N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer's disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk.

BACKGROUND: Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. METHODS: 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aß accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. RESULTS: chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aß accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. CONCLUSION: The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.

Electrospinning-assisted porous skeleton electrolytes for semi-solid Li-O2 batteries.

Solid-state lithium-oxygen batteries offer great promise in meeting the practical demand for high-energy-density and safe energy storage. We have developed fibrous gel polymer electrolytes (GPEs) using a polyacrylonitrile (PAN) matrix via electrospinning. The 3D structure of GPEs enhances electrolyte absorption, while the interconnected design promotes strong interactions between Li+ and polar groups within the PAN matrix, thereby improving ion transport efficiency. In practical tests, both lithium symmetric cells and Li-O2 batteries demonstrated the ability to operate at high current densities over long cycles.

[Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia].

OBJECTIVE: To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. METHODS: 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. RESULTS: The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. CONCLUSION: The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

Targeting EGFR degradation by autophagosome degraders.

Several generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed for the treatment of non-small cell lung cancer (NSCLC) in clinic. However, emerging drug resistance mediated by new EGFR mutations or activations by pass, leads to malignant progression of NSCLC. Proteolysis targeting chimeras (PROTACs) have been utilized to overcome the drug resistance acquired by mutant EGFR, newly potent and selective degraders are still need to be developed for clinical applications. Herein, we developed autophagosome-tethering compounds (ATTECs) in which EGFR can be anchored to microtubule-associated protein-1 light chain-3B (LC3B) on the autophagosome with the assistance of the LC3 ligand GW5074. A series of EGFR-ATTECs have been designed and synthesized. Biological evaluations showed that these compounds could degrade EGFR and exhibited moderate inhibitory effects on certain NSCLC cell lines. The ATTEC 12c potently induced the degradation of EGFR with a DC50 value of 0.98 µM and a Dmax value of 81% in HCC827 cells. Mechanistic exploration revealed that the lysosomal pathway was mainly involved in this degradation. Compound 12c also exhibited promising inhibitory activity, as well as degradation efficiency in vivo. Our study highlights that EGFR-ATTECs could be developed as a new expandable EGFR degradation tool and also reveals a novel potential therapeutic strategy to prevent drug resistance acquired EGFR mutations.

Plant genomic resources at National Genomics Data Center: assisting in data-driven breeding applications.

Genomic data serve as an invaluable resource for unraveling the intricacies of the higher plant systems, including the constituent elements within and among species. Through various efforts in genomic data archiving, integrative analysis and value-added curation, the National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), has successfully established and currently maintains a vast amount of database resources. This dedicated initiative of the NGDC facilitates a data-rich ecosystem that greatly strengthens and supports genomic research efforts. Here, we present a comprehensive overview of central repositories dedicated to archiving, presenting, and sharing plant omics data, introduce knowledgebases focused on variants or gene-based functional insights, highlight species-specific multiple omics database resources, and briefly review the online application tools. We intend that this review can be used as a guide map for plant researchers wishing to select effective data resources from the NGDC for their specific areas of study. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00134-4.

Magnetically modified bacteriophage-triggered ATP release activated EXPAR-CRISPR/Cas14a system for visual detection of Burkholderia pseudomallei.

Burkholderia pseudomallei, widely distributed in tropical and subtropical ecosystems, is capable of causing the fatal zoonotic disease melioidosis and exhibiting a global trend of dissemination. Rapid and sensitive detection of B. pseudomallei is essential for environmental monitoring as well as infection control. Here, we developed an innovative biosensor for quantitatively detecting B. pseudomallei relies on ATP released triggered by bacteriophage-induced bacteria lysis. The lytic bacteriophage vB_BpP_HN01, with high specificity, is employed alongside magnetic nanoparticles assembly to create a biological receptor, facilitating the capture and enrichment of viable target bacteria. Following a brief extraction and incubation process, the captured target undergoes rapid lysis to release contents including ATP. The EXPAR-CRISPR cascade reaction provides an efficient signal transduction and dual amplification module that allowing the generated ATP to guide the signal output as an activator, ultimately converting the target bacterial amount into a detectable fluorescence signal. The proposed bacteriophage affinity strategy exhibited superior performance for B. pseudomallei detection with a dynamic range from 10^2 to 10^7 CFU mL-1, and a LOD of 45 CFU mL-1 within 80 min. Moreover, with the output signal compatible across various monitoring methods, this work offers a robust assurance for rapid diagnosis and on-site environmental monitoring of B. pseudomallei.

Meta Clothing Status Calibration for Long-Term Person Re-Identification.

Recent studies have seen significant advancements in the field of long-term person re-identification (LT-reID) through the use of clothing-irrelevant or insensitive features. This work takes the field a step further by addressing a previously unexplored issue, the Clothing Status Distribution Shift (CSDS). CSDS refers to the differing ratios of samples with clothing changes to those without clothing changes between the training and test sets, leading to a decline in LT-reID performance. We establish a connection between the performance of LT-reID and CSDS, and argue that addressing CSDS can improve LT-reID performance. To that end, we propose a novel framework called Meta Clothing Status Calibration (MCSC), which uses meta-learning to optimize the LT-reID model. Specifically, MCSC simulates CSDS between meta-train and meta-test with meta-optimization objectives, optimizing the LT-reID model and making it robust to CSDS. This framework is designed to prevent overfitting and improve the generalization ability of the LT-reID model in the presence of CSDS. Comprehensive evaluations on seven datasets demonstrate that the proposed MCSC framework effectively handles CSDS and improves current state-of-the-art LT-reID methods on several LT-reID benchmarks.

Unraveling Reactivity Differences: Room-Temperature Ring-Opening Metathesis Polymerization (ROMP) versus Frontal ROMP.

In this study, we explore the distinct reactivity patterns between frontal ring-opening metathesis polymerization (FROMP) and room-temperature solventless ring-opening metathesis polymerization (ROMP). Despite their shared mechanism, we find that FROMP is less sensitive to inhibitor concentration than room-temperature ROMP. By increasing the initiator-to-monomer ratio for a fixed inhibitor/initiator quantity, we find reduction in the ROMP background reactivity at room temperature (i.e., increased resin pot life). At elevated temperatures where inhibitor dissociation prevails, accelerated frontal polymerization rates are observed because of the concentrated presence of the initiator. Surprisingly, the strategy of employing higher initiator loading enhances both pot life and front speeds, which leads to FROMP rates exceeding prior reported values by over 5 times. This counterintuitive behavior is attributed to an increase in the proximity of the inhibitor to the initiator within the bulk resin and to whether the temperature favors coordination or dissociation of the inhibitor. A rapid method was developed for assessing resin pot life, and a straightforward model for active initiator behavior was established. Modified resin systems enabled direct ink writing of robust thermoset structures at rates much faster than previously possible.

Leaf Senescence Database v5.0: A Comprehensive Repository for Facilitating Plant Senescence Research.

Through an extensive literature survey, we have upgraded the Leaf Senescence Database (LSD v5.0; https://ngdc.cncb.ac.cn/lsd/), a curated repository of comprehensive senescence-associated genes (SAGs) and their corresponding mutants. Since its inception in 2010, LSD undergoes frequent updates to encompass the latest advances in leaf senescence research and its current version comprises a high-quality collection of 31,740 SAGs and 1,209 mutants from 148 species, which were manually searched based on robust experimental evidence and further categorized according to their functions in leaf senescence. Furthermore, LSD was greatly enriched with comprehensive annotations for the SAGs through meticulous curation using both manual and computational methods. In addition, it was equipped with user-friendly web interfaces that facilitate text queries, BLAST searches, and convenient download of SAG sequences for localized analysis. Users can effortlessly navigate the database to access a plethora of information, including literature references, mutants, phenotypes, multi-omics data, miRNA interactions, homologs in other plants, and cross-links to various databases. Taken together, the upgraded version of LSD stands as the most comprehensive and informative plant senescence-related database to date, incorporating the largest collection of SAGs and thus bearing great utility for a wide range of studies related to plant senescence.

[Analysis of the Jumping Characteristics and Influencing Factors of Ozone Pollution in Beijing].

Based on environmental monitoring data and meteorological observation data from 2016 to 2022 in Beijing, combined with backward trajectory clustering and potential source area contribution analysis, the characteristics, meteorological impacts, and potential source areas of ozone (O3) pollution were analyzed. The results showed that there was a total of 41 O3 pollution processes with jumping characteristics in Beijing from 2016 to 2022, with an average of 5.9 times a year. The occurrence time was concentrated in May to July, and the day of the jump (OJD2) was higher than the day before the jump (OJD1). The average value of ρ(O3-8h) was 78.3% higher, and the peak concentration was 78.9% higher. The high O3 concentration zone in the OJD2 region exhibited a characteristic of advancing from south to north. The main reasons for the occurrence of jumped O3 pollution in Beijing could be summarized as local accumulation caused by unfavorable meteorological conditions and regional transmission impact. The occurrence of jump-type ozone pollution was characterized by an increase in southerly wind frequency, temperature rise, pressure decrease, and precipitation decrease. The increase in southerly wind frequency provided conditions for the transport of O3 and its precursors, and rapid photochemical reactions occurred under local high temperatures, with less superimposed precipitation, comprehensively pushing up the ozone concentration level of OJD2. Six air mass transporting pathways were identified through clustering analysis; the air mass from the direction north of OJD2 decreased by 11.2%, whereas the air mass from the south and east directions increased by 6.7% and 4.4%, respectively, with the air masses mainly transmitting over short distances. The ozone concentration corresponding to the south and east directions was relatively high, making a significant contribution to Beijing's pollution. The analysis of potential source areas revealed that the main potential source areas of OJD2 ozone pollution were the central, southern, and eastern parts of Beijing-Tianjin-Hebei, which contributed 82.6% to the pollution trajectory. There was a significant contribution of regional transport during jump-type ozone pollution, and it is necessary to strengthen joint prevention and control in the Beijing-Tianjin-Hebei Region.

CircPRDM5 inhibits the proliferation, migration, invasion, and glucose metabolism of gastric cancer cells by reducing GCNT4 expression in a miR-485-3p-dependent manner.

Circular RNA (circRNA) plays a key part in the pathological process of gastric cancer (GC). The study is organized to analyze the function of circPRDM5 in GC cell tumor properties. Expression levels of circPRDM5, miR-485-3p, glucosaminyl (N-acetyl) transferase 4 (GCNT4), ki67, E-cadherin, N-cadherin, and hexokinase 2 (HK2) were analyzed by quantitative real-time polymerase chain reaction (PCR), Western blotting or immunohistochemistry assay. Cell proliferation was assessed by cell colony formation assay and 5-ethynyl-2'-deoxyuridine assay. Cell migration and invasion were investigated by transwell assay. Glycolysis was evaluated by the Seahorse XF Glycolysis Stress Test Kit. Dual-luciferase reporter assay and RNA pull-down assay were performed to identify the associations among circPRDM5, miR-485-3p, and GCNT4. Xenograft mouse model assay was conducted to determine the effects of circPRDM5 on tumor formation in vivo. CircPRDM5 and GCNT4 expression were downregulated, while miR-485-3p expression was upregulated in GC tissues and cells when compared with paracancerous tissues or human gastric epithelial cells. CircPRDM5 overexpression inhibited proliferation, migration, invasion, and glucose metabolism of GC cells; however, circPRDM5 depletion had the opposite effects. CircPRDM5 repressed tumor properties of GC cells in vivo. MiR-485-3p restoration relieved circPRDM5-induced effects in GC cells. GCNT4 overexpression remitted the promoting effects of miR-485-3p mimics on GC cell malignancy. CircPRDM5 acted as a sponge for miR-485-3p, and GCNT4 was identified as a target gene of miR-485-3p. Moreover, circPRDM5 regulated GCNT4 expression by interacting with miR-485-3p.CircPRDM5 acted as a miR-485-3p sponge to inhibit GC progression by increasing GCNT4 expression, proving a potential target for GC therapy.

Dissecting the associations of KCNH2 genetic polymorphisms with various types of cardiac arrhythmias.

BACKGROUND: Cardiac arrhythmia, a common cardiovascular disease, is closely related to genetic polymorphisms. However, the associations between polymorphisms in KCNH2 and various arrhythmias remain inadequately explored. METHODS: Guided by the assumption that KCNH2 genetic polymorphisms significantly contribute to the development of arrhythmias, we thoroughly explored the associations between 85 KCNH2 genetic variations and 16 cardiac arrhythmias in a sample obtained from the UK Biobank (UKBB, N = 307,473). The illnesses documented in the electronic medical records of the sample were mapped to a phecode system for a more accurate representation of distinct phenotypes. Survival analysis was used to test the effect of KCNH2 variants on arrhythmia incidence, and a phenotype-wide association study (PheWAS) was performed to investigate the effect of KCNH2 polymorphisms on 102 traits, including physical measurements, biomarkers, and hematological indicators. RESULTS: Novel associations of variants rs2269001 and rs7789585 in KCNH2 with paroxysmal tachycardia (PT) and atrial fibrillation/flutter (AF/AFL), respectively, were identified. Moreover, with an increase in the number of minor alleles of these two variants, the incidence rates of PT and AF/AFL decreased. In addition, the PheWAS results suggested that these two single nucleotide polymorphisms were associated with multiple parameters in physical measurements and neutrophil percentage. CONCLUSION: The multiple novel associations observed in this study illustrate the importance of KCNH2 genetic variations in the pathogenesis of arrhythmia.

Novel Covalent Probe Selectively Targeting Glutathione Peroxidase 4 In Vivo: Potential Applications in Pancreatic Cancer Therapy.

Glutathione peroxidase 4 (GPX4) emerges as a promising target for the treatment of therapy-resistant cancer through ferroptosis. Thus, there is a broad interest in the development of GPX4 inhibitors. However, a majority of reported GPX4 inhibitors utilize chloroacetamide as a reactive electrophilic warhead, and the selectivity and pharmacokinetic properties still need to be improved. Herein, we developed a compound library based on a novel electrophilic warhead, the sulfonyl ynamide, and executed phenotypic screening against pancreatic cancer cell lines. Notably, one compound A16 exhibiting potent cell toxicity was identified. Further chemical proteomics investigations have demonstrated that A16 specifically targets GPX4 under both in situ and in vivo conditions, inducing ferroptosis. Importantly, A16 exhibited superior selectivity and potency compared to reported GPX4 inhibitors, ML210 and ML162. This provides the structural diversity of tool probes for unraveling the fundamental biology of GPX4 and exploring the therapeutic potential of pancreatic cancer via ferroptosis induction.

Sympathetic nervous system activity is associated with choroidal thickness and axial length in school-aged children.

BACKGROUND/AIMS: We aim to explore the effect of sympathetic nervous system (SNS) on choroid thickness (ChT) and axial length (AL). METHODS: Students of grade 2 and 3 from a primary school were included and followed for 1 year. Visual acuity, refraction, AL and ChT were measured. Morning urine samples were collected for determining SNS activity by analysing concentrations of epinephrine, norepinephrine and dopamine using the liquid chromatography-tandem mass spectrometry. The most important factor (factor 1) was calculated using factor analysis to comprehensively indicate the SNS activity. RESULTS: A total of 273 students were included, with an average age of 7.77±0.69 years, and 150 (54.95%) were boys. Every 1 µg/L increase in epinephrine is associated with 1.60 µm (95% CI 0.30 to 2.90, p=0.02) decrease in average ChT. Every 1 µg/L increase in norepinephrine is associated with 0.53 µm (95% CI 0.08 to 0.98, p=0.02) decrease in the ChT in inner-superior region. The factor 1 was negatively correlated with the ChT in the superior regions. Every 1 µg/L increase in norepinephrine was associated with 0.002 mm (95% CI 0.0004 to 0.004, p=0.016) quicker AL elongation. The factor 1 was positively correlated with AL elongation (coefficient=0.037, 95% CI 0.005 to 0.070, p=0.023). CONCLUSIONS: We hypothesised that chronic stress characterised by elevated level of the SNS, was associated with significant increase in AL elongation, probably through thinning of the choroid.

A multi-institutional study to predict the benefits of DEB-TACE and molecular targeted agent sequential therapy in unresectable hepatocellular carcinoma using a radiological-clinical nomogram.

OBJECTIVE: Exploring the efficacy of a Radiological-Clinical (Rad-Clinical) model in predicting prognosis of unresectable hepatocellular carcinoma (HCC) patients after drug eluting beads transcatheter arterial chemoembolization (DEB-TACE) to optimize the targeted sequential treatment. METHODS: In this retrospective analysis, we included 202 patients with unresectable HCC who received DEB-TACE treatment in 17 institutions from June 2018 to December 2022. Progression-free survival (PFS)-related radiomics features were computationally extracted from HCC patients to build a radiological signature (Rad-signature) model with least absolute shrinkage and selection operator regression. A Rad-Clinical model for postoperative PFS was further constructed according to the Rad-signature and clinical variables by Cox regression analysis. It was presented as a nomogram and evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. And further evaluate the application value of Rad-Clinical model in clinical stages and targeted sequential therapy of HCC. RESULTS: Tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and radiomics score (Rad-score) were found to be independent risk factors for PFS after DEB-TACE treatment for unresectable HCC, with the Rad-Clinical model being the greatest predictor of PFS in these patients (hazard ratio: 2.08; 95% confidence interval: 1.56-2.78; P < 0.001) along with high 6 months, 12 months, 18 months, and 24 months area under the curves of 0.857, 0.810, 0.843, and 0.838, respectively. In addition, compared to the radiomics and clinical nomograms, the Radiological-Clinical nomogram also significantly improved the classification accuracy for PFS outcomes, based on the net reclassification improvement (45.2%, 95% CI 0.260-0.632, p < 0.05) and integrated discrimination improvement (14.9%, 95% CI 0.064-0.281, p < 0.05). Based on this model, low-risk patients had higher PFS than high-risk patients in BCLC-B and C stages (P = 0.021). Targeted sequential therapy for patients with high and low-risk HCC in BCLC-B stage exhibited significant benefits (P = 0.018, P = 0.012), but patients with high-risk HCC in BCLC-C stage did not benefit much (P = 0.052). CONCLUSION: The Rad-Clinical model may be favorable for predicting PFS in patients with unresectable HCC treated with DEB-TACE and for identifying patients who may benefit from targeted sequential therapy.

OPIA: an open archive of plant images and related phenotypic traits.

High-throughput plant phenotype acquisition technologies have been extensively utilized in plant phenomics studies, leading to vast quantities of images and image-based phenotypic traits (i-traits) that are critically essential for accelerating germplasm screening, plant diseases identification and biotic & abiotic stress classification. Here, we present the Open Plant Image Archive (OPIA, https://ngdc.cncb.ac.cn/opia/), an open archive of plant images and i-traits derived from high-throughput phenotyping platforms. Currently, OPIA houses 56 datasets across 11 plants, comprising a total of 566 225 images with 2 417 186 labeled instances. Notably, it incorporates 56 i-traits of 93 rice and 105 wheat cultivars based on 18 644 individual RGB images, and these i-traits are further annotated based on the Plant Phenotype and Trait Ontology (PPTO) and cross-linked with GWAS Atlas. Additionally, each dataset in OPIA is assigned an evaluation score that takes account of image data volume, image resolution, and the number of labeled instances. More importantly, OPIA is equipped with useful tools for online image pre-processing and intelligent prediction. Collectively, OPIA provides open access to valuable datasets, pre-trained models, and phenotypic traits across diverse plants and thus bears great potential to play a crucial role in facilitating artificial intelligence-assisted breeding research.

The P10K database: a data portal for the protist 10 000 genomes project.

Protists, a highly diverse group of microscopic eukaryotic organisms distinct from fungi, animals and plants, exert crucial roles within the earth's biosphere. However, the genomes of only a small fraction of known protist species have been published and made publicly accessible. To address this constraint, the Protist 10 000 Genomes Project (P10K) was initiated, implementing a specialized pipeline for single-cell genome/transcriptome assembly, decontamination and annotation of protists. The resultant P10K database (https://ngdc.cncb.ac.cn/p10k/) serves as a comprehensive platform, collating and disseminating genome sequences and annotations from diverse protist groups. Currently, the P10K database has incorporated 2959 genomes and transcriptomes, including 1101 newly sequenced datasets by P10K and 1858 publicly available datasets. Notably, it covers 45% of the protist orders, with a significant representation (53% coverage) of ciliates, featuring nearly a thousand genomes/transcriptomes. Intriguingly, analysis of the unique codon table usage among ciliates has revealed differences compared to the NCBI taxonomy system, suggesting a need to revise the codon tables used for these species. Collectively, the P10K database serves as a valuable repository of genetic resources for protist research and aims to expand its collection by incorporating more sequenced data and advanced analysis tools to benefit protist studies worldwide.

Electrochemically Promoted Three-Component Reaction to N-Sulfonyl Amidines.

In this study, a multicomponent reaction via the Mannich intermediate was developed using methanol, secondary amine, and sulfonamide as starting materials. This method uses methanol as a green C1 source. The substrate scope is wide, and the yield is good. The mechanistic study shows that methanol generates formaldehyde under electrochemical conditions, and sulfonyl amidine as a nucleophile reacts with Schiff base intermediates to form N-sulfonyl amidine in a single step.

Enhancing Person Re-Identification Performance Through In Vivo Learning.

This research investigates the potential of in vivo learning to enhance visual representation learning for image-based person re-identification (re-ID). Compared to traditional self-supervised learning (which require external data), the introduced in vivo learning utilizes supervisory labels generated from pedestrian images to improve re-ID accuracy without relying on external data sources. Three carefully designed in vivo learning tasks, leveraging statistical regularities within images, are proposed without the need for laborious manual annotations. These tasks enable feature extractors to learn more comprehensive and discriminative person representations by jointly modeling various aspects of human biological structure information, contributing to enhanced re-ID performance. Notably, the method seamlessly integrates with existing re-ID frameworks, requiring minimal modifications and no additional data beyond the existing training set. Extensive experiments on diverse datasets, including Market1501, CUHK03-NP, Celeb-reID, Celeb-reid-light, PRCC, and LTCC, demonstrate substantial enhancements in rank-1 precision compared to state-of-the-art methods.

Discovery of a potent and selective covalent threonine tyrosine kinase (TTK) inhibitor.

Threonine tyrosine kinase (TTK) is a critical component of the spindle assembly checkpoint and plays a pivotal role in mitosis. TTK has been identified as a potential therapeutic target for human cancers. Here, we describe our design, synthesis and evaluation of a class of covalent TTK inhibitors, exemplified by 16 (SYL1073). Compound 16 potently inhibits TTK kinase with an IC50 of 0.016 µM and displays improved selectivity in a panel of kinases. Mass spectrometry analysis reveals that 16 covalently binds to the C604 cysteine residue in the hinge region of the TTK kinase domain. Furthermore, 16 achieves strong potency in inhibiting the growth of various human cancer cell lines, outperforming its relative reversible inhibitor, and eliciting robust downstream effects. Taken together, compound 16 provides a valuable lead compound for further optimization toward the development of drug for treatment of human cancers.