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A reductive cross-coupling strategy for the synthesis of sulfone-containing oxindoles via palladium-catalyzed domino cyclization/alkylsulfonylation reaction of N-substituted arylacrylamides with unactivated alkyl bromides and Na2S2O5 is presented. Moreover, using amines instead of alkyl bromides, a palladium-catalyzed domino cyclization/aminosulfonylation was also established. [ABSTRACT FROM AUTHOR]

Prime editing shows potential as a precision genome editing technology, as well as the potential to advance the development of next-generation nanomedicine for addressing neurological disorders. However, turning in prime editors (PEs), which are macromolecular complexes composed of CRISPR/Cas9 nickase fused with a reverse transcriptase and a prime editing guide RNA (pegRNA), to the brain remains a considerable challenge due to physiological obstacles, including the blood–brain barrier (BBB). This review article offers an up-to-date overview and perspective on the latest technologies and strategies for the precision delivery of PEs to the brain and passage through blood barriers. Furthermore, it delves into the scientific significance and possible therapeutic applications of prime editing in conditions related to neurological diseases. It is targeted at clinicians and clinical researchers working on advancing precision nanomedicine for neuropathologies. [ABSTRACT FROM AUTHOR]

Intrusion detection technology can actively detect abnormal behaviors in the network and is important to the security of Industrial Internet of Things (IIOT). However, there are some issues with the current intrusion detection technology for IIOT, such as extreme imbalance in the number of samples of different classes in the dataset, redundant and meaningless features in the samples, and the inability of traditional intrusion detection methods to meet the requirements of detection accuracy in the increasingly complex IIOT. In view of the extreme imbalance of classes, this paper applies the hierarchical clustering algorithm to the under-sampling technology, which reduces the number of majority samples while reducing the loss of information of majority samples, and solves the problem of missing detection and false detection of minority samples caused by sample imbalance. In order to avoid feature redundancy and interference, this paper proposes an optimal feature selection algorithm based on greedy thought. This algorithm can obtain the optimal feature subset of each type of data in the data set, thus eliminating redundant and interfering features. Aiming at the problem of insufficient detection ability of traditional detection methods, this paper proposes a deep neural network intrusion detection model based on the parallel connection of global and local subnetworks. This model obtains the overall benchmark detection of the dataset through the deep neural network, and then strengthens the detection effect of each subclass through the parallel connection of subnetworks, greatly improving the performance of the intrusion detection algorithm. The experimental results show that the method described in this paper can improve the intrusion detection for IIOT. [ABSTRACT FROM AUTHOR]

ABL tyrosine kinase inhibitors (TKIs) act an irreplaceable role in the management of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). The treatment of these diseases has been revolutionized by the application of immunotherapeutic modalities. However, diseases with ABL kinase domain mutation T315I are resistant to the majority of TKIs, which is responsible for treatment failure. Olverembatinib is a third-generation TKI that has been approved for the treatment of T315I-mutated chronic myeloid leukemia (CML) in China; its usage in Ph+ ALL needs further exploration. Here, we present two cases with relapsed T315I mutation Ph+ ALL who received the combination regimen of blinatumomab and olverembatinib. This regimen, which has not been reported yet, was safe and effective as the patients achieved minimal residual disease (MRD) negative after 1 cycle of therapy. The management of these cases provides evidence of this new chemo-free regimen as an efficient approach for relapsed or refractory(R/R)Ph+ ALL. [ABSTRACT FROM AUTHOR]