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عبارات \غامضة\ عن الصين : مقالات في الجغرافيا البشرية
هذا الكتاب هو الجزء الأول من سلسلة كتب \"الحكمة الصينية\" ويأتي تحت عنوان (عبارات \"غامضة\" عن الصين : مقالات في الجغرافيا البشرية)، وجمع بين دفتيه ما مجموعة أربعة عشر مصطلحا متعلقا بالجغرافيا البشرية، ومن بينها \"الأقاليم التسعة\"، \"العالم\"، \"النهر الأصفر\"، \"سور الصين العظيم\"، \"المدينة\"، \"و\"العاصمة\"، وغيرها، ويتمثل الغرض الرئيسي للكتاب في تعريف الأطفال بالجغرافيا الصينية التقليدية، وتعميم معارف الجغرافيا البشرية في نفس الوقت، وهو الأمر الذي يترك الأطفال يستكشفون المعنى الثقافي وراء المصطلحات والمفردات الشائعة.
Book
Differential Game Model for a Dual-Channel Supply Chain’s Optimal Strategy under the Reference Carbon Emission Effect
Taking into account the impact of time factors on emission reductions and brand reputation, the reference carbon emission effect and dual-channel supply chain are incorporated into a unified analysis framework. We applied differential game theory to build models under centralized decision-making and decentralized decision-making. The aim of the research is to explore the strategies of a single manufacturer and a single retailer on product pricing, low-carbon production, and advertising. The research analyses the impact of reference carbon emission effects, cost coefficients, and interchannel substitutable coefficients on profits. In order to alleviate the double marginal effect brought about by decentralized decision-making, a cost-compensation coordination mechanism is proposed. The conclusions are as follows. First, centralized decision-making is the optimal decision-making mode, but further consultation is required to implement it voluntarily by both parties. Second, a cost-recovery contract occurs when the fixed fee that the retailer gives the manufacturer meets certain conditions. The contract can make the retailer’s advertising investment reach the level of centralized decision-making and improve the member’s profit under the decentralized decision-making. The coordination mechanism is effective. Third, the reference carbon emission effect can bring about an increase in the manufacturer’s low-carbon production input and profits. The retailer’s advertising investment is not affected by the reference carbon emission effect. Fourth, wholesale prices and online or offline retail prices are all positively correlated with the market share of the channel. The price-substitution coefficient between channels is positively correlated with both low-carbon inputs and profits.
Journal Article
Machine learning based early warning system enables accurate mortality risk prediction for COVID-19
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients’ clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464–0.9778), 0.9760 (0.9613–0.9906), and 0.9246 (0.8763–0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
Methods to stratify patients according to mortality risk are essential to allocate limited heath resources during the COVID-19 crisis. Here, using machine learning methods, the authors present a mortality risk prediction model for COVID-19 that uses patients’ clinical data on admission to stratify patients by mortality risk.
Journal Article
Targeting acetyl-CoA carboxylase 1 for cancer therapy
Metabolic adaptation is an emerging hallmark of tumors. De novo fatty acid synthesis is an important metabolic process to produce metabolic intermediates for energy storage, biosynthesis of membrane lipids and generation of signaling molecules. Acetyl-CoA carboxylase 1 (ACC1) is a critical enzyme in the fatty acid synthesis, which carboxylates acetyl-CoA carboxylic acid to form malonyl-CoA. The role of acetyl-CoA carboxylase 1 in fatty acid synthesis makes it a promising therapeutic target for various metabolic diseases such as non-alcoholic fatty liver disease, obesity and diabetes. Tumors have a high energy flow and a strong dependence on fatty acid synthesis. Thus, acetyl-CoA carboxylase inhibition has become a potential choice for anti-tumor therapy. In this review, we first introduced the structure and expression pattern of Acetyl-CoA carboxylase 1. We also discussed the molecular mechanisms of acetyl-CoA carboxylase 1 in the initiation and progression of various cancer types. Furthermore, acetyl-CoA carboxylase1 inhibitors has also been discussed. Collectively, we summarized the interplay between acetyl-CoA carboxylase 1 and tumorigenesis, indicating acetyl-CoA carboxylase 1 as a promising therapeutic target for tumor management.
Journal Article
Bladder cancer stage-associated hub genes revealed by WGCNA co-expression network analysis
Background
Bladder cancer was a malignant disease in patients, our research aimed at discovering the possible biomarkers for the diseases.
Results
The gene chip GSE31684, including 93samples, was downloaded from the GEO datasets and co-expression network was constructed by the data. Molecular complex detection(MCODE) was used to identify hub genes. The most significant cluster including 16 genes:
CDH11
,
COL3A1
,
COL6A3
,
COL5A1
,
AEBP1
,
COL1A2
,
NTM
,
COL11A1
,
THBS2
,
COL8A1
,
COL1A1
,
BGN
,
MMP2
,
PXDN
,
THY1
, and
TGFB1I1
was identified. After annotated by BiNGO, they were suggested associated with collagen fibril organization and blood vessel development. In addition, the Kaplan Meier curves were obtained by UALCAN. The high expression of
THY1
,
AEBP1
,
CDH11
,
COL1A1
,
COL1A2
,
COL11A1
,
MMP2
,
PXDN
,
BGN
,
COL5A1, COL8A1
, and
TGFB1I1
indicated poor prognosis of the patients(
P
< 0.05). Finally, we examined genes’ expression between low and high tumor stage by the Wilcoxon test(P < 0.05),
TGFB1I1
was excluded.
Conclusion
THY1, AEBP1, CDH11, COL1A1, COL1A2, COL11A1, MMP2, PXDN, BGN, COL5A1, COL8A1
associated with the tumor stage as well as tumor patients’ prognosis
. COL5A1, COL8A1
(
P
< 0.01) may serve as therapeutic targets for the disease.
Journal Article
Yiqi Jiedu Huayu Decoction Alleviates Renal Injury in Rats With Diabetic Nephropathy by Promoting Autophagy
Diabetic nephropathy (DN), a common microvascular complication of diabetes, is one of the main causes of end-stage renal failure (ESRD) and imposes a heavy medical burden on the world. Yiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine formula, which has been widely used in the treatment of DN and has achieved stable and reliable therapeutic effects. However, the mechanism of YJHD in the treatment of DN remains unclear. This study aimed to investigate the mechanism of YJHD in the treatment of DN. Sprague-Dawley rats were randomly divided into a normal control group, a diabetic group, an irbesartan group, and three groups receiving different doses of YJHD. Animal models were constructed using streptozotocin and then treated with YJHD for 12 consecutive weeks. Blood and urine samples were collected during this period, and metabolic and renal function was assessed. Pathological kidney injury was evaluated according to the kidney appearance, hematoxylin-eosin staining, Masson staining, periodic-acid Schiff staining, periodic-acid Schiff methenamine staining, and transmission electron microscopy. The expression levels of proteins and genes were detected by immunohistochemistry, western blotting, and real-time qPCR. Our results indicate that YJHD can effectively improve renal function and alleviate renal pathological injury, including mesangial matrix hyperplasia, basement membrane thickening, and fibrosis. In addition, YJHD exhibited podocyte protection by alleviating podocyte depletion and morphological damage, which may be key in improving renal function and reducing renal fibrosis. Further study revealed that YJHD upregulated the expression of the autophagy-related proteins LC3II and Beclin-1 while downregulating p62 expression, suggesting that YJHD can promote autophagy. In addition, we evaluated the activity of the mTOR pathway, the major signaling pathway regulating the level of autophagy, and the upstream PI3K/Akt and AMPK pathways. YJHD activated the AMPK pathway while inhibiting the PI3K/Akt and mTOR pathways, which may be crucial to its promotion of autophagy. In conclusion, our study shows that YJHD further inhibits the mTOR pathway and promotes autophagy by regulating the activity of the PI3K/Akt and AMPK pathways, thereby improving podocyte injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research into YJHD.
Journal Article
Proteomic analysis of watery saliva secreted by white-backed planthopper, Sogatella furcifera
The white-backed planthopper, Sogatella furcifera, is a phloem sap feeder that secretes watery and gelling saliva during feeding. In this study, we identified the major proteins in watery saliva of S. furcifera by shotgun LC-MS/MS analysis combined with transcriptomic analysis. A total of 161 proteins were identified, which were divided into 8 function categories, including enzymes, transporter, calcium ion binding protein, salivary sheath protein, cytoskeleton protein, DNA-, RNA-, and protein-binding or regulating proteins, other non-enzyme proteins and unknown proteins. Gene expression pattern of 11 secretory proteins were analyzed by real time quantitative-PCR. We detected the mucin-like protein, which had a unique expression level in salivary gland, most likely to be a candidate effector involved in regulation of plant defense. This study identified the watery saliva component of S. furcifera and it provided a list of proteins which may play a role in interaction between S. furcifera and rice.
Journal Article
Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization
The COVID-19 pandemic has fostered major advances in vaccination technologies
1
–
4
; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration
4
–
6
. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano–micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.
An inhalable, single-dose dry powder aerosol SARS-CoV-2 vaccine shows good storage stability, results in sustained antigen delivery to antigen-presenting cells in the lungs and induces a potent antiviral immune response.
Journal Article
Targeting TFH cells in human diseases and vaccination: rationale and practice
The identification of CD4+ T cells localizing to B cell follicles has revolutionized the knowledge of how humoral immunity is generated. Follicular helper T (TFH) cells support germinal center (GC) formation and regulate clonal selection and differentiation of memory and antibody-secreting B cells, thus controlling antibody affinity maturation and memory. TFH cells are essential in sustaining protective antibody responses necessary for pathogen clearance in infection and vaccine-mediated protection. Conversely, aberrant and excessive TFH cell responses mediate and sustain pathogenic antibodies to autoantigens, alloantigens, and allergens, facilitate lymphomagenesis, and even harbor viral reservoirs. TFH cell generation and function are determined by T cell antigen receptor (TCR), costimulation, and cytokine signals, together with specific metabolic and survival mechanisms. Such regulation is crucial to understanding disease pathogenesis and informing the development of emerging therapies for disease or novel approaches to boost vaccine efficacy.Yu et al. review the roles played by follicular helper T cells in sustaining germinal center B cell responses and vaccination strategies, as well as potential pathogenic autoimmune responses.
Journal Article
Triptolide suppresses IDH1-mutated malignancy via Nrf2-driven glutathione metabolism
Isocitrate dehydrogenase (IDH) mutation is a common genetic abnormality in human malignancies characterized by remarkable metabolic reprogramming. Our present study demonstrated that IDH1-mutated cells showed elevated levels of reactive oxygen species and higher demands on Nrf2-guided glutathione de novo synthesis. Our findings showed that triptolide, a diterpenoid epoxide from Tripterygium wilfordii, served as a potent Nrf2 inhibitor, which exhibited selective cytotoxicity to patient-derived IDH1-mutated glioma cells in vitro and in vivo. Mechanistically, triptolide compromised the expression of GCLC, GCLM, and SLC7A11, which disrupted glutathione metabolism and established synthetic lethality with reactive oxygen species derived from IDH1 mutant neomorphic activity. Our findings highlight triptolide as a valuable therapeutic approach for IDH1-mutated malignancies by targeting the Nrf2-driven glutathione synthesis pathway.
Journal Article