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High nickel content in LiNi x Co y Mn z O 2 (NCM, x ≥ 0.8, x + y + z = 1) layered cathode material allows high specific energy density in lithium-ion batteries (LIBs). However, Ni-rich NCM cathodes suffer from performance degradation, mechanical and structural instability upon prolonged cell cycling. Although the use of single-crystal Ni-rich NCM can mitigate these drawbacks, the ion-diffusion in large single-crystal particles hamper its rate capability. Herein, we report a strategy to construct an in situ Li 1.4 Y 0.4 Ti 1.6 (PO 4 ) 3 (LYTP) ion/electron conductive network which interconnects single-crystal LiNi 0.88 Co 0.09 Mn 0.03 O 2 (SC-NCM88) particles. The LYTP network facilitates the lithium-ion transport between SC-NCM88 particles, mitigates mechanical instability and prevents detrimental crystalline phase transformation. When used in combination with a Li metal anode, the LYTP-containing SC-NCM88-based cathode enables a coin cell capacity of 130 mAh g −1 after 500 cycles at 5 C rate in the 2.75-4.4 V range at 25 °C. Tests in Li-ion pouch cell configuration (i.e., graphite used as negative electrode active material) demonstrate capacity retention of 85% after 1000 cycles at 0.5 C in the 2.75-4.4 V range at 25 °C for the LYTP-containing SC-NCM88-based positive electrode. Single-crystal Ni-rich cathodes suffer from side reactions with the electrolyte and slow Li-ion transport during high-voltage cycling. Herein, a Li 1.4 Y 0.4 Ti 1.6 (PO 4 ) 3 coating is applied to facilitate the Li-ion transport and improve the cycling life of the cell.

High-capacity Ni-rich layered oxides are promising cathode materials for secondary lithium-based battery systems. However, their structural instability detrimentally affects the battery performance during cell cycling. Here, we report an Al/Zr co-doped single-crystalline LiNi 0.88 Co 0.09 Mn 0.03 O 2 (SNCM) cathode material to circumvent the instability issue. We found that soluble Al ions are adequately incorporated in the SNCM lattice while the less soluble Zr ions are prone to aggregate in the outer SNCM surface layer. The synergistic effect of Al/Zr co-doping in SNCM lattice improve the Li-ion mobility, relief the internal strain, and suppress the Li/Ni cation mixing upon cycling at high cut-off voltage. These features improve the cathode rate capability and structural stabilization during prolonged cell cycling. In particular, the Zr-rich surface enables the formation of stable cathode-electrolyte interphase, which prevent SNCM from unwanted reactions with the non-aqueous fluorinated liquid electrolyte solution and avoid Ni dissolution. To prove the practical application of the Al/Zr co-doped SNCM, we assembled a 10.8 Ah pouch cell (using a 100 μm thick Li metal anode) capable of delivering initial specific energy of 504.5 Wh kg −1 at 0.1 C and 25 °C. Li-ion cathode active materials are transitioning from poly- to single-crystal structures. However, the performance of high Ni-content single-crystal cathodes remains below expectations. Here, via Al/Zr co-doping, the authors propose a strategy to mitigate structural degradation in this class of materials.

With the development of nanotechnology, significant progress has been made in the design, and manufacture of nanoparticles (NPs) for use in clinical treatments. Recent increases in our understanding of the central role of macrophages in the context of inflammation and cancer have reinvigorated interest in macrophages as drug targets. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in cancer and inflammation processes. Thus, NPs tailored to accurately target macrophages have the potential to transform disease treatment. Herein, we first present a brief background information of NPs as drug carriers, including but not limited to the types of nanomaterials, their biological properties and their advantages in clinical application. Then, macrophage effector mechanisms and recent NPs-based strategies aimed at targeting macrophages by eliminating or re-educating macrophages in inflammation and cancer are summarized. Additionally, the development of nanocarriers targeting macrophages for disease diagnosis is also discussed. Finally, the significance of macrophage-targeting nanomedicine is highlighted, with the goal of facilitating future clinical translation.

Ultrafast 3D imaging is indispensable for visualizing complex and dynamic biological processes. Conventional scanning-based techniques necessitate an inherent trade-off between acquisition speed and space-bandwidth product (SBP). Emerging single-shot 3D wide-field techniques offer a promising alternative but are bottlenecked by the synchronous readout constraints of conventional CMOS systems, thus restricting data throughput to maintain high SBP at limited frame rates. To address this, we introduce EventLFM, a straightforward and cost-effective system that overcomes these challenges by integrating an event camera with Fourier light field microscopy (LFM), a state-of-the-art single-shot 3D wide-field imaging technique. The event camera operates on a novel asynchronous readout architecture, thereby bypassing the frame rate limitations inherent to conventional CMOS systems. We further develop a simple and robust event-driven LFM reconstruction algorithm that can reliably reconstruct 3D dynamics from the unique spatiotemporal measurements captured by EventLFM. Experimental results demonstrate that EventLFM can robustly reconstruct fast-moving and rapidly blinking 3D fluorescent samples at kHz frame rates. Furthermore, we highlight EventLFM’s capability for imaging of blinking neuronal signals in scattering mouse brain tissues and 3D tracking of GFP-labeled neurons in freely moving C. elegans. We believe that the combined ultrafast speed and large 3D SBP offered by EventLFM may open up new possibilities across many biomedical applications.By integrating event camera with Fourier light field microscopy, EventLFM robustly captures fast-moving and rapidly blinking 3D fluorescent biological samples at kHz frame rates.

Background Coronavirus disease 2019 (COVID-19) has become a public health emergency of global concern. We aimed to explore the risk factors of 14-day and 28-day mortality and develop a model for predicting 14-day and 28-day survival probability among adult hospitalized patients with COVID-19. Methods In this multicenter, retrospective, cohort study, we examined 828 hospitalized patients with confirmed COVID-19 hospitalized in Wuhan Union Hospital and Central Hospital of Wuhan between January 12 and February 9, 2020. Among the 828 patients, 516 and 186 consecutive patients admitted in Wuhan Union Hospital were enrolled in the training cohort and the validation cohort, respectively. A total of 126 patients hospitalized in Central Hospital of Wuhan were enrolled in a second external validation cohort. Demographic, clinical, radiographic, and laboratory measures; treatment; proximate causes of death; and 14-day and 28-day mortality are described. Patients’ data were collected by reviewing the medical records, and their 14-day and 28-day outcomes were followed up. Results Of the 828 patients, 146 deaths were recorded until May 18, 2020. In the training set, multivariate Cox regression indicated that older age, lactate dehydrogenase level over 360 U/L, neutrophil-to-lymphocyte ratio higher than 8.0, and direct bilirubin higher than 5.0 μmol/L were independent predictors of 28-day mortality. Nomogram scoring systems for predicting the 14-day and 28-day survival probability of patients with COVID-19 were developed and exhibited strong discrimination and calibration power in the two external validation cohorts (C-index, 0.878 and 0.839). Conclusion Older age, high lactate dehydrogenase level, evaluated neutrophil-to-lymphocyte ratio, and high direct bilirubin level were independent predictors of 28-day mortality in adult hospitalized patients with confirmed COVID-19. The nomogram system based on the four factors revealed good discrimination and calibration, suggesting good clinical utility.

Retinoic acid receptor-related orphan receptors (RORs) include RORα (NR1F1), RORβ (NR1F2), and RORγ (NR1F3). These receptors are reported to activate transcription through ligand-dependent interactions with co-regulators and are involved in the development of secondary lymphoid tissues, autoimmune diseases, inflammatory diseases, the circadian rhythm, and metabolism homeostasis. Researches on RORs contributing to cancer-related processes have been growing, and they provide evidence that RORs are likely to be considered as potential therapeutic targets in many cancers. RORα has been identified as a potential therapeutic target for breast cancer and has been investigated in melanoma, colorectal colon cancer, and gastric cancer. RORβ is mainly expressed in the central nervous system, but it has also been studied in pharyngeal cancer, uterine leiomyosarcoma, and colorectal cancer, in addition to neuroblastoma, and recent studies suggest that RORγ is involved in various cancers, including lymphoma, melanoma, and lung cancer. Some studies found RORγ to be upregulated in cancer tissues compared with normal tissues, while others indicated the opposite results. With respect to the mechanisms of RORs in cancer, previous studies on the regulatory mechanisms of RORs in cancer were mostly focused on immune cells and cytokines, but lately there have been investigations concentrating on RORs themselves. Thus, this review summarizes reports on the regulation of RORs in cancer and highlights potential therapeutic targets in cancer.

The self‐assembly of intrinsically disordered proteins (IDPs) into condensed phases and the formation of membrane‐less organelles (MLOs) can be considered as the phenomenon of collective behavior. The conformational dynamics of IDPs are essential for their interactions and the formation of a condensed phase. From a physical perspective, collective behavior and the emergence of phase are associated with long‐range correlations. Here the conformational dynamics of IDPs and the correlations therein are analyzed, using µs‐scale atomistic molecular dynamics (MD) simulations and single‐molecule Förster resonance energy transfer (smFRET) experiments. The existence of typical scale‐free spatio‐temporal correlations in IDP conformational fluctuations is demonstrated. Their conformational evolutions exhibit “1/f noise” power spectra and are accompanied by the appearance of residue domains following a power‐law size distribution. Additionally, the motions of residues present scale‐free behavioral correlation. These scale‐free correlations resemble those in physical systems near critical points, suggesting that IDPs are poised at a critical state. Therefore, IDPs can effectively respond to finite differences in sequence compositions and engender considerable structural heterogeneity which is beneficial for IDP interactions and phase formation. Intrinsically disordered proteins (IDPs), which have large conformational fluctuations, can collectively undergo liquid‐liquid phase separation. This study reveals that IDPs exhibit scale‐free spatiotemporal correlations in their conformation dynamics. It suggests that IDPs are poised at a critical state, providing useful insight into their emergent collective behavior.

Background Chinese hamster ovary (CHO) cells are the predominant cell line used for biotherapeutic production. To reduce the cost of therapeutic recombinant proteins produced in CHO cells, efforts have been made over decades to improve overall yield through media and process optimization, as well as genetic engineering aimed at enhancing cell proliferation or productivity. Within an intricate cellular framework, such as the CHO cell system, it is indisputable that numerous genes with seemingly disparate functions may be involved in the process of expressing recombinant proteins. Results Thrombomodulin (TM), encoded by the Thbd gene, is primarily known for its roles in coagulation, innate immunity, inflammation, and tumor cell proliferation. Our research was the first to reveal that the presence of thrombomodulin is highly correlated with recombinant protein production in CHO cells producing an Fc-fusion protein. Knocking out Thbd resulted in approximately an 82% reduction in recombinant protein yield by the end of fed-batch culture, indicating that TM is essential for efficient production. Further investigation revealed that this loss was due to a dramatic reduction in mRNA levels of the recombinant protein. Re-expression of TM in the Thbd -knockout cell line restored mRNA levels, confirming TM’s role in maintaining transcription. Phosphorylation levels of PKC, MEK, and ERK were elevated in the knockout cells compared to untreated wild-type cells, whereas phosphorylation of mTOR and AKT was decreased. Additionally, overexpression of Thbd led to moderate increases in c-Myc and Bcl2 expression, which appeared to slow the decline in cell viability during cultivation. Functional analyses of different TM domains revealed that both the N-terminal lectin-like domain and the C-terminal cytoplasmic tail have greater impacts on recombinant protein production than the other regions. Conclusions This study demonstrates the essential role of thrombomodulin in recombinant Fc-fusion protein production in Chinese hamster ovary cells, reveals novel biological functions of thrombomodulin, and expands our understanding of the complex cellular machinery underlying recombinant protein expression in CHO cells.

Global Positioning System (GPS) position verification and legal traceability in Australia supports industry, trade, science and innovation and is trusted and recognized domestically and internationally. At the end of 2017, the Australia’s national datum was transitioned from the Geocentric Datum of Australia 1994 (GDA94) to the Geocentric Datum of Australia 2020 (GDA2020). As such, the datum for the legal traceability of GPS positions in Australia has also moved to GDA2020. This paper highlights the importance of legal metrology and measurement in terms of GPS positions in accordance with the National Measurement Act 1960 (Commonwealth of Australia). Here we provide an overview of the process of issuing the so-called ‘Regulation 13 Certificates’ for Continuously Operating Reference Stations (CORS) across Australia. The position verification methodology is detailed, including the quality control, metadata assurance, and dynamic management of the certificates as well as positional uncertainty determination of CORS with varying quality. A quality monitoring system of positions is also discussed along with how measurement traceability is ensured including short-term and long-term position monitoring schemes.

Homogeneous Triebel-Lizorkin spaces with full range of parameters are introduced on stratified Lie groups in terms of Littlewood-Paley-type decomposition. It is shown that the scale of these spaces is independent of the choice of Littlewood-Paley-type decomposition and the sub-Laplacian used for the construction of the decomposition. Some basic properties of these spaces are given. As the main result of this paper, boundedness of a class of singular integral operators on these function spaces is obtained.