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Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention (PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia-reperfusion injury (IRI) and shed light on the underlying molecular mechanism. We generated adult mice with lentivirus-mediated or miRNA (mi1/133TS)-aided cardiac fibroblast-selective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending (LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia-reoxygenation (HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell proliferation. HSP47 upregulation in cardiac fibroblasts promoted TGF

Zeshi Li,1– 3,&ast; He Zhang,1– 3,&ast; Sulaiman Baraghtha,4,5,&ast; Jiabao Mu,6,&ast; Yusanjan Matniyaz,2 Xinyi Jiang,1– 3 Kuo Wang,2,7 Dongjin Wang,1– 3,7 Yun Xing Xue2 1Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5International School, University of Mannheim, Mannheim, Baden-Württemberg, Federal Republic of Germany; 6School of Data Science, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 7Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of XuZhou Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Xing Xue; Dongjin Wang, Email albert_xue@163.com; wangdongjin@njglyy.comPurpose: The postoperative survival of patients with acute type A aortic dissection (aTAAD) remains unsatisfactory. The current study developed an easy-to-use survival prediction model and calculator.Methods: A total of 496 patients with aTAAD undergoing surgical repair were included in this study. The systemic immune-inflammation index (SII) and other clinical features were collected and subjected to logistic and Cox regression analyses. The survival prediction model was based on Cox regression analyses and exhibited as a nomogram. For convenience of use, the nomogram was further developed into calculator software.Results: We demonstrated that a higher preoperative SII was associated with in-hospital death (OR: 4.116, p < 0.001) and a higher postoperative overall survival rate (HR: 2.467, p < 0.001) in aTAAD patients undergoing surgical repair. A survival prediction model and calculator based on SII and four other clinical features were developed. The overall C-index of the model was 0.743. The areas under the curves (AUCs) of the 1- and 3-month and 1- and 3-year survival probabilities were 0.73, 0.71, 0.71 and 0.72, respectively. The model also showed good calibration and clinical utility.Conclusion: Preoperative SII is significantly associated with postoperative survival. Based on SII and other clinical features, we created the first easy-to-use prediction model and calculator for predicting the postoperative survival rate in aTAAD patients, which showed good prediction performance.Keywords: acute type A aortic dissection, mortality, prediction, systemic immune-inflammation index

The atmospheric dust has a great negative impact on the societal harmonious development that starves for an efficient dust suppressant. This paper proposes a novel AES/polyacrylamide strengthen foam (APSF) to improve the dust trapping effectiveness. The APSF structure property and dust suppression capacity are studied and evaluated through the molecular dynamics simulation and experimental tests. The results express that APSF exhibits the stronger structure stability, superior water retention, and slower drainage performance than the traditional water-based foam (WBF). APSF dynamic simulation is studied by the relative concentration, radial distribution function, head group orientation, and mean square displacement. Research shows that APSF introduces water to thicken the hydration layer. The interaction strength between water and surfactant head groups is enhanced by 22.62 and 31.37% in the first and second hydrated water shells. APSF improves the sodium fatty alcohol ether sulfate (AES) orientation and weakens the diffusion of water molecules, which favors the foam stability. APSF exerts a better wettability on the coal dust through the wet settlement and contact angle tests. The APSF liquid film thickness reduces to 58.05 from 64.80 μm that is 3.14 times of WBF according to the foam liquid film decay experiment. Fourier transform infrared (FTIR) spectroscopy analysis indicates that there is an evident reinforcement on the coal surface absorption peak intensity of hydroxyl- and oxygen-containing functional groups treated by APSF. FTIR results are further determined by energy-dispersion spectrum analysis.

Fluorinated compounds are effective mineralization agents for the fabrication of plate-like α-Al2O3. However, in the preparation of plate-like α-Al2O3, it is still an extremely challenging task to reduce the content of fluoride while ensuring a low synthesis temperature. Herein, oxalic acid and NH4F are proposed for the first time as additives in the preparation of plate-like α-Al2O3. The results showed that plate-like α-Al2O3 can be synthesized at a low temperature of 850 °C with the synergistic effect of oxalic acid and 1 wt.% NH4F. Additionally, the synergistic effect of oxalic acid and NH4F not only can reduce the conversion temperature of α-Al2O3 but also can change the phase transition sequence.

Introduction. Burkholderia thailandensis is a clinically rare opportunistic pathogen in the genus Burkholderia , and the genomic features and virulence characteristics of B. thailandensis strains that cause human infection remain unclear. Gap Statement. B. thailandensis strains with different virulence induce different host innate immune responses in vitro. Aim. This work aimed to understand the sequence diversity, phylogenetic relationship, and virulence of B. thailandensis BPM causing human infection. Methodology. The comparative molecular and genomic analyses, and mouse infection studies were applied to analyse the virulence and genomic features of B. thailandensis BPM originating from China. Results. The whole genome sequence analysis showed that the genomes of BPM and other avirulent B. thailandensis strains were broadly similar, comprising two highly syntenic chromosomes with comparable numbers of coding regions (CDs), protein family distributions, and horizontally acquired genomic islands. By examining species-specific genomic regions, we obtained molecular explanations for previously known differences in virulence and discovered the potential specific virulence-associated genes of BPM, which likely work together to confer the virulence of BPM. Significantly reduced LD50 and survival rates during mouse infection experiments were found in BPM compared to the avirulent B. thailandensis E264 (BtE264). Conclusion. Taken together, the results of this study provide basic information on the genomic features and virulence characteristics of the virulent B. thailandensis strain BPM, which is helpful for understanding its evolution as it relates to pathogenesis and environmental adaptability.

Flooding is one of the most common and destructive natural disasters in coastal areas, involving considerable deaths, losses, and other severe consequences in many low-lying regions across the globe. Because of their highly developed economies and dense populations, coastal cities are especially vulnerable to flooding. In recent years and beyond, climate change is anticipated to considerably increase the flood risk in coastal areas. Consequently, it is of ultimate importance to develop efficient flood risk mitigating measures based on numerical models that properly capture the dynamic processes of coastal flooding based on reliable rainfall measurements and forecasts.Radar rainfall measurements have been viewed as potential model input for flood modelling as it is able to provide better representative of rainfall patterns with their variations at high spatial and temporal resolution. Radar forecasts at short lead times are also found to be the most skilled method for producing QPE (Quantitative Precipitation Estimation) and QPF (Quantitative Precipitation Forecast) at high spatiotemporal resolutions. For urbanized catchments in coastal areas, hydrodynamic models driven by high resolution rainfall data provided by radar observation and forecasting may present efficient tool for simulating and predicting the rainfall–runoff responses.This study, therefore, aims to develop a robust way to assess the impact of spatial and temporal variability of floods using radar rainfall data against rain gauge ones over Guangzhou, a typical city in the Pearl River Delta of the Greater Bay Area in the southern China, which is frequently suffered from pluvial flooding. A 2D High-Performance Integrated hydrodynamic Modelling System (HiPIMS) was employed to support the flood modelling, especially for simulating highly transient flooding process in intensely urbanized part of Guangzhou. With the objective of exploring the spatial and temporal heterogeneity of flooding in coastal areas induced by complex rainfall patterns, comparisons were made between the simulations driven by rain gauge measurements and radar QPE and QPF, in terms of maximum inundation conditions and spatiotemporal evolutions. Results of this study may potentially help improve the accuracy of coastal flood forecasts and thus provide information for developing more reliable flood mitigation measures.

Supplementary Figures and Tables

Knowledge mining is a widely active research area across disciplines such as natural language processing (NLP), data mining (DM), and machine learning (ML). The overall objective of extracting knowledge from data source is to create a structured representation that allows researchers to better understand such data and operate upon it to build applications. Each mentioned discipline has come up with an ample body of research, proposing different methods that can be applied to different data types. A significant number of surveys have been carried out to summarize research works in each discipline. However, no survey has presented a cross-disciplinary review where traits from different fields were exposed to further stimulate research ideas and to try to build bridges among these fields. In this work, we present such a survey.

Flood modelling can provide useful information to support flood risk assessment and management. The accuracy of flood simulation results is highly dependent on the quality of input data. In particular, digital elevation models (DEMs) may directly influence the performance of flood predictions and improper representation of complex urban features including buildings and bridges may lead to incorrect prediction of flooding paths and extents, and consequently miscalculate flood risk. In this work, a geographic information system (GIS)-based correction method is proposed to make modifications in high-resolution DEMs by adding building complexes and removing unphysical representations of bridges for a more realistic description of flood paths in considering the flow connectivity in intensely urbanized areas and with the objective of obtaining more accurate flood simulation results. The proposed DEM correction method is applied to support large-scale urban flood modelling in Fuzhou City, China, using an established hydrodynamic flood model known as High-Performance Integrated hydrodynamic Modelling System (HiPIMS). Comparisons are made to the simulation results with and without the DEM improvements using the proposed correction method. The results demonstrate that correct representation of the artificial structures in the urban DEM can significantly improve the flood simulation results.

Facial image-based kinship verification is a rapidly growing field in computer vision and biometrics. The key to determining whether a pair of facial images has a kin relation is to train a model that can enlarge the margin between the faces that have no kin relation while reducing the distance between faces that have a kin relation. Most existing approaches primarily exploit duplet (i.e., two input samples without cross pair) or triplet (i.e., single negative pair for each positive pair with low-order cross pair) information, omitting discriminative features from multiple negative pairs. These approaches suffer from weak generalizability, resulting in unsatisfactory performance. Inspired by human visual systems that incorporate both low-order and high-order cross-pair information from local and global perspectives, we propose to leverage high-order cross-pair features and develop a novel end-to-end deep learning model called the adaptively weighted k-tuple metric network (AWk-TMN). Our main contributions are three-fold. First, a novel cross-pair metric learning loss based on k-tuplet loss is introduced. It naturally captures both the low-order and high-order discriminative features from multiple negative pairs. Second, an adaptively weighted scheme is formulated to better highlight hard negative examples among multiple negative pairs, leading to enhanced performance. Third, the model utilizes multiple levels of convolutional features and jointly optimizes feature and metric learning to further exploit the low-order and high-order representational power. Extensive experimental results on three popular kinship verification datasets demonstrate the effectiveness of our proposed AWk-TMN approach compared with several state-of-the-art approaches. The source codes and models are released.1.

The roadheader cutting process generates massive disorganized dust in the excavation roadway. The cutting azimuth has a remarkable effect on the dust diffusion. Nine representative positions are performed to evaluate the dust spatial characteristics. The large vortex with pressure lower than −5.0 Pa entrains massive dusts in the forepart roadway. The high-concentration dust shows an asymmetry linear decrease distribution in the horizontal. The minimum velocity migration drives the high-concentration area to move with the cutting azimuth change. The middle position makes a minimum stabilization time at 45 s, along with the smallest dust area and wrap volume. The maximum concentration gap reaches 168.1 mg/m3 at the driver. As the cutterhead moves upward, the dust occurrence time delays and the concentration peak/valley number extends by twice. The pollution regions obtained at the variational cutting azimuths provides ctitical guidance for implementing the dynamic dust-proof measures and realizing a sustainable clean production.

The connection between emotional states and physical health has attracted widespread attention. The emotional stress assessment can help healthcare professionals figure out the patient's engagement toward the diagnostic plan and optimize the rehabilitation program as feedback. It is of great significance to study the changes of physiological features in the process of emotional change and find out subset of one or several physiological features that can best represent the changes of psychological state in a statistical sense. Previous studies had used the differences in physiological features between discrete emotional states to select feature subsets. However, the emotional state of the human body is continuously changing. The conventional feature selection methods ignored the dynamic process of an individual's emotional stress in real life. Therefore, a dedicated experimental was conducted while three peripheral physiological signals, i.e., ElectroCardioGram (ECG), Galvanic Skin Resistance (GSR), and Blood Volume Pulse (BVP), were continuously acquired. This paper reported a novel feature selection method based on emotional state transition, the experimental results show that the number of physiological features selected by the proposed method in this paper is 13, including 5 features of ECG, 4 features of PPG and 4 features of GSR, respectively, which are superior to PCA method and conventional feature selection method based on discrete emotional states in terms of dimension reduction. The classification results show that the accuracy of the proposed method in emotion recognition based on ECG and PPG is higher than the other two methods. These results suggest that the proposed method can serve as a viable alternative to conventional feature selection methods, and emotional state transition deserves more attention to promote the development of stress assessment.

RNA flexibility is reflected in its heterogeneous conformation. Existing techniques, such as NMR, crystallography, or cryo-EM, are not suited for studying highly heterogeneous conformation. Through direct visualization using atomic force microscopy (AFM) and the adenosylcobalamin riboswitch aptamer domain as an example, we show that a single RNA sequence folds into conformationally and architecturally heterogeneous structures under near-physiological solution conditions. Recapitulated 3D topological structures from AFM molecular surfaces reveal that all conformers share the same secondary structural elements. Only a population-weighted cohort, not any single conformer, including the crystal structure, can account for the ensemble behaviors. All conformers, except for one, are functionally active in terms of ligand binding. Our findings provide direct visual evidence that the sequence-structure relationship of RNA under physiologically relevant solution conditions is more complex than the one-to-one relationship for well-structured proteins. The direct visualization of conformational and architectural ensembles in solution may prompt a revision to our current views and approaches to RNA structural analyses.

Objective. This study aimed to determine the risk factors of new-onset postoperative atrial fibrillation after ascending aortic replacement in acute type A aortic dissection patients, with emphasis on biochemical parameters. Methods. From Jan 2020 to Dec 2021, a total of 435 acute type A aortic dissection patients who underwent ascending aortic replacement and without a history of atrial fibrillation were retrospectively analyzed in this study. Perioperative data of these patients were obtained from the hospital’s database. The 30-day follow-up was via telephone interviews. The multivariate regression analysis was used to identify risk factors that may be predictive of postoperative atrial fibrillation. Results. 218 (50.1%) patients experienced postoperative atrial fibrillation after ascending aorta replacement surgery. Older age (OR = 1.081 (1.059–1.104), p < 0.001 ), higher total bile acid (OR = 1.064 (1.024–1.106), p = 0.002), glucose (OR = 1.180 (1.038–1.342), p = 0.012), and serum potassium (OR = 2.313 (1.078–4.960), p = 0.031) were identified by multivariate regression analysis as risk factors of postoperative atrial fibrillation. The multivariate regression analysis prediction model incorporating these four factors had a good prediction effect (AUC = 0.769 (0.723–0.816), p < 0.001 ). Conclusions. Older age, higher total bile acid, glucose, and serum potassium were risk factors of postoperative atrial fibrillation after ascending aortic replacement surgery in acute type A aortic dissection patients.

Supplemental Material, sj-pdf-1-ojs-10.1177_23259671231172977 for Clinical Outcomes After Arthroscopic Microfracture Treatment of Coexisting Talar and Tibial Osteochondral Lesions by Yu Wei, Xing Yun, Jianing Song, Wei Qi, Jia Li, Yujie Liu, Qi Quan and Min Wei in Orthopaedic Journal of Sports Medicine

In recent years, various anti-tumor treatment methods have emerged in endlessly. Here in, a novel anti-tumor mechanism is designed and a special double-layer nanoparticles (CMC/MgO @ FA-CS/BODIPY NPs) were prepared. It utilizes the special acidic environment of cell lysosomes to swell violently in lysosomes, destroy lysosomes and release hydrolases. Because the number of tumor cell lysosomes is significantly more than that of normal cells, and the volume is also larger, resulting in the release of a large number of hydrolases to digest the entire tumor cell and cause it to die, while the number of normal cell lysosomes is small, and the destruction of lysosomes is not enough to kill cell. In this paper, animal experiments and the control experiments of tumor cells and normal cells prove that the designed nanoparticles have a broad-spectrum antineoplastic activities and are harmless to normal cells. At the same time, the nanoparticles are mainly composed of carboxymethyl cellulose (CMC), chitosan (CS) and other commonly used pharmaceutical excipients, which have no toxicity. Therefore, this method is a new safe and effective way to treat tumors. It has not been reported in any literature.

Structures of well-folded RNA molecules can be determined with atomic resolution by either X-ray crystallography, cryo-EM, or NMR spectroscopy, but those of conformationally-flexible RNAs often are difficult to study with these methods. However, flexible RNAs have biological relevance and likely represent the majority of the RNA conformational space. Due to the high electron density of the phosphate-sugar backbone, RNA is very sensitive to small-angle X-ray scattering (SAXS), and SAXS data can be recorded with sub-μM concentrations and under near-physiological solution conditions without the need for labeling. For these reasons, SAXS has significant advantages over other techniques for obtaining global structural information of flexible RNAs in the form of molecular envelopes or low-resolution topological structural models. The SAXS-derived information is extremely valuable for bridging secondary structure data, often determined by other techniques, with a three-dimensional structure description. In this chapter, we present a detailed account of the principle, algorithms, and experimental and computational protocols for topological structure determination of RNA molecules in solution. To illustrate the applications of the methodology, we provide several case studies that cover a broad spectrum of the RNA conformational landscape.

Time-resolved structure determination of macromolecular conformations and ligand-bound intermediates is extremely challenging, particularly for RNA. With rapid technological advances in both microfluidic liquid injection and X-ray free electron lasers (XFEL), a new frontier has emerged in time-resolved crystallography whereby crystals can be mixed with ligand and then probed with X-rays (mix-and-inject) in real time and at room temperature. This chapter outlines the basic setup and procedures for mix-and-inject experiments for recording time-resolved crystallographic data of riboswitch RNA reaction states using serial femtosecond crystallography (SFX) and an XFEL.

Background Mechanistic insights of glucagon‐like peptide‐1 receptor agonists remain incompletely identified, despite the efficacy in heart failure observed in clinical trials. Here, we evaluated the effects of dulaglutide on heart complications and illuminated its underlying mechanism. Methods and Results We used mice with high‐fat diet (HFD)/streptozotocin‐induced type 2 diabetes to investigate the effects of dulaglutide upon diabetic cardiac dysfunction. After the onset of diabetes, control and diabetic mice were injected subcutaneously with either dulaglutide (type 2 diabetes‐dulaglutide and control‐dulaglutide groups) or vehicle (type 2 diabetes‐vehicle and control‐vehicle groups) for 8 weeks. Subsequently, heart characteristics, cardiometabolic profile and mitochondrial morphology and function were evaluated. Also, we analyzed the effects of dulaglutide on neonatal rat ventricular myocytes treated with high glucose plus palmitic acid. In addition, wild type and AMP‐activated protein kinase α2 mutant mice were used to evaluate the underlying mechanism. In type 2 diabetes mouse model, dulaglutide ameliorated insulin resistance, improved glucose tolerance, reduced hyperlipidemia, and promoted fatty acid use in the myocardium. Dulaglutide treatment functionally attenuated cardiac remodeling and dysfunction and promoted metabolic reprogramming in diabetic mice. Furthermore, dulaglutide improved mitochondria fragmentation in myocytes, and simultaneously reinstated mitochondrial morphology and function in diabetic hearts. We also found that dulaglutide preserved AMP‐activated protein kinase α2‐dependent mitochondrial homeostasis, and the protective effects of dulaglutide on diabetic heart was almost abated by AMP‐activated protein kinase α2 knockout. Conclusions Dulaglutide prevents diabetic heart failure and favorably affects myocardial metabolic remodeling by impeding mitochondria fragmentation, and we suggest a potential strategy to develop a long‐term activation of glucagon‐like peptide‐1 receptor–based therapy to treat diabetes associated cardiovascular complications.

Non-invasive thermal therapy for subcutaneous tumors with the assistance of gold nanoparticles and surface cooling measures was proposed in the present study. To achieve real-time monitoring of 3-D temperature distribution and accurate measurement of thermal response, we developed a theoretical approach in which the dual-phase-lag (DPL) biological heat transfer model and Henriques' burn estimation model were employed. A closed-form solution for temperature distribution in the skin tissue can be obtained from this new model by employing the Green's function method. In addition, the influences of the embedment of gold nanoparticles, surface cooling, and non-Fourier effects on the temperature, thermal damage, and size of the burnt region were discussed in detail. The present model performs well in addressing the difficult issue of temperature and burn prediction inside human tissue. It is found that the combination of gold nanoparticles and surface cooling can concentrate thermal empyrosis in the subcutaneous tumor to enhance tumor elimination and protect both skin and deeper healthy tissue. This study provides theoretical support for the improvement and development of laser thermotherapy for subcutaneous tumors. Published version

BackgroundThe CAR T-cell therapy is a promising approach to treating hematologic malignancies. However, the application in solid tumors still has many tough challenges, including heterogenicity in antigen expressions and immunosuppressive tumor microenvironment (TME). As a new cancer treatment modality, oncolytic virotherapy can be engineered to circumvent these obstacles for CAR T cell therapy in solid tumors.MethodsIn this study, an oHSV T7011 is engineered to drive ectopic expression of dual-antigens, extracellular domains of CD19 and BCMA, on the solid tumor cell surface to be targeted by approved CAR T cells. In addition, multiple immunomodulators, CCL5, IL-12, and anti-PD-1 antibody are also included to modulate the TME. The antitumor activities of T7011 in combination with CD19 or BCMA CAR T-cell were evaluated in vitro and in vivo.ResultsThe expression of CD19 or BMCA on the tumor cell surface could be detected after T7011 infection. The level of CCL5 in TME was also increased. Efficacy studies demonstrated that combination with T7011 and CAR-TCD19 or CAR-TBCMA cells showed significant synergistic anti-tumor responses in several solid tumor models.ConclusionThese studies indicated that the new generation of oHSV T7011 can be a promising combinational therapy with CD19 or BCMA-specific CAR T cells for the treatment of a broad range of solid tumors.

Arachidonate 5-lipoxygenase (Alox5) belongs to a class of nonheme iron-containing dioxygenases involved in the catalysis of leukotriene biosynthesis. However, the effects of Alox5 itself on pathological cardiac remodeling and heart failure remain elusive.The role of Alox5 in pathological cardiac remodeling was investigated by Alox5 genetic depletion, AAV9-mediated overexpression in cardiomyocytes, and a bone marrow (BM) transplantation approach. Neonatal rat cardiomyocytes were used to explore the effects of Alox5 in vitro. Molecular and signaling pathways were revealed by CUTTag, IP-MS, RNA sequencing and bioinformatic analyses.Untargeted metabolomics showed that serum 5-HETE (a primary product of Alox5) levels were little changed in patients with cardiac hypertrophy, while Alox5 expression was significantly upregulated in murine hypertensive cardiac samples and human cardiac samples of hypertrophy, which prompted us to test whether high Alox5 levels under hypertensive stimuli were directly associated with pathologic myocardium in an enzymatic activity-independent manner. Herein, we revealed that Alox5 deficiency significantly ameliorated transverse aortic constriction (TAC)-induced hypertrophy. Cardiomyocyte-specific Alox5 depletion attenuated hypertensive ventricular remodeling. Conversely, cardiac-specifical Alox5 overexpression showed a pro-hypertrophic cardiac phenotype. Ablation of Alox5 in bone marrow-derived cells did not affect pathological cardiac remodeling and heart failure. Mechanically, Runx2 was identified as a target of Alox5. In this regard, Alox5 PEST domain could directly bind to Runx2 PTS domain, promoting nuclear localization of Runx2 in an enzymatic activity-independent manner, simultaneously contributed to liquid-liquid phase separation (LLPS) of Runx2 at specific domain in the nucleus and increased transcription of EGFR in cardiomyocytes. Runx2 depletion alleviated hypertrophy in Ang II-pretreated Alox5-overexpressing cardiomyocytes.Overall, our study demonstrated that targeting Alox5 exerted a protective effect against cardiac remodeling and heart failure under hypertensive stimuli by disturbing LLPS of Runx2 and substantial reduction of EGFR transcription activation in cardiomyocytes. Our findings suggest that negative modulation of Alox5-Runx2 may provide a therapeutic approach against pathological cardiac remodeling and heart failure.National Natural Science Foundation of China.

Commensal bacteria and other microorganisms that reside in the human body are closely associated with the development and treatment of cancers. Recently, tumor microbiome (TM) has been identified in a variety of cancers such as pancreatic, lung, and breast cancers. TM has different compositions in different tumors and has different effects on tumors. TM plays an important role in the formation of the tumor microenvironment, regulation of local immunity, and modification of tumor cell biology, and directly affects the efficacy of drug treatment for tumors. TM is expected to be a biomarker for tumors, and engineered tumor-targeting bacteria and anti-cancer microbial agents (GEN-001) have an important role in the treatment of tumors. This paper reviews the relevant studies on TM in recent years and describes its distribution in different tumors, its correlation with clinical features, its effect on local immunity, and the research directions of TM in tumor treatment.

South Asia is home to one of the fastest-growing populations in Asia, and human activities are leaving indelible marks on the land surface. Yet the likelihood of successive observed droughts in South Asia (SA) and its four subregions (R-1: semi-arid, R-2: arid, R-3: subtropical wet, and R-4: tropical wet and dry) remains poorly understood. Using the state-of-the-art self-calibrated Palmer Drought Severity Index (scPDSI), we examined the impact of different natural ocean variability modes on the evolution, severity, and magnitude of observed droughts across the four subregions that have distinct precipitation seasonality and cover key breadbaskets and highly vulnerable populations. The study revealed that dryness had significantly increased in R-1, R-2, and R-4 during 1981–2020. Temporal analysis revealed an increase in drought intensity for R-1 and R-4 since the 2000s, while a mixed behavior was observed in R-2 and R-3. Moreover, most of the sub-regions witnessed a substantial upsurge in annual precipitation, but a significant decrease in vapor pressure deficit (VPD) during 1981–2020. The increase in precipitation and the decline in VPD partially contributed to a significant rise in Normalized Difference Vegetation Index (NDVI) and a decrease in dryness. In contrast, a strong positive correlation was found between drought index and precipitation, and NDVI across R-1, R-2, and R-4, whereas temperature and VPD exhibited a negative correlation over these regions. No obvious link was detected with El-Niño Southern Oscillation (ENSO) events, or Indian Ocean Dipole (IOD) and drought evolution, as explored for certain regions of SA. The findings showed the possibility that the precipitation changes over these regions had an insignificant relationship with ENSO, IOD, and drought onset. Thus, the study results highlight the need for considering interactions within the longer climate system in describing observed drought risks rather than aiming at drivers from an individual perspective.

The mechanism of a solid–solid phase transition in an RNA crystal is presented., Solid–solid phase transitions (SSPTs) occur between distinguishable crystalline forms. Because of their importance in application and theory in materials science and condensed-matter physics, SSPTs have been studied most extensively in metallic alloys, inorganic salts and small organic molecular crystals, but much less so in biomacromolecular crystals. In general, the mechanisms of SSPTs at the atomic and molecular levels are not well understood. Here, the ordered molecular rearrangements in biomacromolecular crystals of the adenine riboswitch aptamer are described using real-time serial crystallography and solution atomic force microscopy. Large, ligand-induced conformational changes drive the initial phase transition from the apo unit cell (AUC) to the trans unit cell 1 (TUC1). During this transition, coaxial stacking of P1 duplexes becomes the dominant packing interface, whereas P2–P2 interactions are almost completely disrupted, resulting in ‘floating’ layers of molecules. The coupling points in TUC1 and their local conformational flexibility allow the molecules to reorganize to achieve the more densely packed and energetically favorable bound unit cell (BUC). This study thus reveals the interplay between the conformational changes and the crystal phases – the underlying mechanism that drives the phase transition. Using polarized video microscopy to monitor SSPTs in small crystals at high ligand concentration, the time window during which the major conformational changes take place was identified, and the in crystallo kinetics have been simulated. Together, these results provide the spatiotemporal information necessary for informing time-resolved crystallography experiments. Moreover, this study illustrates a practical approach to characterization of SSPTs in transparent crystals.

采用四种不同的方法制备了一系列含 \begin{document}$ {\rm{SO}}^{2-}_{4} $\end{document} 改性Ce-Fe-Ox催化剂，并研究其NH3选择性催化还原NOx的催化活性。结果表明，水热法制备的Ce-Fe-Ox（Fe-HT）可提高其催化性能。其优异的SCR性能与硫酸的加入有关， \begin{document}$ {\rm{SO}}^{2-}_{4} $\end{document} 的加入会导致CeO2晶体的弱化，提高其催化活性。Fe和Ce协同作用可提高催化剂的氧化还原能力，进而提高化学吸附氧的含量、Ce3+/(Ce4+ + Ce3+)和Fe3+/(Fe3+ + Fe2+)的比例，从而提高催化性能。过量的硫酸盐会导致Fe3+和Ce3+的下降，降低催化性能。

Quorum sensing gene expression in vibrios is regulated by the LuxR/HapR family of transcriptional factors, which includes Vibrio vulnificus SmcR. The consensus binding site of Vibrio LuxR/HapR/SmcR proteins is palindromic but highly degenerate with sequence variations at each promoter. To examine the mechanism by which SmcR recognizes diverse DNA sites, we generated SmcR separation-of-function mutants that either repress or activate transcription but not both. SmcR N55I is restricted in recognition of single base-pair variations in DNA binding site sequences and thus is defective at transcription activation but retains interaction with RNA polymerase (RNAP) alpha. SmcR S76A, L139R and N142D substitutions disrupt the interaction with RNAP alpha but retain functional DNA binding activity. X-ray crystallography and small angle X-ray scattering data show that the SmcR DNA binding domain exists in two conformations (wide and narrow), and the protein complex forms a mixture of dimers and tetramers in solution. The three RNAP interaction-deficient variants also have two DNA binding domain conformations, whereas SmcR N55I exhibits only the wide conformation. These data support a model in which two mechanisms drive SmcR transcriptional activation: interaction with RNAP and a multi-conformational DNA binding domain that permits recognition of variable DNA sites.

Solid–solid phase transitions (SSPTs) are widespread naturally occurring phenomena. Understanding the molecular mechanisms and kinetics of SSPTs in various crystalline materials, however, has been challenging due to technical limitations. In particular, SSPTs in biomacromolecular crystals, which may involve large-scale changes and particularly complex sets of interactions, are largely unexplored, yet may have important implications for time-resolved crystallography and for developing synthetic biomaterials. The adenine riboswitch (riboA) is an RNA control element that uses ligand-induced conformational changes to regulate gene expression. Crystals of riboA, upon the addition of a ligand, undergo an SSPT from monoclinic to triclinic to orthorhombic. Here, solution atomic force microscopy (AFM) and polarized video microscopy (PVM) are used to characterize the multiple transition states throughout the SSPT in both the forward and the reverse directions. This contribution describes detailed protocols for growing crystals directly on mica or glass surfaces for AFM and PVM characterization, respectively, as well as methods for image processing and phase-transition kinetics analysis.

Sepsis rapidly contributed to multiorgan failure affecting most commonly of the cardiovascular and respiratory systems and yet there were no effective therapies. The current study aimed at providing evidence on the cardioprotection of suppression of 5-Lipoxygenase (5-Lox) and identifying the possible mechanism in the mouse model of sepsis. The cecal ligation-perforation (CLP) model was applied to C57BL/6 wild-type (WT) and 5-Lox deficient (5-Lox-/-) mice to induce sepsis. 5-Lox expression was up-regulated in mouse myocardium and leukotriene B4 (LTB4) level was increased in serum after sepsis. Subsequently, we utilized a recombinant adenoviral expression vector (rAAV9) to overexpress Alox5 gene in adult mice. Compared to WT mice, 5-Lox overexpression accelerated CLP-induced myocardial injury and cardiac dysfunction. Oppositely, 5-Lox deficiency offered protection against myocardial injury in a mouse model of sepsis and attenuated sepsis-mediated inflammation, oxidative stress and apoptosis in the mouse heart. Mechanically, 5-Lox promoted LTB4 production, which in turn contributed to the activation of leukotriene B4 receptor 1 (BLT1)/interleukin-12p35 (IL-12p35) pathway and enhanced M1 macrophage polarization. However, the suppression of BLT1 by either gene mutation or antagonist U75302 significantly inhibited the adverse effect of 5-Lox in sepsis. Further study demonstrated that pharmacological inhibition of 5-Lox prevented CLP-induced septic cardiomyopathy (SCM). Our study identified 5-Lox exacerbated sepsis-associated myocardial injury through activation of LTB4 production and promoting BLT1/IL-12p35 pathway. Hence, inhibition of 5-Lox may be a potential candidate strategy for septic cardiac dysfunction treatment.

For the predictions and simulations of energy pile behavior under a combination of thermal and mechanical loads, with a complexity of parameters describing the energy pile, the surrounding soil and their interaction, modelers may be faced with the decision of whether it is better to spend more resource on determining the appropriate value of certain model parameters with high precision or on running more simulations to account for various uncertain input factors. In this study global sensitivity analysis is applied to explore the relative importance of the parameters of interest as model inputs and their contributions to the final results of the energy pile numerical model for different outputs. The interaction of uncertainties between different parameters is also analyzed with second order and total indices. Findings of this study indicate that the sensitivity of numerical energy pile predictions is more complex than previously thought. With a varying external forcing like the mechanical load or temperature change, the influence of input factor (e.g. model parameters) for the predictions of different spatially lumped model outputs is found to change but not always monotonically despite a monotonic variation of the output value. Spatial variability in the influence of the input factors which may be hidden by the spatially lumped analysis is also examined and inhomogeneous distribution of the input factor importance can be revealed along the whole length of the energy pile. The input factors that modelers should prioritize will not only differ depending on the assessed model output, but also on the location of the output and the surrounding circumstances which provide external loads and thermal effects.