Exploring simple triplet representation learning.

Fully supervised learning methods necessitate a substantial volume of labelled training instances, a process that is typically both labour-intensive and costly. In the realm of medical image analysis, this issue is further amplified, as annotated medical images are considerably more scarce than their unlabelled counterparts. Consequently, leveraging unlabelled images to extract meaningful underlying knowledge presents a formidable challenge in medical image analysis. This paper introduces a simple triple-view unsupervised representation learning model (SimTrip) combined with a triple-view architecture and loss function, aiming to learn meaningful inherent knowledge efficiently from unlabelled data with small batch size. With the meaningful representation extracted from unlabelled data, our model demonstrates exemplary performance across two medical image datasets. It achieves this using only partial labels and outperforms other state-of-the-art methods. The method we present herein offers a novel paradigm for unsupervised representation learning, establishing a baseline that is poised to inspire the development of more intricate SimTrip-based methods across a spectrum of computer vision applications. Code and user guide are released at https://github.com/JerryRollingUp/SimTripSystem, the system also runs at http://43.131.9.159:5000/.

Cancer screening in hospitalized ischemic stroke patients: a multicenter study focused on multiparametric analysis to improve management of occult cancers.

Background/aims: The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a "vicious cycle." Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer. Methods: Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research. Results: The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram's strong performance. Conclusions: The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00354-8.

Residual Block Based Nested U-Type Architecture for Multi-Modal Brain Tumor Image Segmentation.

Multi-modal magnetic resonance imaging (MRI) segmentation of brain tumors is a hot topic in brain tumor processing research in recent years, which can make full use of the feature information of different modalities in MRI images, so that tumors can be segmented more effectively. In this article, convolutional neural networks (CNN) is used as a tool to improve the efficiency and effectiveness of segmentation. Based on this, Dense-ResUNet, a multi-modal MRI image segmentation model for brain tumors is created. The Dense-ResUNet consists of a series of nested dense convolutional blocks and a U-Net shaped model with residual connections. The nested dense convolutional blocks can bridge the semantic disparity between the feature maps of the encoder and decoder before fusion and make full use of different levels of features. The residual blocks and skip connection can extract pixel information from the image and skip the link to solve the traditional deep traditional CNN network problem. The experiment results show that our Dense-ResUNet can effectively help to extract the brain tumor and has great clinical research and application value.

Selective Cross-Subject Transfer Learning Based on Riemannian Tangent Space for Motor Imagery Brain-Computer Interface.

A motor imagery (MI) brain-computer interface (BCI) plays an important role in the neurological rehabilitation training for stroke patients. Electroencephalogram (EEG)-based MI BCI has high temporal resolution, which is convenient for real-time BCI control. Therefore, we focus on EEG-based MI BCI in this paper. The identification of MI EEG signals is always quite challenging. Due to high inter-session/subject variability, each subject should spend long and tedious calibration time in collecting amounts of labeled samples for a subject-specific model. To cope with this problem, we present a supervised selective cross-subject transfer learning (sSCSTL) approach which simultaneously makes use of the labeled samples from target and source subjects based on Riemannian tangent space. Since the covariance matrices representing the multi-channel EEG signals belong to the smooth Riemannian manifold, we perform the Riemannian alignment to make the covariance matrices from different subjects close to each other. Then, all aligned covariance matrices are converted into the Riemannian tangent space features to train a classifier in the Euclidean space. To investigate the role of unlabeled samples, we further propose semi-supervised and unsupervised versions which utilize the total samples and unlabeled samples from target subject, respectively. Sequential forward floating search (SFFS) method is executed for source selection. All our proposed algorithms transfer the labeled samples from most suitable source subjects into the feature space of target subject. Experimental results on two publicly available MI datasets demonstrated that our algorithms outperformed several state-of-the-art algorithms using small number of the labeled samples from target subject, especially for good target subjects.

IL-10 produces a dual effect on OGD-induced neuronal apoptosis of cultured cortical neurons via the NF-κB pathway.

As a classic immunoregulatory cytokine, interleukin-10 (IL-10) can provide in vivo and in vitro neuroprotection respectively during cerebral ischemia and after the oxygen-glucose deprivation (OGD)-induced injury. However, its role in cortical neuronal survival at different post-ischemic phases remains unclear. The current study found that IL-10 had distinct effects on the neuronal apoptosis at different OGD stages: at an early stage after OGD, IL-10 promoted the OGD-induced neuronal apoptosis in the cultured primary cortical neurons by activating p65 subunit, which up-regulated Bax expression and down-regulated Bcl-xL expression; at a late OGD stage, however, it attenuated the OGD-induced neuronal apoptosis by activating c-Rel, which up-regulated Bcl-xL expression and down-regulated Bax expression. The early-stage pro-apoptosis and late-stage anti-apoptosis were both partly abolished by PDTC, an NF-κB inhibitor, and promoted by PMA, an NF-κB activator. The optimal anti-apoptotic effect appeared when the cultured neurons were treated with IL-10 at 9-24 h after OGD. Taken together, our findings suggest that IL-10 exerts a dual effect on the survival of the cultured neurons by activating the NF-κB pathway at different stages after OGD injury and that PMA treatment at a late stage can facilitate the IL-10-conferred neuroprotection against OGD-induced neuronal injury.

Enantioselective Copper-Catalyzed Cyanation of Remote C(sp3)-H Bonds Enabled by 1,5-Hydrogen Atom Transfer.

The direct functionalization of C(sp3)-H bonds has led to the development of methods to access molecules or intermediates from basic chemicals in an atom- and step-economic fashion. Nevertheless, achieving high levels of chemo-, regio-, and enantioselectivity in these reactions remains challenging due to the ubiquity and low reactivity of C(sp3)-H bonds. Herein, we report an unprecedented protocol for enantioselective cyanation of remote C(sp3)-H bonds. With chiral Box-Cu complex as the catalyst, the reaction of N-fluorosulfonamide furnishes the corresponding products in excellent yields and high enantiomeric excess (ee) under mild reaction conditions. A radical relay pathway involving 1,5-hydrogen atom transfer (1,5-HAT) of N-center radicals followed by enantioselective cyanation of the in situ-formed benzyl radicals is proposed. This enantioselective copper-catalyzed cyanation thus offers insights into an efficient way for the synthesis of bioactive molecules for drug discovery.

Enantioselective Copper-Catalyzed 1,5-Cyanotrifluoromethylation of Vinylcyclopropanes.

A copper-catalyzed enantioselective 1,5-cyanotrifluoromethylation of vinylcyclopropanes has been developed using a radical relay strategy. This asymmetric reaction has demonstrated high enantioselective control, broad substrate scope, and mild conditions. Initiated by the in situ generated CF3 radical from Togni's reagent, this method offers a new solution for remote enantioselective bifunctionalization of alkenes and thus provides a straightforward way for the synthesis of chiral CF3-containing internal alkenylnitriles.

Highly stereoselective nickel-catalyzed difluoroalkylation of aryl ketones to tetrasubstituted monofluoroalkenes and quaternary alkyl difluorides.

A nickel-catalyzed difluoroalkylation of α-C-H bonds of aryl ketones to furnish highly stereo-defined tetrasubstituted monofluoroalkenes or quaternary alkyl difluorides from secondary or tertiary ketones, respectively, has been established. Mechanistic investigations indicated that these C-H fluoroalkylations proceed via a Ni(i)/Ni(iii) catalytic cycle. An obvious fluorine effect was observed in the reaction, and this reaction has demonstrated high stereoselectivity, mild conditions, and broad substrate scopes, thus enabling the late-stage fluoroalkylation of bioactive molecules. This method offers a solution for expedient construction of monofluoroalkenes from readily available materials, and provides an efficient approach for the synthesis of bioactive fluorinated compounds for the discovery of lead compounds in medicinal chemistry.

Improving the dissolution rate of water-insoluble diflunisal by γ-cyclodextrin metal-organic framework / 药学学报

The aim of this study is to prepare porous γ-cyclodextrin metal-organic framework (CD-MOF) with good biocompatibility to improve the in vitro release properties of water-insoluble drugs. Different sizes of CD-MOF were obtained by controlling the self-assembly of γ-cyclodextrin and potassium ion and the rate of crystal growth. The poorly water-soluble diflunisal (DIF) was selected as the model drug and loaded into the interior of porous CD-MOF by the impregnation method. The DIF loaded CD-MOF (DIF-MOF) was characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), nitrogen adsorption and desorption, Fourier infrared spectrometer and thermogravimetric analysis. In addition, in vitro cytotoxicity and solubilizing capability of CD-MOF were investigated. It revealed that the obtained CD-MOF was cubic-like with a narrow size distribution and high porosity. Negligible cytotoxicity was found after incubation with RAW264.7 cells. Compared with the pure CD-MOF carrier, the morphology and crystal form of DIF-MOF was not damaged during the drug loading process. Moreover, the solubility and release rate of water-insoluble DIF from the DIF-MOF were significantly increased.

Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides.

The selective incorporation of gem-difluoroalkyl groups into biologically active molecules has long been used as an efficient strategy for drug design and discovery. However, the catalytic C(sp3)-CF2 bond-forming cross-coupling reaction for selective incorporation of difluoromethylene group into diverse alkyl chains, especially more sterically demanding secondary and tertiary functionalized alkanes, still remains as a major challenge. Herein, we describe a cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides, which exhibited high efficiency, broad scope and mild conditions. The synthetic utility of this method is demonstrated by late-stage difluoroalkylation of donepezil, a well-known acetylcholinesterase inhibitor used to treat the Alzheimer's disease. Preliminary mechanistic investigations indicate that a difluoroalkyl radical is involved in a Co(I)/Co(III) catalytic cycle. This cobalt-catalyzed fluoroalkylation thus offers insights into an efficient way for the synthesis of fluoroalkylated bioactive molecules for drug discovery.

Netrin-1 Promotes Synaptic Formation and Axonal Regeneration via JNK1/c-Jun Pathway after the Middle Cerebral Artery Occlusion.

As a secreted axon guidance molecule, Netrin-1 has been documented to be a neuroprotective factor, which can reduce infarct volume, promote angiogenesis and anti-apoptosis after stroke in rodents. However, its role in axonal regeneration and synaptic formation after cerebral ischemic injury, and the related underlying mechanisms remain blurred. In this study, we used Adeno-associated vectors carrying Netrin-1 gene (AAV-NT-1) to up-regulate the expression level of Netrin-1 in rats' brain after middle cerebral artery occlusion (MCAO). We found that the up-regulated level of Netrin-1 and its receptor DCC promoted axonal regeneration and synaptic formation; the overexpression of Netrin-1 activated the JNK1 signaling pathway; these effects were partially reduced when JNK1 signaling pathway was inhibited by SP600125 (JNK specific inhibitor). Taken together, these findings suggest that Netrin-1 can facilitate the synaptic formation and axonal regeneration via the JNK1 signaling pathway after cerebral ischemia, thus promoting the recovery of neural functions.

Nickel-Catalyzed Heck-Type Monofluoroacetation of Styrenes for Facile Synthesis of Allylic Fluorides.

An efficient nickel-catalyzed Heck-type reaction between styrenes and fluoroalkyl iodine has been developed. This novel transformation has demonstrated a broad substrate scope, mild reaction conditions and excellent E-stereoselectivity. This efficient synthetic method has been applied to the late-stage monofluoroacetation of biologically active molecules. Mechanistic investigations indicate that a monofluoroalkyl radical is involved in the catalytic cycle.

Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis via the DCC/ERK Pathway.

In the nervous system, Netrin-1 serves as a neural guide, mediating the neuronal development. However, it remains blurred whether Netrin-1 can protect neurons from apoptosis induced by cerebral stroke. In the current study, the cultured rat primary cortical neurons were transfected with Netrin-1-encoding lentivirus before the oxygen-glucose-deprivation (OGD) treatment. Cell death and apoptosis were evaluated by lactate dehydrogenase (LDH) release and flow cytometry. We found that Netrin-1 attenuated OGD-induced cell death and neuronal apoptosis at 24 h after OGD treatment, and that the overexpression of Netrin-1 activated the ERK signaling pathway. These effects were partly abolished by blocking its receptor deleted in colorectal cancer (DCC) or U0126, an inhibitor of the ERK signaling pathway. Netrin-1 overexpression in neurons elevated the expression of DCC, on mRNA level and protein level. Netrin-1 also reduced DNA damage. Taken together, our findings suggest that Netrin-1 attenuates cell death and neuronal apoptosis via the DCC/ERK signaling pathway in the cultured primary cortical neurons after OGD injury, which may involve the mediation of DNA damage in the neurons.

Nickel-Catalyzed Monofluoroalkylation of Arylsilanes via Hiyama Cross-Coupling.

The first example of nickel-catalyzed monofluoroalkylation of arylsilanes has been developed with readily available fluoroalkyl halides. This novel transformation has demonstrated high reactivity, broad substrate scope, excellent functional group tolerance, and mild reaction conditions. The selective activation of a relatively inert C-Si bond for slow release of aryl carbanion is the key reason for reducing the amount of arylmetal species, which makes this method more promising for fluorine-containing modification of complex bioactive molecules. Mechanistic investigations indicate that a free fluoroalkyl radical is involved in this catalytic cycle.

Copper-Catalyzed Decarboxylative Atom Transfer Radical Addition of Iododifluoroacetate to Alkynyl Carboxylic Acids.

The first example of copper-catalyzed decarboxylative atom transfer radical addition of alkynyl carboxylic acids has been developed with a readily available fluoroalkyl halide. This novel protocol has demonstrated a unique difunctionalization of nonterminal alkynes with a broad substrate scope and excellent functional-group tolerance. Mechanistic investigations revealed that the catalytic cycle was initiated by the attack of a difluoroalkyl radical to an in situ generated alkynylcopper species.

Sporolactobacillus pectinivorans sp. nov., an anaerobic bacterium isolated from spoiled jelly.

A Gram-positive-staining, endospore-forming, facultatively anaerobic, lactic-acid-producing bacterium, strain GD201205T, was isolated from spoiled jelly in China. Strain GD201205T fermented glucose, fructose, mannose, sucrose, raffinose and turanose, but negative for nitrate reduction, catalase and oxidase. The predominant fatty acids of the strain were anteiso-C17 : 0 and anteiso-C15 : 0. Whole-cell hydrolysates contained glycine and alanine with meso-iaminopimelic acid as the diagnostic diamino acid. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, glycolipid 1 and glycolipid 2. The DNA G+C content of strain GD201205T was 48.7 mol%. 16S rRNA gene sequence analysis indicated that the strain belonged to the genus Sporolactobacillus and was most closely related to Sporolactobacillus vineaeKCTC 5376T and Sporolactobacillus putidusJCM 15325T with 16S rRNA gene sequence similarities of 97.5 and 96.9 %, respectively. Levels of DNA-DNA relatedness between strain GD201205T and Sporolactobacillus vineaeKCTC 5376Tand Sporolactobacillus putidusJCM 15325T were 29.2 and 47.6 %, respectively. Phylogenetic analysis based on the 16S rRNA gene and gyrB gene revealed that strain GD201205T was clearly distinct from all related species of the genus Sporolactobacillus. On the basis of the phylogenetic, chemotaxonomic and phenotypic evidence given in this study, strain GD201205T should be classified as a representative of a novel species of the genus Sporolactobacillus for which the name Sporolactobacillus pectinivorans is proposed. The type strain is GD201205T (=CICC 23867T=KCTC 15488T).

Nickel-Catalyzed Decarboxylative Difluoroalkylation of α,ß-Unsaturated Carboxylic Acids.

The first example of nickel-catalyzed decarboxylative fluoroalkylation of α,ß-unsaturated carboxylic acids has been developed with commonly available fluoroalkyl halides. This novel transformation has demonstrated broad substrate scope, excellent functional-group tolerance, mild reaction conditions, and excellent stereoselectivity. Mechanistic investigations indicate that a fluoroalkyl radical is involved in the catalytic cycle.

Pd-Catalyzed C(sp(3))-H Carbonylation of Alkylamines: A Powerful Route to γ-Lactams and γ-Amino Acids.

A novel Pd-catalyzed direct C(sp(3))-H carbonylation of alkylamines for the synthesis of γ-lactams and γ-amino acids has been developed, in which TEMPO was used as the crucial sole oxidant. The synthetic prospect was demonstrated by the concise total synthesis of rac-Pregbalin.

Nickel-catalyzed monofluoromethylation of aryl boronic acids.

Aryl boronic acids can be monofluoromethylated under nickel catalysis. The utility of this method is demonstrated by the monofluoromethylation of a borylated and acyl-protected derivative of the statin drug ezetimibe. Mechanistic investigations indicate that a fluoromethyl radical is involved in the Ni(I)/Ni(III) catalytic cycle.

Pd(II)-catalyzed, controllable C-H mono-/diarylation of aryl tetrazoles: concise synthesis of Losartan.

A palladium(II)-catalyzed C-H arylation directed by tetrazole, a metabolically stable surrogate for the carboxylic acid group in drug design, has been developed. Excellent mono-/di-selectivity was achieved through adjustment of the protecting site on the tetrazole ring. The synthetic utility of this new transformation was demonstrated in the concise total synthesis of Losartan.