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"Yang, Xin"
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Dihydroquinazolinones as adaptative C(sp3) handles in arylations and alkylations via dual catalytic C–C bond-functionalization
C–C bond forming cross-couplings are convenient technologies for the construction of functional molecules. Consequently, there is continual interest in approaches that can render traditionally inert functionality as cross-coupling partners, included in this are ketones which are widely-available commodity chemicals and easy to install synthetic handles. Herein, we describe a dual catalytic strategy that utilizes dihydroquinazolinones derived from ketone congeners as adaptative one-electron handles for forging C(
sp
3
) architectures via α C–C cleavage with aryl and alkyl bromides. Our approach is achieved by combining the flexibility and modularity of nickel catalysis with the propensity of photoredox events for generating open-shell reaction intermediates. This method is distinguished by its wide scope and broad application profile––including chemical diversification of advanced intermediates––, providing a catalytic technique complementary to existing C(
sp
3
) cross-coupling reactions that operates within the C–C bond-functionalization arena.
Although derived from feedstock chemicals and therefore in principle abundant, ketones are not widely used as cross-coupling partners in organic synthesis. Herein, the authors use ketone derivatives as one-electron handles for forging C(sp3) architectures via dual photo- and nickel catalysis.
Journal Article
Phagocytosis checkpoints as new targets for cancer immunotherapy
Cancer immunotherapies targeting adaptive immune checkpoints have substantially improved patient outcomes across multiple metastatic and treatment-refractory cancer types. However, emerging studies have demonstrated that innate immune checkpoints, which interfere with the detection and clearance of malignant cells through phagocytosis and suppress innate immune sensing, also have a key role in tumour-mediated immune escape and might, therefore, be potential targets for cancer immunotherapy. Indeed, preclinical studies and early clinical data have established the promise of targeting phagocytosis checkpoints, such as the CD47–signal-regulatory protein α (SIRPα) axis, either alone or in combination with other cancer therapies. In this Review, we highlight the current understanding of how cancer cells evade the immune system by disrupting phagocytic clearance and the effect of phagocytosis checkpoint blockade on induction of antitumour immune responses. Given the role of innate immune cells in priming adaptive immune responses, an improved understanding of the tumour-intrinsic processes that inhibit essential immune surveillance processes, such as phagocytosis and innate immune sensing, could pave the way for the development of highly effective combination immunotherapy strategies that modulate both innate and adaptive antitumour immune responses.
Journal Article
Bat algorithm: a novel approach for global engineering optimization
Purpose - Nature-inspired algorithms are among the most powerful algorithms for optimization. The purpose of this paper is to introduce a new nature-inspired metaheuristic optimization algorithm, called bat algorithm (BA), for solving engineering optimization tasks.Design methodology approach - The proposed BA is based on the echolocation behavior of bats. After a detailed formulation and explanation of its implementation, BA is verified using eight nonlinear engineering optimization problems reported in the specialized literature.Findings - BA has been carefully implemented and carried out optimization for eight well-known optimization tasks; then a comparison has been made between the proposed algorithm and other existing algorithms.Originality value - The optimal solutions obtained by the proposed algorithm are better than the best solutions obtained by the existing methods. The unique search features used in BA are analyzed, and their implications for future research are also discussed in detail.
Journal Article
عقيدتي والآخر : \حكايات مسلمي هونغ كونغ\ : نثر
يتخذ هذا الكتاب مسلمي هونغ كونغ كخط أساسيا، حيث يصف مساجدهم ومنازلهم وأعيادهم وحياتهم اليومية وأسلوب معيشتهم، كما يناقش أيضا بعض الاختلافات بين مسلمي هونغ كونغ وسكان البر الرئيس للصين، ويلقي الضوء على عدد من مشاكلهم التي تسببها الاختلافات الثقافية والعرقية، وذلك عن طريق بعض الخواطر النثرية لهذا الكاتب الذي قضى بضع سنوات من حياته في هونغ كونغ.
Book
Optimization techniques and applications with examples
A guide to modern optimization applications and techniques in newly emerging areas spanning optimization, data science, machine intelligence, engineering, and computer sciences
Optimization Techniques and Applications with Examples introduces the fundamentals of all the commonly used techniquesin optimization that encompass the broadness and diversity of the methods (traditional and new) and algorithms. The author—a noted expert in the field—covers a wide range of topics including mathematical foundations, optimization formulation, optimality conditions, algorithmic complexity, linear programming, convex optimization, and integer programming. In addition, the book discusses artificial neural network, clustering and classifications, constraint-handling, queueing theory, support vector machine and multi-objective optimization, evolutionary computation, nature-inspired algorithms and many other topics.
Designed as a practical resource, all topics are explained in detail with step-by-step examples to show how each method works. The book's exercises test the acquired knowledge that can be potentially applied to real problem solving. By taking an informal approach to the subject, the author helps readers to rapidly acquire the basic knowledge in optimization, operational research, and applied data mining. This important resource:
* Offers an accessible and state-of-the-art introduction to the main optimization techniques
* Contains both traditional optimization techniques and the most current algorithms and swarm intelligence-based techniques
* Presents a balance of theory, algorithms, and implementation
* Includes more than 100 worked examples with step-by-step explanations
Written for upper undergraduates and graduates in a standard course on optimization, operations research and data mining, Optimization Techniques and Applications with Examples is a highly accessible guide to understanding the fundamentals of all the commonly used techniquesin optimization.
eBook
Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice
Background
Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer’s disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model.
Methods
Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl’s and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention.
Results
Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction.
Conclusion
Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.
Journal Article