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DNA nanostructures have been widely explored as an encouraging tool for bioanalysis and cancer therapy due to its structural programmability and good biocompatibility. The incorporation of stimulus-responsive modules enables the accurate targeting and flexible control of structure and morphology, which is benefit to precise bioanalysis and therapy. This mini review briefly discusses the advancements in stimuli-responsive DNA nanostructures construction and their applications in biomolecules sensing and cancer treatment.

Although numerous advances have been made in information technology in the past decades, there is still a lack of progress in information systems dynamics (ISD), owing to the lack of a mathematical foundation needed to describe information and the lack of an analytical framework to evaluate information systems. The value of ISD lies in its ability to guide the design, development, application, and evaluation of large-scale information system-of-systems (SoSs), just as mechanical dynamics theories guide mechanical systems engineering. This paper reports on a breakthrough in these fundamental challenges by proposing a framework for information space, improving a mathematical theory for information measurement, and proposing a dynamic configuration model for information systems. In this way, it establishes a basic theoretical framework for ISD. The proposed theoretical methodologies have been successfully applied and verified in the Smart Court SoSs Engineering Project of China and have achieved significant improvements in the quality and efficiency of Chinese court informatization. The proposed ISD provides an innovative paradigm for the analysis, design, development, and evaluation of large-scale complex information systems, such as electronic government and smart cities.

Endogenous biomolecules in cells are the basis of all life activities. Directly visualizing the structural characteristics and dynamic behaviors of cellular biomolecules is significant for understanding the molecular mechanisms in various biological processes. Single-molecule localization microscopy (SMLM) can circumvent the optical diffraction limit, achieving analysis of the fine structures and biological processes in living cells with nanoscale resolution. However, the large size of traditional imaging probes prevents SMLM from accurately locating fine structures and densely distributed biomolecules within cells. In recent years, nucleic acid probes have emerged as potential tools to replace conventional SMLM probes by virtue of their small size and high specificity. In addition, due to their programmability, nucleic acid probes with different conformations can be constructed via sequence design, further extending the application of SMLM in bioanalysis. Here, we discuss the design concepts of different conformational nucleic acid probes for SMLM and summarize the application of SMLM based on nucleic acid probes in the field of biomolecules. Furthermore, we provide a summary and future perspectives of the nucleic acid probe-based SMLM technology, aiming to provide guidance for the acquisition of nanoscale information about cellular biological processes.

Abstract Based on the current piezoelectric theory, NiO with the centrosymmetric structure is not piezoelectric. However, herein, this study shows the first observation of piezoelectric generation, rectifyingand bulk photovoltaic behaviors in NiO films with [111] orientation and the change in NiO crystal structure in piezoelectric process. The piezoelectric generation, rectifying, and bulk photovoltaic performances are enhanced by increasing (111) orientation, and attenuated and eliminated by applying a persistent stress on the NiO film. The NiO [111] is polar direction, and thus a spontaneous electric field (ES) is in the NiO film with [111] orientation. The existence of Es in (111) oriented NiO film is found to be the physical basis of the piezoelectric generators and photovoltaic and rectifying effects. Thus, NiO piezoelectric, rectifying, and bulk photovoltaic mechanism are presented at the atomic level. The mechanism may rewrite the current piezoelectric theory, and establish a unified theory of polar structure with wide implications. The polar‐orientated films can be used to fabricate piezoelectric generators and other optoelectronic devices with high performances.

SAP30 is a core subunit of the transcriptional corepressor SIN3 complex, but little is known about its role in gene regulation and human cancer. Here, we show that SAP30 was a nonmutational oncoprotein upregulated in more than 50% of human breast tumors and correlated with unfavorable outcomes in patients with breast cancer. In various breast cancer mouse models, we found that SAP30 promoted tumor growth and metastasis through its interaction with SIN3A/3B. Surprisingly, the canonical gene silencing role was not essential for SAP30’s tumor-promoting actions. SAP30 enhanced chromatin accessibility and RNA polymerase II occupancy at promoters in breast cancer cells, acting as a coactivator for genes involved in cell motility, angiogenesis, and lymphangiogenesis, thereby driving tumor progression. Notably, SAP30 formed a homodimer with 1 subunit binding to SIN3A and another subunit recruiting MLL1 through specific Phe186/200 residues within its transactivation domain. MLL1 was required for SAP30-mediated transcriptional coactivation and breast tumor progression. Collectively, our findings reveal that SAP30 represents a transcriptional dependency in breast cancer.

Abstract Background Although reticulocalbin 3 (Rcn3) has a critical role in alveolar epithelial function as well as in pathogenesis of pulmonary fibrosis, no study has yet examined its diagnostic and prognostic values for interstitial lung disease (ILD). This study aimed to evaluate Rcn3 as a potential marker in differential diagnosis of idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) and in reflecting the severity of disease. Methods This was a retrospective observational pilot study included 71 ILD patients and 39 healthy controls. These patients were stratified into IPF group (39) and CTD-ILD group (32). The severity of ILD was evaluated through pulmonary function test. Results Serum Rcn3 level was statistically higher in CTD-ILD patients than that in IPF patients (p = 0.017) and healthy controls (p = 0.010). Serum Rcn3 further showed statistically negative correlation with pulmonary function indexes (TLC% pred and DLCO% pred) and positive correlation with inflammatory indexes (CRP and ESR) (r = − 0.367, p = 0.039; r = − 0.370, p = 0.037; r = 0.355, p = 0.046; r = 0.392, p = 0.026, respectively) in CTD-ILD patients rather than IPF patients. ROC analysis demonstrated that serum Rcn3 had superior diagnostic value for CTD-ILD and a cutoff value of 2.73 ng/mL had a sensitivity of 69%, a specificity of 69% and an accuracy of 45% for diagnose of CTD-ILD. Conclusions Serum Rcn3 levels might be a clinically useful biomarker in screening and evaluating CTD-ILD.

To accurately understand user information needs and provide better search experiences, various methods have been proposed to model user search intent from their search logs. Most traditional methods based on query understanding only consider the similarity between the query and documents while ignoring the user’s session interaction sequence. Some researchers also adopt neural network-based methods to model user search intent. However, most neural network-based models mainly focus on the user’s session interaction sequence without considering the role of topic relevance in modeling user search intent. In this paper, we propose a novel topicality relevance-aware intent model (TRIM) for web search. TRIM consists of a topic relevance predictor and a user short-term intent predictor. The topic relevance predictor utilizes the BERT model to predict the topic relevance between the query and documents. The user short-term search intent predictor utilizes session context information to predict the user’s short-term search intent. We further investigate several fusion strategies to integrate the topic relevance and user short-term search intent for user search intent prediction. We conduct our experiments on two public web search datasets named TianGong-QRef and TianGong-ST. The experiments show that TRIM outperforms all baselines in the document ranking task. On TianGong-QRef dataset, TRIM achieves a 15.19% increase over the best-performing baselines M-Match in terms of Mean Average Precision (MAP). On TianGong-ST dataset, TRIM achieves a 5.77% increase over the best-performing baselines CARS in terms of MAP. The experimental results indicate the effectiveness of topic relevance in user search intent modeling.

Constructing click models and extracting implicit relevance feedback information from interaction between users and search engines are very important for improving the ranking of search results. Neural networks are effective for modeling users’ click behavior, and we propose a novel Filter-Enhanced Transformer Click Model (FE-TCM) for web search. The model uses the powerful Transformer model as the backbone network for feature extraction and innovatively add a filter layer. Firstly, in order to reduce the influence of noise on user behavior data, we use the learnable filters to filter the log noise. Secondly, following the examination hypothesis, we model the attraction estimator and examination predictor respectively to output attractiveness scores and examination probabilities. A novel transformer model is used to learn the deeper representation among different features. Finally, we apply the different combination functions to integrate attractiveness scores and examination probabilities into the click prediction. From our experiments on two real-world session datasets, it is proved that FE-TCM outperforms the existing click models for the click prediction.

BackgroundThe treatment strategy for elderly colorectal cancer patients with intestinal obstruction remains controversial. The choice of reasonable treatment and surgical method directly affects perioperative safety and prognosis. This study investigated the safety and long-term efficacy of radical surgery in elderly colorectal cancer patients over 80 years old with intestinal obstruction.MethodsThe clinicopathological data of elderly patients over 80 years old with intestinal obstruction who underwent colorectal cancer surgery from January 2012 to December 2021 were retrospectively collected and analysed. Patients were assigned to a radical group and a palliative group according to the surgical method. Propensity score matching (PSM) was performed to match patients in the radical group 1:1 with those in the palliative group. The perioperative-related indexes and prognosis were compared between the two groups.ResultsA total of 187 patients were enrolled in this study. After PSM, 58 matched pairs were selected, and the radical and palliative groups were well balanced in terms of the clinical and surgical characteristics (P > 0.05). The proportion of patients transferred to the ICU after surgery in the radical group was significantly higher than that in the palliative group (17.2% vs. 5.2%, P = 0.039). In terms of postoperative complications, the incidence of grade 1–5 complications in the radical group was significantly higher than that in the palliative group (37.9% vs. 15.5%, P = 0.006); however, there was no significant difference in the incidence of grade 3–5 complications between the two groups (6.9% vs. 1.7%, P = 0.364). In addition, the complications were subclassified, and it was found that the incidence of gastrointestinal disorders (20.7% vs. 6.9%, P = 0.031) after surgery was significantly higher in the radical group. The 3-year OS rates were 55.2% and 22.6% in the radical and palliative groups, respectively (P

Abstract Background Identifying cellular and functional heterogeneity within aged prostate is critical for understanding the spatial distribution of prostate diseases. Methods Aged human prostate peripheral zone (PZ) and transitional zone (TZ) tissues were used for single‐cell RNA‐sequencing. Results were validated by immunofluorescence staining. Results We found that club/hillock epithelial cells, compared with other epithelial cells, had significantly higher NOTCH signaling activity and expressed higher levels of neuro‐stems but lower androgen‐related genes. These cells were primarily found in the TZ and provided a stem‐like niche around the proximal prostate ducts. Significant heterogeneity was observed in the aged luminal population. A novel TFF3+ luminal subtype with elevated MYC and E2F pathway activities was observed, primarily in the PZ. Further analysis revealed that epithelial cells in the TZ had higher levels of stem‐ and inflammation‐related pathway activities but lower androgen/lineage‐related pathway activities than those in the PZ. Notably, the activation of MYC, E2F and DNA repair pathways significantly increased in PZ luminal cells. In the immune landscape, we found that the immune microenvironment in the TZ is more complex and disordered with more infiltration of NK and Treg cells. CD8 T cell and macrophage in the TZ exhibit both inflammation activation and suppression phenotypes. In the stroma, the TZ had a higher fibroblast density, and fibroblasts in the TZ exhibited stronger transcriptome activity in immunity and proliferation. Ligand–receptor interaction analysis revealed that fibroblasts could contribute to a NOTCH signaling niche for club/hillock cells in the TZ and balance the prostate immune microenvironment. The activation of stem properties, inflammatory infiltration and loss of androgen/lineage activity are prominent features distinguishing the TZ from PZ. Conclusions Our study explains the heterogeneity between the TZ and PZ of aged prostate, which may help understand the spatial distribution of prostate diseases and establish a foundation for novel target discovery.

Maize, as a glycophyte, is hypersensitive to salinity, but the salt response mechanism of maize remains unclear. In this study, the physiological, biochemical, and molecular responses of two contrasting inbred lines, the salt-tolerant QXH0121 and salt-sensitive QXN233 lines, were investigated in response to salt stress. Under salt stress, the tolerant QXH0121 line exhibited good performance, while in the sensitive QXN233 line, there were negative effects on the growth of the leaves and roots. The most important finding was that QXH0121 could reshift Na+ from shoots into long roots, migrate excess Na+ in shoots to alleviate salt damage to shoots, and also improve K+ retention in shoots, which were closely associated with the enhanced expression levels of ZmHAK1 and ZmNHX1 in QXH0121 compared to those in QXN233 under salt stress. Additionally, QXH0121 leaves accumulated more proline, soluble protein, and sugar contents and had higher SOD activity levels than those observed in QXN233, which correlated with the upregulation of ZmP5CR, ZmBADH, ZmTPS1, and ZmSOD4 in QXH0121 leaves. These were the main causes of the higher salt tolerance of QXH0121 in contrast to QXN233. These results broaden our knowledge about the underlying mechanism of salt tolerance in different maize varieties, providing novel insights into breeding maize with a high level of salt resistance.

DNA sequence preferences or statistical positioning of histones has not explained genomic patterns of nucleosome organisation in vivo. Here, the authors establish DNA shape/mechanics as key elements that have evolved together with binding sites of DNA sequence-specific barriers so that such information directs nucleosome positioning by chromatin remodelers.

Replication stress is associated with cancer formation and progression. Here the authors reveal that the macrophage migration inhibitory factor (MIF) functions as 3’ flap nuclease involved in resolving replication stress affecting overall tumor progression.

Abstract Background Apoptosis-inducing factor (AIF), as a mitochondrial flavoprotein, plays a fundamental role in mitochondrial bioenergetics that is critical for cell survival and also mediates caspase-independent cell death once it is released from mitochondria and translocated to the nucleus under ischemic stroke or neurodegenerative diseases. Although alternative splicing regulation of AIF has been implicated, it remains unknown which AIF splicing isoform will be induced under pathological conditions and how it impacts mitochondrial functions and neurodegeneration in adult brain. Methods AIF splicing induction in brain was determined by multiple approaches including 5′ RACE, Sanger sequencing, splicing-specific PCR assay and bottom-up proteomic analysis. The role of AIF splicing in mitochondria and neurodegeneration was determined by its biochemical properties, cell death analysis, morphological and functional alterations and animal behavior. Three animal models, including loss-of-function harlequin model, gain-of-function AIF3 knockin model and conditional inducible AIF splicing model established using either Cre-loxp recombination or CRISPR/Cas9 techniques, were applied to explore underlying mechanisms of AIF splicing-induced neurodegeneration. Results We identified a nature splicing AIF isoform lacking exons 2 and 3 named as AIF3. AIF3 was undetectable under physiological conditions but its expression was increased in mouse and human postmortem brain after stroke. AIF3 splicing in mouse brain caused enlarged ventricles and severe neurodegeneration in the forebrain regions. These AIF3 splicing mice died 2–4 months after birth. AIF3 splicing-triggered neurodegeneration involves both mitochondrial dysfunction and AIF3 nuclear translocation. We showed that AIF3 inhibited NADH oxidase activity, ATP production, oxygen consumption, and mitochondrial biogenesis. In addition, expression of AIF3 significantly increased chromatin condensation and nuclear shrinkage leading to neuronal cell death. However, loss-of-AIF alone in harlequin or gain-of-AIF3 alone in AIF3 knockin mice did not cause robust neurodegeneration as that observed in AIF3 splicing mice. Conclusions We identified AIF3 as a disease-inducible isoform and established AIF3 splicing mouse model. The molecular mechanism underlying AIF3 splicing-induced neurodegeneration involves mitochondrial dysfunction and AIF3 nuclear translocation resulting from the synergistic effect of loss-of-AIF and gain-of-AIF3. Our study provides a valuable tool to understand the role of AIF3 splicing in brain and a potential therapeutic target to prevent/delay the progress of neurodegenerative diseases.

The Yangtze River Basin (YRB) exhibits great climate heterogeneity, from high-elevated source areas dominated by westerlies to downstream wetlands sensitive to monsoon flows. However, the atmospheric hydrological cycle and associated precipitation changes are rarely being synthetically studied in different sub-basins of the YRB, which are particularly important since floods in the main stream largely result from the superposition of precipitation-runoff peaks from different sub-basins. By dividing the entire YRB into 12 sub-basins, this study presents a preliminary analysis of precipitation features and the associated moisture transport characteristics at the sub-basin scale during 1961–2015. Results suggest that the peak month of precipitation in the northwest sub-basins (July) is one month later than that in the southeast sub-basins (June). The highest total column water vapor (TCWV) contributes to the peak precipitation in July in the northwest sub-basins, while the peak precipitation in June in the southeast sub-basins is more relative to the interaction among multi-circulations (featured by relatively high westerly moisture transport and relatively low south monsoon contribution in the progression process of monsoon precipitation belt). The south monsoon moisture during summer seldom reaches the source region basin (SRB), the Jinshajiang River Basin (JRB), and the Mintuojiang River Basin (MTB). During 1961–2015, the precipitation mainly exhibits an “increase–decrease–increase” pattern from the source region to downstream; however, it is unlikely that this pattern is forced by the TCWV and zonal/meridional moisture transport. In addition, the moisture transport anomalies between wet and dry years are also defined in the 12 sub-basins, and these anomalies are characterized by significantly different moisture transport patterns.

Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.

Epigenetic regulator plays a pivotal role in breast cancer progression. We recently demonstrated that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) mediates breast cancer progression and metastasis by activating hypoxia-inducible factor (HIF). This discovery provides new insights into the molecular mechanism underlying HIF activation and breast cancer progression.

Poly(ADP-ribose) polymerase-1-dependent cell death (known as parthanatos) plays a pivotal role in many clinically important events including ischaemia/reperfusion injury and glutamate excitotoxicity. A recent study by us has shown that uncleaved AIF (apoptosis-inducing factor), but not calpain-hydrolysed truncated-AIF, was rapidly released from the mitochondria during parthanatos, implicating a second pool of AIF that might be present in brain mitochondria contributing to the rapid release. In the present study, a novel AIF pool is revealed in brain mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely associates with the outer mitochondrial membrane on the cytosolic side, in addition to its main localization in the mitochondrial intermembrane space attached to the inner membrane. Immunogold electron microscopic analysis of mouse brain further supports AIF association with the outer, as well as the inner, mitochondrial membrane in vivo . In line with these observations, approx. 20% of uncleaved AIF rapidly translocates to the nucleus and functionally causes neuronal death upon NMDA ( N -methyl- d -aspartate) treatment. In the present study we show for the first time a second pool of AIF in brain mitochondria and demonstrate that this pool does not require cleavage and that it contributes to the rapid release of AIF. Moreover, these results suggest that this outer mitochondrial pool of AIF is sufficient to cause cell death during parthanatos. Interfering with the release of this outer mitochondrial pool of AIF during cell injury paradigms that use parthanatos hold particular promise for novel therapies to treat neurological disorders.

To better understand users' behavior patterns in web search, numerous click models are proposed to extract the implicit interaction feedback. Most existing click models are heavily based on the implicit information to model user behaviors, ignoring the impact of explicit information between queries and documents in search sessions. In this paper, we fully consider the topic relevance between queries and documents in search sessions and propose a novel topic relevance-aware click model (TRA-CM) for web search. TRA-CM consists of a relevance estimator and an examination predictor. The relevance estimator consists of a topic relevance predictor and a click context encoder. In the topic relevance predictor, we utilize the pre-trained BERT model to model the content information of queries and documents in search sessions. Meanwhile, we use transformer to encode users' click behaviors in the click context encoder. We further apply a two-stage fusion strategy to obtain the final relevance scores. The examination predictor estimates the examination probability of each document. We further utilize learnable filters to attenuate log noise and obtain purer input features in both relevance estimator and examination predictor, and investigate different combination functions to integrate relevance scores and examination probabilities into click prediction. Extensive experiment results on two real-world session datasets prove that TRA-CM outperforms existing click models in both click prediction and relevance estimation tasks. [ABSTRACT FROM AUTHOR]