Ischemic stroke caused by arterial occlusion is the most common type of stroke, which is among the most frequent causes of disability and death worldwide. Current treatment approaches involve ...achieving rapid reperfusion either pharmacologically or surgically, both of which are time‐sensitive; moreover, blood flow recanalization often causes ischemia/reperfusion injury. However, even though neuroprotective intervention is urgently needed in the event of stroke, the exact mechanisms of neuronal death during ischemic stroke are still unclear, and consequently, the capacity for drug development has remained limited. Multiple cell death pathways are implicated in the pathogenesis of ischemic stroke. Here, we have reviewed these potential neuronal death pathways, including intrinsic and extrinsic apoptosis, necroptosis, autophagy, ferroptosis, parthanatos, phagoptosis, and pyroptosis. We have also reviewed the latest results of pharmacological studies on ischemic stroke and summarized emerging drug targets with a focus on clinical trials. These observations may help to further understand the pathological events in ischemic stroke and bridge the gap between basic and translational research to reveal novel neuroprotective interventions.
The study of topological phases with unconventional bulk‐boundary correspondences and nontrivial real Chern number has garnered significant attention in the topological states of matter. Using the ...first‐principle calculations and theoretical analysis, a high‐throughput material screening of the 3D obstructed atomic insulators (OAIs) and 3D real Chern insulators (RCIs) based on the Samara Carbon Allotrope Database (SACADA) are performed. Results show that 422 out of 703 3D carbon allotropes are 3D OAIs with multiple bulk‐boundary correspondences, including 2D obstructed surface states (OSSs) and 1D hinge states, which are in 1D and 2Ds lower than the 3D bulk, respectively. The 2D OSSs in these OAIs can be modified when subjected to appropriate boundaries, which benefits the investigation of surface engineering and the development of efficient topological catalysts. These 422 OAIs, which have 2D and 1D boundary states, are excellent platforms for multi‐dimensional topological boundaries research. Remarkably, 138 of 422 OAIs are also 3D RCIs, which show a nontrivial real topology in the protection of spacetime inversion symmetry. This work not only provides a comprehensive list of 3D carbon‐based OAIs and RCIs, but also guides their application in various aspects based on multiple bulk‐boundary correspondences and real topological phases.
A high‐throughput material screening of the 3D obstructed atomic insulators (OAIs) and 3D real Chern insulators (RCIs) based on the Samara Carbon Allotrope Database (SACADA) is performed. Results show 422 out of 703 3D carbon allotropes are 3D OAIs with multiple bulk‐boundary correspondences. Remarkably, 138 of 422 OAIs are also 3D RCIs with a nontrivial real topology.
CXC motif chemokine receptor type 4 (CXCR4) is associated with normal and abnormal development, including oncogenesis. The ligand of CXCR4 is stromal cell-derived factor (SDF), also known as CXC ...motif ligand (CXCL) 12. Through the SDF-1/CXCR4 axis, both homing and migration of hematopoietic (stem) cells are regulated through niches in the bone marrow. Outside of the bone marrow, however, SDF-1 can recruit CXCR4-positive cells from the bone marrow. SDF/CXCR4 has been implicated in the maintenance and/or differentiation of stemness, and tissue-derived stem cells can be associated with SDF-1 and CXCR4 activity. CXCR4 plays a role in multiple pathways involved in carcinogenesis and other pathologies. Here, we summarize reports detailing the functions of CXCR4. We address the molecular signature of CXCR4 and how this molecule and cells expressing it are involved in either normal (maintaining stemness or inducing differentiation) or abnormal (developing cancer and other pathologies) events. As a constituent of stem cells, the SDF-1/CXCR4 axis influences downstream signal transduction and the cell microenvironment.
To investigate the underlying mechanism of Astragaloside IV (AS-IV) in ameliorating diabetic nephropathy (DN) by regulating intestinal microbiota ecology and intestinal mucosal barrier.
Genetically ...db/db mice are used to establish DN mouse model to monitor the therapeutic effects of AS-IV and fecal microbiota transplantation (FMT) against DN. Supplementation with AS-IV dramatically attenuates several clinical indicators of DN in db/db mice. In addition, AS-IV markedly improves intestinal barrier function, modifies intestinal permeability, and reduces inflammation. Moreover, AS-IV treatment remarkably improves intestinal dysbiosis in db/db mice, characterized by an elevated abundance of Akkermansia, Ligilactobacillus, and Lactobacillus, indicating the fundamental role of the microbiome in DN progression. Furthermore, FMT derived from AS-IV-treated db/db mice is potentially efficient in antagonizing renal dysfunction, rebalancing gut microbiota, and improving intestinal permeability in recipient db/db mice. AS-IV-enriched Akkermansia muciniphila dramatically alleviates DN and intestinal mucosal barrier dysfunction in db/db mice. Intriguingly, AS-IV intervention dramatically diminishes ferroptosis in the kidney and colon tissues. CONCLUSION : Intestinal microbiome alterations and ferroptosis modulation by AS-IV may play instrumental roles in this mechanism, providing compelling evidence for the role of the gut-renal axis in DN.
Intricately interwoven topologies are continually being synthesized and are ultimately equally versatile and significant at the nanoscale level; however, reports concerning ravel structures, which ...are highly entwined new topological species, are extremely rare and fraught with tremendous synthesis challenges. To solve the synthesis problem, a tetrapodontic pyridine ligand L1 with two types of olefinic bond units and two Cp*M‐based building blocks (E1, M=Rh; E2, M=Ir) featuring large conjugated planes was prepared to perform the self‐assembly. Two unprecedented 5+10 icosanuclear molecular 4‐ravels containing four crossings were obtained by parallel‐displaced π⋅⋅⋅π interactions in a single‐step strategy. Remarkably, reversible structural transformations between the 4‐ravel and the corresponding metallocage could be realized by concentration changes and solvent‐ and guest‐induced effects. X‐ray crystallographic data and NMR spectroscopy provide full confirmation of these phenomena.
Two unprecedented 5+10 icosanuclear molecular 4‐ravels containing four crossings have been generated using a single‐step strategy. This topology is achieved by utilizing parallel‐displaced π⋅⋅⋅π interactions with carefully selected naphthoquinoyl Cp*M building blocks and X‐shaped pyridyl ligands.
As the main bioactive constituents of
species, ginsenosides possess a wide range of notable medicinal effects such as anti-cancer, anti-oxidative, antiaging, anti-inflammatory, anti-apoptotic and ...neuroprotective activities. However, the increasing medical demand for ginsenosides cannot be met due to the limited resource of
species and the low contents of ginsenosides. In recent years, biotechnological approaches have been utilized to increase the production of ginsenosides by regulating the key enzymes of ginsenoside biosynthesis, while synthetic biology strategies have been adopted to produce ginsenosides by introducing these genes into yeast. This review summarizes the latest research progress on cloning and functional characterization of key genes dedicated to the production of ginsenosides, which not only lays the foundation for their application in plant engineering, but also provides the building blocks for the production of ginsenosides by synthetic biology.
Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical ...activated M1 macrophages and alternatively activated M2 macrophages. The former typically exerts anti-tumor functions, including directly mediate cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; the latter can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis, and lead to tumor progression. Both M1 and M2 macrophages have high degree of plasticity and thus can be converted into each other upon tumor microenvironment changes or therapeutic interventions. As the relationship between TAMs and malignant tumors becoming clearer, TAMs have become a promising target for developing new cancer treatment. In this review, we summarize the origin and types of TAMs, TAMs interaction with tumors and tumor microenvironment, and up-to-date treatment strategies targeting TAMs.
Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical ...challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.
Abstract
We report an
ab initio
investigation of a hydrogen-based high-
T
c
superconductor candidate—crystalized C
4
H
4
in the
cubic-gauche
(
cg
-C
4
H
4
) structure, with the symmetry of space ...group I
213
. We find the
cg
-C
4
H
4
structure to be stable under ambient environment; and the evaluation of the electron-phonon coupling strength indicates that the heavily doped
cg
-C
4
H
4
can generate superconductivity with a
T
c
∼ 72 K. The high frequency vibrational modes of hydrogen atoms are found to play an important role in the total electron-phonon interaction strength, and the reduction of structural symmetry compared with graphene further enhances the electron–phonon coupling of the carbon framework. Our investigation illustrates a BCS route to realizing the hydrogen-based high
T
c
superconductivity.
Wearable or attachable health monitoring smart systems are considered to be the next generation of personal portable devices for remote medicine practices. Smart flexible sensing electronics are ...components crucial in endowing health monitoring systems with the capability of real‐time tracking of physiological signals. These signals are closely associated with body conditions, such as heart rate, wrist pulse, body temperature, blood/intraocular pressure and blood/sweat bio‐information. Monitoring such physiological signals provides a convenient and non‐invasive way for disease diagnoses and health assessments. This Review summarizes the recent progress of flexible sensing electronics for their use in wearable/attachable health monitoring systems. Meanwhile, we present an overview of different materials and configurations for flexible sensors, including piezo‐resistive, piezo‐electrical, capacitive, and field effect transistor based devices, and analyze the working principles in monitoring physiological signals. In addition, the future perspectives of wearable healthcare systems and the technical demands on their commercialization are briefly discussed.
Flexible sensing electronics play crucial roles in wearable health monitoring systems, which is considered to be a convenient and effective way for disease diagnoses and health assessments. The advances of flexible sensing electronics and related nanomaterials in healthcare are summarized.