لم تتوقف عن الصراخ واللهاث والتأوه، ثم أطلقت ضحكة عالية. لم تستطع أن تعرف إن كان ما يحدث نشوة أم اغتصاب. في بادئ الأمر، ظننت أن الصوت ينبعث من الغرفة المجاورة، لكنك سمعت أصواتا على الأرضية فوقك، وبدا أنهما كانا يلعبان ألعابا جنسية على أرضية الغرفة، ربما كان نوعا من الاغتصاب الذي حدثتك عنه مارغريث. لكن ماذا يعني لو كان هذا ما يحدث، كان يحدث في غرفة الفندق، ولم يسأل أحد أسئلة. بعدها، سمعت ضحكة، ضحكة شبقة صاخبة أثارت شهوتك. إلا أن قلبك يعيش في سلام الآن، وهناك الأرغن والجوقة الرائعة ذات الأصوات الصادحة.
BOOK
Mapping global urban land for the 21st century with data-driven simulations and Shared Socioeconomic Pathways
Urban land expansion is one of the most visible, irreversible, and rapid types of land cover/land use change in contemporary human history, and is a key driver for many environmental and societal changes across scales. Yet spatial projections of how much and where it may occur are often limited to short-term futures and small geographic areas. Here we produce a first empirically-grounded set of global, spatial urban land projections over the 21st century. We use a data-science approach exploiting 15 diverse datasets, including a newly available 40-year global time series of fine-spatial-resolution remote sensing observations. We find the global total amount of urban land could increase by a factor of 1.8–5.9, and the per capita amount by a factor of 1.1–4.9, across different socioeconomic scenarios over the century. Though the fastest urban land expansion occurs in Africa and Asia, the developed world experiences a similarly large amount of new development.
Here the authors develop a set of global, long-term, spatial projections of urban land expansion for understanding the planet’s potential urban futures. The global total amount of urban land increases by a factor of 1.8-5.9 over the 21st century, and the developed world experiences as much new urban development as the developing world.
Journal Article
Emerging resistance in genital mycoplasmas: 6-year trends of Ureaplasma spp. and Mycoplasma hominis infections in Eastern China
Background
To investigate the epidemiological profile and antimicrobial resistance patterns of genital mycoplasma in Eastern China and provide evidence-based guidance for clinical management.
Methods
A retrospective analysis was conducted on clinical records, mycoplasma culture results, and antimicrobial susceptibility testing data from patients with suspected urogenital tract infections between 2018 and 2023.
Results
Among 47,619 suspected infected patients, 20,830 cases tested positive for genital mycoplasma infection, with an overall infection rate of 43.74%. The infection rate of pure
Ureaplasma
spp. was 37.00%, for pure
Mycoplasma hominis
(Mh) was 0.66%, and for the co-infections with
Ureaplasma
spp. and Mh was 6.08%. The infection rate in females (44.00%) was significantly higher than that in males (20.12%), with a statistically significant difference (
P
< 0.001). The observed changes in each age group showed statistically significant differences (
P
< 0.001). Seasonally, the infection rate of mycoplasma in spring was slightly higher than that in winter. Regarding drug resistance, genital mycoplasmas generally exhibited a higher resistance rate to fluoroquinolone drugs, while the resistance rates to tetracycline, doxycycline, pristinamycin, and josamycin were relatively low. The average resistance rates to ciprofloxacin and ofloxacin in patients with pure
Ureaplasma
spp. infections were relatively high, at 83.39% and 66.34%, respectively. And the resistance rates showed an increasing trend year by year (
P
< 0.001). Patients with pure Mh infections had the highest resistance rate to ofloxacin (80.32%), followed by ciprofloxacin (69.21%), with no significant differences in resistance rates across the years. Patients co-infected with
Ureaplasma
spp. and Mh had the highest average resistance rates to both ofloxacin and ciprofloxacin, exceeding 90.00%.
Conclusion
The infection rate of genital mycoplasma in Eastern China is relatively high, predominantly
Ureaplasma
spp., with significant resistance to fluoroquinolone drugs. It is necessary for the hospital to enhance monitoring for the genital mycoplasma infections and to conduct drug resistance analysis to guide rational medication use and infection control measures.
Clinical trial number
Not applicable.
Journal Article
Urban land patterns can moderate population exposures to climate extremes over the 21st century
Climate change and global urbanization have often been anticipated to increase future population exposure (frequency and intensity) to extreme weather over the coming decades. Here we examine how changes in urban land extent, population, and climate will respectively and collectively affect spatial patterns of future population exposures to climate extremes (including hot days, cold days, heavy rainfalls, and severe thunderstorm environments) across the continental U.S. at the end of the 21st century. Different from common impressions, we find that urban land patterns can sometimes reduce rather than increase population exposures to climate extremes, even heat extremes, and that spatial patterns instead of total quantities of urban land are more influential to population exposures. Our findings lead to preliminary suggestions for embedding long-term climate resilience in urban and regional land-use system designs, and strongly motivate searches for optimal spatial urban land patterns that can robustly moderate population exposures to climate extremes throughout the 21st century.
Considering changes in urban land extent, population, and climate over the 21
st
century, the authors find spatial urban land patterns can reduce rather than increase population exposures to climate extremes, even heat extremes, at regional scales.
Journal Article
Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-κB/Snail signaling pathway
Background
Parthenolide (PTL) is a natural molecule isolated from
Tanacetum parthenium
that exhibits excellent anti-inflammatory and antitumor activities. Pulmonary fibrosis (PF), especially idiopathic pulmonary fibrosis (IPF), is a chronic lung disease that lacks a proven effective therapy. The present study evaluated the therapeutic effect of PTL on PF.
Methods
Serum-starved primary lung fibroblasts and HFL1 cells were treated with different doses of PTL, and cell viability and the migration rate were measured. Western blot analysis and a dual-luciferase assay were used to analyze the epithelial–mesenchymal transition (EMT)-related transcription factors influenced by PTL treatment in A549 cells and primary lung epithelial cells. Mice with bleomycin (BLM)-induced pulmonary fibrosis were treated with different doses of intragastric PTL, and pathological changes were evaluated using Hematoxylin-eosin (H&E) staining and immunohistochemical analysis.
Results
Our results demonstrated that PTL reduced the cell viability and migration rate of lung fibroblasts and inhibited the expression of EMT-related transcription factors in lung epithelial cells. In vivo studies demonstrated that PTL attenuated BLM-induced pulmonary fibrosis and improved the body weight and pathological changes of BLM-treated mice. We further demonstrated that PTL attenuated BLM-induced PF primarily via inhibition of the NF-κB/Snail signaling pathway.
Conclusion
These findings suggest that PTL inhibits EMT and attenuates BLM-induced PF via the NF-κB/Snail signaling pathway. PTL is a worthwhile candidate compound for pulmonary fibrosis therapy.
Journal Article
Aldosterone enhances high phosphate–induced vascular calcification through inhibition of AMPK‐mediated autophagy
It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)‐enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α‐SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3‐MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate‐activated protein kinase (AMPK) by Compound C attenuated Aldo/MR‐enhanced VC. These results suggested that Aldo facilitates high Pi‐induced VSMC osteogenic phenotypic switch and calcification through MR‐mediated signalling pathways that involve AMPK‐dependent autophagy, which provided new insights into Aldo excess‐associated VC in various settings.
Journal Article
Triglyceride-glucose index in the development of peripheral artery disease: findings from the Atherosclerosis Risk in Communities (ARIC) Study
Background
It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD).
Methods
We included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987–1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively.
Results
Over a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049–1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028–1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132–1.740) and 1.742 (1.294–2.344), respectively] after multivariate adjustments for traditional PAD risk factors.
Conclusions
Higher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches.
Trial registration
: Clinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.
Journal Article