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"Xu, Hong"
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ذات الرداء الأحمر، التي تشعر دائما بالفضول تجاه العالم، تريد زيارة جدتها عبر الغابة بمفردها. لكنها لا تستطيع رؤية طريقها، ما هي الصعوبات التي ستواجهها ؟ كيف يمكنها مواجهة الذئب الكبير بمفردها في الغابة ؟ في طريقها، تلتقي بأرنب وقنفذ وظربان. تتعلم استخدام مشاعرها لإدراك العالم، وشجاعتها وحكمتها لإنقاذ نفسها من المخاطر. والمثير للدهشة أن الذئب الكبير في عينيها لطيف جدا، لم يأكل الذئب السيئ الكبير ذات الرداء الأحمر هذه المرة فحسب، بل ساعد أيضا ذو الرداء الأحمر الصغير في الوصول إلى منزل جدته.
Book
Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autophagy
Parkinson’s disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood–brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.
Journal Article
Macrophage Polarization in Physiological and Pathological Pregnancy
The immunology of pregnancy is complex and poorly defined. During the complex process of pregnancy, macrophages secrete many cytokines/chemokines and play pivotal roles in the maintenance of maternal-fetal tolerance. Here, we summarized the current knowledge of macrophage polarization and the mechanisms involved in physiological or pathological pregnancy processes, including miscarriage, preeclampsia, and preterm birth. Although current evidence provides a compelling argument that macrophages are important in pregnancy, our understanding of the roles and mechanisms of macrophages in pregnancy is still rudimentary. Since macrophages exhibit functional plasticity, they may be ideal targets for therapeutic manipulation during pathological pregnancy. Additional studies are needed to better define the functions and mechanisms of various macrophage subsets in both normal and pathological pregnancy.
Journal Article
Prognostic value and outcome for acute lymphocytic leukemia in children with MLL rearrangement: a case-control study
Purpose
To evaluate the prognostic factors and outcome for acute lymphoblastic leukemia (ALL) in children with MLL rearrangement (MLL-r).
Methods
A total of 124 pediatric patients who were diagnosed with ALL were classified into two groups based on the MLL-r status by using a retrospective case-control study method from June 2008 to June 2020.
Results
The prevalence of MLL-r positive in the whole cohort was 4.9%. The complete remission (CR) rate on Day 33 in the MLL-r positive group was not statistically different from the negative group (96.8% vs 97.8%,
P
= 0.736). Multivariate analysis showed that T-cell, white blood cell counts (WBC) ≥ 50 × 10
9
/L, MLL-AF4, and D15 minimal residual disease (MRD) positive were independent risk factors affecting the prognosis of MLL-r positive children. Stem cell transplantation (SCT) was a favorable independent prognostic factor affecting event-free survival (EFS) in MLL-r positive patients (
P
= 0.027), and there was a trend toward an independent prognostic effect on overall survival (OS) (
P
= 0.065). The 10-year predicted EFS for patients with MLL-AF4, MLL-PTD, MLL-ENL, other MLL partner genes, and MLL-r negative cases were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 77.33 ± 10.81%, respectively (
P
= 0.048). The 10-year predicted OS were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 85.2 ± 9.77%, respectively (
P
= 0.049). The 124 patients with ALL were followed up and eventually 5 (4%) cases relapsed, with a median relapse time of 3.9 years.
Conclusion
Patients with MLL-r positive ALL have moderate remission rates, but are prone to relapse with low overall survival. The outcome of MLL-r positive ALL was closely related to the partner genes, and clinical attention should be paid to screening for MLL partner genes and combining them with other prognostic factors for accurate risk stratification.
Journal Article
Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities
Integrins are transmembrane receptors that possess distinct ligand-binding specificities in the extracellular domain and signaling properties in the cytoplasmic domain. While most integrins have a short cytoplasmic tail, integrin β4 has a long cytoplasmic tail that can indirectly interact with the actin cytoskeleton. Additionally, 'inside-out' signals can induce integrins to adopt a high-affinity extended conformation for their appropriate ligands. These properties enable integrins to transmit bidirectional cellular signals, making it a critical regulator of various biological processes.
Integrin expression and function are tightly linked to various aspects of tumor progression, including initiation, angiogenesis, cell motility, invasion, and metastasis. Certain integrins have been shown to drive tumorigenesis or amplify oncogenic signals by interacting with corresponding receptors, while others have marginal or even suppressive effects. Additionally, different α/β subtypes of integrins can exhibit opposite effects. Integrin-mediated signaling pathways including Ras- and Rho-GTPase, TGFβ, Hippo, Wnt, Notch, and sonic hedgehog (Shh) are involved in various stages of tumorigenesis. Therefore, understanding the complex regulatory mechanisms and molecular specificities of integrins are crucial to delaying cancer progression and suppressing tumorigenesis. Furthermore, the development of integrin-based therapeutics for cancer are of great importance.
This review provides an overview of integrin-dependent bidirectional signaling mechanisms in cancer that can either support or oppose tumorigenesis by interacting with various signaling pathways. Finally, we focus on the future opportunities for emergent therapeutics based on integrin agonists.
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Video Abstract
Journal Article
Stable, crystalline, porous, covalent organic frameworks as a platform for chiral organocatalysts
The periodic layers and ordered nanochannels of covalent organic frameworks (COFs) make these materials viable open catalytic nanoreactors, but their low stability has precluded their practical implementation. Here we report the synthesis of a crystalline porous COF that is stable against water, strong acids and strong bases, and we demonstrate its utility as a material platform for structural design and functional development. We endowed a crystalline and porous imine-based COF with stability by incorporating methoxy groups into its pore walls to reinforce interlayer interactions. We subsequently converted the resulting achiral material into two distinct chiral organocatalysts, with the high crystallinity and porosity retained, by appending chiral centres and catalytically active sites on its channel walls. The COFs thus prepared combine catalytic activity, enantioselectivity and recyclability, which are attractive in heterogeneous organocatalysis, and were shown to promote asymmetric C–C bond formation in water under ambient conditions.
Covalent organic frameworks (COFs) feature periodic layers and ordered pores that make them promising for applications in catalysis, but they typically suffer from poor stability. Now, adding methoxy groups to its pore walls has been shown to strengthen a COF's interlayer interactions, resulting in a stable, crystalline, porous material that can be further converted into chiral organocatalysts.
Journal Article
Proton conduction in crystalline and porous covalent organic frameworks
The design of large-pore proton conductors with well-defined high-order structures is challenging. Proton conduction in a crystalline covalent organic framework 2–4 orders of magnitude higher than microporous polymers is now demonstrated.
Progress over the past decades in proton-conducting materials has generated a variety of polyelectrolytes
1
,
2
,
3
,
4
,
5
and microporous polymers
6
,
7
,
8
,
9
,
10
. However, most studies are still based on a preconception that large pores eventually cause simply flow of proton carriers rather than efficient conduction of proton ions, which precludes the exploration of large-pore polymers for proton transport. Here, we demonstrate proton conduction across mesoporous channels in a crystalline covalent organic framework. The frameworks are designed to constitute hexagonally aligned, dense, mesoporous channels that allow for loading of
N
-heterocyclic proton carriers. The frameworks achieve proton conductivities that are 2–4 orders of magnitude higher than those of microporous and non-porous polymers. Temperature-dependent and isotopic experiments revealed that the proton transport in these channels is controlled by a low-energy-barrier hopping mechanism. Our results reveal a platform based on porous covalent organic frameworks for proton conduction.
Journal Article
Pore partition in two-dimensional covalent organic frameworks
Covalent organic frameworks (COFs) have emerged as a kind of crystalline polymeric materials with high compositional and geometric tunability. Most COFs are currently designed and synthesized as mesoporous (2–50 nm) and microporous (1–2 nm) materials, while the development of ultramicroporous (<1 nm) COFs remains a daunting challenge. Here, we develop a pore partition strategy into COF chemistry, which allows for the segmentation of a mesopore into multiple uniform ultramicroporous domains. The pore partition is implemented by inserting an additional rigid building block with suitable symmetries and dimensions into a prebuilt parent framework, leading to the partitioning of one mesopore into six ultramicropores. The resulting framework features a wedge-shaped pore with a diameter down to 6.5 Å, which constitutes the smallest pore among COFs. The wedgy and ultramicroporous one-dimensional channels enable the COF to be highly efficient for the separation of five hexane isomers based on the sieving effect. The obtained average research octane number (RON) values of those isomer blends reach up to 99, which is among the highest records for zeolites and other porous materials. Therefore, this strategy constitutes an important step in the pore functional exploitation of COFs to implement pre-designed compositions, components, and functions.
The development of ultramicroporous covalent organic frameworks (COFs) remains a daunting challenge. Here, the authors report a pore partition strategy, which allows for the segmentation of mesopores of COFs into multiple uniform ultramicroporous domains.
Journal Article
The double-edged roles of ROS in cancer prevention and therapy
Reactive oxygen species (ROS) serve as cell signaling molecules generated in oxidative metabolism and are associated with a number of human diseases. The reprogramming of redox metabolism induces abnormal accumulation of ROS in cancer cells. It has been widely accepted that ROS play opposite roles in tumor growth, metastasis and apoptosis according to their different distributions, concentrations and durations in specific subcellular structures. These double-edged roles in cancer progression include the ROS-dependent malignant transformation and the oxidative stress-induced cell death. In this review, we summarize the notable literatures on ROS generation and scavenging, and discuss the related signal transduction networks and corresponding anticancer therapies. There is no doubt that an improved understanding of the sophisticated mechanism of redox biology is imperative to conquer cancer.
Journal Article
Association between admission pan-immune-inflammation value and short-term mortality in septic patients: a retrospective cohort study
Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan–Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan–Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09),
P
< 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18),
P
< 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08),
P
= 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.
Journal Article