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Abstract Background The pregnant women with intrahepatic cholestasis were at high risk of fetal distress, preterm birth and unexpected stillbirth. Intrahepatic cholestasis of pregnancy (ICP) was mainly caused by disorder of bile acid metabolism, whereas the specific mechanism was obscure. Methods We performed proteomics analysis of 10 ICP specimens and 10 placenta specimens from patients without ICP through data-independent acquisition (DIA) technique to disclose differentially expressed proteins. We executed metabolomic analysis of 30 ICP specimens and 30 placenta specimens from patients without ICP through UPLC-MS/MS to identify differentially expressed metabolites. Enrichment and correlation analysis was used to obtain the direct molecular insights of ICP development. The ICP rat models were constructed to validate pathological features. Results The heatmap of proteomics analysis showed the top 30 up-regulated and 30 down-regulated proteins. The metabolomic analysis revealed 20 richer and 4 less abundant metabolites in ICP samples compared with placenta specimens from patients without ICP, and enrichment pathways by these metabolites included primary bile acid biosynthesis, cholesterol metabolism, bile secretion, nicotinate and nicotinamide metabolism, purine metabolism and metabolic pathways. Combined analysis of multiple omics results demonstrated that bile acids such as Glycohyocholic acid, Glycine deoxycholic acid, beta-Muricholic acid, Noncholic acid, cholic acid, Gamma-Mercholic Acid, alpha-Muricholic acid and Glycochenodeoxycholic Aicd were significantly associated with the expression of GLRX3, MYL1, MYH7, PGGT1B, ACTG1, SP3, LACTB2, C2CD5, APBB2, IPO9, MYH2, PPP3CC, PIN1, BLOC1S1, DNAJC7, RASAL2 and ATCN3 etc. The core protein ACAT2 was involved in lipid metabolic process and animal model showed that ACAT2 was up-regulated in placenta and liver of pregnant rats and fetal rats. The neonates had low birth weight and Safranin O-Fast green FCF staining of animal models showed that poor osteogenic and chondrogenic differentiation of fetal rats. Conclusion Multiple metabolites-alpha-Muricholic acid, beta-Muricholic acid, Glycine deoxycholic acid and Glycochenodeoxycholic Acid etc. were perfect biomarkers to predict occurrence of ICP. Bile acids were significantly associated with varieties of protein expression and these proteins were differentially expressed in ICP samples. Our study provided several biomarkers for ICP detection and potential therapeutic targets for ICP development.

Abstract As the most abundant organic substances in nature, carbohydrates are essential for life. Understanding how carbohydrates regulate proteins in the physiological and pathological processes presents opportunities to address crucial biological problems and develop new therapeutics. However, the diversity and complexity of carbohydrates pose a challenge in experimentally identifying the sites where carbohydrates bind to and act on proteins. Here, we introduce a deep learning model, DeepGlycanSite, capable of accurately predicting carbohydrate-binding sites on a given protein structure. Incorporating geometric and evolutionary features of proteins into a deep equivariant graph neural network with the transformer architecture, DeepGlycanSite remarkably outperforms previous state-of-the-art methods and effectively predicts binding sites for diverse carbohydrates. Integrating with a mutagenesis study, DeepGlycanSite reveals the guanosine-5’-diphosphate-sugar-recognition site of an important G-protein coupled receptor. These findings demonstrate DeepGlycanSite is invaluable for carbohydrate-binding site prediction and could provide insights into molecular mechanisms underlying carbohydrate-regulation of therapeutically important proteins.

Abstract Background Inherited variations in DNA double-strand break (DSB) repair pathway are known to influence ovarian cancer occurrence, progression and treatment response. Despite its significance, survival-associated genetic variants within the DSB pathway remain underexplored. Methods In the present study, we performed a two-phase analysis of 19,290 single-nucleotide polymorphisms (SNPs) in 199 genes in the DSB repair pathway from a genome-wide association study (GWAS) dataset and explored their associations with overall survival (OS) in 1039 Han Chinese epithelial ovarian carcinoma (EOC) patients. After utilizing multivariate Cox regression analysis with bayesian false-discovery probability for multiple test correction, significant genetic variations were identified and subsequently underwent functional prediction and validation. Results We discovered a significant association between poor overall survival and the functional variant GEN1 rs56070363 C > T (CT + TT vs. TT, adjusted hazard ratio (HR) = 2.50, P T on survival was attributed to its reduced binding affinity to hsa-miR-1287-5p and the resultant upregulation of GEN1 mRNA expression. Overexpression of GEN1 aggregated EOC cell proliferation, invasion and migration presumably by influencing the expression of immune inhibitory factors, thereby elevating the proportion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and then constructing an immunosuppressive tumor microenvironment. Conclusions In conclusion, GEN1 rs56070363 variant could serve as a potential predictive biomarker and chemotherapeutic target for improving the survival of EOC patients.

In the evolving landscape of deep learning technologies, the emergence of Deepfakes and synthetic media is becoming increasingly prominent within digital media production. This research addresses the limitations inherent in existing face image generation algorithms based on Generative Adversarial Networks (GAN), particularly the challenges of domain irrelevancy and inadequate facial detail representation. The study introduces an enhanced face image generation algorithm, aiming to refine the CycleGAN framework. The enhancement involves a two-fold strategy: firstly, the generator's architecture is refined through the integration of an attention mechanism and adaptive residual blocks, enabling the extraction of more nuanced facial features. Secondly, the discriminator's accuracy in distinguishing real from synthetic images is improved by incorporating a relative loss concept into the loss function. Additionally, this study presents a novel model training approach that incorporates age constraints, thereby mitigating the effects of age variations on the synthesized images. The effectiveness of the proposed algorithm is empirically validated through comparative analysis with existing methodologies, utilizing the CelebA dataset. The results demonstrate that the proposed algorithm significantly enhances the realism of generated face images, outperforming current methods in terms of Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index Measure (SSIM), while also achieving notable improvements in subjective visual quality. The implementation of this advanced method is anticipated to substantially elevate the efficiency and quality of digital media production, contributing positively to the broader field of digital media creation.

Summary: Kisspeptin signaling through its G protein-coupled receptor, KISS1R, plays an indispensable role in regulating reproduction via the hypothalamic-pituitary-gonadal axis. Dysregulation of this pathway underlies severe disorders like infertility and precocious puberty. Here, we present cryo-EM structures of KISS1R bound to the endogenous agonist kisspeptin-10 and a synthetic analog TAK-448. These structures reveal pivotal interactions between peptide ligands and KISS1R extracellular loops for receptor activation. Both peptides exhibit a conserved binding mode, unveiling their common activation mechanism. Intriguingly, KISS1R displays a distinct 40° angular deviation in its intracellular TM6 region compared to other Gq-coupled receptors, enabling distinct interactions with Gq. This study reveals the molecular intricacies governing ligand binding and activation of KISS1R, while highlighting its exceptional ability to couple with Gq. Our findings pave the way for structure-guided design of therapeutics targeting this physiologically indispensable receptor.

Abstract Background Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. Methods The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). Results Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. Conclusions CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.

Abstract To explore the optimal cut-off values of Klotho for predicting all-cause and cardiovascular mortality among chronic kidney disease (CKD) patients. Klotho was measured in 40–79-year-old individuals in the NHANES 2007–2016. A total of 2418 patients with stage 1–4 CKD were included. The optimal cut-off values of Klotho were utilized using receiver operator characteristic (ROC) curves and be verified on the effects of all-cause and cardiovascular mortality. Restricted cubic splines were used to examine the relationship between Klotho and all-cause and cardiovascular mortality with the optimal cutpoints as the reference. After a mean follow-up period of 87.9 months, 535 deaths occurred and 188 died of cardiovascular disease. Cubic splines showed that the risk of all-cause and cardiovascular mortality increased gradually for Klotho

Abstract Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

Abstract In the field of world heritage conservation, there has been broad consensus on carrying out heritage conservation research on the basis of spatial integration and interregional and international cooperation. However, there are still many deficiencies in the integration of culture with the environment, regional economic and social development, and the regional, holistic and multimodal conservation and utilization of cultural heritage sites. In China, the Dongjiang-Hanjiang River Basin is a representative area of substantial cultural and ecological value for both Guangdong Province and the whole country. This paper uses the morphological spatial pattern analysis and the minimum cumulative resistance model to integrate cultural ecology sources and establish a cross-regional and large-scale cultural ecology network system that includes 1 main corridor, 22 important corridors and 17 secondary corridors. In addition, based on identified cultural landscape nodes and cultural ecology services, the economy of the cultural ecology corridor could be developed with large-scale co-construction, co-governance and shared working mechanisms to overcome administrative limits and realize the conservation and utilization of multimodal and large-scale heritage sites. This approach has strong theoretical and practical significance for innovative methods in cultural ecology research, as well as for new content in the research of Lingnan culture, ecosystem restoration, and the economic and social development of towns and villages. This article supplements unilateral studies of regional culture and ecology and demonstrates an in-depth application of cultural ecology theory.

With the expansion and implementation of rural revitalization strategies, there is a constant need for new energy sources for the construction of new townships. Consequently, integrated energy systems with the interconnection and interaction of multiple energy sources are developing rapidly. Biomass energy, a renewable green energy source with low pollution and wide distribution, has significant application potential in integrated energy systems. Considering the application of biomass energy in townships, this study established an integrated biomass energy system and proposed a model to optimize its operation. Lowest economic cost and highest clean energy utilization rate were considered as the objective functions. In addition, a plan was suggested to adjust the heat-electricity ratio based on the characteristics of the combined heat and power of the biomass. Finally, a simulation analysis conducted for a town in China was discussed, demonstrating that the construction of a township integrated-energy system and the use of biomass can significantly reduce operating costs and improve the energy utilization rate. Moreover, by adjusting the heat-electricity ratio, the economic cost was further reduced by 6.70%, whereas the clean energy utilization rate was increased by 5.14%.

Closed-loop deep brain stimulation (DBS) shows great potential for precise neuromodulation of various neurological disorders, particularly Parkinson’s disease (PD). However, substantial challenges remain in clinical translation due to the complex programming procedure of closed-loop DBS parameters. In this study, we proposed an online optimized amplitude adaptive strategy based on the particle swarm optimization (PSO) and proportional–integral–differential (PID) controller for modulation of the beta oscillation in a PD mean field model over long-term dynamic conditions. The strategy aimed to calculate the stimulation amplitude adapting to the fluctuations caused by circadian rhythm, medication rhythm, and stochasticity in the basal ganglia–thalamus–cortical circuit. The PID gains were optimized online using PSO, based on modulation accuracy, mean stimulation amplitude, and stimulation variation. The results showed that the proposed strategy optimized the stimulation amplitude and achieved beta power modulation under the influence of circadian rhythm, medication rhythm, and stochasticity of beta oscillations. This work offers a novel approach for precise neuromodulation with the potential for clinical translation.

Closed-loop neuromodulation with intelligence methods has shown great potentials in providing novel neuro-technology for treating neurological and psychiatric diseases. Development of brain-machine interactive neuromodulation strategies could lead to breakthroughs in precision and personalized electronic medicine. The neuromodulation research tool integrating artificial intelligent computing and performing neural sensing and stimulation in real-time could accelerate the development of closed-loop neuromodulation strategies and translational research into clinical application. In this study, we developed a brain-machine interactive neuromodulation research tool (BMINT), which has capabilities of neurophysiological signals sensing, computing with mainstream machine learning algorithms and delivering electrical stimulation pulse by pulse in real-time. The BMINT research tool achieved system time delay under 3 ms, and computing capabilities in feasible computation cost, efficient deployment of machine learning algorithms and acceleration process. Intelligent computing framework embedded in the BMINT enable real-time closed-loop neuromodulation developed with mainstream AI ecosystem resources. The BMINT could provide timely contribution to accelerate the translational research of intelligent neuromodulation by integrating neural sensing, edge AI computing and stimulation with AI ecosystems.

Objective: This study aims to systematically assess the rehabilitative effects of Baduanjin in stroke patients. Methods: Ten electronic databases were systematically searched using MeSH and free terms for relevant studies written in the English or Chinese language, and published on or before 15 February 2023. Studies in which Baduanjin was the only difference in treatment administered to experimental and control groups were included in the review. The studies’ risk of bias was evaluated using the Cochrane criteria. Results: Twenty one studies that involved 1,649 participants were included. Compared to the control group, Baduanjin increased the scores for the Fugl-Meyer Assessment (including both upper and lower extremity components), Berg Balance Scale, Trunk Impairment Scale, Functional Ambulation Categories, 6-minute Walking Distance, Modified Barthel Index, Barthel Index, and total effective rate, but reduced the scores for the Pk254 balance function detection system, National Institutes of Health Stroke Scale and neurological deficit scale (P

As the driving force of modern economic development, the evolution of the global energy patterns during major emergencies deserves attention. This study aims to uncover changes in global energy patterns during the COVID-19 epicenter storm. The results reveal concentrated energy trade volume in a few flows, with high-income countries holding greater influence. Amid the epicenter storm, there was a contraction in global energy trade volume, and trading patterns underwent significant shifts: (1) the global natural gas trading center shifted from the Middle East to western Africa initially, then to the United States and Russia; (2) Brazil, a crucial crude oil exporter, saw a weakened position in global crude oil exports; and (3) in the coal trading network, Australia and Russia maintained their position as trading centers throughout the storm. Swift policy adaptation is crucial for resilience and stability amid evolving global energy patterns.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus etiologically associated with multiple malignancies. Both latency and sporadic lytic reactivation contribute to KSHV-associated malignancies, however, the specific roles of many KSHV lytic gene products in KSHV replication remain elusive. In this study, we report that ablation of ORF55, a late gene encoding a tegument protein, does not impact KSHV lytic reactivation but significantly reduces the production of progeny virions. We found that cysteine 10 and 11 (C10 and C11) of pORF55 are palmitoylated, and the palmytoilation is essential for its Golgi localization and secondary envelope formation. Palmitoylation-defective pORF55 mutants are unstable and undergo proteasomal degradation. Notably, introduction of a putative Golgi localization sequence to these palmitoylation-defective pORF55 mutants restores Golgi localization and fully reinstates KSHV progeny virion production. Together, our study provides new insight into the critical role of pORF55 palmitoylation in KSHV progeny virion production and offers potential therapeutic targets for the treatment of related malignancies.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1–2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment.A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders.During follow-up, a total of 717 subjects died from T2DM. For every 1 μg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019–1.053). Similarly, for every 1 μg/m3 increase in PM1 and PM1–2.5, the adjusted HRs and 95% CIs were 1.032 (1.003–1.062) and 1.085 (1.054–1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049).The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1–2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Abstract Objective Resilience has been reported as an important predictor of better mental health and prognoses in cancer patients, while its mechanisms were not clearly elucidated. In this study, we surveyed a large sample of nasopharyngeal carcinoma patients to investigate the mediating role of illness‐related cognition (illness perception, stigma and meaning in life) on the associations between resilience and symptoms of anxiety and depression. Methods This cross‐sectional study involved 773 participants diagnosed with nasopharyngeal carcinoma. Participants completed a self‐reported structured questionnaire to assess their illness perception, stigma and meaning in life, resilience and symptoms of anxiety and depression. Structural equation models (SEM) were employed to explore the relationship between resilience and symptoms of anxiety and depression in the entire sample, as well as in two subgroups: Subgroup I (0–1 year since diagnosis), and Subgroup II (over 1 year since diagnosis). Results In the entire sample, after adjusting for potential confounders, illness perception, stigma and meaning in life were found to mediate the protective effect of resilience on symptoms of depression (mediating effect proportion: 65.25%) and anxiety (mediating effect proportion: 67.63%). In Subgroup I, direct effects were dominant in the associations between resilience and symptoms of anxiety (mediating effect proportion: 37.95%) and depression (mediating effect proportion: 29.13%). However, in Subgroup II, the associations between resilience and symptoms of anxiety (mediating effect proportion: 98.92%) and depression (mediating effect proportion: 81.04%) were completely mediated. Conclusions Our study suggests that direct and indirect effects of resilience on depression and anxiety dominate in early periods (0–1 year) and long‐term periods (over 1 year) following the cancer diagnosis, respectively. The findings indicate that comprehensive intervention considering both the direct effect of resilience in early stages (e.g., health education prescription and social support groups) and the indirect effects of illness cognition in long‐term periods (e.g., cognitive behavioral therapies) are likely to yield the most favorable outcomes for cancer patients.

The formation mechanism of caves in fissured loess at the edge of the loess platform plateau is complex and is closely related to the occurrence of geological hazards such as landslides, which pose a serious threat to the production and life of people in this region. To address the scientific problem of how internal erosion caves are formed in the fissured loess, four sets of experiments on the formation mechanism of internal erosion caves in loess under different initial fissure opening conditions are carried out using the visualisation of the internal erosion caves formation mechanism model of the fissured loess in the South Plateau of Jingyang as a reference. The results show that the development process from the fractured loess to the internal erosion of caves under water flowing erosion can be divided into three stages, including the hydraulic erosion stage, the infiltration and erosion stage and the gravity collapse stage. The formation mechanism of the internal erosion caves in the fractured loess can be summarized as follows: Softening and sputtering, scouring and widening, erosion and cavitation, and collapsing by gravity. The development rate of seepage erosion in the fractured loess is reflected by the sediment quantity and transport characteristics, which can be divided into the rapid erosion stage, the fluctuation reduction stage and the slow and stable erosion stage. The fracture opening, the erodibility of loess and the ultimate groove depth are important factors affecting the formation of internal erosion caves in the fractured loess. The research results provide theoretical support to further reveal the disaster-causing effects of loess internal erosion.

Quantum key distribution (QKD) technology is a frontier in the field of secure communication, leveraging the principles of quantum mechanics to offer information-theoretically secure keys. Postprocessing is an important part of a whole QKD system because it directly impacts the secure key rate and the security of the system. In particular, with the fast increase in the photon transmission frequency in a QKD system, the processing speed of postprocessing becomes an essential issue. Our study embarks on a comprehensive review of the development of postprocessing of QKD, including five subprotocols, namely, parameter estimation, sifting, information reconciliation, privacy amplification, and channel authentication. Furthermore, we emphasize the issues raised in the implementation of these subprotocols under practical scenarios, such as limited computation or storage resources and fluctuations in channel environments. Based on the composable security theory, we demonstrate how enhancements in each subprotocol influence the secure key rate and security parameters, which can provide meaningful insights for future advancements in QKD.

Change detection (CD) is the main task in the remote sensing field. Binary change detection (BCD), which only focuses on the region of change, cannot meet current needs. Semantic change detection (SCD) is pivotal for identifying regions of change in sequential remote sensing imagery, focusing on discerning “from-to” transitions in land cover. The emphasis on features within these regions of change is critical for SCD efficacy. Traditional methodologies, however, often overlook this aspect. In order to address this gap, we introduce a change-aware guided multi-task network (CGMNet). This innovative network integrates a change-aware mask branch, leveraging prior knowledge of regions of change to enhance land cover classification in dual temporal remote sensing images. This strategic focus allows for the more accurate identification of altered regions. Furthermore, to navigate the complexities of remote sensing environments, we develop a global and local attention mechanism (GLAM). This mechanism adeptly captures both overarching and fine-grained spatial details, facilitating more nuanced analysis. Our rigorous testing on two public datasets using state-of-the-art methods yielded impressive results. CGMNet achieved Overall Score metrics of 58.77% on the Landsat-SCD dataset and 37.06% on the SECOND dataset. These outcomes not only demonstrate the exceptional performance of the method but also signify its superiority over other comparative algorithms.

Administering medication is a crucial strategy in improving the prognosis for advanced endometrial cancer. However, the rise of drug resistance often leads to the resurgence of cancer or less-than-ideal treatment outcomes. Prior studies have shown that autophagy plays a dual role in the development and progression of endometrial cancer, closely associated with drug resistance. As a result, concentrating on autophagy and its combination with medical treatments might be a novel approach to improve the prognosis for endometrial cancer. This study explores the impact of autophagy on drug resistance in endometrial cancer, investigates its core mechanisms, and scrutinizes relevant treatments aimed at autophagy, aiming to illuminate the issue of treatment resistance in advanced endometrial cancer.

Epigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a novel HPTM called benzoylation (Kbz) induced by NAB was discovered. This modification can be catalyzed by ACSS2 (acyl-CoA synthetase short-chain member 2) and acyltransferase P300/CBP, and can be reversed by erase enzymes SIRT2. Studies have indicated that Kbz may regulate insulin secretion, although the exact molecular mechanism remains unclear. In our study, C57BL/6J mice were divided into two groups: the NC group and the 1g/kg NAB water feeding group. In vivo experiments were conducted using β-TC-6 cells, with 6 mM NAB or 100 μM benzoyl-CoA as stimuli, and 10 μM A485 (P300 inhibitor), 5 μM ACSS2 inhibitor (inhibiting benzoyl-CoA synthesis), or 5 μM AGK2 (SIRT2 inhibitor) as intervention factors. Our study found that, although the experimental concentration of NAB is below the maximum allowable concentration in food, it still damaged the insulin secretion function of C57BL/6J mice and induced inflammation and apoptosis of islet β cells. We observed significant differences in serum benzoyl-CoA levels between healthy individuals and patients with type 2 diabetes. Furthermore, NAB concentration-dependently increases benzoyl-CoA and Kbz levels. When Kbz is down-regulated using A485 and ACSS2 inhibitor, we observed a reduction in β cell inflammation, apoptosis, and insulin secretion damage. Conversely, up-regulating Kbz using AGK2 resulted in increased levels of β cell inflammation and apoptosis. In conclusion, our data suggest that NAB, despite being within the safe dose range, may be an overlooked environmental risk factor contributing to the pathogenesis of diabetes through its impact on Kbz.

Abstract Background Limited attempts have been made in trans‐areola single‐site endoscopic thyroidectomy (TASSET) due to technical challenges and the lengthy time for proficiency. This study aimed to define the learning curve of TASSET and to describe improvements in operative performance over time. Methods Based on 222 consecutive TASSET procedures, the learning curve was established according to the operation time by using cumulative sum analysis (CUSUM). The end‐point of learning curve was defined as the number of cases necessitated to reach the initial surgical proficiency stage. The demographic information, surgical and oncological outcomes, surgical stress, and postoperative complications were also analyzed. Results There were 70 cases of simple lobectomy for benign nodules and 152 cases of lobectomy with central neck dissection (CND) for malignancy. The mean operative time was 106.54 ± 38.07 min (range: 46–274 min). The learning curve identified two phases: the skill acquisition phase (Case 1–Case 41) and the proficiency phase (Case 42–Case 222). There were no significant differences in demographic information, drainage amount and duration, oncological outcomes, and postoperative complications between the two phases (p > 0.05). Both operation time and postoperative hospitalization decreased significantly in Phase 2 (154.63 ± 52.21 vs. 95.64 ± 22.96 min, p

In a hyperspectral image, there is a close correlation between spectra and a certain degree of correlation in the pixel space. However, most existing low-rank representation (LRR) methods struggle to utilize these two characteristics simultaneously to detect anomalies. To address this challenge, a novel low-rank representation with dual graph regularization and an adaptive dictionary (DGRAD-LRR) is proposed for hyperspectral anomaly detection. To be specific, dual graph regularization, which combines spectral and spatial regularization, provides a new paradigm for LRR, and it can effectively preserve the local geometrical structure in the spectral and spatial information. To obtain a robust background dictionary, a novel adaptive dictionary strategy is utilized for the LRR model. In addition, extensive comparative experiments and an ablation study were conducted to demonstrate the superiority and practicality of the proposed DGRAD-LRR method.

As the most consumed tea in the world, all kinds of black tea are developed from Wuyi black tea. In this study, quality components, regulatory gene expression, and key enzyme activity during the processing were analyzed to illustrate the taste formation of WBT. Withering mainly affected the content of amino acids, while catechins and tea pigments were most influenced by rolling and the pre-metaphase of fermentation. Notably, regulatory gene expression was significantly down-regulated after withering except for polyphenoloxidase1, polyphenoloxidase2, leucoanthocyanidin dioxygenase, chalcone isomerase, and flavonoid 3′, 5′-hydroxylase. Co-expression of flavonoid pathway genes confirmed similar expression patterns of these genes in the same metabolic pathway. Interestingly, rolling and fermentation anaphase had a great effect on polyphenol oxidase, and fermentation pre-metaphase had the greatest effect on cellulase. Since gene regulation mainly occurs before picking, the influence of chemical reaction was greater during processing. It was speculated that polyphenol oxidase and cellulase, which promoted the transformation of quality components, were the key factors in the quality formation of WBT. The above results provide theoretical basis for the processing of WBT and the reference for producing high-quality black tea.

Abstract GPR84 is an orphan class A G protein-coupled receptor (GPCR) that is predominantly expressed in immune cells and plays important roles in inflammation, fibrosis, and metabolism. Here, we present cryo-electron microscopy (cryo-EM) structures of Gαi protein-coupled human GPR84 bound to a synthetic lipid-mimetic ligand, LY237, or a putative endogenous ligand, a medium-chain fatty acid (MCFA) 3-hydroxy lauric acid (3-OH-C12). Analysis of these two ligand-bound structures reveals a unique hydrophobic nonane tail -contacting patch, which forms a blocking wall to select MCFA-like agonists with the correct length. We also identify the structural features in GPR84 that coordinate the polar ends of LY237 and 3-OH-C12, including the interactions with the positively charged side chain of R172 and the downward movement of the extracellular loop 2 (ECL2). Together with molecular dynamics simulations and functional data, our structures reveal that ECL2 not only contributes to direct ligand binding, but also plays a pivotal role in ligand entry from the extracellular milieu. These insights into the structure and function of GPR84 could improve our understanding of ligand recognition, receptor activation, and Gαi-coupling of GPR84. Our structures could also facilitate rational drug discovery against inflammation and metabolic disorders targeting GPR84.

The WRKY transcription factors are a class of transcriptional regulators that are ubiquitous in plants, wherein they play key roles in various physiological activities, including responses to stress. Specifically, WRKY transcription factors mediate plant responses to biotic and abiotic stresses through the binding of their conserved domain to the W-box element of the target gene promoter and the subsequent activation or inhibition of transcription (self-regulation or cross-regulation). In this review, the progress in the research on the regulatory effects of WRKY transcription factors on plant responses to external stresses is summarized, with a particular focus on the structural characteristics, classifications, biological functions, effects on plant secondary metabolism, regulatory networks, and other aspects of WRKY transcription factors. Future research and prospects in this field are also proposed.

Marigold black spot caused by Alternaria tagetica is a major disease that can decrease marigold production by 40%, resulting in serious economic losses. In this study, we identified many genes responsive to A. tagetica in the resistant and susceptible marigold genotypes. Analyses of differentially expressed genes, expression trends, and a weighted gene co-expression network revealed a series of hub genes with key roles in different A. tagetica infection stages. Additionally, 1 216 unigenes encoding transcription factors from eight families were differentially expressed between Ts and Ma. Moreover, R genes from various families (e.g., N, NL, RLP, and TNL) were differentially expressed in the two marigold genotypes before and after the inoculation with A. tagetica. Pathway diagrams were used to visualize the leaf transcriptional changes in the two marigold genotypes infected by A. tagetica to clarify the effects of A. tagetica on the expression patterns of genes involved in phosphatidylinositol signaling, plant–pathogen interactions, and plant hormone signal transduction. We identified candidate genes related to disease resistance and generated valuable resources for analyzing the candidate gene functions related to black spot resistance in marigold. The study data may be useful for the molecular marker-assisted screening and breeding of marigold lines with increased disease resistance.

Abstract The Hippo pathway is crucial to organ size control and its dysregulation contributes to tumorigenesis. The aberrant activation of YAP1 was identified in gallbladder cancer (GBC). However, the underlying mechanism and role in GBC remains unclear. The C terminal fragment of Mucin16, also known as carbohydrate antigen 125 (CA125) encoded product, MUC16c, plays extensive roles in tumor initiation and development. Our study showed that MUC16c binding with 14‐3‐3ε disrupted the interaction of 14‐3‐3ε and phosphorylated yes‐associated protein 1 (YAP1), which led to the activation of YAP1 in GBC. Furthermore, MUC16c decreased the phosphorylation of YAP1 at serine 397 (ser397) by inhibiting LATS1, which upregulated YAP1 protein stability. Interestingly, there was a potential Src kinase site in the MUC16c fragment. The MUC16c_del15Y polypeptides with the deletion of the Src kinase site promoted the interaction of YAP1 with 14‐3‐3ε and downregulated the YAP1 protein levels. Consistently, SU6656, a Src kinase inhibitor also blocked the activation of YAP1 by MUC16c. The MUC16c_del15Y polypeptides decreased GBC cell proliferation in vitro and the growth of xenograft tumors in vivo. Our study revealed the underlying mechanism of the activation of MUC16c on YAP1 mediated by Src signaling and the antitumor effect of MUC16c_del15Y, providing a potential target for GBC therapy.

ABSTRACT Among various environmental stresses, the depletion of inorganic phosphate, which is an important signaling molecule that modulates virulence production, is notable. In our previous study, we demonstrated that lapA, encoding alkaline phosphatase, plays a key role in Pseudomonas aeruginosa biofilm formation in porcine skin explants, an ex vivo chronic wound model. However, the mechanism by which lapA participates in the virulence and biofilm formation of P. aeruginosa remains unclear. In the present study, the lapA deletion mutant was constructed in P. aeruginosa PAO1, and the phenotypic characterization was assessed. Our data demonstrated that phosphate depletion stress significantly enhanced elastase activity, hemolysis, rhamnolipid production, swarming and swimming motilities, and 3-oxo-C12-homoserine lactone (HSL) production in P. aeruginosa. Moreover, phosphate starvation evidently induced the virulence of P. aeruginosa in Caenorhabditis elegans (C. elegans) through fast-kill and slow-kill infections. Deletion of the lapA gene led to broad phenotypic changes, including reduced elastase activity, swimming motility, C4-HSL, and 3-oxo-C12-HSL production, as well as increased chitinase activity and rhamnolipid production under phosphate depletion stress, which was unrelated to C4-HSL. Deletion of the lapA gene also significantly inhibited PAO1 biofilm formation in porcine skin explants by reducing the expression levels of las and rhl quorum sensing systems and extracellular polymeric substance synthesis. Finally, lapA deletion also reduced the virulence of PAO1 in C. elegans in fast-kill and slow-kill infection assays. Thus, the findings suggest that targeting lapA can help control biofilm formation and reduce virulence in nonhealing-infected wounds, where P. aeruginosa is a persistent problem. IMPORTANCE Our previous study demonstrated that the expression of lapA was induced under phosphate depletion conditions, but its roles in virulence and biofilm formation by Pseudomonas aeruginosa remain largely unknown. This study presents a systematic investigation of the roles of lapA in virulence induction and biofilm formation by constructing a lapA-deficient strain with P. aeruginosa PAO1. The results showed that deletion of the lapA gene evidently reduced elastase activity, swimming motility, C4-HSL, and 3-oxo-C12-HSL production, and increased rhamnolipid production under phosphate depletion stress. Moreover, lapA gene deletion inhibited PAO1 biofilm formation in porcine skin explants by reducing the expression levels of las and rhl quorum sensing systems and extracellular polymeric substance synthesis. Finally, lapA gene deletion also reduced the virulence of PAO1 in Caenorhabditis elegans in fast-kill and slow-kill infection assays. This study provides insights into the roles of lapA in modulating P. aeruginosa virulence and biofilm formation under phosphate depletion stress.

Summary: Niacin, an age-old lipid-lowering drug, acts through the hydroxycarboxylic acid receptor 2 (HCAR2), a G-protein-coupled receptor (GPCR). Yet, its use is hindered by side effects like skin flushing. To address this, specific HCAR2 agonists, like MK-6892 and GSK256073, with fewer adverse effects have been created. However, the activation mechanism of HCAR2 by niacin and these new agonists is not well understood. Here, we present three cryoelectron microscopy structures of Gi-coupled HCAR2 bound to niacin, MK-6892, and GSK256073. Our findings show that different ligands induce varying binding pockets in HCAR2, influenced by aromatic amino acid clusters (W91ECL1, H1614.59, W1885.38, H1895.39, and F1935.43) from receptors ECL1, TM4, and TM5. Additionally, conserved residues R1113.36 and Y2847.43, unique to the HCA receptor family, likely initiate activation signal propagation in HCAR2. This study provides insights into ligand recognition, receptor activation, and G protein coupling mediated by HCAR2, laying the groundwork for developing HCAR2-targeted drugs.

As a major class of biomolecules, carbohydrates play indispensable roles in various biological processes. However, it remains largely unknown how carbohydrates directly modulate important drug targets, such as G-protein coupled receptors (GPCRs). Here, we employed P2Y purinoceptor 14 (P2Y14), a drug target for inflammation and immune responses, to uncover the sugar nucleotide activation of GPCRs. Integrating molecular dynamics simulation with functional study, we identified the uridine diphosphate (UDP)-sugar-binding site on P2Y14, and revealed that a UDP-glucose might activate the receptor by bridging the transmembrane (TM) helices 2 and 7. Between TM2 and TM7 of P2Y14, a conserved salt bridging chain (K2.60-D2.64-K7.35-E7.36 [KDKE]) was identified to distinguish different UDP-sugars, including UDP-glucose, UDP-galactose, UDP-glucuronic acid, and UDP-N-acetylglucosamine. We identified the KDKE chain as a conserved functional motif of sugar binding for both P2Y14 and P2Y purinoceptor 12 (P2Y12), and then designed three sugar nucleotides as agonists of P2Y12. These results not only expand our understanding for activation of purinergic receptors but also provide insights for the carbohydrate drug development for GPCRs.

Previous studies have found that β-Hydroxybutyrate (BHB), the main component of ketone bodies, is of physiological importance as a backup energy source during starvation or induces diabetic ketoacidosis when insulin deficiency occurs. Ketogenic diets (KD) have been used as metabolic therapy for over a hundred years, it is well known that ketone bodies and BHB not only serve as ancillary fuel substituting for glucose but also induce anti-oxidative, anti-inflammatory, and cardioprotective features via binding to several target proteins, including histone deacetylase (HDAC), or G protein-coupled receptors (GPCRs). Recent advances in epigenetics, especially novel histone post-translational modifications (HPTMs), have continuously updated our understanding of BHB, which also acts as a signal transduction molecule and modification substrate to regulate a series of epigenetic phenomena, such as histone acetylation, histone β-hydroxybutyrylation, histone methylation, DNA methylation, and microRNAs. These epigenetic events alter the activity of genes without changing the DNA structure and further participate in the pathogenesis of related diseases. This review focuses on the metabolic process of BHB and BHB-mediated epigenetics in cardiovascular diseases, diabetes and complications of diabetes, neuropsychiatric diseases, cancers, osteoporosis, liver and kidney injury, embryonic and fetal development, and intestinal homeostasis, and discusses potential molecular mechanisms, drug targets, and application prospects.

Summary: Auxilin (DNAJC6/PARK19), an endocytic co-chaperone, is essential for maintaining homeostasis in the readily releasable pool (RRP) by aiding clathrin-mediated uncoating of synaptic vesicles. Its loss-of-function mutations, observed in familial Parkinson’s disease (PD), lead to basal ganglia motor deficits and cortical dysfunction. We discovered that auxilin-knockout (Aux-KO) mice exhibited impaired pre-synaptic plasticity in layer 4 to layer 2/3 pyramidal cell synapses in the primary visual cortex (V1), including reduced short-term facilitation and depression. Computational modeling revealed increased RRP refilling during short repetitive stimulation, which diminished during prolonged stimulation. Silicon probe recordings in V1 of Aux-KO mice demonstrated disrupted visual cortical circuit responses, including reduced orientation selectivity, compromised visual mismatch negativity, and shorter visual familiarity-evoked theta oscillations. Pupillometry analysis revealed an impaired optokinetic response. Auxilin-dependent pre-synaptic endocytosis dysfunction was associated with deficits in pre-synaptic plasticity, visual cortical functions, and eye movement prodromally or at the early stage of motor symptoms.

CYCLOIDEA (CYC)-like genes belong to the TCP transcription factor family and play important roles associated with flower development. The CYC-like genes in the CYC1, CYC2, and CYC3 clades resulted from gene duplication events. The CYC2 clade includes the largest number of members that are crucial regulators of floral symmetry. To date, studies on CYC-like genes have mainly focused on plants with actinomorphic and zygomorphic flowers, including Fabaceae, Asteraceae, Scrophulariaceae, and Gesneriaceae species and the effects of CYC-like gene duplication events and diverse spatiotemporal expression patterns on flower development. The CYC-like genes generally affect petal morphological characteristics and stamen development, as well as stem and leaf growth, flower differentiation and development, and branching in most angiosperms. As the relevant research scope has expanded, studies have increasingly focused on the molecular mechanisms regulating CYC-like genes with different functions related to flower development and the phylogenetic relationships among these genes. We summarize the status of research on the CYC-like genes in angiosperms, such as the limited research conducted on CYC1 and CYC3 clade members, the necessity to functionally characterize the CYC-like genes in more plant groups, the need for investigation of the regulatory elements upstream of CYC-like genes, and exploration of the phylogenetic relationships and expression of CYC-like genes with new techniques and methods. This review provides theoretical guidance and ideas for future research on CYC-like genes.

Abstract Ferroptosis is widely present in fibrosis-related diseases. The basic pathology of premature ovarian insufficiency (POI) involves ovarian tissue fibrosis, and there are currently fewer relevant studies addressing the association between ferroptosis and POI. This study aimed to demonstrate that ferroptosis induced by cisplatin (CDDP) caused ovarian tissue fibrosis, leading to POI. Vitamin E (VE), a ferroptosis inhibitor, could repair damaged ovarian function. CDDP was used to establish a rat model of POI, and VE was administered to reverse the reproductive toxicity of CDDP. Ovarian function was assessed by histological section staining, follicle counts, sex hormone levels, as well as fertility assays. The extent of ferroptosis was assessed by transmission electron microscopy (TEM), malondialdehyde (MDA), Perls staining. CCK-8, Ethynyl-2-Deoxyuridine (EdU), and scratch assays were used to determine the effect of CDDP and VE on ovarian granulosa cell (GC) viability. Western blot, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to evaluate ferroptosis-related molecular changes. Our results showed that CDDP caused follicle development disorders and ovarian tissue fibrosis, the levels of sex hormones suggested impaired ovarian function, and VE could reverse the reproductive toxicity of CDDP. The results of TEM, MDA and Perls staining suggested that the typical mitochondrial signature of ferroptosis was altered in ovarian GCs from the CDDP group, with significantly higher levels of lipid peroxidation and significant iron deposition in ovarian tissue, whereas VE mitigated the extent of ferroptosis. Molecular experiments then confirmed that the ferroptosis-related molecules acetyl CoA synthetase long chain family member 4 (ACSl4), 15-lipoxygenase-1 (ALOX15), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were differentially expressed in each group. In summary, our study preliminarily demonstrated that CDDP may promote GCs to undergo ferroptosis, cause follicle development disorders, ovarian tissue fibrosis, and induce POI by regulating the expression of ACSl4, ALOX15, SLC7A11, and GPX4, while VE improved impaired ovarian function.

Endothelin receptors (ETAR and ETBR) are critical for vasoregulation and are targets for cardiovascular diseases treatment. Here, the authors offer a structural basis for peptide recognition selectivity and activation of both endothelin receptors.

Abstract Background The HOXB9 gene, which plays a key role in embryonic development, is also involved in the regulation of various human cancers. However, the potential relationship between HOXB9 and endometrial cancer (EC) has not yet been comprehensively analyzed and fully understood. Methods We used multiple bioinformatics tools to explore the role of HOXB9 in EC. Results The expression of HOXB9 was significantly upregulated in pan-cancer, including EC (P 60 years, and high expression of HOXB9 were risk factors strongly associated with OS in EC patients (P

Apple stem grooving virus (ASGV) is one of the most widespread and asymptomatic main viruses, that restricts the production of apples worldwide. Establishment of rapid, simple, and effective early detection methods of apple virus is important. In this study, we established and optimized a one-step reverse transcription - recombinase polymerase amplification (RT-RPA) method, using the target-specific primers of ASGV coat protein gene sequence, and M-MLV reverse transcriptase. This method could be completed within 30 min at 40 °C, followed by a visual detection of the results within 5 min by using lateral flow dipstick (LFD). The specificity results showed that only samples infected with ASGV showed a test line, while no test line appeared in the ASGV-negative samples. In addition, when crude extract of leaves was used, the whole detection could be completed within 1 h, which was shortened by 4 to 6 times compared with the RT-PCR method. The detection made on more field samples showed that the RT-RPA-LFD method is of high stability and reliability for ASGV diagnosis, with a great potential in the rapid on-site detection of plant viruses.

At present, in arbitrary-oriented object detection, the angular periodicity problem of rotated bounding box described by angle causes an object to have different numerical representations, which leads to uncertainty of rotated bounding box regression. To eliminate the angular periodicity problem, in this article, we propose a novel and simple ellipse parameters representation method for arbitrary-oriented object, which hides the angle of the object in the focal vector of ellipse to avoid direct angle prediction. Moreover, the proposed representation method can enable the arbitrary-oriented object to have only one numerical representation, which is beneficial to alleviate the uncertainty of bounding box regression. In order to adapt the proposed ellipse parameters representation method, we adopt 2-D Gaussian distribution label assign for coarse samples selection, then the Kullback–Leibler divergence loss and SimOTA are used to refine the coarse samples to obtain the best positive samples. We extend the YOLOX with medium parameters as an oriented ship detector according to the proposed ellipse parameters representation method, and conduct the experiments on HRSC2016, RSDD-SAR, and RHRSID to demonstrate the effectiveness of the proposed method. The experimental results show that the proposed representation method achieves impressive results compared with state-of-the-art arbitrary-oriented object detection methods.

Background: Many factors were reported associated with the pregnancy rate of intrauterine insemination (IUI), which played key role is still debated. Aims: The aim of this study was to explore related clinical pregnancy outcome factor in IUI cycles of non-male factor. Settings and Design: The clinical data of 1232 IUI cycles in 690 couples experiencing infertility who attended the Reproductive Center of Jinling Hospital between July 2015 and November 2021 were retrospectively analysed. Materials and Methods: Female and male age, body mass index (BMI), anti-Müllerian hormone (AMH), male semen parameters before and after wash, endometrial thickness (EMT), artificial insemination timing and ovarian stimulation (OS) protocols were compared between the pregnant group and the non-pregnant group in order to explore any correlation. Statistical Analysis Used: Continuous variables were analysed using independent-samples t-test, and Chi-square test was used for comparison of measurement data between the two groups. P 4.5 ng/ml, EMT between 8 and 12 mm and letrozole + human menopausal gonadotropin stimulation with higher clinical pregnancy. However, there were no differences between the pregnant group and the non-pregnant group amongst the female and male age, BMI, hormones on baseline and day of human chorionic gonadotrophin, number of ovulated oocytes, sperm parameters before and after wash, treatment protocols and the timing of IUI (P > 0.05). Furthermore, there were 240 couples who not pregnant received one or more cycles of in vitro fertilisation/intracytoplasmic sperm injection/ pre-implantation genetic technology treatment, and another 182 couples forgo follow-up treatment. Conclusion: The results of the present study demonstrate that the clinical IUI pregnancy rate is correlated with the factors of female AMH, EMT and OS protocol; more studies and samples are necessary to evaluate whether other factors affect pregnancy rate.

The low rank and sparse representation (LRSR) technique has attracted increasing attention for hyperspectral anomaly detection (HAD). Although a large quantity of research based on LRSR for HAD is proposed, the detection performance is still limited, due to the unsatisfactory dictionary construction and insufficient consideration of global and local characteristics. To tackle the above-mentioned concern, a novel HAD method, termed dual collaborative constraints regularized low-rank and sparse representation via robust dictionaries construction, is proposed in this article. Concretely, a robust dictionary construction strategy, which thoroughly excavates the potential of the density estimation model and local outlier factor, is proposed to yield pure and representative dictionary atoms. To fully exploit the global and local characteristics of hyperspectral images, dual collaborative constraints corresponding to the background and anomaly components are imposed on the LRSR model. Notably, two weighted matrices are further exerted on the representation coefficients to improve the effect of collaborative constraints, considering the fact that the surrounding pixels similar to the testing pixel should be given a large weight, otherwise the weight is expected to be small. In this way, the background and anomaly components can be well modeled. Additionally, a nonlinear transformation operation, which combines the output of the density estimation model and local outlier factor with the detection result derived from the LRSR model, is developed to suppress the background. The experiments conducted on one simulated dataset and three real datasets demonstrate the superiority of the proposed method compared with the four typical methods and four state-of-the-art methods.

Follicle stimulating hormone (FSH) is a glycoprotein hormone the functions of which are mediated by a G protein-coupled receptor, FSHR. Here, Duan et al. report cryo-EM structures of FSHR in active and inactive states, suggesting the molecular basis of FSH and small allosteric agonist-mediated FSHR activation.

Sparse representation (SR)-based approaches and collaborative representation (CR)-based methods are proved to be effective to detect the anomalies in a hyperspectral image (HSI). Nevertheless, the existing methods for achieving hyperspectral anomaly detection (HAD) generally only consider one of them, failing to comprehensively exploit them to further promote the detection performance. To address the issue, a novel HAD method, which integrates both SR and CR, is proposed in this article. To be specific, an SR model, whose overcomplete dictionary is generated by means of the density-based clustering algorithm and superpixel segmentation method, is first constructed for each pixel in an HSI. Then, for each pixel in an HSI, the used atoms in SR model are sifted to form the background dictionary corresponding to the CR model. To fully exploit both SR and CR information, we further combine the residual features obtained from both SR and CR model by the nonlinear transformation function to generate the response map. Finally, to preserve contour information of the objects, a postprocessing operation with guided filter is imposed into the response map to acquire the detection result. Experiments conducted on simulated and real datasets demonstrate that the proposed SRCR outperforms the state-of-the-art methods.

The Atlantic cold tongue, which typically peaks in boreal summer, exerts a pronounced regional and global impact on the climate and socio-economy. Projected future changes in the Atlantic cold tongue are full of uncertainty, mainly arising from a model bias in simulating its mean state, with less biased models projecting a stronger weakening in amplitude. However, the underlying mechanisms remain unknown. Here, we find that model bias exerts its influence through modulating atmospheric thermal damping and upwelling of subsurface anomalous warming induced by the weakened Atlantic meridional overturning circulation (AMOC). In less biased models, the Atlantic cold tongue, compared to the western equatorial Atlantic, features a cooler mean climate sea surface temperature (SST), and is subjected to smaller thermal damping induced by mean climate evaporation and consequently, faster SST warming. Moreover, equatorial subsurface warming associated with a reduced AMOC is advected to the surface via mean climate upwelling, enhancing faster SST warming in the east, a feedback stronger in less biased models that produce greater climatological upwelling. The above asymmetric SST warming would be amplified by the Bjerknes feedback, leading to a weakened Atlantic cold tongue. These findings may help to predict future changes in the Atlantic cold tongue and its influences.

Chrysanthemums are one of the top ten most well-known traditional famous flowers in China and one of the top four cut flowers worldwide, holding a significant position in landscape gardening. The cold temperatures of winter restrict the cultivation, introduction, and application of chrysanthemum, resulting in high costs for year-round production. This severely impacts the ornamental and economic value of chrysanthemum. Therefore, research on cold tolerance is of vital importance for guiding chrysanthemum production and application. With the development of genomics, transcriptomics, metabolomics, and other omics approaches, along with high-throughput molecular marker technologies, research on chrysanthemum cold tolerance has been continuously advancing. This article provides a comprehensive overview of the progress in cold tolerance research from various aspects, including chrysanthemum phenotype, physiological mechanisms, the forward genetics, molecular mechanisms, and breeding. The aim is to offer insights into the mechanisms of cold tolerance in chrysanthemum and provide reference for in-depth research and the development of new cold tolerance chrysanthemum varieties.

Histone lysine crotonylation was first identified as a new type of post-translational modification in 2011. In recent years, prominent progress has been made in the study of histone and nonhistone crotonylation in reproduction, development, and disease. Although the regulatory enzyme systems and targets of crotonylation partially overlap with those of acetylation, the peculiar CC bond structure of crotonylation suggests that crotonylation may have specific biological functions. In this review, we summarize the latest research progress regarding crotonylation, especially its regulatory factors and relationship with diseases, which suggest further research directions for crotonylation and provide new ideas for developing disease intervention and treatment regimens.