Epitaxial Growth of Two-Dimensional Nonlayered AuCrS2 Materials via Au-Assisted Chemical Vapor Deposition.

Two-dimensional (2D) nonlayered transition metal dichalcogenide (TMD) materials are emergent platforms for various applications from catalysis to quantum devices. However, their limited availability and nonstraightforward synthesis methods hinder our understanding of these materials. Here, we present a novel technique for synthesizing 2D nonlayered AuCrS2 via Au-assisted chemical vapor deposition (CVD). Our detailed structural analysis reveals the layer-by-layer growth of [AuCrS2] units atop an initial CrS2 monolayer, with Au binding to the adjacent monolayer of CrS2, which is in stark contrast with the well-known metal intercalation mechanism in the synthesis of many other 2D nonlayered materials. Theoretical calculations further back the crucial role of Cr in increasing the mobility of Au species and strengthening the adsorption energy of Au on CrS2, thereby aiding the growth throughout the CVD process. Additionally, the resulting free-standing nanoporous AuCrS2 (NP-AuCrS2) exhibits exceptional electrocatalytic properties for the hydrogen evolution reaction.

Small molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in estrogen receptor-positive breast cancer overcomes tamoxifen resistance.

INTRODUCTION: Estrogen receptor (ER) positive patients compromise about 70% of breast cancers. Tamoxifen, an antagonist of ERα66 (the classic ER), is the most effective and the standard first-line drug. However, its efficacy is limited by the development of acquired resistance. METHODS: A specific inhibitor of Hsp70-Bim protein-protein interaction (PPI), S1g-2, together with an inhibitor of Hsp70-Bag3 PPI, MKT-077 and an ATP-competitive inhibitor VER155008, were used as chemical tools. Cell viability assays, co-immunoprecipitation and gene knockdown were used to investigate the role of Hsp70 in tamoxifen resistance. A xenograft model was established in which tamoxifen-resistant breast cancer (MCF-7/TAM-R) cells maintained in the presence of 5 µM tamoxifen were subcutaneously inoculated. The anti-tumor efficiency of S1g-2 was measured after a daily injection of 0.8 mg/kg for 14 days. RESULTS: It was revealed that Hsp70-Bim PPI protects ERα-positive breast cancer from tamoxifen-induced apoptosis through binding and stabilizing ERα36, rather than ERα66, resulting in sustained EGFR mRNA and protein expression. Disruption of Hsp70-Bim PPI and downregulation of ERα36 expression in tumor samples are consistent with the in vitro functions of S1g-2, resulting in about a three-fold reduction in tumor volume. CONCLUSIONS: The in vivo activity and safety of S1g-2 illustrated that it is a potential strategy for Hsp70-Bim disruption to overcome tamoxifen-resistant ER-positive breast cancer.

Yeast Bxi1/Ybh3 mediates conserved mitophagy and apoptosis in yeast and mammalian cells: convergence in Bcl-2 family.

The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate both apoptosis and mitophagy. However, whether similar pathways exist in lower eukaryotes where conical Bcl-2 members are absent remained unclear. Here, a specific inhibitor of the Hsp70-Bim PPI, S1g-10 and its analogs were used as chemical tools to explore the role of yeast Bxi1/Ybh3 in regulating mitophagy and apoptosis. Using Om45-GFP processing assay, we illustrated that yeast Ybh3 mediates a ubiquitin-related mitophagy pathway in both yeast and mammalian cells through association with Hsp70, which is in the same manner with Bim. Moreover, by using Bax/Bak double knockout MEF cells, Ybh3 was identified to induce apoptosis through forming oligomerization to trigger mitochondrial outer membrane permeabilization (MOMP) like Bax. We not only illustrated a conserved ubiquitin-related mitophagy pathway in yeast but also revealed the multi-function of Ybh3 which combines the function of BH3-only protein and multi-domain Bax protein as one.

scAce: an adaptive embedding and clustering method for single-cell gene expression data.

MOTIVATION: Since the development of single-cell RNA sequencing (scRNA-seq) technologies, clustering analysis of single-cell gene expression data has been an essential tool for distinguishing cell types and identifying novel cell types. Even though many methods have been available for scRNA-seq clustering analysis, the majority of them are constrained by the requirement on predetermined cluster numbers or the dependence on selected initial cluster assignment. RESULTS: In this article, we propose an adaptive embedding and clustering method named scAce, which constructs a variational autoencoder to simultaneously learn cell embeddings and cluster assignments. In the scAce method, we develop an adaptive cluster merging approach which achieves improved clustering results without the need to estimate the number of clusters in advance. In addition, scAce provides an option to perform clustering enhancement, which can update and enhance cluster assignments based on previous clustering results from other methods. Based on computational analysis of both simulated and real datasets, we demonstrate that scAce outperforms state-of-the-art clustering methods for scRNA-seq data, and achieves better clustering accuracy and robustness. AVAILABILITY AND IMPLEMENTATION: The scAce package is implemented in python 3.8 and is freely available from https://github.com/sldyns/scAce.

An Improved OMP Algorithm for Enhancing the Anti-Interference Performance of Array Antennas.

The demand for precise positioning in noisy environments has propelled the development of research on array antenna radar systems. Although the orthogonal matching pursuit (OMP) algorithm demonstrates superior performance in signal reconstruction, its application efficacy in noisy settings faces challenges. Consequently, this paper introduces an innovative OMP algorithm, DTM_OMP_ICA (a dual-threshold mask OMP algorithm based on independent component analysis), which optimizes the OMP signal reconstruction framework by utilizing two different observation bases in conjunction with independent component analysis (ICA). By implementing a mean mask strategy, it effectively denoises signals received by array antennas in noisy environments. Simulation results reveal that compared to traditional OMP algorithms, the DTM_OMP_ICA algorithm shows significant advantages in noise suppression capability and algorithm stability. Under optimal conditions, this algorithm achieves a noise suppression rate of up to 96.8%, with its stability also reaching as high as 99%. Furthermore, DTM_OMP_ICA surpasses traditional denoising algorithms in practical denoising applications, proving its effectiveness in reconstructing array antenna signals in noisy settings. This presents an efficient method for accurately reconstructing array antenna signals against a noisy backdrop.

Paeoniflorin Promotes Ovarian Development in Mice by Activating Mitophagy and Preventing Oxidative Stress.

During the development of animal organs, various adverse stimuli or toxic environments can induce oxidative stress and delay ovarian development. Paeoniflorin (PF), the main active ingredient of the traditional Chinese herb Paeonia lactiflora Pall., has protective effects on various diseases by preventing oxidative stress. However, the mechanism by which PF attenuates oxidative damage in mouse ovaries remains unclear. We evaluated the protective effects of PF on ovaries in an H2O2-induced mouse oxidative stress model. The H2O2-induced mouse ovarian oxidative stress model was used to explore the protective effect of PF on ovarian development. Histology and follicular development were observed. We then detected related indicators of cell apoptosis, oxidative stress, and autophagy in mouse ovaries. We found that PF inhibited H2O2-induced ovarian cell apoptosis and ferroptosis and promoted granulosa cell proliferation. PF prevented oxidative stress by increasing nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression levels. In addition, the autophagic flux of ovarian cells was activated and was accompanied by increased lysosomal biogenesis. Moreover, PF-mediated autophagy was involved in clearing mitochondria damaged by H2O2. Importantly, PF administration significantly increased the number of primordial follicles, primary follicles, secondary follicles, and antral follicles. PF administration improved ovarian sizes compared with the H2O2 group. The present study suggested that PF administration reversed H2O2-induced ovarian developmental delay and promoted follicle development. PF-activated mitophagy is crucial for preventing oxidative stress and improving mitochondrial quality.

[Application of discrete element method (DEM) in pharmaceutical process of solid traditional Chinese medicine preparations].

In recent years, the application of numerical simulation in the research and development(R&D) as well as the pharmaceutical processes of new drugs has expanded considerably. The discrete element method(DEM), an important approach among numerical simulation methods, offers an effective tool for the simulation of discontinuous media. Referring to the research progress of DEM and the formulation of solid traditional Chinese medicine(TCM) preparations in recent years, this paper summarizes and analyzes the application of DEM in the pharmaceutical processes of solid TCM preparations, and discusses the challenges of its application in these processes, in order to provide new methods and ideas for promoting the high-quality production of TCM preparations.

[Current situation and development trend of digital traditional Chinese medicine pharmacy].

The 21st century is a highly information-driven era, and traditional Chinese medicine(TCM) pharmacy is also moving towards digitization and informatization. New technologies such as artificial intelligence and big data with information technology as the core are being integrated into various aspects of drug research, manufacturing, evaluation, and application, promoting interaction between these stages and improving the quality and efficiency of TCM preparations. This, in turn, provides better healthcare services to the general population. The deep integration of emerging technologies such as artificial intelligence, big data, and cloud computing with the TCM pharmaceutical industry will innovate TCM pharmaceutical technology, accelerate the research and industrialization process of TCM pharmacy, provide cutting-edge technological support to the global scientific community, boost the efficiency of the TCM industry, and promote economic and social development. Drawing from recent developments in TCM pharmacy in China, this paper discussed the current research status and future trends in digital TCM pharmacy, aiming to provide a reference for future research in this field.

[Critical influencing factors on quality of traditional Chinese medicine preparations from perspective of process and equipment].

The quality of traditional Chinese medicine preparations is directly related to the safety of patients. Among the various factors, the process and corresponding critical equipment are critical factors influencing the quality of the preparations. To improve the quality of traditional Chinese medicine preparations, this article summarizes and analyzes the problems in the process links and corresponding critical equipment in the manufacturing process of traditional Chinese medicine preparations. Furthermore, a critical quality attribute evaluation system is established based on safety and effectiveness combined with the drug properties, preparation process, and preparation characteristics, providing a basis for the process and equipment improvements aimed at quality enhancement.

[Scientific connotation of temperature control in processing of Chinese medicinal materials based on theory of quality evaluation through morphological identification].

Processing of Chinese medicinal materials is an important part in the Chinese medicine heritage, and the temperature control in the processing has a direct impact on the quality and efficacy of traditional Chinese medicines. However, the processing of Chinese medicinal materials has the problems of subjective temperature judgement, determination of the end point based on experience, unclear processing mechanism, unstable quality of products, and inconsistent processing standards. The temperature control in the processing is reflected in the appearance and internal quality of Chinese medicinal materials. The theory of quality evaluation through morphological identification is developed based on the comprehensive evaluation of the shape, color, taste, and components, which is associated with the temperature control in the processing. To solve the problems above, this paper puts forward the following solutions. The first is literature mining. By review of the ancient medical works and pharmaceutical experience, the temperature control in processing and the evolution of processing methods can be revealed. Second, according to the ancient method, the processing principle can be explored, on the basis of which the processing technology can be innovated. Third, the standard operating procedure(SOP) should be established to quantify the fire temperature, providing a theoretical basis for the formulation of Chinese medicinal material processing standards. Moreover, it provides a basis for improving the quality of processed products and increasing the safety and effectiveness of traditional Chinese medicines.

Adsorptive decontamination of antibiotics from livestock wastewater by using alkaline-modified biochar.

Efficient abatement of antibiotics from livestock wastewater is in urgent demand, but still challenging. In this study, alkaline-modified biochar with larger surface area (130.520 m2 g-1) and pore volume (0.128 cm3 g-1) was fabricated and explored for the adsorption of different types of antibiotics from livestock wastewater. Batch adsorption experiments demonstrated that the adsorption process was mainly determined by chemisorption and was heterogeneous, which could be moderately affected by the variations of solution pH (3-10). Furthermore, the computational analysis based on density functional theory (DFT) indicated that the -OH groups on biochar surface could serve as the dominant active sites for antibiotics adsorption due to the strongest adsorption energies between antibiotics and -OH groups. In addition, the antibiotics removal was also evaluated in multi-pollutants system, where biochar performed synergistic adsorption towards Zn2+/Cu2+ and antibiotics. Overall, these findings not only deepen our understandings on the adsorption mechanism between biochar and antibiotics, but also promote the application of biochar in the remediation of livestock wastewater.

Hsp70-Bim interaction facilitates mitophagy by recruiting parkin and TOMM20 into a complex.

BACKGROUND: For cancer therapy, the identification of both selective autophagy targets and small molecules that specifically regulate autophagy is greatly needed. Heat shock protein 70 (Hsp70) is a recently discovered BH3 receptor that forms a protein‒protein interaction (PPI) with Bcl-2-interacting mediator of cell death (Bim). Herein, a specific inhibitor of the Hsp70-Bim PPI, S1g-2, and its analog S1, which is a Bcl-2-Bim disruptor, were used as chemical tools to explore the role of Hsp70-Bim PPI in regulating mitophagy. METHODS: Co-immunoprecipitation and immunofluorescence assays were used to determine protein interactions and colocalization patterns. Organelle purification and immunodetection of LC3-II/LC3-I on mitochondria, endoplasmic reticulum (ER) and Golgi were applied to identify specific types of autophagy. Cell-based and in vitro ubiquitination studies were used to study the role of the Hsp70-Bim PPI in parkin-mediated ubiquitination of outer mitochondrial membrane 20 (TOMM20). RESULTS: We found that after the establishment of their PPI, Hsp70 and Bim form a complex with parkin and TOMM20, which in turn facilitates parkin translocation to mitochondria, TOMM20 ubiquitination and mitophagic flux independent of Bax/Bak. Moreover, S1g-2 selectively inhibits stress-induced mitophagy without interfering with basal autophagy. CONCLUSIONS: The findings highlight the dual protective function of the Hsp70-Bim PPI in regulating both mitophagy and apoptosis. S1g-2 is thus a newly discovered antitumor drug candidate that drives both mitophagy and cell death via apoptosis.

Enhanced Readout from Spatial Interference Fringes in a Point-Source Cold Atom Inertial Sensor.

When the initial size of an atom cloud in a cold atom interferometer is negligible compared to its size after free expansion, the interferometer is approximated to a point-source interferometer and is sensitive to rotational movements by introducing an additional phase shear in the interference sequence. This sensitivity on rotation enables a vertical atom-fountain interferometer to measure angular velocity in addition to gravitational acceleration, which it is conventionally used to measure. The accuracy and precision of the angular velocity measurement depends on proper extraction of frequency and phase from spatial interference patterns detected via the imaging of the atom cloud, which is usually affected by various systematic biases and noise. To improve the measurement, a pre-fitting process based on principal component analysis is applied to the recorded raw images. The contrast of interference patterns are enhanced by 7-12 dB when the processing is present, which leads to an enhancement in the precision of angular velocity measurements from 6.3 µrad/s to 3.3 µrad/s. This technique is applicable in various instruments that involve precise extraction of frequency and phase from a spatial interference pattern.

Dual-Signal Feature Spaces Map Protein Subcellular Locations Based on Immunohistochemistry Image and Protein Sequence.

Protein is one of the primary biochemical macromolecular regulators in the compartmental cellular structure, and the subcellular locations of proteins can therefore provide information on the function of subcellular structures and physiological environments. Recently, data-driven systems have been developed to predict the subcellular location of proteins based on protein sequence, immunohistochemistry (IHC) images, or immunofluorescence (IF) images. However, the research on the fusion of multiple protein signals has received little attention. In this study, we developed a dual-signal computational protocol by incorporating IHC images into protein sequences to learn protein subcellular localization. Three major steps can be summarized as follows in this protocol: first, a benchmark database that includes 281 proteins sorted out from 4722 proteins of the Human Protein Atlas (HPA) and Swiss-Prot database, which is involved in the endoplasmic reticulum (ER), Golgi apparatus, cytosol, and nucleoplasm; second, discriminative feature operators were first employed to quantitate protein image-sequence samples that include IHC images and protein sequence; finally, the feature subspace of different protein signals is absorbed to construct multiple sub-classifiers via dimensionality reduction and binary relevance (BR), and multiple confidence derived from multiple sub-classifiers is adopted to decide subcellular location by the centralized voting mechanism at the decision layer. The experimental results indicated that the dual-signal model embedded IHC images and protein sequences outperformed the single-signal models with accuracy, precision, and recall of 75.41%, 80.38%, and 74.38%, respectively. It is enlightening for further research on protein subcellular location prediction under multi-signal fusion of protein.

An Ultrasonic RF Acquisition System for Plant Stems Based on Labview Double Layer Multiple Triggering.

Ultrasound is widely used in medical and engineering inspections due to its non-destructive and easy-to-use characteristics. However, the complex internal structure of plant stems presents challenges for ultrasound testing. The density and thickness differences in various types of stems can cause different attenuation of ultrasonic signal propagation and the formation of different echo locations. To detect structural changes in plant stems, it is crucial to acquire complete ultrasonic echo RF signals. However, there is currently no dedicated ultrasonic RF detection equipment for plant stems, and some ultrasonic acquisition equipment has limited memory capacity that cannot store a complete echo signal. To address this problem, this paper proposes a double-layer multiple-timing trigger method, which can store multiple trigger sampling memories to meet the sampling needs of different plant stems with different ultrasonic echo locations. The method was tested in experiments and found to be effective in acquiring complete ultrasonic RF echo signals for plant stems. This approach has practical significance for the ultrasonic detection of plant stems.

Analysis of Intestinal Metabolites in SR-B1 Knockout Mice via Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry.

Scavenger receptor class B type 1 (SR-B1), a multiligand membrane receptor, is expressed in a gradient along the gastrocolic axis. SR-B1 deficiency enhances lymphocyte proliferation and elevates inflammatory cytokine production in macrophages. However, whether SR-B1 affects intestinal metabolites is unclear. In this study, we detected metabolite changes in the intestinal tissue of SR-B1-/- mice, including amino acids and neurotransmitters, by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and HPLC. We found that SR-B1-/- mice exhibited changes in intestinal lipid metabolites and metabolic pathways, including the glycerophospholipid, sphingolipid, linoleic acid, taurine, and hypotaurine metabolic pathways. SR-B1 deficiency influenced the contents of amino acids and neurotransmitters in all parts of the intestine; the contents of leucine (LEU), phenylalanine (PHE), tryptophan (TRP), and tyrosine (TYR) were affected in all parts of the intestine; and the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were significantly decreased in both the colon and rectum. In summary, SR-B1 deficiency regulated intestinal lipids, amino acids, and neurotransmitter metabolism in mice.

Ectopic BH3-Only Protein Bim Associates with Hsp70 to Regulate Yeast Mitophagy.

Mitophagy, a form of selective autophagy, plays an essential role to maintain a population of healthy and functional mitochondria for normal cellular metabolism. Acting mainly as one of the B-cell lymphoma 2 (Bcl-2) family pro-apoptotic members, Bim (also known as BCL2L11) was identified to be a co-chaperone of Hsp70 to promote mitophagy in mammalian cells. Herein, with the help of a specific Hsp70/Bim disruptor and Om45-GFP processing assay, we illustrated that ectopic BimEL is able to promote mitophagy through Hsp70/Bim interaction in yeast, where Bax/Bak is absent. The Hsp70/Bim-mediated mitophagy is conserved in eukaryotes, from yeast to humans.

[Current status, trends, and challenges of continuous manufacturing technology for oral traditional Chinese medicine solid preparations].

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.

A Near-Infrared Light-Activated Photocage Based on a Ruthenium Complex for Cancer Phototherapy.

Conventional photocages only respond to short wavelength light, which is a significant obstacle to developing efficient phototherapy in vivo. The development of photocages activated by near-infrared (NIR) light at wavelengths from 700 to 950 nm is important for in vivo studies but remains challenging. Herein, we describe the synthesis of a photocage based on a ruthenium (Ru) complex with NIR light-triggered photocleavage reaction. The commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated to the RuII center to create the Ru-based photocage that is readily responsive to NIR light at 760 nm. The photocage inherited the anticancer properties of THC. As a proof-of-concept, we further engineered a self-assembled photocage-based nanoparticle system with amphiphilic block copolymers. Upon exposure to NIR light at 760 nm, the Ru complex-based photocages were released from the polymeric nanoparticles and efficiently inhibited tumor proliferation in vivo.

Identification of cuproptosis-related lncRNAs for prognosis and immunotherapy in glioma.

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis-related genes have prognostic predictive value has not been clarified. In this study, uni-/multi-variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis-related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high- and low-risk groups. Either for grade 2-3 or for grade 4, glioma patients with high-risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high-risk group was functionally associated with immune responses and cancer-related pathways. The high-risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high-risk group were significantly higher than those in the low-risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T-cell co-stimulation pathways. In conclusion, we established a risk model based on cuproptosis-related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno-microenvironment status of glioma.