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Abstract Wearable ultrasound imaging technology has become an emerging modality for the continuous monitoring of deep-tissue physiology, providing crucial health and disease information. Fast volumetric imaging that can provide a full spatiotemporal view of intrinsic 3D targets is desirable for interpreting internal organ dynamics. However, existing 1D ultrasound transducer arrays provide 2D images, making it challenging to overcome the trade-off between the temporal resolution and volumetric coverage. In addition, the high driving voltage limits their implementation in wearable settings. With the use of microelectromechanical system (MEMS) technology, we report an ultrasonic phased-array transducer, i.e., a 2D piezoelectric micromachined ultrasound transducer (pMUT) array, which is driven by a low voltage and is chip-compatible for fast 3D volumetric imaging. By grouping multiple pMUT cells into one single drive channel/element, we propose an innovative cell–element–array design and operation of a pMUT array that can be used to quantitatively characterize the key coupling effects between each pMUT cell, allowing 3D imaging with 5-V actuation. The pMUT array demonstrates fast volumetric imaging covering a range of 40 mm × 40 mm × 70 mm in wire phantom and vascular phantom experiments, achieving a high temporal frame rate of 11 kHz. The proposed solution offers a full volumetric view of deep-tissue disorders in a fast manner, paving the way for long-term wearable imaging technology for various organs in deep tissues.

Objective: Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs. Materials and Methods: First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula. Results: The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales. Conclusions: Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.

Renal toxicity is one of common reasons for a failure of drug research. Thus it is imperative to establish a reliable method of evaluating drug nephrotoxicity. Recently a novel in vitro research model of organoid has attracted growing attention. Organoids are capable of highly simulating the functional structures of tissues and organs in vivo and possessing stable genetic traits. With real organ structures and functions, renal organoids have great application values and development potentials for evaluating drug nephrotoxicity. This review summarized the construction of kidney organoids and their applications in drug safety evaluations. It provided theoretical rationale for drug toxicity assessment and screening for potential adverse reactions of related drugs.

The CXC chemokine ligand-10/CXC receptor-3 (CXCL10/CXCR3) axis, a crucial pathway mediating Th1-type immunity, substantially contributes to the development of acute respiratory distress syndrome(ARDS) by enhancing inflammatory storms. It additionally promotes vascular endothelial apoptosis and impedes vasculature repair, elevating the risk of pulmonary vascular thrombosis. Conversely, this axis plays a protective role in limiting extra-cellular matrix deposition and modulating cell migration, thereby mitigating pulmonary fibrosis. The various mechanisms of the CXCL10/CXCR3 axis in the pathogenesis and progression of ARDS could offer novel insights for the diagnosis and treatment of ARDS.

Introduction This study aimed to investigate the effects of nicotine on the activation of pancreatic stellate cells (PSCs) and pancreatic fibrosis in chronic pancreatitis (CP), along with its underlying molecular mechanisms. Methods This was an in vivo and in vitro study. In vitro, PSCs were cultured to study the effects of nicotine on their activation and oxidative stress. Transcriptome sequencing was performed to identify potential signaling pathways involved in nicotine action. And the impact of nicotine on mitochondrial Ca2+ levels and Ca2+ transport-related proteins in PSCs was analyzed. The changes in nicotine effects were observed after the knockdown of the mitochondrial calcium uniporter (MCU) in PSCs. In vivo experiments were conducted using a mouse model of CP to assess the effects of nicotine on pancreatic fibrosis and oxidative stress in mice. The alterations in nicotine effects were observed after treatment with the MCU inhibitor Ru360. Results In vitro experiments demonstrated that nicotine promoted PSCs activation, characterized by increased cell proliferation, elevated α-SMA and collagen expression. Nicotine also increased the production of reactive oxygen species (ROS) and cellular malondialdehyde (MDA), exacerbating oxidative stress damage. Transcriptome sequencing revealed that nicotine may exert its effects through the calcium signaling pathway, and it was verified that nicotine elevated mitochondrial Ca2+ levels and upregulated MCU expression. Knockdown of MCU reversed the effects of nicotine on mitochondrial calcium homeostasis, improved mitochondrial oxidative stress damage and structural dysfunction, thereby alleviating the activation of PSCs. In vivo validation experiments showed that nicotine significantly aggravated pancreatic fibrosis in CP mice, promoted PSCs activation, exacerbated pancreatic tissue oxidative stress, and increased MCU expression. However, treatment with Ru360 significantly mitigated these effects. Conclusions This study confirms that nicotine upregulates the expression of MCU, leading to mitochondrial calcium overload and exacerbating oxidative stress in PSCs, and ultimately promoting PSCs activation and exacerbating pancreatic fibrosis in CP.

Abstract X-ray detection is widely used in various applications. However, to meet the demand for high image quality and high accuracy diagnosis, the raw data increases and imposes challenges for conventional X-ray detection hardware regarding data transmission and power consumption. To tackle these issues, we present a scheme of in-X-ray-detector computing based on CsPbBr3 single-crystal detector with convenient polarity reconfigurability, good linear dynamic range, and robust stability. The detector features a stable trap-free device structure and achieves a high linear dynamic range of 106 dB. As a result, the detector could achieve edge extraction imaging with a data compression ratio of ~50%, and could also be programmed and trained to perform pattern recognition tasks with a high accuracy of 100%. Our research shows that in-X-ray-detector computing can be used in flexible and complex scenarios, making it a promising platform for intelligent X-ray imaging.

Abstract Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.

Cigarette smoke(CS) contains a large number of toxic and carcinogenic compounds. CS induces severe lung infections through different molecular and cellular mechanisms of alteration of respiratory tract structure, innate and adaptive immunity and microbiome homeostasis. CS is strongly associated with poor prognosis in corona virus disease 2019(COVID-19). The different mechanisms through which CS effects contribute to the understanding of the pathophysiology of CS-induced severe pneumonia and explore potential medicine.

This paper introduces stochastic disturbances into a semi-parametric SEIR model with infectivity in an incubation period. The model combines the randomness of disease transmission and the nonlinearity of transmission rate, providing a flexible framework for more accurate description of the process of infectious disease transmission. On the basis of the discussion of the deterministic model, the stochastic semi-parametric SEIR model is studied. Firstly, we use Lyapunov analysis to prove the existence and uniqueness of global positive solutions for the model. Secondly, the conditions for disease extinction are established, and appropriate stochastic Lyapunov functions are constructed to discuss the asymptotic behavior of the model’s solution at the disease-free equilibrium point of the deterministic model. Finally, the specific transmission functions are enumerated, and the accuracy of the results are demonstrated through numerical simulations.

In this paper, we present a novel three-dimensional (3D) coupled configuration of piezoelectric micromachined ultrasound transducers (pMUTs) by combing a curved and an annular diaphragm for transmit performance optimization in biomedical applications. An analytical equivalent circuit model (EQC) is developed with varied excitation methods to incorporate the acoustic–structure coupling of the curved and annular diaphragm-coupled pMUTs (CAC-pMUTs). The model-derived results align well with the reference simulated by the finite element method (FEM). Using this EQC model, we optimize the key design parameters of the CAC-pMUTs in order to improve the output sound pressure, including the width of the annular membrane, the thickness of the passive layer, and the phase difference of the driving voltage. In the anti-phase mode, the designed CAC-pMUTs demonstrate a transmit efficiency 285 times higher than that of single annular pMUTs. This substantial improvement underscores the potential of CAC-pMUTs for large array applications.

Alternaria mycotoxins are the secondary metabolites of Alternaria species, which have obvious toxicity （mutagenicity, teratogenicity and carcinogenicity, etc） to humans and animals. Alternariol （AOH）, alternariol monomethyl ether （AME）, alternuene （ALT）, tenuazonic acid （TeA） and tenoxin （TEN） are the most studied at present. Alternaria mycotoxins was reported in apples, orange, tomatoes, corns and other agricultural products. Eating these foods contaminated by Alternaria mycotoxins will cause serious harm to human health. In this paper, the pollution status and the detection technology of Alternaria mycotoxins were summarized, and the future research direction of Alternaria mycotoxins was prospected. The purpose was to provide references for the risk assessment, detection and prevention of Alternaria mycotoxins in foods.

Abstract Lead halide perovskites have recently emerged as promising X/γ-ray scintillators. However, the small Stokes shift of exciton luminescence in perovskite scintillators creates problems for the light extraction efficiency and severely impedes their applications in hard X/γ-ray detection. Dopants have been used to shift the emission wavelength, but the radioluminescence lifetime has also been unwantedly extended. Herein, we demonstrate the intrinsic strain in 2D perovskite crystals as a general phenomenon, which could be utilized as self-wavelength shifting to reduce the self-absorption effect without sacrificing the radiation response speed. Furthermore, we successfully demonstrated the first imaging reconstruction by perovskites for application of positron emission tomography. The coincidence time resolution for the optimized perovskite single crystals (4 × 4 × 0.8 mm3) reached 119 ± 3 ps. This work provides a new paradigm for suppressing the self-absorption effect in scintillators and may facilitate the application of perovskite scintillators in practical hard X/γ-ray detections.

Abstract Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.

The Euodia genus comprises numerous untapped medicinal plants that warrant thorough evaluation for their potential as valuable natural sources of herbal medicine or food flavorings. In this study, untargeted metabolomics and in vitro functional methods were employed to analyze fruit extracts from 11 significant species of the Euodia genus. An investigation of the distribution of metabolites (quinolone and indole quinazoline alkaloids) in these species indicated that E. rutaecarpa (Euodia rutaecarpa) was the most widely distributed species, followed by E. compacta (Euodia compacta), E. glabrifolia (Euodia glabrifolia), E. austrosinensis (Euodia austrosinensis), and E. fargesii (Euodia fargesii). There have been reports on the close correlation between indole quinazoline alkaloids and their anti-tumor activity, especially in E. rutaecarpa fruits which exhibit effectiveness against various types of cancer, such as SGC-7901, Hela, A549, and other cancer cell lines. Additionally, the E. rutaecarpa plant contains indole quinazoline alkaloids, which possess remarkable antibacterial properties. Our results offer novel insights into the utilization of Euodia resources in the pharmaceutical industry.

Lithium (Li) metal batteries (LMBs) are regarded as promising next-generation rechargeable batteries owing to the high theoretical specific capacity and the lowest potential of the Li metal anode (LMA). Nevertheless, the practical applications of LMA have been restricted by uncontrollable Li dendrite growth, enormous volume change and unstable interfaces between LMA and electrolyte. Among all the available strategies, the rational designs of artificial interphase layers (AILs) are the promising methods to solve these problems at the interfaces between LMA and electrolyte. In this review, we generally summarize the recent typical examples of in/ex-situ formed AILs for stabilizing LMA/electrolyte interfaces. Particular considerations have been taken on the components and structure characterizations in the design principle of AILs for suppressing uncontrollable Li dendrites growth, constructing stable interfaces and addressing the huge volume variation. Finally, the remaining challenges and the research direction for high performance AILs for safe and stable LMBs are provided.

Obesity has become a global pandemic. WDTC1 is a WD40-containing protein that functions as an anti-obesity factor. WDTC1 inhibits adipogenesis by working as an adaptor of the CUL4-DDB1 E3 ligase complex. It remains unclear about how WDTC1 is regulated. Here, we show that the TRiC/CCT functions as a chaperone to facilitate the protein folding of WDTC1 and proper function in adipogenesis. Through tandem purification, we identified the molecular chaperone TRiC/CCT as WDTC1-interacting proteins. WDTC1 bound the TRiC/CCT through its ADP domain, and the TRiC/CCT recognized WDTC1 through the CCT5 subunit. Disruption of the TRiC/CCT by knocking down CCT1 or CCT5 led to misfolding and lysosomal degradation of WDTC1. Furthermore, the knockdown of CCT1 or CCT5 eliminated the inhibitory effect of WDTC1 on adipogenesis. Our studies uncovered a critical role of the TRiC/CCT in the folding of WDTC1 and expanded our knowledge on the regulation of adipogenesis.

Abstract Our general purpose was to examine the effect of condensed Fuzheng extract (CFE) on the alleviation of immunosuppression. A mouse model of immunosuppression was established by intraperitoneal injection of CTX. A healthy control group received no CTX and no CFE; different intragastric doses of CFE were administered to three groups of mice for 28 days (4500, 2250, or 1125 mg/kg/day); a negative control received CTX alone, and a positive control received CTX and levamisole hydrochloride. We evaluated the effects of CFE on the immune system organs, cells, and molecules by comparing the different groups. CFE significantly improved immune system organs (spleen and thymus indices and histology), stimulated immune cell activities (number of white blood cells and lymphocytes, phagocytosis of mononuclear phagocytes, proliferation of splenic lymphocytes, antibody formation, and NK cell activity), and increased the levels of immunoglobulins (IgA, IgG, and IgM) and cytokines (IL‐2 and IFN‐γ). Thus CFE effectively alleviated CTX‐mediated immunosuppression and oxidative stress and enhanced the immunological functions of mice.

EGFR is aberrantly activated in many cancer types. Here the authors show that small GTPase ARF6 mediates the trafficking of palmitoylated EGFR from Golgi to plasma membrane and the blockade of this sorting system inhibits the growth of EGFR overexpression tumours.