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Light‐sheet fluorescence microscopy (LSFM) introduces fast scanning of biological phenomena with deep photon penetration and minimal phototoxicity. This advancement represents a significant shift in 3‐D imaging of large‐scale biological tissues and 4‐D (space + time) imaging of small live animals. The large data associated with LSFM require efficient imaging acquisition and analysis with the use of artificial intelligence (AI)/machine learning (ML) algorithms. To this end, AI/ML‐directed LSFM is an emerging area for multiorgan imaging and tumor diagnostics. This review will present the development of LSFM and highlight various LSFM configurations and designs for multiscale imaging. Optical clearance techniques will be compared for effective reduction in light scattering and optimal deep‐tissue imaging. This review will further depict a diverse range of research and translational applications, from small live organisms to multiorgan imaging to tumor diagnosis. In addition, this review will address AI/ML‐directed imaging reconstruction, including the application of convolutional neural networks (CNNs) and generative adversarial networks (GANs). In summary, the advancements of LSFM have enabled effective and efficient post‐imaging reconstruction and data analyses, underscoring LSFM's contribution to advancing fundamental and translational research. [ABSTRACT FROM AUTHOR]

Early‐stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non‐invasive and cost‐effective detection method for early‐stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on‐skin sensor with low electrode‐skin contact impedance for early‐stage NAFLD detection is fabricated. A method is developed to synthesize platinum nanoparticles and reduced graphene quantum dots onto the on‐skin sensor to reduce electrode‐skin contact impedance by increasing double‐layer capacitance, thereby enhancing detection accuracy. Furthermore, an attention‐based deep learning algorithm is introduced to differentiate impedance signals associated with early‐stage NAFLD in high‐fat‐diet‐fed low‐density lipoprotein receptor knockout (Ldlr−/−) mice compared to healthy controls. The integration of an adhesive, soft on‐skin sensor with low electrode‐skin contact impedance and the attention‐based deep learning algorithm significantly enhances the detection accuracy for early‐stage NAFLD, achieving a rate above 97.5% with an area under the receiver operating characteristic curve (AUC) of 1.0. The findings present a non‐invasive approach for early‐stage NAFLD detection and display a strategy for improved early detection through on‐skin electronics and deep learning. [ABSTRACT FROM AUTHOR]

The characterization of atherosclerotic plaques to predict their vulnerability to rupture remains a diagnostic challenge. Despite existing imaging modalities, none have proven their abilities to identify metabolically active oxidized low‐density lipoprotein (oxLDL), a marker of plaque vulnerability. To this end, we developed a machine learning‐directed electrochemical impedance spectroscopy (EIS) platform to analyze oxLDL‐rich plaques, with immunohistology serving as the ground truth. We fabricated the EIS sensor by affixing a six‐point microelectrode configuration onto a silicone balloon catheter and electroplating the surface with platinum black (PtB) to improve the charge transfer efficiency at the electrochemical interface. To demonstrate clinical translation, we deployed the EIS sensor to the coronary arteries of an explanted human heart from a patient undergoing heart transplant and interrogated the atherosclerotic lesions to reconstruct the 3D EIS profiles of oxLDL‐rich atherosclerotic plaques in both right coronary and left descending coronary arteries. To establish effective generalization of our methods, we repeated the reconstruction and training process on the common carotid arteries of an unembalmed human cadaver specimen. Our findings indicated that our DenseNet model achieves the most reliable predictions for metabolically vulnerable plaque, yielding an accuracy of 92.59% after 100 epochs of training. [ABSTRACT FROM AUTHOR]

Author(s): Chen Wang [1]; Qiyuan He [2]; Udayabagya Halim [2]; Yuanyue Liu [3]; Enbo Zhu [1]; Zhaoyang Lin [2]; Hai Xiao [3]; Xidong Duan [4]; Ziying Feng [2]; Rui Cheng [...]

Proton exchange membrane fuel cells (PEMFCs) have attracted significant interest as a promising alternative technology to the combustion engine to power next‐generation vehicles with zero emission. Among the various technological targets, system cost and durability are currently identified as the main obstacles toward large‐scale implementation of PEMFCs. Platinum‐group‐metal‐based (PGM‐based) catalysts are the most efficient catalyst for the rate‐limiting cathodic oxygen reduction reaction in PEMFCs and take the highest share in the cost breakdown. Therefore, the stability of PGM‐based electrocatalysts plays a significant role in the development of PEMFCs. This review will summarize the recent progress made on the understanding of both the fundamental chemical and structural stability of PGM‐based catalysts, and their durability in operational PEMFC devices. It calls for systematic studies on the chemical, structural, and operational durability of the PGM‐based catalyst and the need to coin practical descriptors for catalyst design with both superior activity and durability for cost‐effective and high‐performance PEMFCs. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: The heterojunction‐type structure has shown significant merits in tuning the optical properties and carrier physics. Inspired by the excellent absorption capability of halide perovskite materials for visible light, a series of CsPbBr3/TiO2 heterojunction‐type photocatalysts with various all‐inorganic‐perovskite/TiO2 ratios are successfully fabricated by the ligand‐assisted reprecipitation (LARP) method. The heterojunction structure extends the light absorption of TiO2 with good chemical and structural stability. A Pb‐O interaction at the CsPbBr3/TiO2 interface is observed by the XPS and confirmed by the TRPL showing improved interface carrier transport and stability. The heterojunction‐type catalyst shows drastically enhanced photocatalytic activity towards the direct oxidation of toluene with O2 molecule, as an important reaction for organic chemical synthesis. The optimized sample shows an activity of 2356 μmol·g–1·h–1 at 75 °C, 4 times of that of the naked CsPbBr3 nanocrystals, and 3 times of that of the bare TiO2. Based on the investigation with trapping agents, a reaction mechanism is hence proposed suggesting that the photo‐generated hole may be involved in the rate‐limiting step. This work demonstrates the potential of inorganic halide perovskite‐based heterojunction structure for photocatalytic applications. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: The heterojunction‐type structure has shown significant merits in tuning the optical properties and carrier physics. Inspired by the excellent absorption capability of halide perovskite materials for visible light, a series of CsPbBr3/TiO2 heterojunction‐type photocatalysts with various all‐inorganic‐perovskite/TiO2 ratios are successfully fabricated by the ligand‐assisted reprecipitation (LARP) method. The heterojunction structure extends the light absorption of TiO2 with good chemical and structural stability. A Pb‐O interaction at the CsPbBr3/TiO2 interface is observed by the XPS and confirmed by the TRPL showing improved interface carrier transport and stability. The heterojunction‐type catalyst shows drastically enhanced photocatalytic activity towards the direct oxidation of toluene with O2 molecule, as an important reaction for organic chemical synthesis. The optimized sample shows an activity of 2356 μmol·g–1·h–1 at 75 °C, 4 times of that of the naked CsPbBr3 nanocrystals, and 3 times of that of the bare TiO2. Based on the investigation with trapping agents, a reaction mechanism is hence proposed suggesting that the photo‐generated hole may be involved in the rate‐limiting step. This work demonstrates the potential of inorganic halide perovskite‐based heterojunction structure for photocatalytic applications. [ABSTRACT FROM AUTHOR]

Pt‐based alloy nanocrystals have shown great success in oxygen reduction electrocatalysis owing to their unique surface and electronic structures. However, they suffer from severe stability issues due to the dissolution of non‐noble metal elements, leading to the "trade‐off" between activity and stability. In this work, targeting the stability issue of a PtxCuy‐based alloy, Pt2CuW0.25 ternary alloy nanoparticles are synthesized by thermal reduction strategy based on wet‐chemical method using W(CO)6 as a reductant. Apart from the competitive activity, the obtained Pt2CuW0.25/C shows remarkable stability, whereby the area specific activity and mass activity maintain 89.5% and 95.9% of the initial values, respectively, after 30 000 cycles of accelerated polarization between 0.6 and 1.1 V (vs reversible hydrogen electrode). By using vacancy formation energy of surface Pt as the descriptor, it is found that the enhanced stability of Pt2CuW0.25/C originates mainly from the stronger bonding between W and Pt/Cu atoms, acting as an "adhesive" to stabilize the atoms from dissolution, which is further verified by chemical stability experiments. This work demonstrates a rational design strategy for ternary alloy nano‐electrocatalyst that has high thermodynamic stability while maintaining high activity by employing high‐melting‐point metal. [ABSTRACT FROM AUTHOR]

Background Exercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)-related muscle actions associated with aging are poorly understood. Here we observed that in a senescence-accelerated mouse prone 10 (SAMP10) model, long-term ET modulated muscle-regenerative actions. Methods 25-week-old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months. Mice that were maintained in a sedentary condition served controls. Results ET ameliorated aging-related muscle changes in microstructure, mitochondria, and performance. The amounts of proteins or mRNAs for p-AMPKα, p-Akt, p-ERK1/2, p-mTOR, Bcl-XL, p-FoxO3, peroxisome proliferators-activated receptor-γ coactivator, adiponectin receptor1 (adpoR1), and cytochrome c oxidase-IV, and the numbers of CD34+/integrin-α7+ muscle stem cells (MuSCs) and proliferating cells in the muscles and bone-marrow were enhanced by ET, whereas the levels of p-GSK-3α and gp91phox proteins and apoptotic cells were reduced by ET. The ET also resulted in increased levels of plasma adiponectin and the numbers of bone-marrow (BM)-derived circulating CD34+/integrin-α7+ MuSCs and their functions. Integrin-α7+ MuSCs of exercised mice had improved changes of those beneficial molecules. These ET-mediated aged muscle benefits were diminished by adiponectin and AdipoR1 blocking as well as AMPK inhibition. Finally, recombinant mouse adiponectin enhanced AMPK and mTOR phosphorylations in BM-derived integrin-α7+ cells. Conclusions These findings suggest that ET can improve aging-related impairments of BM-derived MuSC regenerative capacity and muscle metabolic alterations via an AMPK-dependent mechanism that is mediated by an adiponectin/AdipoR1 axis in SAMP10 mice. [ABSTRACT FROM AUTHOR]

Bimetallic PtCu nanocrystals (NCs) with well-defined hexa-pod morphology were synthesized via a wet chemistry approach. The as-synthesized convex NCs with dimensions of around 20 nm show exposed low-index (111) facets on the seeds and various high-index facets on the pods. The growth mechanism involved preferred growth along the <100> crystallographic direction on cuboctahedral seeds. The synthetic protocol could be applied to the synthesis of PtCu NCs with various Cu/Pt ratios. The electro-catalytic activity of the hexa-pod PtxCuy NCs supported on carbon black towards the oxygen reduction reaction (ORR) was studied. The hexa-pod PtCu/C catalysts exhibit the highest specific activity (3.7 mA/cm) and mass activity (2.4 A/mg) reported to date for PtCu. Comparison with other morphological forms of PtCu indicated that the enhanced activity originated from morphological factors. The existence of high-index facets as well as abundant edges and steps on the pods could reasonably explain the enhanced catalytic activity. The hexa-pod PtCu/C catalysts also show high morphological stability and activity after accelerated durability tests. The as-synthesized hexa-pod PtCu NCs have high potential as cathode electro-catalysts for proton exchange membrane fuel cells. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the “lowLVEF” group) and the 90 patients showing LVEF values ≥ 40% (the “highLVEF” group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = −0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84–0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF. [ABSTRACT FROM AUTHOR]

In this study, we report a facile one-pot strategy towards highly monodisperse and hexagonal shaped bimetallic Pt–Cu nanocrystals with a pure Cu-core coated with a PtCu alloy shell (designated as Cu@PtCu nanocrystals). The Cu@PtCu nanocrystals can be deposited on commercial carbon black evenly and the Cu core in the Cu@PtCu nanocrystal can be selectively etched. The resulting hollow-PtCu/C is a high-performance electro-catalyst for methanol oxidation. It has been demonstrated that the hollow-PtCu/C had a methanol oxidation specific activity of 1.77 mA cm−2 and a mass activity of 0.889 A mgPt−1, which are far better than those of solid-PtCu/C and commercial Pt/C catalysts. The hollow-PtCu/C also exhibited better tolerance to poisoning species and is more stable under electro-oxidation conditions. The results reported herein suggest that superior catalysts can be developed by engineering the structure/composition of the nanocrystals. [ABSTRACT FROM AUTHOR]

Objective— Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types of cancer cells. Here, we investigated the cross talk between CatS and HADC6 in injury-related vascular repair in mice. Approach and Results— Ligation injury to the carotid artery in mice increased the CatS expression, and CatS-deficient mice showed reduced neointimal formation in injured arteries. CatS deficiency decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and toll-like receptor 2 expression in ligated arteries. The genetic or pharmacological inhibition of CatS also alleviated the increased phosphorylation of p38 mitogen-activated protein kinase, Akt, and HDAC6 induced by platelet-derived growth factor BB in cultured vascular smooth muscle cells (VSMCs), and p38 mitogen-activated protein kinase inhibition and Akt inhibition decreased the phospho-HDAC6 levels. Moreover, CatS inhibition caused decrease in the levels of the HDAC6 activity in VSMCs in response to platelet-derived growth factor BB. The HDAC6 inhibitor tubastatin A downregulated platelet-derived growth factor–induced VSMC proliferation and migration, whereas HDAC6 overexpression exerted the opposite effect. Tubastatin A also decreased the intimal VSMC proliferation and neointimal hyperplasia in response to injury. Toll-like receptor 2 silencing decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and VSMC migration and proliferation. Conclusions— This is the first report detailing cross-interaction between toll-like receptor 2–mediated CatS and HDAC6 during injury-related vascular repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for the control of vascular diseases that are involved in neointimal lesion formation.

Strukturverstärkte katalytische Aktivität: Ein Netzwerk aus mehrfach verzwillingten Platinnanodrähten wirkt als effektiver Elektrokatalysator (siehe Bild). Das Material hat eine größere elektrochemisch aktive Oberfläche und zeigt eine deutlich höhere Aktivität in der Sauerstoffreduktion und Methanoloxidation als kommerzielle Pt/C ‐ Katalysatoren. [ABSTRACT FROM AUTHOR]

Gold rush: Nanoporous palladium particles are decorated with gold clusters by galvanic replacement. The bimetallic pPd@Au nanocatalysts feature a well‐defined nanoporous morphology coupled to a highly accessible surface area with segregated Au clusters, and are highly active in both benzyl alcohol oxidation and formic acid electro‐oxidation. The amount of Au in the catalyst system determines the extent of alloying as well as the accessibility to catalytically more active Pd surface atoms. [ABSTRACT FROM AUTHOR]

Designing a highly active doped‐carbon‐based oxygen reduction reaction (ORR) electrocatalyst with optimal stability is a must if large‐scale implementations of fuel cells are to be realized. Developing controllable doping strategies is essential for achieving highly active catalysts. Herein, a facile doping strategy is developed by designing a precursor material with unique core–shell nanostructure, whereby the Materials Institute Lavoisier (MIL) metal–organic framework (MOF) and polyaniline are core and shell components, and serving as oxygen and nitrogen precursors, respectively. A novel hollow loofah‐like carbon tube (HLCT) catalyst is derived from precursor material with controllable heteroatom‐doping concentrations through modulating the mass ratio of MOF/aniline. The optimal HLCT‐1/2 catalyst, with a MOF/aniline mass ratio of 1/2, exhibits excellent ORR activity and stability in an alkaline medium. Remarkably, the half‐wave potential (0.88 V) and the current density (4.35 mA cm−2) at 0.85 V of HLCT‐1/2 catalyst surpass that of commercial Pt/C. Such superior catalytic properties can be attributed to the high specific surface area and abundant active sites of loofah‐shape carbon tubes. Moreover, the O dopant modulates the content and distribution of N species, leading to the enhanced adsorption strength of oxygen molecules on catalyst surface, promoting the activation of oxygen, and thus achieving higher electrocatalytic activity. [ABSTRACT FROM AUTHOR]

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 with a spatial resolution of 3.6 μm laterally and 6 μm axially. 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, and in the hippocampus of behaving mice. These results collectively establish SLIM as a versatile and robust imaging tool for high-speed microscopy applications.

Light-sheet fluorescence microscopy (LSFM) introduces fast scanning of biological phenomena with deep photon penetration and minimal phototoxicity. This advancement represents a significant shift in 3-D imaging of large-scale biological tissues and 4-D (space + time) imaging of small live animals. The large data associated with LSFM requires efficient imaging acquisition and analysis with the use of artificial intelligence (AI)/machine learning (ML) algorithms. To this end, AI/ML-directed LSFM is an emerging area for multi-organ imaging and tumor diagnostics. This review will present the development of LSFM and highlight various LSFM configurations and designs for multi-scale imaging. Optical clearance techniques will be compared for effective reduction in light scattering and optimal deep-tissue imaging. This review will further depict a diverse range of research and translational applications, from small live organisms to multi-organ imaging to tumor diagnosis. In addition, this review will address AI/ML-directed imaging reconstruction, including the application of convolutional neural networks (CNNs) and generative adversarial networks (GANs). In summary, the advancements of LSFM have enabled effective and efficient post-imaging reconstruction and data analyses, underscoring LSFM's contribution to advancing fundamental and translational research., Competing Interests: CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP 3/28 ), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP 3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP 3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)