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خواطر نثرية للأديب الصيني ما يوي تشن، يسرد فيها مجموعة من المقتطفات النثرية التي تعكس تكوينه الذاتي ومشاعره تجاه قوميته، يتحدث فيها عن مشاهداته وانطباعاته ويومياته في نثر أدبي شديد العذوبة. ومنها أن تكون وحيدا، عين الروح، الطفو على سطح البحر، نهر الأمس، الانسياب مع أحداث الماضي، الأمور الحياتية كالدخان ... وموضوعات أخرى.‪‪‪

N6-methyladenosine (m6A) has emerged as an abundant modification throughout the transcriptome with widespread functions in protein-coding and noncoding RNAs. It affects the fates of modified RNAs, including their stability, splicing, and/or translation, and thus plays important roles in posttranscriptional regulation. To date, m6A methyltransferases have been reported to execute m6A deposition on distinct RNAs by their own or forming different complexes with additional partner proteins. In this review, we summarize the function of these m6A methyltransferases or complexes in regulating the key genes and pathways of cancer biology. We also highlight the progress in the use of m6A methyltransferases in mediating therapy resistance, including chemotherapy, targeted therapy, immunotherapy and radiotherapy. Finally, we discuss the current approaches and clinical potential of m6A methyltransferase-targeting strategies.

Uncharacterized biosynthetic genes in plant genomes suggest that plants make a plethora of specialized metabolites. Huang et al. reconstructed three biosynthetic networks from the small mustard plant Arabidopsis thaliana . Promiscuous acyltransferases and dehydrogenases contributed to metabolite diversification. The plant may use these specialized metabolites to modulate the microbiota surrounding its roots. Disruption of the pathways and intervention with purified compounds caused changes in the root microbiota. Science , this issue p. eaau6389 A widely studied model plant produces a range of metabolites that regulate the microbial community around its roots. Plant specialized metabolites have ecological functions, yet the presence of numerous uncharacterized biosynthetic genes in plant genomes suggests that many molecules remain unknown. We discovered a triterpene biosynthetic network in the roots of the small mustard plant Arabidopsis thaliana. Collectively, we have elucidated and reconstituted three divergent pathways for the biosynthesis of root triterpenes, namely thalianin (seven steps), thalianyl medium-chain fatty acid esters (three steps), and arabidin (five steps). A. thaliana mutants disrupted in the biosynthesis of these compounds have altered root microbiota. In vitro bioassays with purified compounds reveal selective growth modulation activities of pathway metabolites toward root microbiota members and their biochemical transformation and utilization by bacteria, supporting a role for this biosynthetic network in shaping an Arabidopsis- specific root microbial community.

Noncoding RNAs (ncRNAs) represent a large segment of the human transcriptome and have been shown to play important roles in cellular physiology and disease pathogenesis. Increasing evidence on the functional roles of ncRNAs in cancer progression emphasizes the potential of ncRNAs for cancer treatment. Here, we summarize the roles of ncRNAs in disease relapse and resistance to current standard chemotherapy and radiotherapy; the current research progress on ncRNAs for clinical and/or potential translational applications, including the identification of ncRNAs as therapeutic targets; therapeutic approaches for ncRNA targeting; and ncRNA delivery strategies in potential clinical translation. Several ongoing clinical trials of novel RNA-based therapeutics were also emphasized. Finally, we discussed the perspectives and obstacles to different target combinations, delivery strategies, and system designs for ncRNA application. The next approved nucleic acid drug to treat cancer patients may realistically be on the horizon.

Purpose: It is revealed that Xiaoyaosan could reduce glutamate level in the hippocampus of depressed rats, whose metabolism leads to the pathophysiology of depression. However, the underlying mechanism remains unclear. This study aims to explore the effect of Xiaoyaosan on glutamate metabolism, and how to regulate the excitatory injury caused by glutamate. Methods: Rats were induced by chronic unpredictable mild stress, then divided into control, vehicle (distilled water), Xiaoyaosan, fluoxetine, vehicle (DMSO), Xiaoyaosan + Ly294002 and Ly294002 groups. Ly294002 was microinjected into the lateral ventricular catheterization at 5 mM. Xiaoyaosan (2.224 g/kg) and fluoxetine (2.0 mg/kg) were orally administered for three weeks. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to assess depressive behavior. The glutamate and corticosterone (CORT) levels were detected by ELISA. Western blot, immunochemistry or immunofluorescence were used to detect the expressions of NR2B, MAP2, PI3K and P-AKT/Akt in the hippocampal CA1 region. The mRNA level of MAP2, NR2B and PI3K were detected by RT-qPCR. Results: Compared to the rats in control group, body weight and food intake of CUMS rats was decreased. CUMS rats also showed depression-like behavior as well as down regulate the NR2B and PI3K/Akt signaling pathway. Xiaoyaosan treatments could increase food intake and body weight as well as improved time spent in the central area, total distance traveled in the OFT. Xiaoyaosan could also decrease the immobility time as well as increase the sucrose preference in SPT. Moreover, xiaoyaosan decreased the level of glutamate in the hippocampal CA1 region and serum CORT in CUMS rats. Furthermore, xiaoyaosan improved the expression of MAP2 as well as increased the expression of NR2B, PI3K and the P-AKT/AKT ratio in the hippocampal CA1 region in the CUMS rats. Conclusion: Xiaoyaosan treatment can exert the antidepressant effect by rescuing hippocampal neurons loss induced by the glutamate-mediated excitotoxicity in CUMS rats. The underlying pathway maybe through NR2B and PI3K/Akt signaling pathways. These results may suggest the potential of Xiaoyaosan in preventing the development of depression.

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood–brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche. Understanding how the organs form and how their cells behave is essential to finding the causes and treatment for developmental disorders, as well as understanding certain diseases. However, studying most organs in live animals or humans is technically difficult, expensive and invasive. To address this issue, scientists have developed models called ‘organoids’ that recapitulate the development of organs using stem cells in the lab. These models are easier to study and manipulate than the live organs. Brain organoids have been used to recapitulate brain formation as well as developmental, degenerative and psychiatric brain conditions such as microcephaly, autism and Alzheimer’s disease. However, these brain organoids lack the vasculature (the network of blood vessels) that supplies a live brain with nutrients and regulates its development, and which has important roles in brain disorders. Partly due to this lack of blood vessels, brain organoids also do not develop a blood brain barrier, the structure that prevents certain contents of the blood, including pathogens, toxins and even certain drugs from entering the brain. These characteristics limit the utility of existing brain organoids. To overcome these limitations, Sun, Ju et al. developed brain organoids and blood vessel organoids independently, and then fused them together to obtain vascularized brain organoids. These fusion organoids developed a robust network of blood vessels that was well integrated with the brain cells, and produced more neural cell precursors than brain organoids that had not been fused. This result is consistent with the idea that blood vessels can regulate brain development. Analyzing the fusion organoids revealed that they contain structures similar to the blood-brain barrier, as well as microglial cells (immune cells specific to the brain). When exposed to lipopolysaccharide – a component of the cell wall of certain bacteria – these cells responded by initiating an immune response in the fusion organoids. Notably, the microglial cells were also able to engulf connections between brain cells, a process necessary for the brain to develop the correct structures and work normally. Sun, Ju et al. have developed a new organoid system that will be of broad interest to researchers studying interactions between the brain and the circulatory system. The development of brain-blood-barrier-like structures in the fusion organoids could also facilitate the development of drugs that can cross this barrier, making it easier to treat certain conditions that affect the brain. Refining this model to allow the fusion organoids to grow for longer times in the lab, and adding blood flow to the system will be the next steps to establish this system.

This paper investigates the generation of the ultra-broadwidth (0.1–30 THz) terahertz (THz) radiation carrying fractional/integer orbital angular momentums (OAMs) via the interaction of the two-color ( ω 0 and 2 ω 0 ) laser field carrying initial fractional topological charges (TCs) with air in a moderate pump intensity regime (20 TW cm −2 < I pump < 50 TW cm −2 ). The two four-wave mixing (FWM) processes (i.e., ω 0 + ω ′ 0 − 2 ω 0 → ω THz and 2 ω 0 − ω 0 − ω ′ 0 → ω THz ) are responsible for THz generation. The two processes can produce two THz pulses. They interfere with each other and THz interference vortex beams are obtained. More importantly, the generation probability from the first FWM process grows while that of the second process declines in the positive frequency region over distance. This is largely due to the combined action of phase mismatch and the blue shift of the THz center frequency. For a longer distance, THz fractional vortex beams (FVBs)/integer vortex beams (IVBs) are produced by the dominant FWM process ( ω 0 + ω ′ 0 − 2 ω 0 → ω THz ). Therefore, via employing different combinations of the initial TCs of the ω 0 and 2 ω 0 pulses, one can manipulate the generation of the THz vortex beams with arbitrary fractional-order or integer-order TCs at some specific propagation distances. What is even more interesting is that, when employing half-integer TCs, THz FVBs with varying TC over distance can be produced, companied with birth and annihilation of the alternative vortex pair. This is principally due to diffraction-related effects and the unstable nature of the fractional vortex structures. This simple manipulation for THz waves carrying arbitrary fractional or integer TCs in this scheme encourages the applications for optically rotation, manipulation of molecular or cell assays and image edge enhancement in the field of biomedicine.

Flexible Bi2Te3‐based thermoelectric devices can function as power generators for powering wearable electronics or chip‐sensors for internet‐of‐things. However, the unsatisfied performance of n‐type Bi2Te3 flexible thin films significantly limits their wide application. In this study, a novel thermal diffusion method is employed to fabricate n‐type Te‐embedded Bi2Te3 flexible thin films on flexible polyimide substrates, where Te embeddings can be achieved by tuning the thermal diffusion temperature and correspondingly result in an energy filtering effect at the Bi2Te3/Te interfaces. The energy filtering effect can lead to a high Seebeck coefficient ≈160 µV K−1 as well as high carrier mobility of ≈200 cm2 V−1 s−1 at room‐temperature. Consequently, an ultrahigh room‐temperature power factor of 14.65 µW cm−1 K−2 can be observed in the Te‐embedded Bi2Te3 flexible thin films prepared at the diffusion temperature of 623 K. A thermoelectric sensor is also assembled through integrating the n‐type Bi2Te3 flexible thin films with p‐type Sb2Te3 counterparts, which can fast reflect finger‐touch status and demonstrate the applicability of as‐prepared Te‐embedded Bi2Te3 flexible thin films. This study indicates that the thermal diffusion method is an effective way to fabricate high‐performance and applicable flexible Te‐embedded Bi2Te3‐based thin films. In this study, flexible n‐type Bi2Te3‐based thin‐films are successfully prepared through facile thermal diffusion method and further induce Te/Bi2Te3 heterojunctions and energy filtering effect at the Te/Bi2Te3 interfaces to optimize the thermoelectric performance through tuning the diffusion temperature.

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.