Explore the vast range of titles available.

استنادا إلى فاعليات حقيقية وقعت بداية التسعينيات ؛ إذ أهلك مصيبة الإيدز قرى بأكملها، قرى سعى سكانها، بتحفيز من المسؤولين المحليين، الفرار من الفقر المدقع من خلال بيع الدم. وقائع قد تظهر من \"ديستوبيا\" متخيلة ؛ من فساد المسؤولين وصمت الحكام إلى تهديد الإنس وتسليعهم، ومن خبث التجار وانحطاط الأخلاق إلى جهل القرويين الحالمين بالثراء العاجل. تلك حكاية عن الوفاة والتنصل من المسؤوليات، عن جرائم بدون قصاص، عن جشع يمسخ علاقات الأسرة وأحلام كالنبوءات. بنثر آسر الحسن، ونبرة ولد بريء، نقرأ رواية \"يان ليانكه\"، وهو يؤسطر الزمان الماضي المطموس رسميا.

Tumour metastasis is a major reason accounting for the poor prognosis of colorectal cancer (CRC), and the discovery of targets in the primary tumours that can predict the risk of CRC metastasis is now urgently needed. In this study, we identified autophagy-related protein 9B (ATG9B) as a key potential target gene for CRC metastasis. High expression of ATG9B in tumour significantly increased the risk of metastasis and poor prognosis of CRC. Mechanistically, we further find that ATG9B promoted CRC invasion mainly through autophagy-independent manner. MYH9 is the pivotal interacting protein for ATG9B functioning, which directly binds to cytoplasmic peptide segments aa368–411 of ATG9B by its head domain. Furthermore, the combination of ATG9B and MYH9 enhance the stability of each other by decreasing their binding to E3 ubiquitin ligase STUB1, therefore preventing them from ubiquitin-mediated degradation, which further amplified the effect of ATG9B and MYH9 in CRC cells. During CRC cell invasion, ATG9B is transported to the cell edge with the assistance of MYH9 and accelerates focal adhesion (FA) assembly through mediating the interaction of endocytosed integrin β1 and Talin-1, which facilitated to integrin β1 activation. Clinically, upregulated expression of ATG9B in human CRC tissue is always accompanied with highly elevated expression of MYH9 and associated with advanced CRC stage and poor prognosis. Taken together, this study highlighted the important role of ATG9B in CRC metastasis by promoting focal adhesion assembly, and ATG9B together with MYH9 can provide a pair of potential therapeutic targets for preventing CRC progression.

After the 2008 financial crisis, under the double effects of enterprise value maximization and the decline of real economy marginal profit, the relationship between enterprise financialization and technological innovation is worth exploring in depth. On the basis of testing the impact of non-financial enterprise financialization on technological innovation, this paper explores the impact mechanism as well as the heterogeneity among different types of enterprises. This paper selects non-financial listed enterprises in China from 2007 to 2017 as samples to study the influence of enterprise financialization on technological innovation and its mechanism through panel regression and mediating effect models. Moreover, the heterogeneity among different types of enterprises is further studied. The main conclusions are as follows. First, the financialization of enterprises has a significant \"crowding out\" effect on technological innovation. Second, the “crowding out” effect of enterprise financialization on technological innovation is formed through capital structure rather than performance. Third, enterprises are faced with different attributes and external environment, thus the influence of financialization on technological innovation is heterogeneous. Fourth, there are significant differences in the impact of financialization on technological innovation between enterprises’ attributes and the external environment they face, and the deviation degree caused by attributes is much greater than that caused by the external environment.

Drought forecasting can effectively reduce the risk of drought. We proposed a hybrid model based on deep learning methods that integrates an autoregressive integrated moving average (ARIMA) model and a long short-term memory (LSTM) model to improve the accuracy of short-term drought prediction. Taking China as an example, this paper compares and analyzes the prediction accuracy of six drought prediction models, namely, ARIMA, support vector regression (SVR), LSTM, ARIMA-SVR, least square-SVR (LS-SVR), and ARIMA-LSTM, for standardized precipitation evapotranspiration index (SPEI). The performance of all the models was compared using measures of persistence, such as the Nash-Sutcliffe efficiency (NSE). The results show that all three hybrid models (ARIMA-SVR, LS-SVR, and ARIMA-LSTM) had higher prediction accuracy than the single model, for a given lead time, at different scales. The NSEs of the hybrid models for the predicted SPEI1 are 0.043, 0.168, and 0.368, respectively, and the NSEs of SPEI24 is 0.781, 0.543, and 0.93, respectively. This finding indicates that when the lead time remains unchanged, the hybrid model has high prediction accuracy for SPEI on long time scales and low prediction accuracy for SPEI on short time scales, and the prediction accuracy of the model with a 1-month lead time is higher than that of the model with a 2-month lead time. In addition, the ARIMA-LSTM model has the highest prediction accuracy at the 6-, 12-, and 24-month scales, indicating that the model is more suitable for the forecasting of long-term drought in China.

Sustainable and safe food is an important issue worldwide, and it depends on cost-effective analysis tools with good sensitivity and reality. However, traditional standard chemical methods of food safety detection, such as high-performance liquid chromatography (HPLC), gas chromatography (GC), and tandem mass spectrometry (MS), have the disadvantages of high cost and long testing time. Those disadvantages have prevented people from obtaining sufficient risk information to confirm the safety of their products. In addition, food safety testing, such as the bioassay method, often results in false positives or false negatives due to little rigor preprocessing of samples. So far, food safety analysis currently relies on the enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), HPLC, GC, UV-visible spectrophotometry, and MS, all of which require significant time to train qualified food safety testing laboratory operators. These factors have hindered the development of rapid food safety monitoring systems, especially in remote areas or areas with a relative lack of testing resources. Surface-enhanced Raman spectroscopy (SERS) has emerged as one of the tools of choice for food safety testing that can overcome these dilemmas over the past decades. SERS offers advantages over chromatographic mass spectrometry analysis due to its portability, non-destructive nature, and lower cost implications. However, as it currently stands, Raman spectroscopy is a supplemental tool in chemical analysis, reinforcing and enhancing the completeness and coverage of the food safety analysis system. SERS combines portability with non-destructive and cheaper detection costs to gain an advantage over chromatographic mass spectrometry analysis. SERS has encountered many challenges in moving toward regulatory applications in food safety, such as quantitative accuracy, poor reproducibility, and instability of large molecule detection. As a result, the reality of SERS, as a screening tool for regulatory announcements worldwide, is still uncommon. In this review article, we have compiled the current designs and fabrications of SERS substrates for food safety detection to unify all the requirements and the opportunities to overcome these challenges. This review is expected to improve the interest in the sensing field of SERS and facilitate the SERS applications in food safety detection in the future.

HighlightsThe cationic waterborne polyurethanes microspheres with Diels-Alder bonds were synthesized for the first time.The electrostatic attraction not only endows the composite with segregated structure to gain high electromagnetic-interference shielding effectiveness, but also greatly enhances mechanical properties.Efficient healing property was realized under heating environment.It is still challenging for conductive polymer composite-based electromagnetic interference (EMI) shielding materials to achieve long-term stability while maintaining high EMI shielding effectiveness (EMI SE), especially undergoing external mechanical stimuli, such as scratches or large deformations. Herein, an electrostatic assembly strategy is adopted to design a healable and segregated carbon nanotube (CNT)/graphene oxide (GO)/polyurethane (PU) composite with excellent and reliable EMI SE, even bearing complex mechanical condition. The negatively charged CNT/GO hybrid is facilely adsorbed on the surface of positively charged PU microsphere to motivate formation of segregated conductive networks in CNT/GO/PU composite, establishing a high EMI SE of 52.7 dB at only 10 wt% CNT/GO loading. The Diels–Alder bonds in PU microsphere endow the CNT/GO/PU composite suffering three cutting/healing cycles with EMI SE retention up to 90%. Additionally, the electrostatic attraction between CNT/GO hybrid and PU microsphere helps to strong interfacial bonding in the composite, resulting in high tensile strength of 43.1 MPa and elongation at break of 626%. The healing efficiency of elongation at break achieves 95% when the composite endured three cutting/healing cycles. This work demonstrates a novel strategy for developing segregated EMI shielding composite with healable features and excellent mechanical performance and shows great potential in the durable and high precision electrical instruments.

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases. A hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive Androgenetic alopecia (AGA) treatment. The V-R-MNs promote angiogenesis and improve the immune microenvironment around the hair follicle, fostering the proliferation and development of hair follicle cells. In comparison to the clinical drug minoxidil for AGA treatment, V-R-MN exhibits a hair regeneration effect in AGA model mice characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. [Display omitted] •Designed a HA-hydrogel microneedles, simultaneously integrated VEGF and Ritlecitinib contained in PHA NPs for AGA treatment.•R-PHA NP addition enhances microneedle hardness, aiding minimally invasive transdermal delivery of microneedles.•V-R-MN group showed faster, superior hair regeneration than monotherapy (V-MN, R-MN, Ritlecitinib, and Minoxidil).•V-R-MN shows high biocompatibility with skin, ensuring safety and feasibility for transdermal drug delivery.

Cellular senescence serves as a fundamental and underlying activity that drives the aging process, and it is intricately associated with numerous age-related diseases, including Alzheimer's disease (AD), a neurodegenerative aging-related disorder characterized by progressive cognitive impairment. Although increasing evidence suggests that senescent microglia play a role in the pathogenesis of AD, their exact role remains unclear. In this study, we quantified the levels of lactic acid in senescent microglia, and hippocampus tissues of naturally aged mice and AD mice models (FAD 4T and APP/PS1). We found lactic acid levels were significantly elevated in these cells and tissues compared to their corresponding counterparts, which increased the level of pan histone lysine lactylation (Kla). We aslo identified all histone Kla sites in senescent microglia, and found that both the H3K18 lactylation (H3K18la) and Pan-Kla were significantly up-regulated in senescent microglia and hippocampus tissues of naturally aged mice and AD modeling mice. We demonstrated that enhanced H3K18la directly stimulates the NFκB signaling pathway by increasing binding to the promoter of Rela (p65) and NFκB1(p50), thereby upregulating senescence-associated secretory phenotype (SASP) components IL-6 and IL-8. Our study provides novel insights into the physiological function of Kla and the epigenetic regulatory mechanism that regulates brain aging and AD. Specifically, we have identified the H3K18la/NFκB axis as a critical player in this process by modulating IL-6 and IL-8. Targeting this axis may be a potential therapeutic strategy for delaying aging and AD by blunting SASP.

An ability to develop sequence-defined synthetic polymers that both mimic lipid amphiphilicity for self-assembly of highly stable membrane-mimetic 2D nanomaterials and exhibit protein-like functionality would revolutionize the development of biomimetic membranes. Here we report the assembly of lipid-like peptoids into highly stable, crystalline, free-standing and self-repairing membrane-mimetic 2D nanomaterials through a facile crystallization process. Both experimental and molecular dynamics simulation results show that peptoids assemble into membranes through an anisotropic formation process. We further demonstrated the use of peptoid membranes as a robust platform to incorporate and pattern functional objects through large side-chain diversity and/or co-crystallization approaches. Similar to lipid membranes, peptoid membranes exhibit changes in thickness upon exposure to external stimuli; they can coat surfaces in single layers and self-repair. We anticipate that this new class of membrane-mimetic 2D nanomaterials will provide a robust matrix for development of biomimetic membranes tailored to specific applications. Biomimetic membranes can be used for various applications such as sensors and separations. Here, Chen et al . report the assembly of lipid-like peptoids into stable and self-repairing 2D membrane nanomaterials that change in thickness when under external stimuli.