Prognostic significance and immune landscape of a cell cycle progression-related risk model in bladder cancer.

BACKGROUND: A greater emphasis has been placed on the part of cell cycle progression (CCP) in cancer in recent years. Nevertheless, the precise connection between CCP-related genes and bladder cancer (BCa) has remained elusive. This study endeavors to establish and validate a reliable risk model incorporating CCP-related factors, aiming to predict both the prognosis and immune landscape of BCa. METHODS: Clinical information and RNA sequencing data were collected from the GEO and TCGA databases. Univariate and multivariate Cox regression analyses were conducted to construct a risk model associated with CCP. The performance of the model was assessed using ROC and Kaplan-Meier survival analyses. Functional enrichment analysis was employed to investigate potential cellular functions and signaling pathways. The immune landscape was characterized using CIBERSORT algorithms. Integration of the risk model with various clinical variables led to the development of a nomogram. RESULTS: To build the risk model, three CCP-related genes (RAD54B, KPNA2, and TPM1) were carefully chosen. ROC and Kaplan-Meier survival analysis confirm that our model has good performance. About immunological infiltration, the high-risk group showed decreased levels of regulatory T cells and dendritic cells coupled with increased levels of activated CD4 + memory T cells, M2 macrophages, and neutrophils. Furthermore, the nomogram showed impressive predictive power for OS at 1, 3, and 5 years. CONCLUSION: This study provides new insights into the association between the CCP-related risk model and the prognosis of BCa, as well as its impact on the immune landscape.

Alzheimer's Disease Pathophysiology in the Retina.

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid ß-protein (Aß) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aß deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.

Universal origin of glassy relaxation as recognized by configuration pattern matching.

Relaxation processes are crucial for understanding the structural rearrangements of liquids and amorphous materials. However, the overarching principle that governs these processes across vastly different materials remains an open question. Substantial analysis has been carried out based on the motions of individual particles. Here, as an alternative, we propose viewing the global configuration as a single entity. We introduce a global order parameter, namely the inherent structure minimal displacement (IS Dmin), to quantify the variability of configurations by a pattern-matching technique. Through atomic simulations of seven model glass-forming liquids, we unify the influences of temperature, pressure and perturbation time on the relaxation dissipation, via a scaling law between the mechanical damping factor and IS Dmin. Fundamentally, this scaling reflects the curvature of the local potential energy landscape. Our findings uncover a universal origin of glassy relaxation and offer an alternative approach to studying disordered systems.

Focal ischemic myocardial fibrosis assessed by late gadolinium enhancement cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), ischemic myocardial fibrosis assessed by late gadolinium enhancement (I-LGE) using cardiovascular magnetic resonance (CMR) have been reported. However, the clinical significance of I-LGE has not been completely understood. We aim to evaluate the I-LGE differ phenotypically from HCM without LGE or nonischemic myocardial fibrosis assessed by late gadolinium enhancement (NI-LGE) in the left ventricle (LV). METHODS: The patients with HCM whom was underwent CMR were enrolled, using cine cardiac magnetic resonance to evaluate LV function and LGE to detect the myocardial fibrosis. Three groups were assorted: 1) HCM without LGE; 2) HCM with LGE involved the subendocardial layer was defined as I-LGE; 3) HCM with LGE not involved the subendocardial layer was defined as NI-LGE. RESULTS: We enrolled 122 patients with HCM in the present study. LGE was detected in 58 of 122 (48%) patients with HCM, and 22 (18%) of patients reported I-LGE. HCM with I-LGE had increased higher left ventricular mass index (LVMI) (P < 0.0001) than HCM with NI-LGE or without LGE. In addition, HCM with I-LGE had a larger LV end- systolic volume (P = 0.045), lower LV ejection fraction (LVEF) (P = 0.026), higher LV myocardial mass (P < 0.001) and thicker LV wall (P < 0.001) more than HCM without LGE alone. The I-LGE were significantly associated with LVEF (OR: 0.961; P = 0.016), LV mass (OR: 1.028; P < 0.001), and maximal end-diastolic LVWT (OR: 1.567; P < 0.001). On multivariate analysis, LVEF (OR: 0.948; P = 0.013) and maximal end-diastolic LVWT (OR: 1.548; P = 0.001) were associated with higher risk for I-LGE compared to HCM without LGE. Noticeably, the maximal end-diastolic LVWT (OR: 1.316; P = 0.011) was the only associated with NI-LGE compared to HCM without LGE. CONCLUSIONS: I-LGE is not uncommon in patients with HCM. HCM with I-LGE was associated with significant LV hypertrophy, extensive LGE and poor LV ejection fraction. We should consider focal ischemic myocardial fibrosis when applying LGE to risk stratification for HCM.

Engineering a polyvinyl butyral hydrogel as a thermochromic interlayer for energy-saving windows.

Achieving mastery over light using thermochromic materials is crucial for energy-saving glazing. However, challenges such as high production costs, limited durability, and recyclability issues have hindered their widespread application in buildings. Herein, we develop a glass interlayer made of a polyvinyl butyral-based hydrogel swollen with LiCl solution. In addition to a fast, isochoric, and reversible transparency-to-opacity transition occurring as ambient temperatures exceed thermally comfortable levels, this hydrogel uniquely encompasses multiple features such as frost resistance, recyclability, scalability, and toughness. The combination of these features is achieved through a delicate balance of polyvinyl butyral's amphiphilicity and the suppression of network-forming phase separation. This design endows a nanostructured polyvinyl butyral-LiCl composite gel with swollen molecular segments linked by dispersed cross-linking sites in the form of hydrophobic nano-nodules. Upon laminating this hydrogel (a thickness of 0.3 mm), the resultant glazing product demonstrates approximately 90% luminous transmittance even at sub-zero temperatures, along with a significant modulation of solar and infrared radiation at 80.8% and 68.5%, respectively. Through simulations, we determined that windows equipped with the hydrogel could reduce energy consumption by 36% compared to conventional glass windows in warm seasons. The widespread adoption of polyvinyl butyral in construction underscores the promise of this hydrogel as a thermochromic interlayer for glazing.

Kilohertz volumetric imaging of in-vivo dynamics using squeezed light field microscopy.

Volumetric functional imaging of transient cellular signaling and motion dynamics poses a significant challenge to current microscopy techniques, primarily due to limitations in hardware bandwidth and the restricted photon budget within short exposure times. In response to this challenge, we present squeezed light field microscopy (SLIM), a computational imaging method that enables rapid detection of high-resolution three-dimensional (3D) light signals using only a single, low-format camera sensor area. SLIM pushes the boundaries of 3D optical microscopy, achieving over one thousand volumes per second across a large field of view of 550 µm in diameter and 300 µm in depth. Using SLIM, we demonstrated blood cell velocimetry across the embryonic zebrafish brain and in a free-moving tail exhibiting high-frequency swinging motion. The millisecond temporal resolution also enables accurate voltage imaging of neural membrane potentials in the leech ganglion. These results collectively establish SLIM as a versatile and robust imaging tool for high-speed microscopy applications.

Light-triggered AND logic tetrapeptide dynamic covalent assembly.

We demonstrate light-triggered dynamic covalent assembly of a linear short tetrapeptide containing two terminal cysteine residues in an AND logic manner. A photobase generator is introduced to accomplish light-mediated pH regulation to increase the reduction potential of thiols in the tetrapeptide, which activates its oxidative polymerization through disulfide bonds. Interestingly, it is elucidated that under light irradiation, mere co-existence of photobase generator and the oxidizing agent permits the polymerization performance of this tetrapeptide. Hence, a light-triggered AND logic dynamic covalent assembly of a tetrapeptide is achieved. Further, upon redox response, the reversible aggregation and disaggregation can be transformed for numerous times due to the dynamic covalent feature of disulfide bond. As a comparison, no assembly occurs for a short peptide containing one terminal cysteine residue under the same stimuli condition. This work offers a new approach to remotely control programmable molecular assembly of short linear peptides based on dynamic covalent bond, holding great potential in wide bioapplications.

An enzymatic continuous-flow reactor based on a pore-size matching nano- and isoporous block copolymer membrane.

Continuous-flow biocatalysis utilizing immobilized enzymes emerged as a sustainable route for chemical synthesis. However, inadequate biocatalytic efficiency from current flow reactors, caused by non-productive enzyme immobilization or enzyme-carrier mismatches in size, hampers its widespread application. Here, we demonstrate a general-applicable and robust approach for the fabrication of a high-performance enzymatic continuous-flow reactor via integrating well-designed scalable isoporous block copolymer (BCP) membranes as carriers with an oriented and productive immobilization employing material binding peptides (MBP). Densely packed uniform enzyme-matched nanochannels of well-designed BCP membranes endow the desired nanoconfined environments towards a productive immobilized phytase. Tuning nanochannel properties can further regulate the complex reaction process and fortify the catalytic performance. The synergistic design of enzyme-matched carriers and efficient enzyme immobilization empowers an excellent catalytic performance with >1 month operational stability, superior productivity, and a high space-time yield (1.05 × 105 g L-1 d-1) via a single-pass continuous-flow process. The obtained performance makes the designed nano- and isoporous block copolymer membrane reactor highly attractive for industrial applications.

GPRC5A promotes paclitaxel resistance and glucose content in NSCLC.

Lung cancer is one of the most common and malignant cancers worldwide. Chemotherapy has been widely used in the clinical setting, and paclitaxel is the first-line therapy for lung cancer patients but paclitaxel resistance is the main problem. First, we successfully established paclitaxel-resistant lung cancer cells treated with elevated doses of paclitaxel for 3 months, as confirmed by the CCK-8 assay. Paclitaxel-resistant cancer cells increased glucose content. Second, Gtex, Oncomine, and gene expression omnibus database data mining identified GPRC5A, G protein-coupled receptor, as the most prominent differentially expressed gene in drug-resistant datasets including gemcitabine, paclitaxel, and gefitinib overlapped with the microarray data from cancer cell metabolism. Third, qPCR analysis and western blot technique showed that GPRC5A mRNA and protein levels were significantly enhanced in paclitaxel-resistant lung cancer cells. Fourth, functional analysis was conducted by siRNA-mediated transient knockdown of GPRC5A. Silencing GPRC5A significantly decreased paclitaxel resistance and glucose content. In the end, retinoic acid substantially upregulated GPRC5A proteins and promoted glucose content in two lung cancer cells. Kaplan-Meier plot also confirmed that lung cancer patients with high expression of GPRC5A had a relatively lower survival rate. Our study provided a potential drug target GPRC5A, which may benefit lung cancer patients with acquired paclitaxel resistance in the future and a theoretical basis for future preclinical trials.

The Profiles of Venous Thromboembolism at Different High Altitudes.

Xiong, Shiqiang, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, and Haifeng Pei. The profiles of venous thromboembolism at different high altitudes High Alt Med Biol. 00:000-000, 2024.-This study investigated the incidence of venous thromboembolism (VTE) in high altitude (HA) and very HA areas. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) diagnosed between 2004 and 2022 in Yecheng, China, were retrospectively analyzed. The results showed that patients with PE at very HA had a higher risk of lower extremity DVT (OR 16.3 [95% CI 1.2-223.2], p = 0.036), than those at HA, especially in the early stages of very HA entry, and the harsh environment of very HA further exacerbated the risk of VTE. These findings emphasize the higher risk of PE development in very HA and the need for enhanced prevention and treatment in this area.

Early properties of magnesium phosphate cement repairing material used in slab track.

Magnesium phosphate cement (MPC) is a high-performance repairing material suitable for the interfacial disease of slab track. In this study, the early properties of MPC were optimized using central composite design (CCD) approach based on response surface methodology (RSM). Three factors with five levels and three responses were considered. The significance of the factors and their interactions were verified by using analysis of variance (ANOVA). The result show that the mass ratio of water-to-binder (W/b) affects fluidity, while the mass ratio of magnesia-to-phosphate (M/P) and borax-to-magnesia (B/M) impact the setting time of MPC. Higher W/b results in higher fluidity, while an increase in M/P reduces the setting time by increasing the neutralization reaction. Borax addition retards the reaction, prolonging the setting time. The three factors significantly affect the early compressive strength of MPC. At M/P = 3.5, the interweaving of MgO and K-struvite (MKP) forms a dense network structure, enhancing the strength. Borax and W/b interact to affect compressive strength, with borax retarding MKP crystal growth and higher W/b reducing compactness. Combined with microscopic property test, the strength generation mechanism of MPC with optimized mixing ratio was revealed, And the feasibility of field application of MPC was verified by strength test.

Study on Plastic Constitutive Relation and Ductile Fracture Criterion of AM60B Magnesium Alloy.

It is currently a challenge to accurately predict the deformation and fracture behavior of metal parts in automobile crashes. Many studies have shown that the deformation and fracture behavior of materials are significantly affected by the stress state during automobile crashes with complex stress state characteristics. In order to further promote the application of die-cast magnesium alloys in automobiles, it is particularly important to study the material deformation and fracture behavior of die-cast magnesium alloys. In this paper, the mechanical properties of the AM60B die-cast magnesium alloy sheet under four stress states (shear, tension, R10 notch tension, and cupping) were designed and tested. Based on the von Mises isotropic constitutive model and Swift weighted Hockett-Sherby hardening model, the plastic constitutive model of die-cast magnesium alloy was established. Based on the plastic model and the fracture model (JC, MMC, and DIEM) considering the influence of three stress states, the deformation and fracture behavior of the AM60B die-cast magnesium alloy front-end members in three-point bending were predicted by experiments and finite element simulation. The experimental results show that the deformation mode and loading-displacement curve trend of the AM60B die-cast magnesium alloy front members are the same, the crack initiation point and crack initiation time are the same, and the crack shape is similar. The results show that the complex stress state constitutive model parameters and the DIEM fracture model obtained in this paper can accurately predict the deformation and fracture failure behavior of the AM60B die-cast magnesium alloy sheet.

Living Growth Kinetics of Polymeric Micelles on a Substrate.

Living growth of micelles on the substrate is an intriguing phenomenon; however, little is known about its growth kinetics, especially from a theoretical viewpoint. Here, we examine the living growth kinetics of polymeric micelles on a hydrophobic substrate immersed in an aqueous solution. The block copolymers first assemble into short cylinder seeds anchored on the substrate. Then, the small aggregates of block copolymers in the solutions fuse onto the active ends of the anchored seeds, leading to micelle growth on the substrate. A theoretical model is proposed to interpret such living growth kinetics. It is revealed that the growth rate coefficient on the substrate is independent of the copolymer concentration and the multistep feedings; however, it is significantly affected by the surface hydrophobicity. Brownian dynamics simulations further support the proposed growth mechanism and the kinetic model. This work enriches living assembly systems and provides guidance for fabricating bioinspired surface nanostructures.

Elastic Relaxor Ferroelectric by Thiol-ene Click Reaction.

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

Lichen pectin-containing polysaccharide from Xanthoria elegans and its ability to effectively protect LX-2 cells from H2O2-induced oxidative damage.

Xanthoria elegans, a drought-tolerant lichen, is the original plant of the traditional Chinese medicine "Shihua" and effectively treats a variety of liver diseases. However, thus far, the hepatoprotective effects of polysaccharides, the most important chemical constituents of X. elegans, have not been determined. The aim of this study was to screen the polysaccharide fraction for hepatoprotective activity by using free radical scavenging assays and a H2O2-induced Lieming Xu-2 cell (LX-2) oxidative damage model and to elucidate the chemical composition of the bioactive polysaccharide fraction. In the present study, three polysaccharide fractions (XEP-50, XEP-70 and XEP-90) were obtained from X. elegans by hot-water extraction, DEAE-cellulose anion exchange chromatography separation and ethanol gradient precipitation. Among the three polysaccharide fractions, XEP-70 exhibited the best antioxidant activity in free radical scavenging capacity and reducing power assays. Structural studies showed that XEP-70 was a pectin-containing heteropolysaccharide fraction that was composed mainly of (1 â†’ 4)-linked and (1 â†’ 4,6)-linked α-D-Glcp, (1 â†’ 4)-linked α-D-GalpA, (1 â†’ 2)-linked, (1 â†’ 6)-linked and (1 â†’ 2,6)-linked α-D-Manp, and (1 â†’ 6)-linked and (1 â†’ 2,6)-linked ß-D-Galf. Furthermore, XEP-70 exhibited effectively protect LX-2 cells against H2O2-induced oxidative damage by enhancing cellular antioxidant capacity by activating the Nrf2/Keap1/ARE signaling pathway. Thus, XEP-70 has good potential to protect hepatic stellate cells against oxidative damage.

Improved data assimilation for algal bloom dynamics simulation in the Three Gorges Reservoir using particle filter.

Algal blooms have been increasingly prevalent in recent years, especially in lakes and reservoirs; their accurate prediction is essential for preserving water quality. In this study, the observed chlorophyll a (chl-a) levels were assimilated into the Environmental Fluid Dynamics Code (EFDC) of algal bloom dynamics by using a particle filter (PF), and the state variables of water quality and model parameters were simultaneously updated to achieve enhanced algal bloom predictive performance. The developed data assimilation system for algal blooms was applied to Xiangxi Bay (XXB) in the Three Gorges Reservoir (TGR). The results show that the ensemble mean accuracy and reliability of the confidence intervals of the predicted state variables, including chl-a and indirectly updated phosphate (PO4), ammonium (NH4), and nitrate (NO3) levels, were considerably improved after PF assimilation. Thus, PF assimilation is an effective tool for the dynamic correction of parameters to represent their inherent variations. Increased assimilation frequency can effectively suppress the accumulation of model errors; therefore, the use of high-frequency water quality data for assimilation is recommended to ensure more accurate and reliable algal bloom prediction.

In-Synthesis Se-Stabilization Enables Defect and Doping Engineering of HgTe Colloidal Quantum Dots.

Colloidal Quantum Dots (CQDs) of mercury telluride (HgTe) hold particular appeal for infrared photodetection due to their widely tunable infrared absorption and good compatibility with silicon electronics. While advances in surface chemistry have led to improved CQD solids, the chemical stability of HgTe material is not fully emphasized. In this study, it is aimed to address this issue and identifies a Se-stabilization strategy based on the surface coating of Se on HgTe CQDs via engineering in the precursor reactivity. The presence of Se-coating enables HgTe CQDs with improved colloidal stability, passivation, and enhanced degree of freedom in doping tuning. This enables the construction of optimized p-i-n HgTe CQD infrared photodetectors with an ultra-low dark current 3.26 × 10-6 A cm⁻2 at -0.4 V and room-temperature specific detectivity of 5.17 × 1011 Jones at wavelength ≈2 um, approximately one order of magnitude improvement compared to that of the control device. The stabilizing effect of Se is well preserved in the thin film state, contributing to much improved device stability. The in-synthesis Se-stabilization strategy highlights the importance of the chemical stability of materials for the construction of semiconductor-grade CQD solids and may have important implications for other high-performance CQD optoelectronic devices.

Corrigendum: Genome-wide survey reveals the genetic background of Xinjiang Brown cattle in China.

[This corrects the article DOI: 10.3389/fgene.2023.1348329.].

Effects of interaction of multiple large-scale atmospheric circulations on precipitation dynamics in China.

Different scenarios of precipitation, that lead to such phenomena as droughts and floods are influenced by concurrent multiple teleconnection factors. However, the multivariate relationship between precipitation indices and teleconnection factors, including large-scale atmospheric circulations and sea surface temperature signals in China, is rarely explored. Understanding this relationship is crucial for drought early warning systems and effective response strategies. In this study, we comprehensively investigated the combined effects of multiple large-scale atmospheric circulation patterns on precipitation changes in China. Specifically, Pearson correlation analysis and Partial Wavelet Coherence (PWC) were used to identify the primary teleconnection factors influencing precipitation dynamics. Furthermore, we used the cross-wavelet method to elucidate the temporal lag and periodic relationships between multiple teleconnection factors and their interactions. Finally, the multiple wavelet coherence analysis method was used to identify the dominant two-factor and three-factor combinations shaping precipitation dynamics. This analysis facilitated the quantification and determination of interaction types and influencing pathways of teleconnection factors on precipitation dynamics, respectively. The results showed that: (1) the Atlantic Multidecadal Oscillation (AMO), EI Niño-Southern Oscillation (ENSO), East Asia Summer Monsoon (EASM), and Indian Ocean Dipole (IOD) were dominant teleconnection factors influencing Standardized Precipitation Index (SPI) dynamics; (2) significant correlation and leading or lagging relationships at different timescales generally existed for various teleconnection factors, where AMO was mainly leading the other factors with positive correlation, while ENSO and Southern Oscillation (SO) were mainly lagging behind other factors with prolonged correlations; and (3) the interactions between teleconnection factors were quantified into three types: enhancing, independent and offsetting effects. Specifically, the enhancing effect of two-factor combinations was stronger than the offsetting effect, where AMO + NAO (North Atlantic Oscillation) and AMO + AO (Atlantic Oscillation) had a larger distribution area in southern China. Conversely, the offsetting effect of three-factor combinations was more significant than that of the two-factor combinations, which was mainly distributed in northeast and northwest regions of China. This study sheds new light on the mechanisms of modulation and pathways of influencing various large-scale factors on seasonal precipitation dynamics.