Toward universal cell embeddings: integrating single-cell RNA-seq datasets across species with SATURN.

Analysis of single-cell datasets generated from diverse organisms offers unprecedented opportunities to unravel fundamental evolutionary processes of conservation and diversification of cell types. However, interspecies genomic differences limit the joint analysis of cross-species datasets to homologous genes. Here we present SATURN, a deep learning method for learning universal cell embeddings that encodes genes' biological properties using protein language models. By coupling protein embeddings from language models with RNA expression, SATURN integrates datasets profiled from different species regardless of their genomic similarity. SATURN can detect functionally related genes coexpressed across species, redefining differential expression for cross-species analysis. Applying SATURN to three species whole-organism atlases and frog and zebrafish embryogenesis datasets, we show that SATURN can effectively transfer annotations across species, even when they are evolutionarily remote. We also demonstrate that SATURN can be used to find potentially divergent gene functions between glaucoma-associated genes in humans and four other species.

Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

Cuproptosis: Mechanism, role, and advances in urological malignancies.

Prostate, bladder, and kidney cancers are the most common malignancies of the urinary system. Chemotherapeutic drugs are generally used as adjuvant treatment in the middle, late, or recurrence stages after surgery for urologic cancers. However, traditional chemotherapy is plagued by problems such as poor efficacy, severe side effects, and complications. Copper-containing nanomedicines are promising novel cancer treatment modalities that can potentially overcome these disadvantages. Copper homeostasis and cuproptosis play crucial roles in the development, adaptability, and therapeutic sensitivity of urological malignancies. Cuproptosis refers to the direct binding of copper ions to lipoylated components of the tricarboxylic acid cycle, leading to protein oligomerization, loss of iron-sulfur proteins, proteotoxic stress, and cell death. This review focuses on copper homeostasis and cuproptosis as well as recent findings on copper and cuproptosis in urological malignancies. Furthermore, we highlight the potential therapeutic applications of copper- and cuproptosis-targeted therapies to better understand cuproptosis-based drugs for the treatment of urological tumors in the future.

Construction of an Ohmic Contact Cathode by Two Metal Sulfides for efficient Capture and Catalysis of Polysulfide.

The slow reaction kinetics and severe shuttle effect of lithium polysulfide make Li-S battery electrochemical performance difficult to meet the demands of large electronic devices such as electric vehicles. Based on this, an electrocatalyst constructed by metal phase material (MoS2) and semiconductor phase material (SnS2) with ohmic contact is designed for inhibiting the dissolution of lithium polysulfide with improving the reaction kinetics. According to the density-functional theory calculations, it is found that the heterostructured samples with ohmic contacts can effectively reduce the reaction-free energy of lithium polysulfide to accelerate the sulfur redox reaction, in addition to the excellent electron conduction to reduce the overall activation energy. The metallic sulfide can add more sulfophilic sites to promote the capture of polysulfide. Thanks to the ohmic contact design, the carbon nanotube-MoS2-SnS2 achieved a specific capacity of 1437.2 mAh g-1 at 0.1 C current density and 805.5 mAh g-1 after 500 cycles at 1 C current density and is also tested as a pouch cell, which proves to be valuable for practical applications. This work provides a new idea for designing an advanced and efficient polysulfide catalyst based on ohmic contact.

Regulate the Solvation Structure and Interface by Nitrate in Phosphate-Based Electrolytes for 4.5 V-Class Ni-Rich Batteries.

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety.

Reactive Oxygen Species-Responsive Composite Fibers Regulate Oxidative Metabolism through Internal and External Factors to Promote the Recovery of Nerve Function.

It is challenging to sufficiently regulate endogenous neuronal reactive oxygen species (ROS) production, reduce neuronal apoptosis, and reconstruct neural networks under spinal cord injury conditions. Here, hydrogel surface grafting and microsol electrospinning are used to construct a composite biomimetic scaffold with "external-endogenous" dual regulation of ROS. The outer hydrogel enhances local autophagy through responsive degradation and rapid release of rapamycin (≈80% within a week), neutralizing extracellular ROS and inhibiting endogenous ROS production, further reducing neuronal apoptosis. The inner directional fibers continuously supply brain-derived neurotrophic factors to guide axonal growth. The results of in vitro co-culturing show that the dual regulation of oxidative metabolism by the composite scaffold approximately doubles the neuronal autophagy level, reduces 60% of the apoptosis induced by oxidative stress, and increases the differentiation of neural stem cells into neuron-like cells by ≈2.5 times. The in vivo results show that the composite fibers reduce the ROS levels by ≈80% and decrease the formation of scar tissue. RNA sequencing results show that composite scaffolds upregulate autophagy-associated proteins, antioxidase genes, and axonal growth proteins. The developed composite biomimetic scaffold represents a therapeutic strategy to achieve neurofunctional recovery through programmed and accurate bidirectional regulation of the ROS cascade response.

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.

Analyzing the photoassociation spectrum of ultracold 85Rb 133Cs molecule in (3)3Σ+ state.

We establish a theoretical model to analyze the photoassociative spectroscopy of 85Rb 133Cs molecules in the (3)3Σ+ state. The vibrational energy, spin-spin coupling constant, and hyperfine interaction constant of the (3)3Σ+ state are determined based on nine observed vibrational levels. Consequently, the Rydberg-Klein-Rees potential energy curve of the (3)3Σ+ state is obtained and compared with the ab initial potential energy curve. Our model can be adopted to analyze the photoassociative spectroscopy of other heteronuclear alkali-metal diatomic molecules in the (3)3Σ+ state.

[Immune mechanism of Daphnes Cortex and its processed products on CIA rats based on B7/CD28/CTLA-4 pathway].

This study investigates the effects of Daphnes Cortex and its processed products on the differentiation of Th17/Treg cells in SD rats with type Ⅱ collagen-induced arthritis(CIA).Sixty-four SD rats were randomly divided into the normal group(normal),model group(model),fried Daphne giraldii Nitsche low-dose and high-dose groups(FDGN-L group, FDGN-H group),raw D. giraldii Nitsche low-dose and high-dose groups(RDGN-L group, RDGN-H group),daphnetin group(DAPH group),and tripterygium glycosides group(GTW group).Except for the normal group, the CIA model was immunized on the seventh day after the first immunization, and was gavaged for 28 days after the second immunization.After sampling, the inflammation of articular synovial membrane in CIA rats was observed by hematoxylin-eosin(HE)staining; the levels of transforming growth factor-ß(TGF-ß),interferon-γ(IFN-γ),interleukin(IL)-2,IL-4,and IL-10 in serum were detected by enzyme-linked immunosorbent assay(ELISA); real-time reverse transcription-PCR(qRT-PCR)and Western blot were used to detect the mRNA and protein expressions of cluster of differentiation(CD) 80(B7-1),CD 86(B7-2),CD28,and cytotoxic T lymphocyte-associated antigen 4(CTLA-4)in the synovial membrane of rats; flow cytometry was used to detect the proportion of Th17 and Treg cells in the synovial membrane of rats.The results showed that compared with the normal group, the joint synovial inflammation of rats in the model group was significantly aggravated, the arthritis index was significantly increased, and the immune organ index was increased(P<0.01).Compared with the model group, each drug administration group could improve the joint inflammation of rats to varying degrees, reduce the arthritis index, inhibit synovial hyperplasia, and reduce the immune organ index; compared with the model group, the serum levels of IL-2 and IFN-γ in each drug administration group were significantly decreased(P<0.01),TGF-ß,IL-4,and IL-10 were significantly increased(P<0.01),the mRNA and protein expressions of B7-1 and CTLA-4 in the synovial membrane were significantly increased(P<0.01),and the proportion of Th17 cells and Treg cells in the joint tissue was significantly decreased(P<0.01).In conclusion, Daphnes Cortex inhibits the expression of Th17 cells in CIA rats and promotes the expression of Treg cells by regulating the B7/CD28/CTLA-4 pathway and the balance of Th17/Treg, thereby treating rheumatoid arthritis.

Manipulating the metal-to-insulator transitions of VO2 by combining compositing and doping strategies.

Vanadium dioxide (VO2) exhibits the most abrupt metal-to-insulator transition (MIT) property near room temperature among the representative 3d-orbital correlated oxides, and its structural variation during the MIT usually results in poor mechanical properties as bulk pellets. Moreover, compositing with highly resistive oxides has been reported to improve the mechanical strength of bulk VO2 since the generation and propagation of microcracks is suppressed upon thermocycling across the MIT; further, their respective impacts on electrical transportation are yet unclear. Herein, we demonstrate the role of these highly resistive oxide composites (e.g., HfO2, CoO and Al2O3) in reducing charge leakage along the microcracks within the insulating phase of VO2, leading to more abrupt MIT properties from the perspective of electrical transportation. This enables the possibility of simultaneously regulating the critical temperature and abrupt MIT transition, as well as the mechanical properties of the VO2 bulk pellets via compositing with oxides with different melting points using spark plasma-assisted reactive sintering (SPARS).